journal

Transcription

journal

VOL. 16 - (1) - APRIL 2006
ISSN 1018-2357
The European Journal of
Companion
Animal Practice
Canine inflammatory bowel disease 33
The safe use of cytotoxic drugs in companion animal practice 51
Mandibulectomy and maxillectomy as a treatment for
bone invasive oral neoplasia in the dog 73
Feline paediatric medicine 83
THE OFFICIAL JOURNAL OF FECAVA
Federation of European Companion Animal Veterinary Associations
www.fecava.org
(EJCAP)
Volume 16 (1) April 2006
The Official Journal of the Federation
of European Companion Animal
Veterinary Associations (FECAVA).
Editor
Dr. Keith DAVIES
43, Hill Top Road - Newmillerdam
GB-WF2 6PZ Wakefield
Tel.: (44) 1924 250486 (UK)
(33) 4 68 39 50 29 (F)
Fax: (44) 1924 259572
Email: [email protected]
Production Committee
Dr Ellen BJERKÅS, FECAVA President
Dr. Keith DAVIES, Editor
Dr. Maurice ROZE
Dr. Joaquin ARAGONES
Dr. Peter STERCHI
Dr. Tiina TOOMET
Dr. Johan VAN TILBURG
Dr. Simon KLEINJAN
Editorial board (for new work)
DERMATOLOGY
Didier-Noël CARLOTTI (F)
CARDIOLOGY
Anna TIDHOLM (S)
INTERNAL MEDICINE Åke HEDHAMMAR (S)
ORTHOPAEDICS
Aldo VEZZONI (I)
SURGERY
Simon ORR (GB)
IMAGING
Ingrid GIELEN (B)
Eiliv SVALASTOGA (DK)
REPRODUCTION
Stefano ROMAGNOLI (I)
DENTISTRY
Peter FAHRENKRUG (D)
OPHTHALMOLOGY Ellen BJERKÅS (N)
NEUROLOGY
Andre JAGGY (CH)
ENDOCRINOLOGY
Mike HERRTAGE (GB)
ONCOLOGY
Jane DOBSON (GB)
Material should be sent to:
Prof.Ellen BJERKÅS,
Norwegian School of Veterinary Science,
PO Box 8146-Dep, N- 0033, Oslo.
Advertisement bookings
Sould be sent to:
The Editor (see above)
Circulation
Members of the Associations belonging to the
Federation of European Companion Animal
Veterinary Associations receive the European
Journal of Companion Animal Practice at no
charge (30,000 copies).
Purchase of copies
For others interested in purchasing copies the
price is 52 € per Volume (2 issues). Orders
should be sent to:
FECAVA Bookkeeping - Valeriusstraat 255-2
NL-1075 GB Amsterdam
The Netherlands
Thanks
The production Committee of EJCAP thanks:
Dr. Keith Davies
Prof. Peter Holt
Dr. Tim Hutchinson
Dr. Edmund Shillabeer
Dr. Paul Wotton
who have spent time correcting the translations.
DISCLAIMER
“The Federation of European Companion Animal
Veterinary Associations and the Production
Committee of the European Journal of Companion
Animal Practice accept no responsibility for any
omissions and/or errors in information printed in
this journal.We specifically draw readers attention
to the need to follow instructions of manufacturers
products. In any specific situation readers are
strongly advised not merely to rely on the material
contained in the journal. Any views and opinions
expressed are those of the writer and not the
Federation or the Production Committee.”
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Direttore Responsabile : Antonio MANFREDI.
Roto Smeets GrafiServices,
p.o. box 7052, 3502 KB Utrecht,
The Netherlands. Tel +31 (30) 282 28 22
The European Journal of
Companion
Animal Practice
CONTENTS
The Federation of European Companion Animal Veterinary
Associations (FECAVA)..................................................................2
EDITORIAL .......................................................................................5
NEWS .......................................................................................................10
DERMATOLOGY
Application of honey in the treatment of skin wounds
P.A.M. Overgaauw, J.Kirpensteijn.............................................. 17
ORTHOPEADICS
A case of periosteal proliferative polyarthritis in a cat
M. Karayannopoulou, Z.S. Polizopoulou, A.F. Koutinas,
M.N. Patsikas,G. Kazakos, A. Fytianou...................................... 21
Putting theory into practice - best practice
management for osteoarthritis
Stuart Carmichael ..................................................................... 27
GASTROINTESTINAL SYSTEM
Canine inflammatory bowel disease: retrospective
analysis of diagnosis and outcome in 80 cases (1995-2002)
M. Craven, J. W. Simpson, A. E. Ridyard, M. L. Chandler .......... 33
URINARY TRACT
Transpelvic urethrostomy (TPU) in the cat: a new
technique. Prospective survey: 19 cases
A. Bernardé, E. Viguier.............................................................. 41
ONCOLOGY
The safe use of cytotoxic drugs in companion
animal practice
Nick Bexfield ............................................................................. 51
The future of Biomarkers and Personalised Medicine
in Companion Animal Practice
S. Mian, K. Slater, T. Cave ......................................................... 63
Mandibulectomy and maxillectomy as a treatment
for bone invasive oral neoplasia in the dog –
a retrospective analysis of 31 patients
Martin Kessler ........................................................................... 73
INTERNAL MEDICINE
Feline paediatric medicine
Kit Sturgess ................................................................................ 83
PARASITOLOGY
Autochthonous infections with Angiostrongylus
vasorum in dogs in Switzerland and Germany
S. Staebler, H. Ochs, F. Steffen, F. Naegeli, N. Borel,
N. Sieber-Ruckstuhl, P. Deplazes................................................ 95
PRACTICE MANAGEMENT
Patterns in Practice ownership: a UK perspective
F. J. Marshall ........................................................................... 101
Book Reviews...............................................................................106
Calendar of main European national meetings and other
continuing education opportunities ............................................110
Secretariat or address to contact for information .......................112
THE FEDERATION OF EUROPEAN
COMPANION ANIMAL
VETERINARY ASSOCIATIONS
(FECAVA)
FECAVA Headquarter's address:
C/O Federation of Veterinarians of Europe
rue Defacqz, 1 B-1000 Brussels
Tel: +32 2 538 29 63 – Fax: +32 2 537 28 28
FECAVA Website: www.fecava.org
Participating Associations:
– AFVAC (CNVSPA) (Association Française des
Vétérinaires pour Animaux de Compagnie)
Director: Dr. Maurice ROZE
– AIVPA (Associazione Italiana Veterinari Piccoli
Animali)
Director: Dr. Guiseppe TRANCHESE
– APMVEAC (Associação Portuguese de Médicos
Veterinários Especialistas em Animais
de Companhia)
Director: Dr. Joaquim Vieira LOPEZ
– AVEPA (Associatión Veterinaria Española
de Especialistas en Pequeños Animales)
Director: Dr. Juan Francisco RODRIGUEZ
– BASAV (Bulgarian Small Animal Veterinarians)
Director: Dr. Boyko GEORGIEV
– BHSAVA (Bosnia and Herzegovina
Small Animal Veterinary Association)
Director: Dr. Josip KRASNI
– BSAVA (British Small Animal Veterinary
Association)
Director: Dr. Simon ORR
– CSAVA (Czech Small Animal Veterinary
Association)
Director: Dr. Jiri BERANEK
– CSAVS (Croatian Small Animal Veterinary
Section)
Director: Dr. Davorin LUKMAN
– DSAVA (Danish Small Animal Veterinary Association)
Director: Dr. Joergen MIKKELSEN
– ESAVA (Estonian Small Animal Veterinary
Association)
Director: Dr. Tiina TOOMET
– FAVP (Finnish Association of Veterinary
Practitioners)
Director: Dr. Kai SITTNIKOW
– GSAVA (German Small Animal Veterinary
Association)
Director: Dr. Peter FAHRENKRUG
– HSAVA (Hungarian Small Animal Veterinary
Association)
Director: Dr. Julianna THUROCZY
– HVMS (Hellenic Veterinary Medical Society)
Director: Dr. Katerina LOUKAKI
– LAK (Letzebuerger Associatioun vun de
Klengdeiere - Pracktiker)
Director: Dr. Liz JUNIO
– LSAPS (Latvian Small Animal Practitioners Section
of The Latvian Association of Veterinarians)
Director: Dr. Lita KONOPORE
– LSAVA (Lithuanian Small Animal Veterinary
Association)
Director: Dr. Saulius LAURUSEVICIUS
– MSAVA (Macedonion (Fyrom) Small Animal
Veterinary Association)
Director: Dr. S. COKREVSKI
– MVA (Malta Veterinary Association)
Director: Dr. L. VELLA, Dr. A. GRUPETTA
– NACAM (Netherlands Association for
Companion animal Medicine)
Director: Dr. Leen DEN OTTER
– NSAVA (Norwegian Small Animal Veterinary
Association)
Director: Dr. Kjetil DAHL
– PSAVA (Polish Small Animal Veterinary
Association)
Director: Dr. Jerzy GAWOR
– RSAVA (Russian Small Animal Veterinary
Association)
Director: Dr. S. SEREDA
– SAVAB (Small Animal Veterinary Association
of Belgium)
Director: Dr. J. van TILBURG
– SCIVAC (Società Culturale Italiana
Veterinari per Animali da Compagnia)
Director: Dr. Dea BONELLO
– SkSAVA (Slovakia Small Animal Veterinary
Association)
Director: Dr. Tibor BRAUNER
– SMASAP (Serbia and Montenegro Association of
Small Animal Practitioners)
Director: Dr. Denis NOVAK
– SSAVA (Swedish Small Animal Veterinary
Association)
Director: Dr. Anne CARLSWÄRD
– SVK/ASMPA (Schweizerische Vereinigung für
Kleintiermedizin/Association Suisse pour la
Médecine des Petits Animaux)
Director: Dr. Peter STERCHI
– SZVMZ (Slovensko Zdruzenje Veterinariev Za Male
Zivali)
Director: Dr. Bojan ZORKO
– TSAVA (Turkish Small Animal Veterinary
Association)
Director: Prof. Mustafa AKTAS
– USAVA (Ukrainian Small Animal Veterinary
Association)
Director: Dr. Vladlen Mykhaylovich USHAKOV
– VICAS (Veterinary Ireland Companion Animal
Society)
Director: Dr. Peter A. MURPHY
– VÖK (Vereinigung Österreichischer Kleintier
mediziner)
Director: Dr. Silvia LEUGNER
Associate Associations:
– EAVS (European Association for Veterinary
Specialisation)
Contact: Dr. Hans KOCH
– ECVD (European College of Veterinary Dermatology)
Contact: Dr. Dominique HERIPRET
– ECVS (European College of Veterinary Surgeons)
Contact: Mrs Monika GUTSCHER
– ESVC (European Society of Veterinary Cardiology)
Contact: Dr. Chris AMBERGER
– ESFM (European Society for Feline Medicine)
Contact: Claire BESSANT
– ESVCE (European Society of Veterinary Clinical
Ethology)
Contact: Dr. Sarah HEATH
– ESVD (European Society of Veterinary Dermatology)
Contact: Dr. Chiara NOLI
– ESVIM (The European Society of Veterinary Internal
Medicine)
Contact: Dr. F.P. GASCHEN
– ESVN (European Society of Veterinary Neurology)
Contact: Dr. Gualtiero GANDINI
– ESVOT (European Society of Veterinary
Orthopaedics & Traumatology)
Contact: Dr. Aldo VEZZONI
– EVDS (European Veterinary Dental Society)
President: Dr. Margarita GRACIS
– EVSSAR (European Veterinary Society for Small
Animal Reproduction)
Contact: Dr. Catherina LINDE-FORSBERG
FECAVA Officers:
Dr. Ellen BJERKÅS (NSAVA)
President
Dr. Andrew BYRNE (VICAS)
Vice-President
Dr. Simon KLEINJAN (NACAM)
Senior Vice-President
Dr. Simon ORR (BSAVA)
Secretary
Dr Johan van TILBURG (SAVAB)
Treasurer
®
IAM S C L IN ICAL N UT R IT IO N SY MPO S I U M
®
“Life is movement; movement is life”
(Aristotle 384-322BC)
International experts discuss advances in veterinary and human medicine to improve mobility
When we think of “quality of
between human and canine mobility, and in particular how
life”, whether it is for humans or
canine mobility and state-of-the-art joint replacement can
pets, freedom of movement is a
benefit human health. It seems that both human doctors
key component and is associated
and veterinarians are increasingly treating behaviour and
with health and positive interac-
lifestyle-influenced diseases which are in fact preventable.
tion with the environment. Yet
with the prevalence of mobility-
The press conference, featuring a panel of leading veterinary
related morbidity on the rise,
experts, also confirmed that trends in human sedentary life-
nutrition and physical activity are
styles are being replicated in pets and it is known that an
playing an increasingly important role in preventative care.
overweight pet owner is more likely to have an overweight
Veterinarians play a crucial role in providing advice, treatment
pet. It was concluded that veterinary expertise combined with
and guidance on many aspects relating to pets’ mobility.
the education of the pet owner was ultimately the route to
improving the mobility and long-term well-being of pets, and
To discuss these important areas of veterinary medicine, The
could also help improve the owner’s lifestyle and well-being.
Iams Company brought together renowned expert speakers
The Iams Company is celebrating its 60th anniversary this
and 240 veterinary guests from 20 European countries and
year and has been setting the standards in innovative dog
South Africa for a Clinical Nutrition Symposium on “Mobility
– a multi-disciplined approach”, held on 11 February 2006
in Montreux, Switzerland.
The speakers approached the topic of mobility from many
different angles: from diagnostic imaging, to arthroscopy and
surgical joint repair, as well as the impact that nutrition,
physiotherapy and rehabilitation can have on the orthopaedic
patient. The symposium highlighted an interesting parallel
Speakers from left to right: Professor Dr. H. van Bree, Veterinary Faculty, Ghent University,
Belgium. John Houlton, Cambridge University Veterinary School, United Kingdom.
Dr. Jean-François Bardet, Veterinary Clinic Neuilly Sur Seine, France. Dr. Daniel Carey,
Research and Development Division, The Iams Company, Ohio, USA. Professor Dr. Ulrike
Matis, Ludwig-Maximilians-University Munich, Germany. Professor Dr. Volkmar Jansson,
University Clinic Grosshadern, München, Germany. Barbara Bockstahler, University of
Veterinary Medicine, Vienna, Austria. Erik Hemmingsson, Karolinska University Hospital
Stockholm, Sweden. David Morgan, The Iams Company, Geneva, Switzerland.
and cat nutrition for decades. For more information about
the Iams Clinical Nutrition Symposium, a copy of the proFrom left to right: Erik Hemmingsson, Karolinska University Hospital, Stockholm, Sweden,
Dr. Jean-François Bardet, Veterinary Clinic Neuilly Sur Seine, France, Dr. Daniel Carey,
Research and Development Division, The Iams Company, Ohio, USA, Barbara Bockstahler,
University of Veterinary Medicine, Vienna, Austria, David Morgan, The Iams Company,
Geneva, Switzerland
ceedings or the press conference report, please contact your
Iams Veterinary Sales Representative or download from
www.eukanuba-scienceonline.com.
EDITORIAL
THE CHANGING STYLE OF
VETERINARY PRACTICE
What will tomorrow’s companion animal veterinary practice be like? What will be the main influences on this ?
The traditional style of practice has evolved over the years. In many countries practices used to be mixed,
treating all species, large and small, and they were at one time predominantly single-vet practices. Over the years,
practice size has grown to multi-vet and multi-branch in many countries and specialization has occurred. Initially
demarcation was by main species groups e.g. Companion animal, Equine and Farm Animal etc. As veterinary
science has evolved, specialization by clinical discipline has grown. Initially this was largely confined to veterinary
teaching institutions but now private specialist referral practices are becoming increasingly common.
All these changes mirror the scientific developments within the field of veterinary medicine and surgery, and
the trend towards continuous post-graduate education.
The commercial aspect of practice is an integral part of delivering quality veterinary services. It is perhaps
inevitable that as the scientific evolution of practice has developed that practice management is open to influence by
business models for service delivery from other sectors. We are now seeing an evolution in the style of delivery of
veterinary services that mirror the demands of the consumer more than just mirroring the trends in education and
scientific development. These evolutionary shifts challenge the traditional models of ownership, organization, style
and delivery. These new models include corporate groups of chain practices in which the ownership is centralized
within a limited company or shared between a central investment group and the owner-operator of the individual
practice unit. Individual presentation of premises is replaced in some by a branded corporate identity. The
traditional range of services is challenged with the advent of selected service clinics e.g. vaccination clinics and
neutering clinics. The introduction of after-hours emergency centres is also spreading in some European countries.
Precedents are established and dissemination of ideas is probably inevitable. This is change – some of which will be
judged to be progressive and welcome while some will be regarded as challenging traditional values and therefore
unwelcome.
FECAVA wishes to highlight some these new models to inform and stimulate debate. Therefore the “practice
profile” in this issue will illustrate a selection of examples of some of the new practice service models. There is no
implicit endorsement or criticism of any of the systems. The intention is simply to illustrate the type of change that is
occurring within companion animal practice in Europe.
Andrew Byrne, Vice President FECAVA
5
Avian influenza - An update
At the time of going to press, avian influenza cases had been diagnosed in wild birds, mainly swans, in several European
countries, and the first confirmation of a H5N1 virus in a turkey farm in France had hit the headlines. By the time you
read this, the Asian H5N1 virus has probably spread to even more regions in Europe. Poultry farmers and veterinarians
are on a permanent look-out.
But companion animal veterinarians too, are confronted daily with questions from their clients. Here’s some
background information to fill in some (possible) gaps.
What is avian influenza and what are the clinical signs?
Avian influenza (AI) is a highly infectious disease affecting many
avian species, including commercial, wild and pet birds. It is
caused by a Type A influenza virus.
Clinical disease in terrestrial (non aquatic) birds is severe.
Typically, the disease occurs suddenly with affected birds
showing oedema of the head, cyanosis of the comb and wattles,
dullness, lack of appetite, respiratory distress, diarrhoea and
drop in egg production. In severe cases, birds may die without
any signs of disease. However, there is considerable variation in
the clinical picture and severity of the disease, depending on the
strain of virus and the type of bird infected. For example,
waterfowl are less likely to be clinically affected and therefore
more likely to spread the disease.
Post-mortem findings vary considerably but congestion and
haemorrhages affecting any organs usually predominate.
Necrotic foci may be found in the liver, lungs, spleen and
kidneys. There may also be exudates in the air sacs and
peritoneum and occasionally a fibrinous pericarditis.
How does the disease spread to humans? And between
humans?
For AI, close contact with birds that have been infected by (or
recently died from) the H5N1 virus is required. In Vietnam and
Thailand, several intra-familial clusters of infection have been
observed. Epidemiological investigation showed that each
cluster had a common source of exposure: either their own
backyard poultry or dead birds at home.
However, the number of human cases in South-East Asia is
extremely low: less than 180 cases (of which 90 fatalities)
occurred in a region with a population of over two billion —
over a two-and-a-half year period. Horizontal transmission is
also low: only a couple of infections have occurred in persons
(family or nursing staff) caring for a clinically sick patient.
I work with birds / have birds at home. How can I protect
myself?
Again, AI is primarily a disease of birds — not humans. And AI
is not the only infection that can be transmitted from birds to
people: salmonellosis, chlamydiosis, psittacosis and
campylobacteriosis are well-known zoonoses. Good hygiene
precautions, which should always be used when working with
birds, will also control the risk of exposure to AI. These include:
regular hand-washing, avoiding hand-to-mouth contact,
thorough cleaning and covering of all cuts and grazes, and
eating away from the area where birds are.
Furthermore, hand-feeding semi-wild birds such as ducks and
swans should be avoided in case of an AI outbreak. So far, no
infected pigeons have been detected in Europe.
Can I protect myself by having a ‘flu vaccination? Or by
taking antivirals?
Seasonal influenza vaccines for people have an antigenic
composition that is changed annually to match the antigenic drift
of the current human epidemic strains: H1N1, H3N2 and
influenza-B virus. The likelihood that the N1 antigen of the
vaccine might confer cross-protection against H5N1 is remote.
Nevertheless, in case of an H5N1 pandemic, it may be
recommended for exposed health care professionals to be
vaccinated against the seasonal ‘flu in order to avoid a
concurrent infection with different viral strains.
Antiviral drugs such as oseltamavir (Tamiflu®) might have
adverse effects and should not be taken lightly, and certainly not
as a prophyaxis if there is no immediate risk. However, they
may be used as treatment within 36 hours of the onset of clinical
symptoms, and can be taken if so advised by your Health
Authorities.
Finally, since Pneumococcus is a common pathogen in severe
pulmonary infections, the use of a pneumococcal vaccine is
considered as a reasonable protection against possible
complications.
I heard that cats may catch avian influenza, is that true?
Experimental studies have shown that felines are highly sensitive
to the Asian strain of H5N1 infection. But in these studies, a high
titre of inoculum was used. And although there is also some
experimental evidence that the virus could spread from cat to
cat, there is considerable uncertainty about whether this would
take place in a natural setting.
Unpublished data indicate that tigers in Thailand became
infected after being fed cadavers of infected birds. But as cats
are hunters rather than scavengers, the risk that domestic cats
would be infected by eating dead (but still infectious) birds
during an outbreak, is considered very low.
What about a pandemic?
AI is primarily a disease of birds. Transmission to humans in
close contact with poultry or other birds occurs rarely and only
with some strains of AI.
There is potential for mutation of AI viruses to new forms of
virus that could cause severe disease in humans and spread
easily from person to person. Such a mutation may occur
tomorrow. Or in ten years. Or never. Nobody is able to predict
this.
Update prepared by Karin de Lange DVM - [email protected]
- with thanks to Vincent Dedet, DVM, Auzalide Santé Animale.
Editor’s note
Further information can be obtained by navigating the following Websites:
In English: DEFRA http://www.defra.gov.uk and for human concerns http://www.hpa.org.uk
In Spanish: http://www.msc.es/Diseno/enfermedadesLesiones/enfermedades_transmisibles.htm
In French: www.sante.gouv.fr/htm/dossiers/grippe_aviaire/sommaire.htm
FVE :
http://www.fve.org
WHO: http://www.who.int/en
WSAVA: http://www.wsava. OIE: www.oie.int
8
FECAVA NEWS
FECAVA FIRST AGAIN !
Ellen Bjerkås takes over as President
FECAVA is the first of the three main European Veterinary
Federations to elect a woman as its President. At the
FECAVA Council meeting in Krakow, Ellen Bjerkås was
unanimously elected as the Federation’s 6th President.
Ellen became a member of the FECAVA Council
nine years ago representing Norway. More
recently she was FECAVA Treasurer for 2 years
carefully managing budgets and financial policy.
After this she served two years as Vice-President
of the Federation. In addition Ellen has been
very active in EJCAP affairs, being a member of
the management committee for the last 7 years.
She has always been a guardian of the maintenance of high
scientific standards in published work, but also has been
particularly keen to see a good representation in EJCAP of all
Member Associations. In 2000 we started to seek new, non
reprint ,work for the Journal and Ellen became Chairman of the
Editorial Board. A lot of new work has been submitted, but
Ellen has always endeavoured to ensure that papers are carefully
peer reviewed. Inevitably this has meant that many papers have
been rejected.
great demand as an advisor to the Norwegian
salmon industry. Whilst she enjoys this very
much she tells me that a downside is the
necessity of sea trips, often in very inclement
weather! In the Norwegian School of Veterinary
Science she is highly regarded as a teacher and
this means she is a regular speaker in many
European countries.
I was fortunate to have a good chance to talk to Ellen prior to
her assuming office in Krakow. I was a little surprised to find
she still has time for non-veterinary hobbies in addition to
FECAVA work, teaching and research commitments. Her
passions include classical music and a house on the Costa
Blanca. The latter is convenient for contacting our Spanish
Ellen is highly regarded as a teacher
It is difficult to see how Ellen manages to find time to undertake
all this work for FECAVA. She is Professor in the Small Animal
Section at the Norwegian School of Veterinary Science. She has
also an international reputation in fish eye disease and is in
Working in the field – Salmon eye examination
10
EJCAP - Vol. 16 - Issue 1 - April 2006
An accomplished family – L>R Inger, Ellen and Astrid
Director who has a practice in Alicante – but not quite so simple
for others to make contact as her telephone only works on the
roof sun terrace!
annual FECAVA international congresses, FECAVA continuing
education courses and the EJCAP.’ She went on to detail how
financial support is provided to national associations with
restricted budgets to help them arrange high-quality CE courses.
‘An essential source of good scientific information is the our
journal (EJCAP), which has developed significantly during the
last few years. The journal is probably the most important “gift”
from FECAVA to the federation’s members, and new ideas and
improvements are constantly discussed and implemented’ said
Ellen.
Ellen has two accomplished daughters, the elder, Astrid, is the
Editor of the Norwegian Veterinary Journal. Her new ideas and
journalistic skills have made a big impact on that Journal. Family
background possibly also plays a part as her father is also a
Professor in the Norwegian School of Veterinary Science. Her
other daughter Inger, has a non-veterinary career as a
salesperson for the Dior Company and is also trained as an
actress and singer.
She told me that she feels that FECAVA should also continue to
be actively involved in establishing formal recognition for
different groups of practitioners based on quality-controlled
continuing education and encourage companion animal
practitioners to be constantly concerned about the standard of
the clinical work delivered.
I asked Ellen how she felt she could help further develop
FECAVA. She told me that with the rapid increase in companion
animal practice in Europe seen over the last 10-15 years, there
are certainly challenges ahead. She said ‘I see the role of FECAVA
as being both a political body as well as an organisation involved
in continuing education. The latter is achieved through the
She feels that science and politics are closely linked, as has been
seen at the annual FECAVA symposia concerning animal welfare
and hereditary disease control programmes. She went on to say
‘I see the role of FECAVA in these matters not so much as a body
repeating the good work that is already being done by different
groups, but more as a co-ordinator of efforts and an organisation
arranging for people sharing the same interests and concerns to
meet and discuss’.
Ellen’s ophthalmological skills are appreciated even outside
Europe!
‘The role of both companion animal veterinarians is changing.
We will have to be more concerned about the human-animal
bond and the role of pet animals in a modern society, and we
also have a role in educating the public. For this, I think the
FECAVA statements are very important. They show our concern
in important political matters, and I would like to see more
policy statements being discussed and agreed upon.’
The interview was over, as Ellen had to give a lecture at the
PSAVA Congress!
Keith Davies
Editor of EJCAP
11
FECAVA NEWS
FECAVA NEWS
• Journal News
• Election of New FECAVA Board
The November 2005 FECAVA Council meeting took place in
Krakow, Poland. During the meeting, a new Board was elected:
President:
Ellen Bjerkås (Norway)
Vice President
Andrew Byrne (Ireland)
Senior Vice President
Simon Kleinjan (The Netherlands)
Secretary
Simon Orr (United Kingdom)
Treasurer
Johan Van Tilburg (Belgium)
Outgoing President, Simon Kleinjan, said it had been a privilege
to be at the helm of FECAVA over the last two years and thanked
the Board and all Directors for their support and fellowship. In
taking over, Ellen Bjerkås complemented Simon on his hard work
and enthusiasm and then set out her vision for the next two
years. A profile of Ellen is given elsewhere in this issue – we are
looking forward to another successful two years!
EJCAP Readers’ survey
From Ellen Bjerkås (E-mail:[email protected])
The results of the EJCAP readers’ survey that was available on
the FECAVA web page (www.fecava.org) have now been
edited. As promised, there was a prize draw among those who
responded, and the winners of free registration to the
FECAVA/WSAVA/CSAVA congress in Prague and of textbooks
have been notified. Unfortunately we did not have as many
responders as we wished for. However, we extend a great
thank you to all who took the time to answer our questions, as
a readers’ survey is essential to learn the strengths and
weaknesses of the journal.
The statistical value of the responses to the different questions
is restricted, with a low response from readers. Still, among
those who responded, a majority expressed that they read most
of the journal and found it to contain useful information with
the scientific value being reliable and high. About half on those
who responded sometimes discussed the content of the papers
with colleagues; however, there were also people who rarely
read the scientific papers.
Almost half were interested in practice management; this
probably reflects that the majority were private practitioners and
owners of clinics. It might also be worth noting that almost 1/5
were not particularly interested in ethical issues. Still, this topic
is so important that it needs to be focused upon on a regular
basis.
It would not be wise to base the future of the journal on a
restricted number of opinions, but the survey has given the
Editor and production subcommittee some guidelines in the
development of a better journal for all our readers. As we do
value the input from the readers, please e-mail your comments
if you have any, or suggestions for improvements. In addition,
we plan to repeat the reader survey in some years, hopefully
with a somewhat better compliance.
Again, thank you to all who responded, your opinion is very
valuable in our work with the journal.
The new Board L>R: Simon Orr, Ellen Bjerkås, Simon
Kleinjan, Andrew Byrne and Johan Van Tilburg
• Council meeting in Krakow
Jerzy Gawor and our Polish hosts organised a well-attended
scientific congress as well as an excellent entertainment
programme. The gala dinner featured a display of local traditional
dancing. I have to admit this was not what I was expecting from
a “pole-dancing” evening – nevertheless I am looking forward to
a future meeting in Lapland (silly English joke!).
Discussion in Krakow
Our new president felt that it was important to maintain high
scientific standards in the articles, yet to acknowledge that the
majority of members were practitioners rather than specialists.
The Board of the Italian association (SCIVAC) had made some
constructive suggestions regarding changes to the editorial board
of the journal, and these were in line with the way things had
been evolving under the supervision of Ellen Bjerkås .
Pole Dancing
Oncology theme
This issue has three Oncology papers, each of interest and
importance for different reasons.
FECAVA likes to keep its members informed about new and
exciting trends in the scientific field. The paper ‘The future of
Biomarkers and Personalised Medicine in Companion Animal
Practice’ is a good example.Whilst on the face of it the paper may
12
appear very technical and ‘State of the Art’ this technology is
already becoming available to practising vets, and it is something
we will hear a lot more of in the future.
The Commissioned paper on the safe use of cytotoxic drugs in
companion animal practice contains important essential information for practices using this type of therapy.
• An acknowledged Companion Animal
Veterinary Practitioner
As highlighted in the last issue of FECAVA News, a paper on
Acknowledged Veterinarians was to be presented at the
November 2005 round of UEVP/FVE meetings. This paper was
adopted by the FVE. Acknowledged Veterinarians were defined
as practitioners who worked mainly (greater than 50% of their
time) with particular species and who had obtained additional
experience and qualifications. Such a title was intended to be
readily attainable by veterinarians in practice and hence was seen
as at a much lower level than the specialisation as defined by the
European Board of Veterinary Specialisation. Evaluation might
involve a specified period working with an acknowledged/
competent veterinarian, the attendance of targeted CPD courses
and perhaps an examination supervised by an acknowledged/
competent veterinary body. Prof Stefano Romagnoli of the
European Society for Feline Medicine addressed the delegates at
the FECAVA Council on this issue. He discussed the provisions in
more detail and suggested that ESFM might be well placed to be
the competent European body for the acknowledged feline
practitioner. The discussion that followed indicated that some
directors present favoured a “companion animal” category rather
than separate canine and feline one, though this did not seem
possible in terms of the accepted UEVP/FVE proposition. (See
also report of debate on specialisation at AFVAC Congress
Toulouse Overleaf).
The ‘Lincoln Baby Lab’ L>R : Alan Woodford (IT expert,
Lincoln), Kerstin Meints (Lincoln University), Soraya Verbeke
(Blue Dog Artist) and Tny De Keuster (Blue Dog Trust
Chairman)
Ray Butcher gave a presentation on the project in Krakow and
this was well received by an audience of vets, breeders and
teachers. It also attracted significant media interest, and we hope
to build on this for Prague.
• Vet Nursing
The Spring 2005 edition of FECAVA News mentioned the
proposed partnership of FECAVA with VETNNET in the Dasvent
project. This is aimed at the development of a voluntary
accreditation system for veterinary nurse training courses in
Europe, and the agreement was finally signed in the autumn of
2005.
The main aims of the project include:
– The formation of an Accreditation Board (consisting mainly of
employers).
– The formation of a Visitation Committee (made up of
VETNNET, veterinary organisations, vet nurse organisations and
qualifying bodies).
– Adaptation of the USA Accreditation systems to European
Standards (see also WSAVA Activities p. 15).
– Development of a syllabus of agreed “competences” for
European veterinary nurses.
– Testing the accreditation system for acceptability.
• Evaluation of Veterinary Schools
Dr Olivier Glardon (Switzerland) gave an update to the FVE
Assembly on the evaluation of European veterinary schools. Of
the 102 schools that were members of the European Association
of Establishments for Veterinary Education (EAEVE), 71 had been
evaluated at least once and 38 of these had “passed” and were on
the so-called “positive” list. One has to wonder about the 33 that
have been inspected and not passed, or indeed about the 31 that
have never been inspected at all! For more information see
www.eaeve.org.
Dasvent project coordinator Renze Holwerda (Principal of
Groenhorst College) and the then FECAVA Secretary Andrew
Byrne signing the agreement.
• Blue Dog
The Blue Dog project continues to gain momentum, and the
BLUE DOG TRUST was finally established as a distinct legal
entity in November 2005. Tiny De Keuster of Belgium was
elected as Chairman. At the time of writing, the interactive CD is
being scientifically tested at the Lincoln University BabyLab. This
research project has been funded largely from support given by
FECAVA and NACAM (the Small Animal Association of the
Netherlands), with additional funds being donated by the BSAVA
and the Norwegian Association for pet Behaviourists. The
research should be completed by the spring of 2006 and will be
presented at the FECAVA/WSAVA congress in Prague in October
2006.
13
FECAVA NEWS
countries. They have been working with colleagues from the
successful NAVC in Florida to bring in additional expertise and
variety and yet maintain a distinct Spanish feel. Watch this space!
• Next FECAVA Congress
The next FECAVA Congress will be held together with the
WSAVA and the Czech Small Animal Veterinary Association in the
beautiful and historic city of Prague, October 11 – 14, 2006. For
further information check the website: www.wsava2006.cz
• Toulouse hosts AFVAC Annual Congress
Delegates at the Dasvent meeting
From Keith Davies, Editor Ejcap
It was a privilege to represent FECAVA at the Annual Congress of
AFVAC, the French Small Animal Veterinary Association held in
Toulouse. AFVAC (CNVSPA) probably has the strongest link with
FECAVA of all its Member Associations. The first FECAVA
President was Didier-Noël Carlotti of CNVSPA ,who was in fact
instrumental in founding FECAVA.
At the Congress Dr. Carlotti was re-elected as President of
AFVAC. Maurice Roze, AFVAC’s current representative in
FECAVA, was also elected as President of the newly formed
Francophone Federation, both these appointments cementing the
strong links of AFVAC with FECAVA.
The AFVAC Annual Congress has made the bold decision not to
locate in Paris each year, but rather to move around the regions
of France. Whilst this may slightly reduce the numbers who
would attend in the metropolis, it does give veterinarians in other
parts of the country a chance to take part without having too
much travel. The large attendance of 2825 delegates in Toulouse
and the extensive commercial exhibition, attests to the fact that
changing the venue does not result in a less successful congress.
Didier-Noël Carlotti has also made a big effort to develop
Continuing Education activity in regions throughout the whole of
France. Another feature of AFVAC’s structure is the key role of
specialist divisions within the Association.
As I mentioned the Francophone Federation was founded at the
Conference. Represenatives from Algeria, Belgium, France,
Luxemburg, Morocco, Switzerland and Tunisia, attended the
meeting. At first I was a little unclear regarding the reasons for
founding such a Federation. It seemed to me that whilst it
obviously must be a little irksome to non-English speaking
With regard to nursing, AVEPA continue to build on their
successful nurse programme in Spain. As well as a nurse session
at their annual congress and a number of regional meetings held
throughout the year, they have just launched a new Journal
aimed at nurses.
• Medicines
The changes in medicines legislation within Europe continue to
be a concern of FECAVA Directors. The last issue of FECAVA
News highlighted the proposed changes in the UK. These
became law on 31st October 2005, and practitioners are still
facing up to the implications these will have on their business
and the way they work on a day-to-day basis. Further information
is available on www.bsava.com, www.vmd.gov.uk or
www.dti.gov.uk
• Veterinary Homeopathy – views of the
establishment strengthen against its use
The debate as to the relative merits of Homeopathy has been
raging for some time - antagonists claiming it has no place in
evidence-based veterinary medicine, while supporters point to a
growing request from the public for such a service.
Perhaps the recent declared positions of major European
veterinary groups reflects the tightening of the medicines
legislation, but whatever the reason the matter has featured in the
pages of New Scientist (10th December 2005). This article
highlights that in April 2005, “the European Board of Veterinary
Specialisation issued a statement warning that its members could
lose their status if they offer non-evidence based treatments”.
Further to this, in November 2005, the FVE issued a policy
statement urging its 200,000 members “to work only on the basis
of scientifically proven and evidence-based methods and to stay
away from non-evidence-based methods”. Finally, the New
Scientist article quotes Jan Vaarten, Executive Director of FVE, as
saying “When vets go into homeopathy, it creates a false
impression that it is also evidence-based”.
I am sure the arguments will continue!
From L>R: Didier-Noël Carlotti (President of AFVAC),
Francisco Florit (AVEPA) and Javier Villamor (AVEPA).
• AVEPA - Enhancement of their future
national Congresses
AVEPA have announced their plans to enlarge their annual
congress in Barcelona to make it more attractive to their own
members as well as to attract delegates from other European
14
countries, to see the increasing acceptance of English as the main
language for international Veterinary communication, this
progression was inevitable. Maurice Roze told me there was no
conflict of interest here.. French he said, is widely spoken
throughout the world, particularly in Europe and Africa. Many
Veterinarians in these countries do not read English, and the
French language provides an important avenue for the
communication of knowledge. The common language binds
these countries together both historically and culturally. A
Spanish and Portuguese speaking Federation was successfully
formed two years ago. The goal of federations such as these
should be to offer a complementary tool to already existing
international veterinary associations for continuous education and
progress in animal health and welfare.
I attended a Seminar on the subject of Specialisation in France. It
was clear that the same worries and concerns were common to
those experienced in other countries. There was a fear by current
diplomates and highly specialised and competent veterinary
surgeons that the levels of specialisation not requiring full time
training and attainable by vets working in practice could
constitute a threat. On the other hand there was a strong feeling
that practising vets who were unable to take time off to attend
full time training should be allowed to achieve some specialist
status. The debate was heated and lively and was skilfully chaired
by Maurice Roze allowing all the different opinions to be aired.
Symposia and subjects which could be regarded as contentious
are an important and newly developing feature of AFVAC
congresses.
The Gala evening at a French congress is almost legendary and
an event not to be missed. This year I was a little disappointed to
notice that “food” was not part of the evening, an unusual
The Halle aux Grains
omission in France! I was also apprehensive about the thought of
classical music with a humourous twist. Le Quatuor, however
held the audience spellbound. Their undoubted ability to perform
classical music to a high standard enabled them to introduce
humour in an acceptable way. The concert was held in the Halle
aux Grains, a historic and attractive venue, kindly provided for
the use of AFVAC by the Mayor of Toulouse.
In the past I have been to many AFVAC (CNVSPA) national
congresses and have always had a very enjoyable weekend. This
year was no exception. FECAVA members who do not travel to
European Congressess outside there own country are missing
exciting scientific and social opportunities.
WSAVA ACTIVITIES
From Dr Walt Ingwersen WSAVA Editor
• WSAVA Adopts Policy on Dangerous Dogs
responsibilities in educating the public to enable them to select
a suitable dog. They should help advise on the provision of
an appropriate environment, and to discourage breeding and
distribution of animals with undesirable behaviour traits.
Legislative recommendations
Effective legislation is required to address the problems posed by
individual dangerous dogs. Special regulations regarding the
registration/identification of the offending animal with local
authorities is needed. Regulations may include the following:
1. Whilst at home, the dog should be kept indoors or in a secure
dog-proof enclosure.
2. The owner should be required to display warning signs at the
premises, including a sign that children can understand.
3. When the dog is taken off the owner’s premises, it must be
muzzled, leashed, and under the effective control of the owner
at all times.
4. If a declared dangerous dog becomes a stray, it must be
humanely destroyed.
5. If a dog is transported, then it should be within a child-proof
enclosure.
6. A declared dangerous dog must have permanent (microchip)
identification and wear a collar that is easily recognizable an
1. The WSAVA supports the development of dangerous dog
legislation, provided it refers to an individual dog’s measurable
actions.
2. The WSAVA does not support the targeting of specific breeds
under dangerous dog legislation.
Background
There are community concerns about the keeping of certain
breeds of dog. People keep dogs for many reasons including
guarding of property or persons, and historically for fighting.
Canine behaviour may be influenced by several factors including
genetic predisposition, early socialization and learning, current
environment, as well as owner attitudes and training. Certain
breeds or lines within breeds have been bred for particular
behavioural characteristics; some of these include aggressive
behaviour. However, all behaviours are not necessarily uniform
within breeds and may or may not be present within individuals.
De-sexing, obedience training and/or behaviour modification
including psychopharmacotherapy may assist in modifying
aggressive behaviour. Veterinarians, breed societies, breeders,
welfare agencies, pet shops and owners, should accept their
15
FECAVA NEWS
as a WSAVA Member Association to small animal veterinarians
around the globe who are striving for practice excellence.
which identifies the dog as dangerous.
7. Resale of dangerous dogs should be regulated, policed, and
permits issued.
WSAVA partners with its Member Associations to share
Member Services
AAHA Standards of Accreditation to be Available for WSAVA
Member Associations
The American Animal Hospital Association Standards of
Accreditation are recognized around the world as the benchmark
for quality care in veterinary medicine. Approximately 3,000
veterinary practices in the U.S. and Canada are accredited by
AAHA and adhere to the AAHA Standards. For practices in other
countries, these standards provide a framework for reaching new
levels of excellence.
WSAVA members will be able to view the AAHA Standards by
following a link available on the WSAVA Home Page. There are
more than 900 AAHA Standards, which cover quality patient care,
client service, and staff empowerment and recognition.
To view the standards, a user name and password will be
required and this is available through your WSAVA member
association (to see if your local/national association is a WSAVA
member, visit the member association pages of the WSAVA
website).
So, contact your WSAVA Member Association and tap into this
exciting and wonderful resource kindly made available by AAHA
• Proceedings Available On-Line
Proceedings from the WSAVA/FIAVAC/AMMVEPE 2005 World
Congress are now available on-line via the WSAVA website (link
on the right-hand column of the Homepage). Contents include
Congress abstracts as well as proceedings from more than 250
lectures covering 26 different disciplines by 110 speakers. Most
disciplines are covered The proceedings are also available for the
animal welfare forum as well as the practice management track
and 4 separate State of the Art Lectures (SOTAL) providing
cutting-edge information on current topics from world-renowned
veterinary scientists.
And it’s all just a mouse-click away from the comfort of your own
chair!
• Future Congresses
31st WSAVA/12th FECAVA/14th Czech Small Animal Veterinary
Association Congress, Prague, Czech Republic – October 11-14,
2006. Full details are featured in this and past issues of EJCAP
Sydney Convention Centre, Sydney, Australia – August 19-23,
2007
Dublin, Ireland – August, 2008
Sao Paulo, Brazil – 2009 (Specific date to be determined).
UEVP NEWS
European Union enlargement and UEVP
From Christopher Buhot, UEVP President
• Continuous Professional Development or
Life Long Learning
voluntary although highly recommended for veterinarians
working in general practice. Making it compulsory without
proper policing is of little use. However, 3L for acknowledged or
specialized veterinarians should be mandatory in order for them
to receive and hold their title.
The hours spent on 3L should be noted by veterinarians on their
personal record card (probably in the future on a professional ID
card).Veterinarians working in general practice should obtain at
least 100 scientific meeting attendance hours over 5 years and
100 hours by other forms of 3L, in other words an average of 40
hours yearly.
Scientific attendance hours can be obtained by attending national
and international 3L courses or congresses, other forms of 3L
hours such as by reading articles in national or international
veterinary journals, e-learning or self-assesment.
3L scope is not only limited to veterinary medicine and surgery.
However, it must be closely linked to the veterinarian’s main
activity. It includes all topics relevant and profitable to the
practitioner's professional life. 3L courses must be evaluated by
the participants, and the evaluation forms should be sent to the
National 3L Committee, which it is recommended are set up in
each country and will be in charge of accrediting 3L providers
and 3L courses and controlling veterinarians’ 3L records. Finally,
as we seek harmonisation in the EU, a European 3L committe
has been set up. Already The European Coordination Committee
for Veterinary Training has already agreed to take over this duty.
The R.C.V.S. (Royal College of Veterinary Surgeons – UK
statutory body) gives an excellent definition of CPD viz “The
systematic maintenance, improvement and broadening of
knowledge and skill and the development of personal qualities
necessary for the execution of professional and technical duties
throughout the veterinarian's working life.”
CPD can be regarded as an ethical obligation, and is in full
accordance with the FVE Code of Good Veterinary Practice.
Following recent meetings in Bologna, it has been decided that
the term CPD should be replaced by the name of L.L.L. or 3L
which stands for Life Long Learning.
At the UEVP Spring General Assembly all delegates adopted the
position paper on 3L. It was agreed that a single qualification no
longer gives the right to practise for life without competition and
control. Practitioners must keep their professional knowledge up
to date to provide the best service to their clients and patients.
Furthermore, veterinarians have to be able to respond to the
increasing demand for the development of advanced scientific
skills.The delegates affirmed that we must also keep in mind the
possible consequences on professional liability. The assembly felt
strongly that the veterinary profession must be in charge of its
own 3L in order to control its content and its quality so that our
profession does not fall into disrepute.
At the moment, UEVP proposes to do all in its power to make 3L
16
REPRINT PAPER (NL)
A pplication of honey in the
treatment of skin wounds
P.A.M. Overgaauw(1) J.Kirpensteijn(2)
S
U
M
M
A
R
Y
This paper reviews the current knowledge about the use of honey in the treatment of skin wounds. Most
experience has been gained in human medicine, but first reports of its use in animals are available. Honey
has, after application to wounds, an antibacterial effect against several bacteria and shows reduced oedema
and discharge. Moreover, it helps in generating granulation and epithelial tissue and has an odour neutralizing
effect. The need to use sterilized honey products free from pesticide and antibiotic residues is explained.
INTRODUCTION
This paper originally
appeared in:
Tijdschrift voor
Diergeneeskunde*
(2005)130, p 115-116
and amoxicillin with clavulanic acid, against
the most common skin bacteria. Important in
this context is an adequate concentration of
active antibiotics in the blood before the wound
is operated on. This is best achieved by
intravenous administration of the antibiotic just before the
induction of anaesthesia. There are no medical grounds for the
local application of antibiotics. Anecdotes do exist however, of
substances enhancing the wound healing process, such as
honey, which has reportedly been used for centuries for its
favourable effect on the wound healing process. This effect is
explained by the fact that honey has a cleansing effect, absorbs
oedema and odours, displays anti-microbial and infection
inhibiting effects, and induces granulation, epithelialisation,
tissue generation and bloodsupply in the wound area [4,8].
Dog and cat skin wounds are a common
occurrence and are brought into vet practices
every day. When treating them, both vet and
owner often initially apply local medications. There is a
preference for “something” to apply on a wound and a number
of ointments and creams are marketed for this purpose. They
generally are unnecessary and often even counterproductive, as
virtually every medication will retard the wound healing process.
Recently, however, two medications were reported as being
proven to help the wound healing process by local application,
i.e. 65% glycerol [12,16] and honey. The latter product is
discussed in more detail below.
WOUND HEALING
ANTIBACTERIAL EFFECT OF
HONEY
Freshly incurred wounds are best cleansed with a physiological
salt solution, and then sutured. Superficial wounds do not require
antibiotics when treated properly and where extensive tissue
damage is not evident. Only infected, deep wounds require
antibiotic treatment [10].
Honey has an antibacterial effect against several bacteria such
as Pseudomonas, staphylococci, streptococci and E. coli. Even
some antibiotic-resistant bacteria, such as MRSA (Methicillin
Resistant Staphylococcus Aureous) and VRE (Vancomycin
Resistant Enterococci) are reportedly sensitive [2,3,9]. A
This involves the systemic administration, for a minimum of 5
to 7 days, of a broad-spectrum antibiotic such as cephalosporines
(1) Certified Veterinary Microbiologist, Certified Parasitologist, Molecaten 57, NL - 3772 LJ Barneveld. E-mail: [email protected]
(2) Diplomate of the European and American Colleges of Veterinary Surgery, Department of Companion Animal Medicine, Veterinary Faculty, Utrecht University,
Yalelaan 8, NL - 3508 TD Utrecht
* Presented by NACAM (The Netherlands)
17
Application of honey in the treatment of skin wounds
OTHER EFFECTS OF HONEY
Animal experimental research has shown that honey reduces the
number of neutrophils cells infiltrating the wound. Clinical
studies showed moreover, reduced oedema and discharge. The
hyperosmolarity of honey and stimulation of body enzymes
induces autolysis of necrotic tissue in a wound, achieving
remoral of debris.
Honey helps in the generation of granulation and epithelia
tissues because hydrogen peroxide stimulates angiogenesis and
the growth of fibroblasts. Also, low pH values and enhanced
angiogenesis help release oxygen, stimulating tissue
regeneration.
The odour neutralizing effect is achieved because bacteria in the
wound are being inhibited, thus also reducing debris volumes.
Also, once the honey has been applied, the bacteria will utilize
the sugars it contains. This generates the odourless milk acid [5].
Sutured wound on dog’s paw, Day O.
HUMAN AND ANIMAL
CLINICAL RESEARCH
For skin burns, very good results were found comparing honey
treatment to treatment with a silver-sulfadiazin [13] and
polyurethane film [14]. The sterile antibacterial wound ointment
with a honey basis (50% v/v)*, available in the Netherlands, was
used in a multi-centre case-report study of 139 nursing homes
and GP practice patients suffering from ulcers, decubital ulcers,
abrasions and burns [15]. On several wounds, different wound
treatment products were used (e.g. Betadine ointment®,
Duoderm®, silver-sulfadiazin) and their effects compared in the
same patient. Depending on the type of wound, a 14-47% faster
healing process has been reported. However, no statistical
analysis of the results was carried out. The specific wound
ointment with a honey basis* also showed an anti-fungal effect
against Candida albicans. Now, the manufacturer has the first
dog and cat case-studies available.
Application of sterile honey ointment.
NEED FOR AND USE OF
STERILE HONEY
concentration of 10% v/v is sufficient for full inhibition of wound
bacteria [5]. The antibacterial effect is caused, among other
things, by hyper-osmosis, low 3.6 pH, and the presence of a
thermo unstable substance named inhibine, hydrogen peroxide
and enzymes such as catalysts. Hydrogen peroxide is generated,
along with glucose acid, from honey as a result of an reaction
of the enzyme glucose oxidase (created by the bee) with the
glucose. This reaction occurs after the honey has been diluted
in the wound. The gradually released hydrogen peroxide has an
adverse affect on bacteria but not on the normal cells, thus
creating no cellulour damage. The assumption is that also other
antibacterial substances also occur, originating from various
flowers [17]. Studies show that bacteria display a different
sensitivity to monofloral honey from differing species of plants
[1,17].
It is evidently an attractive option to use a natural product for
the treatment of patients, however one important aspect must
be emphasized before problems arise for man and animals.
Only a very few studies state that sterile honey was used [14].
This fact is often not stated, or the honey is presumed to be
sterile [13]. This however is a major misconception. Honey may
contain Bacillus sp. and Clostridium traces and thus cause
botulism [6,11]. The use of natural honey on necrotic wounds
is therefore contraindicated in such cases counter indicated.
Also, honey may contain pesticides as well as antibiotic residues
such as tetracyclines used on bees.
The recommendation therefore is to use only honey for medical
purposes that originates from specific pathogen free (SPF) nonmedicated bees living in areas where no pesticides are in use.
Also irradiated honey produces a sterile product, without any
* Mesitran®; Klinion® series, Medeco BV (www.medeco.nl).
18
P.A.M. OVERGAAUW J. KIRPENSTEIJN
[3] COOPER (R.A.), MOLAN (P.C.), HARDING (K.G.) - The
sensitivity to honey of Gram-positive cocci of clinical
significance isolated from wounds. J Appl Microbiol ,2002, 93:
857-863
[4] EFEM (S.) - Clinical observations of the wound healing properties
of honey. Br J Surg 1988, 75: 579-581
[5] EILDERS (M.), ZWAGA (S.) - (Honey, the bee as wound
caretater). Pharma Selecta, 2003, 19 : 96-100
[6] MIDURA (T.F.) et al - Isolation of Clostridium botulinum from
honey. J Clin Microbiol ,1979, 9: 282-283
[7] MOLAN (P.C.), ALLEN (K.L.) - The effect of gamma-irradiation
on the antibacterial activity of honey. J Pharm Pharmacol, 1996,
48: 1206-1209
[8] MOLAN (P.C.) - Potential of honey in the treatment of wounds
and burns. Am J Clin Dermatol, 2001, 2: 13-19
[9] NATARAJAN (S.), WILLIAMSON (D.), GREY (J.), HARDING
(K.G.), COOPER (R.A.) - Healing of an MRSA-colonized,
hydroxyurea-induced leg ulcer with honey. J Dermatol Treat,
2001, 12: 33-36
[10] OVERGAAUW (P.A.M.) - (The treatment of bitewounds in dogs
and cats). Diergeneesk Vademecum, 2003, 3 (7): 1-2
[11] POSTMES (Th.), BOGAARD (A.E.A.M.) VAN DEN - Honey for
wounds, ulcers, and skin graft preservation. Lancet, 1993, 342:
756-757
[12] RAVISHANKER (R.), BATH (A.S.), ROY (R.) - Amnion Bank the use of long term glycerol preserved amniotic membranes
in the management of superficial and superficial partial
thickness burns. Burns, 2003 Jun, 29 (4): 369-374
[13] SUBRAHMANYAM (M.) - Topical application of honey in
treatment of burns. Br J Surg, 1991, 78: 479-478
[14] SUBRAHMANYAM (M.) - Honey impregnated gauze versus
polyurethane film (Opsite®) in the treatment of burns – a
prospective randomised study. Br J Plastic Surg ,1993, 46: 322323
[15] VANDEPUTTE (J. L.) - Mesitran clinical reports study. 2002.
[16] VLOEMANS (A.F.P.M.), SCHREINEMACHERS (M.C.J.M),
MIDDELKOOP (E.), KREIS (R.W.) - The use of glycerolpreserved allografts in the Beverwijk Burn Centre: a
retrospective study. Burns, 2002 Oct; 28 Suppl 1: S21-25
[17] WILLIX (D.J.) MOLAN (P.C.), HARFOOT (C.G.) - A comparison
of the sensitivity of wound-infecting species of bacteria to the
antibacterial activity of manuka honey and other honey. J Appl
Bact, 1992, 73: 388-394
Wound on paw after one week of daily treatment.
change in properties [7,11]. In the Netherlands, a sterile honey
ointment for human use is available in tubes of 20 and 50 g *.
The ointment may be used in combination with wound dressings
and the product information sheet states that application once
a day is sufficient.
Scientific research into the wound healing effect of honey in
(domesticated) animals has not been performed and this will
need to be done in the future to obtain independent proof that
honey ointment is a useful addition to the existing treatments
of (infected) wounds in veterinary practices (figures 1 and 2).
REFERENCES
[1] ALLEN (K.L.), MOLAN (P.C.), REID (G.M.) - A survey of the
antibacterial activity of some New Zealand honeys. J Pharm
Pharmacol. 1991, 43: 817-822
[2] COOPER (R.A.), HALAS (E.), MOLAN (P.C.) - The efficacy of
honey in inhibiting strains of Pseudomonas aeruginosa from
infected burns. J Burn Care Rehabil, 2002, 23: 366-370
19
REPRINT PAPER (GR)
A case of periosteal proliferative
polyarthritis in a cat
M. Karayannopoulou(1), Z.S. Polizopoulou(2), A.F. Koutinas(3), M.N. Patsikas(1), G. Kazakos(1), A. Fytianou.(2)
S
U
M
M
A
R
Y
In this paper a case of periosteal proliferative polyarthritis is described in an 11-year old, female Siamese cat,
that was admitted to the Surgery Clinic of the Veterinary School, A.U.Th., with a 6-month history of nonweight bearing lameness of the left thoracic limb. At physical examination, restricted range of motion of the
left elbow joint, local swelling and pain were detected. In the radiological examination of the affected joint
the main finding was an extensive periarticular and irregular periosteal new bone formation. The results of
the complete blood count and routine serum biochemistry were within normal limits and the cat was
serologically negative for FeLV and FIV. Synovial fluid examination showed a lymphoplasmacytic pleocytosis,
while the bacterial culture was negative. Prednisolone given at an anti-inflammatory dose for two consecutive
weeks resulted in a marked improvement of the clinical sings. However, two months after the end of the
treatment lameness reappeared, but this time in the contralateral thoracic limb, due to the involvement of
the same joint. Radiology revealed the same type of lesions in the right elbow joint, while the left became
ankylosed. Again, prednisolone given at an immunosuppressive dose for two weeks gave only moderate
improvement in both the clinical conditions and the radiological changes in the animal. For this reason
azathioprine at the dose of 1 mg/kg BW, every 48 hours, was added to therapy that lasted for 5 months.
Transient mild leukopenia, that resolved after decreasing the dose of azathioprine by 25% was the only adverse
side effect noticed. At the end of the treatment, regression of the radiographical lesions in both elbows
enabled the cat to walk with a stilted gait despite the development of joint ankylosis bilaterally. The disease
was kept in remission during the 12-month follow up period.
INTRODUCTION
Schrader and Sherding 1994, Thomson 1994,
Roush 1997, Day 1999, Hay and Manley 2000);
however, synovial immune-complex deposition
may be involved (Day 1999, Davidson 2002).
Joint diseases, similar to feline PPP, have been
described in both humans (Reiter’s arthritis)
(Bennett and Nash 1988, Goring and Beale
1993, Thompson 1994, Schrader 1995, Pedersen et al 2000) and
dogs (Bennett and Nash 1988, Bennett 1990, May and Bennett
1994, Day 1999). In general, the prognosis is guarded to poor,
as CPP tends be progressive making euthanasia necessary when
the quality of life becomes unacceptable (Day 1999). The
purpose of this article is to present the clinical and radiological
appeared in: The Journal of
the Hellenic Veterinary Medical
Society* (2004) 55, p 46-54
Periosteal proliferative polyarthritis (PPP) is the
most common form of feline chronic
progressive polyarthritis (CPP), an uncommon
erosive joint disease that was first studied by
Pedersen and associates in 1980. Despite its association with
FeSFV, FeLV (Pedersen et al 1980, Lipowitz 1985, Schrader 1995,
Tizard 2000) or occasionally FIV infection (Taylor 2003), PPP is
still considered an immune-mediated disorder, although the
precise mechanism that triggers the immunologic reaction
remains unknown (Nelson and Couto 1992, Bennett 1994,
(1) Clinic of Surgery,
(2) Laboratory of Clinical Diagnosis and Clinical Pathology,
(3) School of Veterinary Medicine, Clinic of Companion Animal Medicine, A.U.Th. Greece
Corresponding author: Z.S. Polizopoulou, 11 St. Voutyra str. ,GR-546 27, Thessaloniki. E-mail: [email protected]
* Presented by HVMS (Greece)
21
Subsequently, the cat was put on oral prednisolone (Prezolon®)
at the anti-inflammatory dose of 2 mg/kg BW, once daily, for
two consecutive weeks which resulted in a marked improvement
of the functional state of the affected limb. A gradual tapering
of the prednisolone dosage was further suggested, but the owner
stopped giving it on his own initiative.
findings, as well as the response to treatment of a cat with PPP,
which, to our knowledge, has never been reported in the greek
literature.
CASE DESCRIPTION
An 11-year old, female Siamese cat, weighing 6 kg, was admitted
to the Surgery Clinic, School of Veterinary Medicine, Aristotle
University of Thessaloniki, Greece, with a 6-month progressive
and non-weight bearing lameness of the left thoracic limb as the
main complaint; no medical treatment, of any kind, had been
attempted prior to admission. At physical examination, restricted
range of motion of the left elbow joint, local swelling and pain
were detected upon palpation. Radiological examination of the
affected joint showed excessive periarticular soft tissue
radiopacity accompanied by extensive and irregular periosteal
new bone formation (figure 1). The other limb joints as well as
the thoracic and abdominal cavity and the vertebral column
appeared radiographically normal. The results of complete blood
count (haematocrit, haemoglobin, leucocyte and platelet counts,
differential white blood cell count), routine serum biochemistry
(total protein, albumin, ALP, ALT, γ-GT, BUN, creatinine) and
FeLV+FIV ELISA serology were found to be within normal limits
or negative, respectively. Synovial cytology of the affected joint
disclosed the presence of numerous lymphocytes and plasma
cells, while the bacterial culture came back negative. Synovial
biopsy was also suggested but declined by the owner.
Approximately two months after the end of the aforementioned
treatment, the cat started limping, but on the right thoracic limb
this time. The painful swelling of the ipsilateral elbow joint,
along with the already ankylosed left elbow joint, made the cat
reluctant to jump and walk. Radiological examination of the
right elbow showed the presence of periosteal proliferation at
the attachment site of the joint capsule (figure 2); the left elbow
lesions were well demarcated and had more regular margins
than the first time. Again, the radiographs of the other limb
joints did not disclose anything abnormal. Oral prednizolone was
re-instituted, but at an immunosuppressive dose this time (4
mg/kg BW, per os, once daily) for two consecutive weeks,
tapered gradually over a period of three additional weeks. The
radiological examination, at the end of the treatment, revealed
that the lesions of the left elbow joint remained unchanged
while those of the contralateral joint appeared much worse
(figure 3). Thereupon, it was decided to use azathioprine
(Azathioprin®), at the dose of 1 mg/kg BW, per os, every 48
hours, along with 1 mg/kg BW prednizolone, every 24 hours,
tapered to 0.5 mg/kg BW. This dose was subsequently used
along with azathioprine, on an alternate day basis. The
combination therapy was administered for a 5-month period,
during which the cat was being monitored clinically and
clinicopathologically (every 15 days), as well as radiographically
(every month). Because of a transient leukopenia (4,900/µl) that
appeared approximately one month after the beginning of the
treatment, the dose of azathioprine was lowered by 25% until
the number of WBC’s was restored to normal range (5,00018,900/µl). The radiological examination of the right elbow
showed a substantial regression of the lesions at the end of the
Figure 1. Lateral radiograph of the left elbow on the day of first
admission, showing the increased radiopacity of the
expanded periarticular soft tissues, as well as the extensive
periarticular new bone formation
Figure 2. Lateral radiograph of the right elbow just before the
institution of the immunosuppressive treatment,
demonstrating periosteal new bone formation at the
attachment site of the joint capsule.
22
M. KARAYANNOPOULOU
this cat (Pedersen et al 1980, Bennett and Nash 1988, Schrader
and Sherding 1994).
The typical radiological finding in PPP is a periarticular extensive
and profound periosteal proliferation, that ultimately may lead
to ankylosis of the affected joint(s) (Bennett and Nash 1988,
Nelson and Couto 1992, Schrader and Sherding 1994, De Haan
and Beale 1995) and was also noticed in this cat. Subchondral
erosions of mild degree, usually located at the margins of the
articular cartilage, may also occur in PPP (Bennett and Nash
1988, Bennett 1994, May and Bennett 1994, Schrader and
Sherding 1994, Day 1999); but they were not demonstrated in
either of the elbow joints of our feline patient, as it has also been
reported in other cases (Lipowitz 1985, Nelson and Couto 1992,
Goring and Beale 1993, De Haan and Beale 1995, Schrader 1995,
Hay and Manley 2000). In the deforming erosive or rheumatoidlike form of feline CPP, subchondral erosions and cysts are quite
visible in radiographs and may eventually lead to the subluxation
or luxation of the affected joint (Bennett and Nash 1988, Goring
and Beale 1993, Schrader and Sherding 1994, Hay and Manley
2000, Pedersen et al 2000, Taylor 2003). Also, the frequently
observed deformity and instability of the carpal and other distal
joints (Taylor 2003) was not part of the clinical picture in this
cat.
Since the idiopathic form of feline immune-mediated nonerosive
polyarthritis shares some clinical features with PPP, the diagnosis
was mainly based on the marked periarticular new bone
formation over the affected joints of the cat (Bennett and Nash
1988, Nelson and Couto 1992, Day 1999, Pedersen et al 2000).
The same kind of polyarthritis, that appears secondarily to
infections, neoplasms, drugs or vaccines (Day 1999, Hay and
Manley 2000, Pedersen et al 2000, Taylor 2003), was also
excluded from the list of differentials from a historical and clinical
standpoint. Systemic lupus erythematosus, an extremely
uncommon cause of nonerosive polyarthritis in cats (Bennett and
Nash 1988, Pedersen et al 1989) was also ruled out from the
beginning because its polysystemic nature did not fit into the
clinical picture of this cat. Interestingly, this animal did not
exhibit anorexia, fever and / or peripheral lymphadenopathy,
which are, at least initially, common manifestations in PPP,
(Pedersen et al 2000, Taylor 2003). This could be explained by
the delayed first admission of the animal, although these
symptoms were not manifested on the second admission, as
well.
Figure 3. Lateral radiograph of the right elbow after the
immunosuppressive treatment with prednisolone, showing
the worsening of the periarticular new bony tissue formation.
treatment period (figure 4a). At the same time, a decreased
radiopacity of the periarticular new bony tissue in the left elbow
was clearly visible (figure 4b). In spite of the fact that ankylosis
was well established in both elbow joints, the absence of pain
enabled the cat to walk with a stilted gait. The clinical condition
of the animal remained unchanged within the 12-month followup period, whereas the lesions did not deteriorate further in the
left and improved moderately in the right elbow joint.
DISCUSSION
PPP occurs exclusively in intact or neutered male adult cats,
regardless of their breed (Pedersen et al 1980, Moise and
Crissman 1982, Bennett and Nash 1988, Schrader and Sherding
1994, Roush 1997, Pedersen et al 2000). The appearance of PPP
in female or elderly patients, like the cat of our report, is only
seldom witnessed (Pedersen et al 1980, Bennett and Nash 1988).
The disease in this cat was not associated with either FeLV or
FIV infection, which have not been proven to cause PPP, at
least experimentally (Taylor 2003). Synovial fluid testing for
FeSFV was not considered necessary because the virus has been
isolated from either the affected or normal feline joints (Day
1999). Lesions tend to have a symmetrical distribution, with the
carpal and tarsal joints being more frequently affected compared
to the stifle, shoulder, hip or the elbow joint, as was the case in
In the erosive types of feline polyarthritis the continual
assessment of the animals is important because the true nature
of the disease may only become apparent as it progresses, while
certain individual factors will decide how it will be finally
manifested (Bennett 1995). Since the radiographic changes
(periosteal new bone formation, cyst-like metaphyseal defects,
destruction of articular cartilage, subchondral bone
development) in both the bacterial L-form and mycoplasmal
(Mycoplasma gatae, Mycoplasma felis) polyarthritis are similar
to those of PPP (Carro 1994, Schrader and Sherding 1994) these
differentials should have also been pursued diagnostically.
However, these wall-less and prokaryotic bacteria necessitate the
use of specific media to grow (Carro et al. 1989), which
23
a
b
Figure 4. Lateral radiograph of the right (a) and the left (b) elbow, immediately after the end of the 5-month immunosuppressive therapy with
azathioprine and prednisolone, showing substantial regression (a) and decreased radiopacity (b) of the periarticular new bony tissue.
unfortunately were not available. Since these bacterial infections
cannot be excluded on clinical and radiological grounds alone,
tetracyclines, lincomycin and tylosin (Carro et al. 1989) should
have been tried prior to institution of the immunosuppressive
treatment.
of glucocorticosteroids (Beale 1988, May and Bennett 1994, Hay
and Manley 2000, Pedersen et al 2000, Tizard 2000).
The use of azathioprine in cats is reportedly associated with a
life-threatening leukopenia and thrombocytopenia (Beale 1990,
Beale et al 1992, Plumb 1999, Scott et al 2001), that could be
attributed to the low erythrocyte thiopurine methyltransferase
activity in this animal species (Foster et al 2000, Papich 2000,
White et al 2000). Lower doses of azathioprine, such as 0.3
mg/kg BW, once daily (Papich 2000), 0.3-0.5 mg/kg BW every
48 hours (Birchard and Sherding 2000) or 1.5-3.125 mg/cat every
48 hours (Papich 1995), are thought to be relatively safer. The
dose of 1 mg/kg BW every 48 hours, that was used in this cat,
has also been recommended, provided that a close monitoring
for early detection of side effects is regularly pursued (Plumb
1999, Pedersen et al 2000, Boothe and Mealey 2001); however
even this dose is still considered unacceptably high (Papich
2000).
Periarticular exostoses in hypervitaminosis A, that may also lead
to lameness, are very similar to those of PPP, but the dietary
history (commercial cat food) of the cat ruled-out this possibility
(Bennett 1994, Schrader and Sherding 1994, Harari 1997, Johnson
and Watson 2000); furthermore, no exostoses could be seen in
the radiographs of the cervical spinal column (Bennett 1994,
Harari 1997, Johnson and Watson 2000).
In PPP, lifelong immunosuppressive therapy is often required
in an attempt to halt the progression of the lesions and to obtain
clinical remission, because in the majority of cases the clinical
signs relapse when there is a decrease of the dosage or no
medication at all (Schrader and Sherding 1994, Day 1999,
Pedersen et al 2000, Taylor 2003). In this cat, the initial use of
prednisolone at an antiinflammatory dose could be justified by
the one joint involvement of the lesions, which made the
diagnosis of PPP uncertain. The clinical improvement, noticed
initially, would have been more prolonged had the owner
complied with the full course of treatment. The recurrence
of clinical signs in both frontlimbs made the diagnosis of PPP
more certain and, therefore, the use of prednisolone at
immunosuppressive dosage necessary. Azathioprine had to be
added subsequently, because of the aggravation of the right elbow
lesions, along with the development of ankylosis in the
contralateral joint. Combination immunosuppressive therapy is
recommended in small animal immune-mediated arthritides, not
only for the achievement of longer remission periods, but to lower
the risk of side effects that are associated with the prolonged use
Since azathioprine is generally considered unsafe for the cat
(Bennett 1995, Papich 2000, Taylor 2003) it is strongly advised
to use cyclophosphamide or chlorambucil instead, along with
prednisolone at low immunosuppressive dosage (Taylor 2003).
Combination therapy with the use of prednisolone, azathioprine
(7.5 mg/cat every 48 hours) and cyclophosphamide was applied
in 5 CPP cats with moderate to poor results (Pedersen et al
1980). In the same study, two of the treated animals died of druginduced side effects, although the detrimental role of
azathioprine could not be assessed. Transient leukopenia, that
was also noticed in our feline patient at the 16th azathioprine
administration, subsided when its dose was lowered by 25%.
When a similar dosage (1.1 mg/kg BW, every 48 hours) was used
in 8 cases of feline pemphigus foliaceus, 4 of these cats
developed leukopenia after the 8th administration (Caciolo et al
24
M. KARAYANNOPOULOU
methyltransferase activity in the erythrocytes of cats. J Vet Intern
Med, 14: 552-554
GORING (R.L.), BEALE (B.S.) (1993) - Immune-mediated
arthropathies. In: Disease Mechanisms in Small Animal Surgery.
2nd ed, Lea and Febiger, Philadelphia: 742-757
HARARI (J.) (1997) - Diseases of bone. In: Handbook of Small
Animal Practice. 3rd ed, WB Saunders Company, Philadelphia:
830-845
HAY (C.W.), MANLEY (P.A.) (2000) - Immune-mediated arthritis. In:
Manual of Small Animal Practice. 2nd ed, WB Saunders
Company, Philadelphia: 1228-1232
JOHNSON (K.A.), WATSON (A.D.J.) (2000) - Skeletal diseases. In:
Textbook of Veterinary Internal Medicine. 5th ed, WB Saunders
LIPOWITZ (A.J.) (1985) - Immune-mediated arthropathies. In:
Textbook of Small Animal Orthopedics. JB Lippincott Company,
Philadelphia: 1055-1077
MAY (C.), BENNETT (D.) (1994) - Immune mediated arthritides. In:
Manual of Small Animal Arthrology. BSAVA, Cheltenham: 8699
MOISE (N.S.), CHRISSMAN (J.W). (1982) - Chronic progressive
polyarthritis in a cat. J Am Anim Hosp Assoc, 18:965-969
NELSON (R.W.), COUTO (C.G.) (1992) - Disorders of the joints. In:
Essentials of Small Animal Internal Medicine. Mosby-Year Book
Inc, St Louis, Missouri: 820-828
PAPICH (M.G.) (1995) - Table of common drugs: approximate
dosages. In: Kirk’s Current Veterinary Therapy XII Small Animal
Practice. WB Saunders Company, Philadelphia: 1429-1430
PAPICH (M.G.) (2000) - Handbook of Veterinary Drugs. WB
Saunders Company, Philadelphia: 43-44
PEDERSEN (N.C.), POOL (R.C.), O’BRIEN (T). (1980) - Feline
chronic progressive polyarthritis. Am J Vet Res, 41: 522-535
PEDERSEN (N.C.), WIND (A.), MORGAN( J.P.), POOL (R.R). (1989)
- Joint diseases of dogs and cats. In: Textbook of Veterinary
Internal Medicine. 3rd ed, WB Saunders Company, Philadelphia:
2329-2377
PEDERSEN (N.C.), MORGAN (J.P.), VASSEUR (P.B.) (2000) - Joint
diseases of dogs and cats. In: Textbook of Veterinary Internal
Medicine. 5th ed, WB Saunders Company, Philadelphia: 18621886
PLUMB (D.C.) (1999) - Veterinary Drug Handbook. 3rd ed, Iowa
State University Press, Ames: 71-73
ROUSH (J.K.) (1997) - Diseases of the joints and ligaments. In:
Handbook of Small Animal Practice. 3rd ed, WB Saunders
SCHRADER (S.C.) (1995) - Joint diseases of the dog and cat. In: Small
Animal Orthopedics, Mosby-Year Book Inc, St Louis, Missouri:
437-471
SCHRADER (S.C.), SHERDING (R.G.) (1994) - Disorders of the
skeletal system. In: Diseases and Clinical Management. 2nd ed,
Churchill Livingstone Inc, New York: 1599-1647
SCOTT (D.W.), MILLER (W.H.), GRIFFIN (C.E.) (2001) - Immunemediated diseases. In: Muller and Kirk’s Small Animal
Dermatology. 6th ed, WB Saunders Company, Philadelphia:
667-779
TAYLOR (S.M.) (2003) - Joint disorders. In: Small Animal Internal
Medicine. 3rd ed, Mosby Inc, St Louis, Missouri: 1079-1092
TIZZARD (I.R.) (2000) - Veterinary Immunology. 6th ed, WB
Saunders Company, Philadelphia: 391-395
WHITE (S.D.), ROSYCHUK (R.A.W.), OUTERBRIDGE (C.A.),
FIESELER (K.V.), SPIER (S.), IHRKE (P.J.), CHAPMAN (P.L.)
(2000) - Thiopurine methyltransferase in red blood cells of
dogs, cats and horses. J Vet Intern Med, 14: 499-502
WILKINSON (G.T.), ROBINS (G.M.) (1979) - Chronic progressive
polyarthritis in a cat. J Small Anim Pract, 20: 293-297
1984), while doses twice as high (2.2 mg/kg BW, every 48 hours)
led to severe leukopenia (<3000 leukocytes/µl) after
approximately 1.5 months of continuous administration (Beale
1992). The absence of life-threatening side effects in our feline
patient, even after the 5-month treatment period, may indicate that
this dose can be tolerated can be tolerated, at least by some cats.
Interestingly, the higher degree of periosteal bony tissue
regression in the right elbow joint, where the
immunosuppressive treatment started as early as two weeks
after the appearance of the clinical signs, indicates that its early
application is associated with a better outcome (Wilkinson and
Robins 1979, Schrader and Sherding 1994).
REFERENCES
BEALE (K.M.) (1988) - Azathioprine for treatment of immunemediated diseases of dogs and cats. J Am Vet Med Assoc, 192:
1316-1318
Beale (K.M.) (1990) - Azathioprine toxicity in the domestic cat. In:
Advances in Veterinary Dermatology, Proceedings of the First
World Congress of Veterinary Dermatology, Dijon, France,
September 1989. WB Saunders Company, London: 457-458
BEALE (K.M.), ALTMAN (D.), CLEMMONS (R.R.), BOLON (B.)
(1992) - Systemic toxicosis associated with azathioprine
administration in domestic cats. Am J Vet Res, 53: 1236-1240
BENNETT (D.) (1990) - Joints and joint diseases. In: Canine
Orthopedics. 2nd ed, Lea and Febiger, Philadelphia: 761-853
Bennett (D.) (1994) - The musculoskeletal system. In: Feline
Medicine and Therapeutics. 2nd ed, Blackwell Scientific
Publications, Oxford: 132-191
BENNETT (D.) (1995) - Treatment of the immune-based
inflammatory arthropathies of the dog and cat. In: Kirk’s Current
Veterinary Therapy XII Small Animal Practice. WB Saunders
BENNETT (D.), NASH (A.S.) (1988) - Feline immune-based
polyarthritis: a study of thirty-one cases. J Small Anim Pract, 29:
501-523
BIRCHARD (S.J.), SHERDING (R.G.) (2000) - Manual of Small Animal
Practice. 2nd ed, WB Saunders Company, Philadelphia: 1570
BOOTHE (D.M.), MEALEY (K.A.) (2001) - Glucocorticoid therapy
in the dog and cat. In: Small Animal Pharmacology and
Therapeutics. WB Saunders Company, Philadelphia: 313-329
CACIOLO (P.L.), NESBITT (G.H.), HURVITZ (A.I.) (1984) Pemphigus foliaceus in eight cats and results of induction
therapy using azathioprine. J Am Anim Hosp Assoc, 20: 571-577
CARRO (T.) (1994) - Polyarthritis in cats. Compend Contin Educ
Pract Vet, 16: 57-67
CARRO (T.), PEDERSEN (N.C.), BEAMAN (B.L.), MUNN (R.) (1989)
- Subcutaneous abscesses and arthritis caused by a probable
bacterial L-form in cats. J Am Vet Med Assoc, 194: 1583-1588
DAVIDSON (A.P). (2002) - Immune-mediated polyarthritis. In:
Textbook of Small Animal Surgery. 3rd ed, WB Saunders
DAY (M.J.) (1999) - Immunology of the Dog and Cat. Manson
Publishing Ltd, London: 133-140
DE HAAN (J.J.), BEALE (B.S.) (1995) - The skeletal system. In:
Geriatrics and Gerontology of the Dog and Cat. WB Saunders
FOSTER (A.P.), SHAW (S.E.), DULEY (J.A.), SHOBOWALE-BAKRE
(E.), HARBOUR (D.A.) (2000) - Demonstration of thiopurine
25
REPRINT PAPER (HILL’S)
P utting theory into practice - best
practice management for osteoarthritis
Stuart Carmichael(1)
I
N
T
R
O
D
U
C
T
I
O
N
Osteoarthritis (OA) is an insidiously progressive disease producing pain and loss of function in affected
joints. The suffering and restrictions on exercise that the active disease produces, make a profound impact
on the quality of life of the patient. Fortunately, although the disease is widespread, estimated to affect one
in five of all dogs, it is not always associated with debilitating disease [1]. Indeed it has been speculated that
only animals with moderate to severe OA pathology are identified and presented as clinical problems [2].
These facts set the scene for any discussions aimed at identifying management strategies for the disease.
OBJECTIVES OF
OSTEOARTHRITIS
MANAGEMENT
This paper is based on
a lecture given at the Hill’s
European Symposium on
Osteoarthritis and Joint
Health*
clinical problem in an osteoarthric joint [6].
Radiography is vital to confirm the existence of
disease in a joint and to eliminate other possible
causes of clinical signs (Figure 1). It should not
be used to estimate the clinical severity of the
condition. Many of the signs accompanying OA
are caused by pain and evaluation of this is best
achieved by observation and clinical assessment. The classical
signs are listed in Table 1. It is the appearance and identification
of these signs and how obvious they are that guides the clinician
to judge the severity of the disease. These are also used to judge
the effectiveness of any management strategy employed.
Increasingly, alterations of behaviour indicative of chronic pain
are also being assessed as more subtle indicators of an ongoing
problem [7]. Assessment of patient behaviour is difficult in the
consulting room and relies on the observational skills of the
owner (figure 2). In studies attempting to evaluate the accuracy
of these owner observations, they were found to compare very
favourably with objective assessment of disability provided by
force plate measurements on the same animals [8, 9]. This
information is extremely useful to allow construction of plans
to assist measures to alleviate the consequences of the disease.
The goals for management of OA can be
identified in global terms as [3, 4]
1. Controlling Pain
2. Maintaining and improving the range of movement and
stability of affected joints
3. Limiting functional impairment of the patient
These general objectives should underpin any attempts at
management. OA is a complex disease and a very clear
understanding of the disease process is essential to advise
selection of treatment. It has been suggested that best results in
human patients are obtained by an individualised and patientcentred approach involving multiple strategies [5]. It would
appear that management of the condition in animals is no
different. This type of approach delivers the necessary focus to
sustain successful management of any affected patient through
meeting long-term requirements.
RECOGNISING OSTEOARTHRITIS AS A PROBLEM
OSTEOARTHRITIS AS A
CHRONIC DISEASE
The simplest method of recognition is by radiographic review;
however there is poor correlation between radiographic
appearance and the extent or even existence of a significant
It is worth considering the consequences of the chronic nature
of OA and how this impacts on the disease itself and any
(1) Faculty of Veterinary Medicine University of Glasgow, Bearsden Road, Glasgow, GB-G611QH. E-mail: [email protected]
* The lecture on which this paper was based was given at the 9th Annual Hill’s Symposium held in Genova 25th-27th April 2005. Stuart
Carmichael is Professor of Veterinary Clinical Studies in the Faculty of Veterinary Medicine at the Glasgow University Veterinary School
27
Putting theory into practice - best practice management for osteoarthritis
AIMS OF MANAGEMENT
OA is a dynamic condition in which a number of different clinical
phases can be recognised (Figure 3). Three clearly recognisable
phases are ‘Chronic Phase Silent Disease’, ‘Chronic Phase Active
Disease’ and ‘End Stage Disease’. The phase will be determined
by the pathological changes already present within the joint and
the pain that the animal is experiencing. Several examinations
conducted at different time intervals are necessary properly to
establish this judging the success or failure of different control
measures.
Looking at this model (Figure 3) there is a gradual deterioration
of the affected joint to end stage disease. The clinical picture may
be punctuated by periods of ‘active’ disease, where clinical signs
are apparent, and ‘silent’ disease, where there are few or no
clinical signs and no pain. Using this judgement the initial aim
Figure 1. Hip Radiograph. Radiographic features of OA can be
distinctive but are not closely related to function.
attempts at treatment. OA remains a slowly progressive condition
fuelled by constant release of inflammatory mediators from a
chronic low grade inflammatory reaction. Constant stimulation
of nociceptive receptors in affected joints can lead to an altered
perception of pain with hypersensitivity, hyperalgesia, allodynia
and genetic alteration in central transmission pathways to
enhance pain sensation. [10, 11] This means that small or even
normal stimuli such as normal joint movement can be perceived
as painful as a result of physiological re-programming. This can
be a very difficult state to reverse once well established.
The other, more obvious, consequence of chronic joint debility
and inflammation is the increasing involvement of the structures
surrounding the joint, producing a much more complex
pathological equation. Muscles will atrophy very rapidly as a
result of lack of activity and reflex neurogenic feedback
stimulated by intra-articular pain. Muscles can suffer focal
damage with mediator release and so become a source of
diffuse, poorly localised pain. Muscle wastage can also increase
problems and pain in the joint by reducing protective support.
Changes in subchondral bone can also result in increased pain
[12]. Fibrous thickening of joint capsule, ligaments and tendons
can accompany muscle wastage. Fibrosis and changes in joint
shape caused by new bone formation will produce stiffness and
alter joint movement.
All of these events add to the cyclic deterioration of the
osteoarthritic joint but also create an urgent need for early
intervention to avoid escalation of the pathology and so maintain
reversibility of clinical signs. The more advanced the condition
the more difficult it is to treat.
Lameness
Stiffness
Reduced movement in joint
Reluctance or difficulty with
exercise
Figure 2. Great Dane with OA.
Aged behaviour can be a result of chronic pain due to an
underlying osteoarthritis problem.
of management will be to try to convert active joints to clinically
silent phase where signs are minimal. The second aim will be
to keep them in this state. The third aim will be to slow the
progression along the horizontal axis to end stage disease.
OPTIONS FOR THE
MANAGEMENT OF
OSTEOARTHRITIS
There are a number of methods that have been used in the past
to good effect and continue to be the main components of any
strategy designed to reduce the effects of osteoarthritis in a
patient. These can be placed in broad groups as follows
1. Non-pharmacological methods
2. Pharmacological or Medical methods
3. Surgical Interventions
Crepitus
Swollen joints
Muscle atrophy
The majority of animals with clinical OA are managed without
surgery, but surgery can be the best option depending on the
joint involved (hips) and state of pathology. Euthanasia is an
option which must be considered in intractable cases.
Table 1. Classical signs of osteoarthritis.
28
STUART CARMICHAEL
MANAGEMENT PLANS FOR
OSTEOARTHRITIS
Clinical Assessment
Assessment o
off OA
OA
Chronic Active
Acute
The whole process of managing osteoarthritis can be
summarised as follows
1. Identification of a problem
2. Assessment of the problem
3. Review possibilities and select an intervention strategy
4. Assess success of this within a set time frame
5. Continue, modify, replace or add to intervention(s)
6. Re-assess etc. (maintenance phase)
End Stage
Stage
Chronic Silent
The process must be simple to use, successful in achieving rapid
success, sustainable long term and must bring the clinical
problem under the control of all concerned. It must also be
practical to use and economically feasible.
One way of ensuring that there is a controlled approach to the
problem is by using pre-determined management plans, which
are customised for each patient. These have the multimodal
approach embedded but require judgements to be made about
priorities for treatment. They often combine pharmacological
and non-pharmacological methods and, if properly designed,
will evolve to meet the changing needs of a chronic disease
process. This last point provides sustainability.
Successful plans depend on good quality assessments being
made at different times during the management process. These
Figure 3. Phases of osteoarthritis.
Non-pharmacological methods
Non-pharmacological methods can be divided into 1) dietary
restriction or manipulation, often to achieve weight loss, 2)
instructions about mobility including warm-up exercises,
exercise plans, physiotherapy and hydrotherapy, and 3) a third
group concerned with mechanical aids to assist or facilitate
movement and common sense measures to minimise discomfort.
The application of these methods, with the possible exception
of dietary intervention to lose weight (Figure 4), is often
haphazard and poorly maintained in the animal population.
Pharmacological methods
The main group of medical agents used to gain control of the
signs of OA are the Non-steroidal anti-inflammatory drugs
(NSAIDs). These inhibit the cyclo-oxgenase enzyme, which is a
key component in the arachidonic acid cycle of inflammation.
In the management of human OA, NSAIDs are widely used and
are the most frequently requested by arthritis sufferers. We are
very fortunate to have a range of reliable and relatively safe
NSAIDs licensed for use in dogs. As such, many strategies for
OA management centre on these agents. As toxicity is a
significant risk with NSAIDs strategies have to be constructed
around avoiding toxic side-effects.
Other medical agents used include corticosteroids, again for
anti-inflammatory effects, and opioids for pain relief.
There has been an increasing trend to identifying and employing
agents which may modify the articular cartilage, synovial fluid
and synovium of affected joints. These are often classed as ‘Slow
Acting Drugs’ for OA or ‘Disease Modifying Agents’. Included
in this group are parenterally administered polysulphated
glycosaminoglycans (PSGAG), pentosan polysulphate and
hyaluronic acid. The biggest group of agents in the group are
the orally administered so-called ‘nutraceuticals’, including
glucosamine and chondroitin sulphate. There are numerous
commercially available products containing these agents alone
or in combination. These are often used in combination with
NSAID medication.
The main problem in arthritis management is processing all of
the choices available and selecting an appropriate agent to meet
the objectives. Many attempts at management are based around
a single drug strategy. This contradicts the evidence of the
effectiveness of a multimodal approach suggested previously.
Figure 4. Bull mastiff with OA. Weight loss in obese animals is
a key requisite in any management plan.
29
Putting theory into practice - best practice management for osteoarthritis
Primary
Secondary
Tertiary
A Analgesia
NSAID
Other medical strategies,
anti-depressants, relaxants
B Bodyweight
C Complications
Comfort
Dietary Control
Screen blood
Special bed
D Disease
Joint mobility
Nutraceuticals
Directed exercise
Opiates
Acupuncture
Specific diets, Hydrotherapy
Further medication
High surveillance
Mobility aids
Intra-articular
therapy
Hydrotherapy
E Exercise
Touch therapy,
heat, massage
Modification or
salvage surgery
Physical therapy
Table 2. Management plan options. Applying these options allows complex plans to be constructed which may be necessary in the
management of ongoing complex cases.
A Analgesia
B Bodyweight
C Complications
Comfort
D Disease
E Exercise
First Visit
Second Visit
Third Visit
NSAID started at
maintenance dose
BCS 5
Targets set
Diet provided
Bloods normal
Urine normal
Special bed
Nutraceuticals started
Exercise chart
position 5
Warm up exercises
NSAID dose reduced
Every other day NSAID
BCS 4
Diet continued
Hydrotherapy
BCS 3
Maintenance diet
Urine
Touch therapy institiuted
Continue
Exercise chart
position 4
Ramp for car
Radiograph joint, Nutraceuticals
Exercise chart
position 2
Table 3. Maintenance plan and records. This scheme allows complex plans to be constructed which may be necessary in the
management of ongoing complex cases. BCS = body condition score using a five point scale.
must be repeatable and allow comparison, not only with the last
assessment, but with all assessments recorded. This is the key
to exerting control over chronic evolving disease processes.
Records must be reliable and assessment easy to do, but also
able to detect variations in the clinical state. Assessment of a
complex disease like OA is not an easy feat and is by necessity
largely subjective. Measuring pain and quality of life is much
more difficult than evaluating range of movement and force
plate measured weight bearing. Many attempts have been made
to construct a scale that can be used to give repeatable
measurements of pain with limited success. Carefully constructed
client questionnaires seem to be the most useful way of judging
the subtle changes that can indicate early improvement or
deterioration.
early identification of developing problems and rapid adjustment
of the plan. The approach is particularly useful in ensuring that
non-pharmacological measures are being maintained and
optimised. In many cases veterinary nurses can manage a large
component of the maintenance phase.
PROPOSED MANAGEMENT
STRATEGY FOR
OSTEOARTHRITIS
A ‘Five-Point Plan’ for OA management is proposed to satisfy
the requirements outlined above. The plan identifies five
separate areas of management which can be addressed
simultaneously to deliver a multimodal approach. These areas
are analgesia, bodyweight, complications and care, disease and
exercise (Table 2). One area should be identified as a priority
at the stage of the disease. The plan simplifies the process by
providing prepared options in each area and tracking these over
time (Table 3). It is supported by feed charts, body condition
score information and exercise charts as part of this preparation.
Exercise charts, with a number of different levels of exercise
clearly explained, are a great time saver and aid to compliance
with these plans. The key features can be listed hereafter:
Maintenance and management plans
A critical way in which the approach to the OA patient can be
improved is to develop a maintenance approach and include it
in the plan. Regular visits at set times should be arranged for the
animal to be checked rather than the animal only being
presented when a problem occurs. These are initiated once the
presenting signs are brought under control and the plan evolves
to concentrate on the long term management issues. This
approach is particularly useful in chronic diseases where regular
assessments can be used to map gradual progress. It also allows
30
STUART CARMICHAEL
[6]
DIEPPE (P.A.), CUSHNAGHAN (J.), SHEPSTONE (L.) - The
Bristol OA500 study progression of osteoarthritis (OA) over
3 years and the relationship between clinical and radiographic
features at the knee joint. Osteoarthritis and Cartilage, 1997,
5: 87-97.
[7] WEISMAN (M.L.), NOLAN (A.M.), REID (J.) - et al. Preliminary
study on owner reported behaviour changes associated with
chronic pain in dogs Vet Rec, 2001, 149: 423-424.
[8] VASSEUR (P.B.), JOHNSON(A.L.), BUDSBERG (S.C.) - et al.
Randomised, controlled trial of the efficacy of carprofen, a
non-steroidal anti-inflammatory drug, in the treatment of
osteoarthritis in dogs. JAVMA, 1995, 206: 807-811.
[9] HIELM-BJORKMAN (A.K.), KUUSELA (E.), LINMAN (A.), et al.
- Evaluation of methods of assessment of pain associated with
chronic osteoarthritis in dogs. JAVMA, 2003, 222: 1552-1558.
[10] MUIR (W.W.), WOOLF (C.J.) - Mechanisms of pain and their
therapeutic implications. JAVMA, 2001, 219: 1346-1356.
[11] POCKETT (S.) - Spinal cord synaptic plasticity and chronic
pain. Anaesth Analg, 1995, 80: 173-179.
[12] ARNOLDI (C.C.), DJURHUUS (J.C.), HEERFORDT (J.), et al. Interosseous phlebography, intraosseous pressure
measurements and 99mTc polyphosphate scintigraphy in
patients with painful conditions in the hip and knee. Acta
Orthopaedica Scandinavica, 1980, 51: 19-28.
– It allows a multimodal plan to be set-up and implemented
very easily
– All of the practice members are working from the same
strategy
– Different members of the team may have different roles to
play
– The owner can be informed and instructed easily
– Evolution of care progresses with the changing disease
requirements
– Complex problems can be managed by extending into the
secondary or tertiary options identified for each problem
whilst still following the strategy. These may be nonresponsive cases or cases with intercurrent disease (hepatic,
renal etc.)
– It allows incorporation of new developments without altering
the basic planning process.
Assessment sheets will be analysed to give a specific and global
view of the progress over time. In this way a highly focused and
sophisticated plan can be used and maintained with the
minimum of effort but to the maximum benefit of the affected
animal and owner.
Best practice can be easily delivered within realistic financial
targets.
REFERENCES
[1]
[2]
[3]
[4]
[5]
JOHNSON (J.A.), AUSTIN (C.), BREUER (G.J.) et al. - Incidence
of canine appendicular musculoskeletal disorders in 16
veterinary teaching hospitals from 1980-1989. VCOT, 1994, 7:
56-69.
FOX (S.M.) - Pathophysiology of Osteoarthritic Pain. In:
Proceedings of 1st World Orthopaedic Veterinary Congress,
Munich 2002: 85-87.
ALTMAN (R.D.), HOCHBERG (M.C.), MOSKOWITZ (R.W.), et
al. - Recommendations for the medical management of
osteoarthritis of the hip and knee Arthritis Rheum, 2000, 19051915.
PENDLETON (A.), ARDEN (N.), DOUGADOS (M.), et al. EULAR recommendations for the management of knee
osteoarthritis: report of a task force of the Standing Committee
for International Clinical Studies Including Therapeutic Trials
(ESCISIT) Ann Rheum Dis, 2000, 59: 936-944.
GRAINGER (R.), CICUTTINI (F.M.) - Medical management of
osteoarthritis of the knee and hip joints. MJA, 2004, 180: 232236
NOTES FOR CONTRIBUTORS TO EJCAP
Information relating to material to be directly submitted for
Publication in EJCAP can be found as follows:
• FECAVA WEBSITE
www.fecava.org
• IN EJCAP
EJCAP 15(1) p65
31
REPRINT PAPER (UK)
C anine inflammatory bowel disease:
retrospective analysis of diagnosis and
outcome in 80 cases (1995-2002)
M. Craven(1), J. W. Simpson(1), A. E. Ridyard(1), M. L. Chandler(1)
S
U
M
M
A
R
Y
The case records of 80 dogs in which idiopathic inflammatory bowel disease (IBD) had been diagnosed were
reviewed, and owners were contacted for follow-up information using a telephone questionnaire. The types
of IBD encountered were lymphocytic (n=6), lymphocytic-plasmacytic (n=38), eosinophilic (n=6) and mixed
inflammation (n=30). Prednisolone, sulphasalazine, metronidazole and tylosin were the most frequently
prescribed medications. At follow-up, 21 dogs (26 per cent) were classified as being in remission (for a median
of 14 months), 40 dogs (50 per cent) had intermittent clinical signs (for a median of 17 months) and three
dogs (4 per cent) had uncontrolled disease (for a median of 19 months). Ten dogs (13 per cent) had been
euthanased due to refractory IBD and four of these had entered remission for a median of 21 months prior
to developing severe relapse and refractoriness to further treatment. Six dogs (8 per cent) had been euthanased
or had died for reasons unrelated to IBD. Hypoalbuminaemia at the time of diagnosis was significantly
associated with a negative outcome (P=0.0007). No association was found between the site (P=0.75), type
(P=0.44) and severity (P=0.75) of disease. Dietary change to single protein and carbohydrate commercial diets
had no association with outcome (P=0.12). Owner assessment of quality of life at follow-up was significantly
associated with outcome (P=0.006).
INTRODUCTION
immune response to a commensal bacterium;
and an infection with a pathogenic organism
that either remains in the tissues resulting in
chronic inflammation, or creates ongoing
dysregulation of the immune response after
resolution of infection (Hendrickson and others
2002). Recent advances in human medicine also
point to the significance of genetic factors in the predisposition,
modulation and perpetuation of IBD (Ardizzone and Porro
2002).
appeared in: The Journal of
Small Animal Practice*
(2004) 45, p.336–342
The term ‘inflammatory bowel disease’ (IBD) is
applied in veterinary medicine to idiopathic
inflammation arising from any area of the
gastrointestinal tract (Jergens and others 1992).
The predominant types of IBD described in dogs are
lymphocytic-plasmacytic, eosinophilic and granulomatous
(Jacobs and others 1990, Jergens and others 1992). Crohn’s
disease and ulcerative colitis are the main forms of IBD in
humans, and they are both characterised by a chronic,
intermittent or continuous course. Several theories exist about
the pathogenesis of IBD in humans including: an autoimmune
response to a luminal or mucosal antigen; a dysfunctional
It is widely recognised that canine IBD behaves in a similar
manner and animal models of disease have been demonstrated
to share some of the pathophysiological features of human IBD.
For example, the role of CD4+ T cells, tumour necrosis factor
(1) 4 Hurdles Way, Duxford, Cambridge GB - CB24PA E-mail: [email protected].
* Presented by BSAVA (UK)
33
Canine inflammatory bowel disease
Feature
Human IBD
Canine IBD
Site of inflammation
Transmural in Crohn’s disease
Mucosal in ulcerative colitis
Segmental disease occurs
Arthritis, arthralgias, renal disease, pyrexia,
mucocutaneous lesions, heptobiliary disease,
ophthalmologic complications, osteopenia
Surgical, medical
Intestinal fistulae, strictures, perianal tags,
anal fissures, intramural abscessation,
intestinal obstruction, intestinal perforation
Worse for Crohn’s disease
Lymphoid malignancies
Myeloid malignancies
Intestinal adenocarcinoma
75 to 85 per cent first remission
50 to 75 per cent first relapse
Mucosal
Extraintestinal
manifestations of disease
Treatment modalities
Complications
Prognosis
Neoplastic transformation
Remission rates
Relapse rates
? Thrombocytopenia
Medical
Rare
? Worse for eosinophilic disease
Not reported
Not reported
Not reported
Table 1. Comparative features of human and canine inflammatory bowel disease (IBD)
and interleukin (IL)-12 in mediating intestinal inflammation and
the response to antigens derived from commensal bacteria
(Hendrickson and others 2002, German and others 2003). Some
of the comparative features of canine and human IBD are shown
in Table 1.
maintenance therapy than induction of remission (Thompson
1991).
A definitive association exists between human IBD and later
development of intestinal neoplasia, for both Crohn’s disease and
ulcerative colitis (Ribeiro and others 1996, van Hogezand and
others 2002), but this concept has not been explored in dogs.
In contrast to humans, there exists a relative sparsity of
information in the veterinary literature regarding the long term
disease outcome (Churcher and Watson 1997, Stokes and others
2001).
The anatomical site of disease is known to have prognostic
significance in human IBD. Patients with Crohn’s ileocolitis are
reported to have a greater number of relapses than those with
ileitis or colitis alone (Wright 1992). In ulcerative colitis, the
greater the extent of colon involved, the more frequent and
serious the complications (Sales and Kirsner 1983). The
importance of the anatomical site of disease in canine IBD is
unknown.
The aims of this study were to describe the clinical aspects,
treatment, quality of life and long term outcome of canine
idiopathic IBD. The site of disease, histopathological type,
severity of disease, duration of clinical signs prior to treatment
and serum protein status were assessed for use as prognostic
indicators. Aspects of drug treatment and diet were also
compared with disease outcome.
Disease type has also been demonstrated to have prognostic
value in humans, ulcerative colitis generally having a more
favourable prognosis than Crohn’s disease (Moum 2000, Witte
and others 2000). Prognostic significance has been attached to
the histopathological type of canine IBD, in that eosinophilic
enteritis has been associated anecdotally with common
recurrence and a guarded prognosis (Hall and Simpson 2000).
MATERIALS AND METHODS
The treatment of canine IBD is largely empirical due to the poor
understanding of aetiopathogenesis and lack of therapeutic trials.
Human clinical trials are numerous (Brignola and others 1992,
Elton and Hanauer 1996, Stein and Lichtenstein 2001) and
conventional treatment strategies for canine disease have been
based upon extrapolation of human research. Corticosteroids,
sulphasalazine, azathioprine, antibiotics and dietary trials are
currently the mainstay of treatment for all histological types of
human IBD, either singly or in combination. The efficacy of
such therapeutics in canine IBD has not been determined, and
there is no discrimination between drugs prescribed for either
induction or maintenance of remission. In humans, for example,
it has been reported that sulphasalazine is more effective for
Hospital records of dogs in which IBD had been diagnosed at
the University of Edinburgh’s Hospital for Small Animals were
retrospectively reviewed. Criteria for inclusion in the study were:
histopathological evidence of gastric, small intestinal or colonic
inflammation on either endoscopic or surgical biopsies; clinical
signs consistent with IBD; exclusion of other possible causes of
symptoms, such as exocrine pancreatic insufficiency, infectious
agents, endoparasites or neoplasia; and owner availability for
follow-up information.
The following information was accrued: signalment, clinical
signs on presentation, duration of clinical signs prior to diagnosis,
haematological and biochemical abnormalities, histopathological
34
M. CRAVEN
diagnosis of disease type, site and severity, and treatment
prescribed. Follow-up information was obtained from the
owners using a telephone questionnaire (Fig 1). Referring
veterinary surgeons were also contacted if additional information
was needed.
dogs was 4.3 years (mean 4.9 years, range six months to 14
years). Forty-nine dogs were male (38 entire, 11 neutered) and
31 were female (eight entire, 23 neutered). Seventy-three dogs
representing 27 purebreeds were affected as well as seven dogs
of mixed breed. The most commonly affected breeds were
German shepherd dogs (n=18), golden retrievers (n=8), West
Highland white terriers (n=6), boxers (n=6), Labradors (n=4),
Border collies (n=3) and weimaraners (n=3).
Disease outcome at the time of follow-up was described as
either ‘remission,’ ‘intermittent signs’ or ‘uncontrolled disease’.
Dogs in remission were defined as having been free of clinical
signs for the preceding six months. Those with intermittent
clinical signs were defined as experiencing clinical signs
maximally every 14 days. Dogs with uncontrolled disease were
defined as those experiencing clinical signs more frequently
than every 14 days. Quality of life was defined by the owner’s
perception of the animal’s general demeanour and well-being,
ability and willingness to perform its usual daily activities, and
level of interaction with the owner.
Clinical signs and site of disease
Animals were classified according to histopathology as having
‘upper’ disease (gastritis and/or enteritis, n=22), ‘lower’ disease
(colitis, n=32) or ‘diffuse’ disease (upper and lower, n=26). The
clinical signs according to site of disease are shown in Table 2.
The median duration of clinical signs prior to diagnosis (Fig 2)
was 9.5 months (mean 13.8 months, range 0.5 to 78).
Laboratory findings
The Kruskal-Wallis test was used to compare the disease
outcome with site of disease, histopathological diagnosis, protein
status and treatment. Spearman Rank Correlation was employed
to compare the disease severity, the duration of clinical signs
prior to diagnosis and the quality of life score with outcome. The
comparisons of diet and treatment with outcome were examined
with the Wilcoxon-Mann-Whitney test. Statistical significance
was associated with a P value less than 0.05.
Haematology was performed for 77 dogs and abnormalities
(Table 3) were present in 25 dogs (32 per cent), including
anaemia in nine dogs (12 per cent), leucocytosis in five dogs (6
per cent) and leucopenia in six dogs (8 per cent). Of the three
dogs with eosinophilia, none had eosinophilic enteritis.
RESULTS
Serum biochemical abnormalities (Table 3) were observed in 67
out of 77 dogs tested (87 per cent). Hypoproteinaemia was
present in 50 dogs (65 per cent) and, of these dogs, 31 (40 per
cent) had a low total serum protein level and normal albumin
and globulin level. Twelve animals (16 per cent) were hypoalbuminaemic (five upper, six diffuse, one lower), three (4 per
Fifteen dogs (19 per cent) had platelet abnormalities. Ten dogs
(13 per cent) were thrombocytopenic and thrombocytosis was
present in five dogs (6 per cent).
Signalment
Eighty dogs, identified from hospital case records between 1995
and 2002, fulfilled the inclusion criteria. The median age of the
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Is the patient still alive?
Yes
If dead, what was the cause of death?
How is the patient?
Remission
Intermittent signs
Clinical signs when diagnosed:
Vomiting
Diarrhoea
Tenesmus
Mucus
Frequency
Haematochezia
Melaena
Haematemesis
Weight
Appetite
Quality of life at the time of diagnosis? (1-10)
Quality of life now? (1-10)
When did the patient last show clinical signs?
How frequently do clinical signs occur?
When did the patient last need drug therapy?
What drugs have been prescribed and what was the response?
Diet at the time of diagnosis?
Fig 1. Canine Inflammatory bowel disease questionnaire
35
No
Uncontrolled disease
Clinical sign*
Upper
n=22
(per cent)
Lower
n=32
(per cent)
Diffuse
n=26
(per cent)
Vomiting
Diarrhoea
Haematochezia
Frequency†
Mucus
Tenesmus
Melaena
Haematemesis
Weight loss
Polyphagia
Inappetence
15 (68)
13 (59)
3 (14)
1(5)
3 (14)
1 (5)
1 (5)
2 (9)
11 (50)
4 (18)
2 (9)
16 (50)
29 (91)
19 (59)
17 (53)
26 (81)
12 (38)
1 (3)
0
12 (38)
2 (6)
9 (28)
19 (73)
23 (89)
14 (54)
9 (35)
16 (62)
12 (46)
2 (77)
3 (12)
13 (50)
4 (15)
5 (19)
(6/16) was 155 iu/litre (range 3 to 429). Alkaline phosphatase
was elevated in 18 dogs (23 per cent); mean elevation in those
not on steroids (12/18) was 57 iu/litre (range 2 to 187) and in
those on steroids (6/18) was 998 iu/litre (range 54 to 3390).
Hyperlipasaemia occurred in 12 dogs (16 per cent), and
hyperamylasaemia occurred in 11 dogs (14 per cent). Urea was
elevated in 10 dogs (13 per cent) and creatinine was elevated
in 14 dogs (18 per cent). Three dogs (4 per cent) were
hypocalcaemic. However, following correction for hypoalbuminaemia all were normal, except one dog in which
corrected calcium was 1.86 mmol/litre (reference range 2 to 3)
with unknown cause.
Folate was increased in 18 dogs (mean elevation 3.9 µg/litre,
range 2.0 to 25.0) and decreased in three dogs (mean reduction
2.6 µg/litre, range 1.0 to 4.7). Cobalamin was decreased in five
dogs (mean reduction 92.7 ng/litre, range 76.4 to 100.0).
Absolute values are not reported since the reference ranges for
these parameters changed during the study period.aa
*Most animals had multiple clinical signs
†Increased frequency of defaecation
Table 2. Clinical signs reported for 80 dogs according to site of
disease
Histopathology
Endoscopy was performed in 77 dogs and biopsies were
diagnostic of IBD in 70. Surgical biopsies were obtained in 10
dogs: four in which endoscopic biopses were normal, one with
a non-diagnostic endoscopic biopsy, two in which the small
intestine could not be entered endoscopically, and three with
severe clinical signs. Histopathology was diagnostic of IBD in
all of these dogs. Interestingly, inflammation was found to be
submucosal in two dogs.
cent) were hypoglobulinaemic (two diffuse, one lower) and
four (5 per cent) were panhypoproteinaemic (two upper, two
diffuse).
Alanine aminotransferase was elevated in 16 dogs (21 per cent);
mean elevation in those not receiving steroids (10/16) was 40
iu/litre (range 1 to 119 iu/litre) and in those receiving steroids
Table 3. Biochemical and haematological abnormalities for 77 dogs
Laboratory
abnormality
Number
(per cent)
Mean
Unit
Range
Reference
range
Anaemia (PCV)
Thrombocytosis
Thrombocytopenia
Leucocytosis
Leucopenia
Neutrophilia
Neutropenia
Eosinophilia
Low total protein
Hypoalbuminaemia
Hypoglobulinaemia
Panhypoproteinaemia
Elevated urea
Elevated creatinine
Elevated ALT
Elevated AP
Hyperlipasaemia
Hyperamylasaemia
Hypocalcaemia
9 (12)
5 (7)
10 (13)
5 (7)
6 (8)
5 (7)
2 (3)
3 (4)
31 (40)
12 (16)
3 (4)
4 (5)
10 (13)
14 (18)
16 (21)
18 (23)
12 (16)
11 (14)
1(1)
30
750
145
20.4
5.0
17.4
3.0
1.4
55.1
19
16.2
25.4
1.3*
14.2*
83.1*
370*
385.4*
10.0*
1.86
per cent
109/litre
109/litre
109/litre
109/litre
109/litre
109/litre
109/litre
g/litre
g/litre
g/litre
g/litre
mmol/litre
µmol/litre
Iu/litre
Iu/litre
iu/litre
µmol/litre
mmol/litre
17 to 37
576 to 942
66 to 195
17.2 to 29.0
4.4 to 5.6
12.9 to 26.0
2.8 to 3.1
1.3 to 1.5
47.7 to 57.9
7.2 to 25.7
15.6 to 16.0
19.8 to 30.2
0.1 to 4.3*
2 to 40*
1 to 429*
2 to 3390*
7 to 1915*
1.5 to 19.8*
39 to 55
200 to 500
200 to 500
6 to 15
6 to 25
3·6 to 12
3·6 to 12
0 to 1
58 to 73
26 to 35
18 to 37
58 to 73
*Mean elevation in parameter (due to changes in the laboratory reference range)
PVC Packed cell volume, ALT Alanine aminotransferase, AP Alkaline phosphatase
36
2 to 3
M. CRAVEN
Duration of clinical signs (months)
84 -
•
72 60 -
approaches statistical significance, in that the nonimmunosuppressed animals had a better outcome (P=0.051).
•
Of the 32 dogs with lower disease, 17 received immunosuppressive treatment and 15 did not. In animals with diffuse
disease, 17 were immunosuppressed and five were not. No
significant association between treatment and outcome was
demonstrated for either of these groups (P=0.37 and P=0.12,
respectively).
•
•
48 -
•
36 -
•
24 -
Diet
12 0-
Remission
Intermittent
Prescription diets were fed to 38 dogs (51 per cent), the normal
diet was continued in 30 dogs (40 per cent) and the diet was
not known for the remaining six dogs (8 per cent). The type of
diet was not associated with outcome (P=0.64).
Uncontrolled Euthanased due to IBD
Fig 2. Duration of clinical signs before diagnosis of inflammatory
bowel disease (IBD)
Quality of life
The quality of life at diagnosis and follow-up (Fig 3) was
reported for 63 of the 74 dogs still alive. The score at the time
of diagnosis was allocated retrospectively for some animals, and
11 of the 74 owners felt either unable to recall their dog’s quality
of life at the time of diagnosis or unable to equate quality of life
with a numerical score. The median quality of life score at the
time of diagnosis was 3 (interquartile range 2 to 5) and at followup this had increased to 9 (interquartile range 8 to 10). The
median change in quality of life score between diagnosis and
follow-up was 5 (interquartile range 3 to 6.5). Only three (5 per
cent) of the dogs were thought to have had no change in quality
of life and none had a decrease in quality of life. The quality of
life at follow-up was found to be significantly associated with
outcome (P= 0.006) (Fig 4).
Inflammation was described as lymphocytic in six dogs (7.5 per
cent), lymphocytic-plasmacytic in 38 dogs (47.5 per cent),
eosinophilic in six dogs (7.5 per cent) and non-specific (ie, a
mixed inflammatory cell population) in 30 dogs (37.5 per cent).
The disease was reported to be severe in 12 dogs (15 per cent),
moderate in 39 dogs (49 per cent) and mild in 29 dogs (36 per
cent). The severity of disease was subjectively assessed by each
pathologist by consideration of the degree of inflammatory
infiltrate and architectural changes within the mucosa, lamina
propria, crypt epithelium and deeper tissues when visualised.
In 16 out of 80 dogs (20 per cent), gastric Helicobacter was also
present. Gastric inflammation was present in 14 of these dogs,
but none had exclusively gastric inflammation (six upper, one
lower and nine diffuse). Animals were excluded from the study
if inflammation was confined to the gastric mucosa in the
presence of gastric Helicobacter.
Outcome
At follow-up, 21 out of 80 dogs (26 per cent) were classified as
being in ‘remission’. Of these dogs, 19 (90 per cent) were no
longer receiving treatment and two (10 per cent) were receiving
intermittent or ‘pulse’ treatment. The median duration of
remission was 14 months (mean 20 months, range six to 55
months).
Treatment
Medications prescribed most frequently were prednisolone
(n=45/74, 61 per cent) and sulphasalazine (n=26/74, 35 per
cent). Azathioprine was prescribed infrequently as primary
treatment (n=1, 1.4 per cent) and was more often used when
other treatments had failed (n=9, 12 per cent). Metronidazole was
prescribed for 14 dogs (19 per cent), tylosin for 17 dogs (23 per
cent) and oxytetracycline for one (1.4 per cent). Ranitidine,
omeprazole and sucralfate were the remaining drugs prescribed.
Initial therapy usually consisted of more than one drug and
many different combinations were given. Meaningful statistical
analysis was difficult given the variety of drug combinations.
Analysis was therefore confined to the effects on outcome of
immunosuppressive (azathioprine 1 to 2 mg/kg/day and
prednisolone 1 to 4 mg/kg/day) versus non-immunosuppressive treatment (prednisolone <1 mg/kg/day, sulphasalazine,
metronidazole, tylosin, oxytetracycline, ranitidine, omeprazole
and sucralfate).
Forty dogs (50 per cent) were classified as having an
‘intermittent’ status, for a median duration of 17 months (mean
19 months, range seven to 64 months). Of these, 26 (65 per
cent) were still receiving treatment (eight pulse, 18 continuous).
The median frequency of relapse was approximately every three
months, ranging from every 14 days to every five months.
Three dogs (4 per cent) were classified as having ‘uncontrolled’
IBD, for a median duration of 19 months (mean 18 months,
range 10 to 25 months).
Ten dogs were euthanased due to refractory IBD. Prior to severe
relapse and subsequent euthanasia, four had been in complete
remission and off treatment for a median period of 21 months
(mean 21 months, range eight to 32 months). Three had had an
intermittent status for a median of 10 months prior to euthanasia
(mean nine months, range six to 11 months). The remaining
three dogs had failed to respond to initial treatment for
a median period of three months (mean three months, range one
Of the 20 dogs with upper disease, 13 received immunosuppressive treatment (three had mild disease, seven moderate
and three severe) and seven did not (two had mild disease and
five moderate). The association with outcome for these animals
37
30 -
40 -
20 -
30 -
15 -
Number of dogs
Number of dogs
25 -
10 501
2
3
4
5
6
7
8
9
10
20 -
10 -
Quality of life
Score at diagnosis
Score at follow-up
00
Fig 3. Quality of life at the time of diagnosis and at follow-up
12
24
36
48
60
Length of follow-up (months)
72
84
Fig 5. Length of follow-up after diagnosis of inflammatory bowel
disease
10 -
DISCUSSION
Quality of life score
98-
The signalment, clinical signs, laboratory findings and type of
disease reported in this paper are similar to previous studies
(Jacobs and others 1990, Jergens and others 1992). Comparison
of signalment with the hospital population over the same time
period was not possible due to its system of record keeping.
76543-
Ten animals (12.5 per cent) were thrombocytopenic and it has
been postulated that this may be causally associated with IBD in
both humans and dogs (Ridgway and others 2001). The incidence
of thrombocytopenic dogs in the previous study was lower, at 2.5
per cent of the authors’ population, and an immunological basis
was hypothesised. It is reported in humans that the
thrombocytopenia may or may not resolve with treatment of IBD,
and unfortunately follow-up platelet counts for dogs are rarely
available. Thrombocytosis was present in five dogs (7 per cent)
and, although it is a common human extraintestinal manifestation
of IBD, a causal association has not been reported in dogs. In
human studies, the thrombocytosis is proportional to the activity
of the disease, and is related to a reduced half-life and increased
platelet turnover (Talstad and others 1973). Subjectively, there
did not appear to be any association with severity of disease in
the present study. These findings suggest that abnormalities in
platelet number may have a causal association with canine IBD,
and further investigation is needed to discover the
pathophysiological mechanisms involved.
21Remission
Intermittent signs Uncontrolled disease
Fig 4. Quality of life and outcome
to five months). Interestingly, seven of these animals were
hypoalbuminaemic at the time of diagnosis and two had
achieved clinical remission for 18 and eight months prior to
severe relapse and subsequent euthanasia.
The remaining six dogs had been euthanased for reasons
unrelated to IBD or had died of an unrelated cause. These six
dogs were excluded from further statistical analysis as the status
of their IBD was unknown.
The median duration of clinical signs prior to diagnosis was 9.5
months (mean 13.8 months, range two weeks to 78 months) and
this was not significantly associated with outcome (P=0.85) (Fig
2). The median length of follow-up after diagnosis of IBD (Fig
5) was 17 months (range one to 64 months) and this was found
to have no association with outcome (P=0.18).
Hypoalbuminaemia was strongly associated with a poor
outcome (P=0.0007). The pathophysiology of hypoproteinaemia
may involve reduced appetite, malabsorption due to a reduction
in intestinal surface area, such as with villus atrophy or fibrosis,
haemorrhage or exudation of protein into the gastrointestinal
tract, and increased intestinal permeability. Hypoalbuminaemia may be expected to occur with disease of greater severity
and indeed this has been reported in human IBD (Griffiths and
others 1986, Cabral and others 2001). Surprisingly, the
histopathological severity of disease in four out of seven severely
hypoalbuminaemic animals (albumin <15 g/litre) was graded
No association was found between outcome and the site
(P=0.75), type (P=0.44) or severity of disease (P=0.75) (Table 4).
Hypoalbuminaemia, however, was strongly associated with a
negative outcome (P=0.0007), whereas low total protein and
normal protein were not associated with outcome.
38
M. CRAVEN
Site of disease
Remission
Intermittent signs
Uncontrolled disease
Euthanased due to IBD
Upper (n=20)
(gastritis and/or enteritis)
Lower (n=32)
(colitis)
Diffuse (n=22)
(upper and lower)
9 (45)
6 (30)
0 (0)
5 (25)
6 (19)
23 (72)
2 (6)
1 (3)
6 (27)
11 (50)
1 (5)
4 (18)
IBD Inflammatory bowel disease
Table 4. Number (per cent) of dogs with each outcome by site of disease
as mild or moderate. The authors found no association between
the site, type and severity of disease and outcome. These
parameters, therefore, appear to be of little prognostic value, and
in particular the association of a worse outcome with
eosinophilic disease previously mentioned is not supported.
may have had subclinical disease. It is interesting to note, however,
that the vast majority of animals in remission (90 per cent) did not
receive medical therapy, in contrast to the intermittent group in
which 65 per cent were receiving medical treatment.
The variable length of follow-up and the retrospective nature of
this study did not permit accurate assessment of relapse rates.
In human IBD, one-year relapse rates are generally reported as
being around 50 per cent (Kornbluth and others 1995, Elton
and Hanauer 1996), and a longer duration of remission has been
associated with a lower relapse rate (Ardizzone and others 1999).
It is alarming to note that four of the animals that were
euthanased due to IBD had achieved remission times ranging
from between eight and 32 months in length, prior to severe
relapse and euthanasia.
The remission rate reported here was 26 per cent, and this is
considerably lower than for human IBD, where reported first
remission rates are 75 to 85 per cent (Brignola and others 1992,
Kornbluth and others 1995, Moum 2000). However, the criteria
used to define remission are incomparable. Activity indices,
specifically the Crohn’s Disease Activity Index (Best and others
1976) and the Harvey Bradshaw Index (Harvey and Bradshaw
1980) have been widely employed in human clinical trials, and
scores below a certain threshold are indicative of clinical
remission. Faecal calprotectin, microalbuminuria, intestinal
permeability measurements, serum C-reactive protein and gut
lavage inflammatory markers have also been correlated with
disease activity in humans (Arnott and others 2002).
The association between human IBD, in particular ulcerative
colitis, and colorectal cancer is well recognised (Ribeiro and
others 1996, van Hogezand and others 2002). An increased
incidence of neoplastic disease was not discovered among the
animals in the present study; however, in the 10 animals that
were euthanased due to refractory IBD, postmortem examination
was not performed and thus neoplasia cannot be excluded.
Currently, there are no recognised criteria for characterisation of
the clinical status of canine IBD. The criterion applied in this
study were based on the frequency of recurrence of clinical
signs, and it is accepted that the criteria for remission (free of
clinical signs for six months) may be inappropriate, thus resulting
in an artificially lower remission rate. The reason for the
somewhat strict remission criterion is attributable to the
retrospective nature of the study. Very few owners kept records
of their pet’s health, and the assumption was that memory recall
would be more likely to lead to underestimation of symptomatic
episodes as opposed to overestimation. The six month period
was therefore applied in the hope that this would identify a
group of dogs in which clinical signs had been quiescent for
reasonably long periods of time. Development of canine activity
indices (Jergens 2002) and evaluation of potential markers of
disease, such as faecal alpha-1 protease inhibitor and
microalbuminuria, may in the future enable more accurate
assessment of clinical status.
Owner-evaluated quality of life at follow-up was significantly
associated with outcome (P=0.006). Given the subjectivity of
this parameter, such a strong association was unexpected and
implies that owner perceptions are a valid aspect of disease
monitoring.
The present study could have been improved had the
histopathology been interpreted by one pathologist using
predefined criteria. Significant interobserver variation in
histopathological evaluation of tissues has been reported (Willard
and others 2002). However, currently no widely accepted
histopathological grading schemes for the diagnosis of canine
IBD exist.
Little useful information has been gleaned from this study
regarding the treatment of canine IBD, and this is perhaps not
surprising with retrospective evaluation of a disease with such
varied treatment options. Well-designed prospective clinical
trials will better serve this purpose, and are long overdue in this
field. Widespread standardisation of clinical and pathological
The importance of histological remission as well as clinical
remission is recognised, and it is well accepted in human IBD that
these two descriptors may not be coincident (Arnott and others
2002). Repeat biopsy was rarely performed in this study, hence it
is possible that some of the animals classified as being in remission
39
– implications for therapy. Journal of Feline Medicine and
Surgery 4, 179-182
KORNBLUT (A.), MARION (J.F.), SALOMON (P.), JANOWITZ (H.D.)
(1995) - How effective is current medical therapy for severe
ulcerative and Crohn’s colitis? An analytic review of selected
trials. Journal of Clinical Gastroenterology 20, 280-284
MOUM (B.) (2000) - Medical treatment: does it influence the natural
course of inflammatory bowel disease? European Journal of
Internal Medicine 11, 197-203
RIDGWAY (J.), JERGENS (A.E.), NIYO (Y.) (2001) - Possible causal
association of idiopathic inflammatory bowel disease with
thrombocytopenia in the dog. Journal of the American Animal
Hospital Association 37, 65-74
RIBEIRO (M.B.), AUFSES (A.H.) jr., BALASUBRAMANIAN (S.),
BARTH, (J.), GREENSTEIN (A.J.), HARPAZ (N.), HEIMANN
(T.M.), SACHAR (D.B.), (1996) - Colorectal adenocarcinoma in
Crohn’s disease. Annals of Surgery 223, 186-193
SALES (D.J.), KIRSNER (J.B.) (1983) - The prognosis of inflammatory
bowel disease. Archives of Internal Medicine 143, 294-299
STEIN (R.B.), LICHTENSTEIN (G.R.) (2001) - Medical
therapy for Crohn’s disease: the state of the art. Surgery Clinics
of North America 81, 71-101
STOKES (J.E.), KRUGER (J.M.), MULLANEY (T.), HOLAN (K.),
SCHALL (W.J.) (2001) - Histiocytic ulcerative colitis in three
non-boxer dogs. Journal of the American Animal Hospital
Association 37, 461-465
TALSTAD (I.), ROOTWELT (K.), GJONE (E.) (1973) Thrombocytosis in ulcerative colitis and Crohn’s disease.
Scandinavian Journal of Gastroenterology 8, 135
THOMPSON (A.B.R.) (1991) - New developments in the use of 5aminosalicylic acid in patients with inflammatory bowel disease.
Alimentary Pharmacology and Therapeutics 5, 449
WILLARD (M.D.), JERGENS (A.E.), DUNCAN (R.B.), LEIB (M.S.),
MCCRACKEN (M.D.), DENOVO (R.C.), HELMAN (R.G.), SLATER
(M.R.), HARBISON (J.L.) (2002) - Interobserver variation among
histopathologic evaluations of intestinal tissues from dogs and
cats. Journal of the American Veterinary Medical Association
220, 1177-1182
WITTE (J.), SHIVANANDA (S.), LENNARD-JONES (J.E.), BELTRAMI
(M.), POLITI (P.), BONANOMI (A.), TSIANO (E.V.), MOUZAS
(I.), SCHULZ (T.B.), MONTEIRO (E.), CLOFENT (J.), ODES (S.),
LIMONARD (C.B.), STOCKBRUGGER (R.W.), RUSSEL (M.G.)
(2000) - Disease outcome in inflammatory bowel disease:
mortality, morbidity, and therapaeutic management of a 796person inception cohort in the European Collaborative Study
on Inflammatory Bowel Disease (EC-IBD). Scandinavian
Journal of Gastroenterology 12, 1272- 1277
WRIGHT (J.P.) (1992) - Factors influencing first relapse in patients
with Crohn’s disease. Journal of Clinical Gastroenterology 15,
12-16
VAN HOGEZAND (R.A.), EICHHORN (R.F.), CHOUDRY (A.),
VEENENDAAL (R.A), LAMERS (C.B.) (2002) - Malignancies in
inflammatory bowel disease: fact or fiction? Scandinavian
Journal of Gastroenterology 236, 48-53
grading systems and definition of criteria denoting clinical status
will be of paramount importance for such therapeutic trials to
be of comparative value.aa
ACKNOWLEDGEMENTS
The authors would like to thank Robert Lee, of the Medical
Statistics Unit, University of Edinburgh, for performing the
statistical analysis.
REFERENCES
ARDIZZONE (S.), PETRILLO (M.), IMBESI (V.), CERUTTI, (R.),
BOLLANI (S.), PORRO (B.G.) (1999) - Is maintenance therapy
always necessary for patients with ulcerative colitis in remission?
Alimentary Pharmacology and Therapeutics 13, 373-379
ARDIZZONE (S.), PORRO (G.B.) (2002) - Inflammatory bowel
disease: new insights into pathogenesis and treatment. Journal
of Internal Medicine 252, 475-496
ARNOTT (I.D.R.), WATTS (D.), GHOSH (S.) (2002) Review article:
is clinical remission the optimum therapeutic goal in the
treatment of Crohn’s disease? Alimentary Pharmacology and
Therapeutics 16, 857-867
BEST (W.R.), BECKTEL (J.M.), SINGLETON (J.W.), KERN (F.) JR.
(1976) - Development of a Crohn’s disease activity index.
National Cooperative Crohn’s Disease Study. Gastroenterology
70, 439-444
BRIGNOLA (C.), DE SIMONE (G.), IANNONE (P.), BELLOLI (C.),
EVANGELISTI (A.), CAMPIERI (M.), BELLUZZI (A.),
GIONCHETTI (P.), TAMPIERI (M.), BERTINELLI (E). (1992) Influence of steroid treatment’s duration in patients with active
Crohn’s disease. Agents Actions C90-92
CABRAL (V.L.), DE CARVALHO (L.), MISZPUTEN (S.J.) (2001) Importance of serum albumin values in nutritional assessment
and inflammatory activity in patients with Crohn’s disease.
Arquivos de Gastroenterologia 38, 104-108
CHURCHER (R.K.), WATSON (A.D.) (1997) - Canine histiocytic
ulcerative colitis. Australian Veterinary Journal 75, 710-713
ELTON (E.), HANAUER (S.B.) (1996) - Review article:
the medical management of Crohn’s disease. Alimentary
Pharmacology and Therapeutics 10, 1-22
GERMAN (A.J.) HALL, (E.J.), DAY (M.J.) (2003) - Chronic intestinal
inflammation and intestinal disease in dogs. Journal of
Veterinary Internal Medicine 17, 8-20
GRIFFITHS (A.M.), DROBNIES (A.), SOLDIN (S.J.), HAMILTON
(J.R.) (1986) - Enteric protein loss measured by fecal alpha 1antitrypsin clearance in the assessment of Crohn’s disease
activity: a study of children and adolescents. Journal of
Pediatric Gastroenterology 5, 907-911
HALL (E.), SIMPSON (K.) (2000) - Diseases of the small intestinal
disease. In: Textbook of Veterinary Internal Medicine. Eds S. J.
Ettinger and E. C. Feldman. W. B. Saunders, Philadelphia. pp
1137-1182
HENDRICKSON (B.A.), GOKHAL (R.), CHO (J.H.) (2002) - Clinical
aspects and pathophysiology of inflammatory bowel disease.
Clinical Microbiology Reviews 15, 79-74
HARVEY (R.F.), BRADSHAW (J.M.) (1980) - A simple index of
Crohn’s-disease activity. Lancet 1, 514
JACOBS (G.), COLLINS-KELLY (L.), LAPPIN (M.), TYLER (D.) (1990)
- Lymphocytic-plasmacytic enteritis in 24 dogs. Journal of
Veterinary Internal Medicine 4, 45-53
JERGENS (A.E.), MOORE (F.M. HAYNES (J.S.), MILES, (K.G.) (1992)
- Idiopathic inflammatory bowel disease in dogs and cats: 84
cases (1987-1990) Journal of the American Veterinary Medical
Association 201, 1603-1608
JERGENS (A.E.) (2002) - Understanding gastrointestinal inflammation
More about FECAVA and EJCAP visit:
www.fevava.org
40
REPRINT PAPER (F)
T ranspelvic urethrostomy (TPU)
in the cat: a new technique.
Prospective survey: 19 cases
A. Bernardé(1), E. Viguier(2)
S
U
M
M
A
R
Y
The purpose of this prospective study was to investigate the feasibility and long-term outcome of a modified
subpubic urethrostomy in the cat, termed transpelvic urethrostomy (TPU). Nineteen male cats with unrelievable
obstructive lower urinary tract disease (LUTD) were selected for TPU. In each case, the stoma was made
from the pelvic urethra, exposed ventrally after an ischial ostectomy. There were no intraoperative
complications or accidents. The pelvic urethra and bulbourethral glands were easily recognized and a patent
urethral stoma, at least 2 mm in diameter, was created in all cases. There was no evidence of symptomatic
urethral stricture at follow-up examinations (mean 19 months). Only 1 cat had transient postoperative urinary
incontinence that resolved within 4 weeks. Three cats showed one or several episodes of LUTD after the 2
months re-examination, that were responsive to medical therapy.
TPU is a successful procedure of urinary diversion in the cat with few and minor complications. This technique
may be considered at least as a salvage procedure in cases of perineal urethrostomy failure (an alternative
to prepubic and subpubic techniques) and possibly as a primary urinary diversion method (an alternative to
perineal urethrostomy) for obstructive LUTD.
KEY WORDS: Urethrostomy – Transpelvic – Cat - LUTD
INTRODUCTION
This paper was originally
published in : Prat Méd
Chir Anim Comp*
(2003) 38:p.437-446
Feline urologic syndrome (FUS) is common in
cats. Lower urinary tract disease (LUTD) or
interstitial cystitis are acceptable terms also used
to name this idiopathic inflammatory process
of the feline lower urinary tract, that sometimes
results in partial or complete urethral obstruction in male cats
[1-4]. Obstructions affecting the penile urethra are treated by
perineal urethrostomy (PU) if appropriate nonsurgical treatments
(urethral catheterisation, urethral irrigations, cystostomy tubing)
have failed to restore the urethral patency [4-6]. Some proximal
urethral obstructions may not be amenable to such management.
In these cases, more proximal urinary diversions, such as prepubic
(i.e. antepubic) urethrostomy (PPU) or subpubic
urethrostomy (SPU) are indicated. These
techniques have also been proposed as primary
treatments of penile urethral obstructions, or as
salvage procedures in case of PU failure [7-10].
PU, PPU and SPU techniques in cats have been
extensively described previously [5,7-14]. Potential complications
are associated with these techniques. One of the most serious
complication is stricture formation, mostly associated with PU.
It is well recognized now that this complication is primarily due
to technical errors, making the stoma too small into the proximal
penile urethra (less than 1 mm in diameter) instead of the larger
pelvic urethra(2 to 2.4 mm) situated below the bulbourethral (or
(1) Clinique Vétérinaire des Quais, 31 quai Ulysse Besnard, F- 41000 Blois. E-Mail : [email protected]
(2) Service de Pathologie Chirurgicale des Carnivores Domestiques, Ecole Nationale Vétérinaire de Lyon, BP 83, F- 69280 Marcy-L’Etoile.
* Presented by AFVAC (France)
41
Transpelvic urethrostomy (TPU) in the cat
bulboerectil) glands. [11-15] Postoperative subcutaneous urine
leakage and subsequent granulation tissue formation may also
induce a late stoma stenosis after PU and PPU. Urinary and fecal
incontinence may occur if the pelvic nerves are damaged during
the dissection around the pelvic urethra. Rectal prolapse has
been reported following PU in cats [14-18]. PU, and more often
PPU, are associated with a high prevalence of urinary tract
infection (UTI) postoperatively due to the underlying
urethropathy and probably also to anatomic alterations of the
urethral meatus (PU) and muscles (PPU) compromising intrinsic
defence mechanisms10, [14-18]. Urinary incontinence and UTI
are major complications after PPU. [7,8,10] Data are lacking to
describe the potential complications of the SPU technique, as it
was reported in one case only. [9] SPU was used successfully as
a salvage method after a failed PU and as an alternative to PPU.
The author chose an anatomical urethral diversion site situated
between a PU site and a PPU site. By creating the stoma
effectively from the pelvic urethra, he minimised the risk of
stricture associated with PU. By creating it far enough from the
vesico-urethral junction of the preprostatic urethra (considered
as the internal urethral sphincter), he minimised the risk of UTI
and incontinence commonly associated with PPU.
mg/kg/24h or cefalexin (Rilexine; Virbac, France) at 20
mg/kg/12h. Anaesthesia was induced with either an
intramuscular injection of a combination of medetomidine
(Domitor; Pfizer) at 4 μg/kg and ketamine (Imalgène; Merial,
France) at 3-5 mg/kg, or with ketamine intravenously following
subcutaneous premedication with morphine sulfate (Morphine
Lavoisier; Laboratoires Chaix et Du Marais, France) at 0.02 mg/kg
and acepromazine (Calmivet, Vétoquinol) at 0.1 mg/kg.
Anaesthesia was maintained using isoflurane in oxygen after
tracheal intubation.
All cats were prepared for aseptic perineal and ventral surgery
in a routine manner. They were positioned in dorsal
recumbency, with the feet secured to the surgical table in a
cranial position (Fig. 1).
Surgical technique
The surgical procedure, described below, is composed of 6
steps, numbered from 1 to 6. The first step is optional: it was
used systematically for the first 13 cases of the series and
abandoned later.
1. Cystotomy and placement of a urethral catheter from the
urinary bladder to the urethral obstruction site.
A ventral midline coeliotomy was carried out in order to expose
the bladder 1.5 to 2 cm cranial to the cranial pubic margin. The
ventral bladder wall was secured to the skin with 4 orthogonal
sutures, and a ventral cystotomy, 4 to 6 mm long, was performed.
The bladder contents were aspirated and the bladder cavity
flushed with a sterile saline solution. A 6 French (2 mm) urinary
catheter (for dogs) was inserted into the bladder and the
proximal urethra up to the obstruction site, in order to allow later
identification of the pelvic urethra. While maintained in this
position, the catheter was secured to the bladder wall with a
temporary purse string suture in order to avoid any urine leakage
into the abdominal cavity.
The purpose of this study was to document the feasibility and
the long term outcome of a modified subpubic technique for
urethral diversion in male cats, termed transpelvic urethrostomy
(TPU), performed as a primary or secondary (salvage) technique
for obstructive LUTD.
All cats undergoing TPU between January 1997 and April 2002
were considered for this study. All of them were client-owned cats,
presented for unrelievable obstructive LUTD, whether this event
was a first occurrence, a recurrence, or the result of a failed PU.
The minimum criteria for inclusion were owner approval and a
minimum follow-up period of 6 months. Cats with urethropathy
suspected to be of a different origin than a LUTD (neoplastic or
traumatic) and cats with a concurrent disease were excluded from
the study. In all cases, a biochemical blood analysis was done at
admission, including at least measurements of uremia, creatinemia,
proteinemia, glycemia, natremia, chloremia, kalemia, and base
excess. Some urine was collected aseptically via cystocentesis
and submitted for urinalysis and microscopic examination. Urine
culture was requested in cases of leucocyturia, nitrite
accumulation, or microscopic evidence of bacteriuria.
2. Ventral penis and subpubic adductor muscles exposure.
An elleptical skin incision was made to excise the scrotum and
prepuce as is done routinely for a perineal urethrostomy. This
incision was extended cranially up to the cranial margin of the
pubis. In entire males, the testicles were then exposed and
castration was performed. The penis, being extended caudally,
was undermined ventrally. After removal of some fat tissue, the
caudal and ventral aspects of the pubis were exposed. The
Bulbo-urethral glands, ischiocavernosus and ischiourethralis
muscles were identified and left intact. Fibres from the adductor
muscles, gracilis and external obturator were easily recognized,
forming large V opening caudally (Fig. 2) . The caudal pubic
margin was palpated at the caudal aspect of these muscles. Their
median attachment corresponding to the ventral aspect of the
ischio-pubic symphysis was also identified (Fig. 2).
A temporary diversion technique was carried out initially, by a
urethral catheterisation or a cystostomy tube technique. [19] The
urethral obstruction was considered unrelievable when the
obstruction recurred within 48 hours after urethral catheter
removal, or when the urethral obstruction persisted despite a
cystotomy tube maintained for 3 to 5 days. In such cases, the
cats were considered for surgical management.
3. Ventral exposure of the ischio-pubic symphysis, ischial
ostectomy and pelvic urethra exposure.
Bilateral lateral muscle elevations were made in order to expose
an area of the ventral aspect of the publis approximately 1.21.5 cm wide, and 1.4-1.6 cm long. Bone forceps were introduced
around the pubis in a caudo-cranial direction and a progressive
Surgical preparation
All cats received perioperative intravenous antibiotic therapy,
with either marbofloxacin (Marbocyl; Vétoquinol, France) at 2
42
A. BERNARDE, E. VIGUIER
Fig. 1 The cat is positioned in dorsal recumbency, with the feet
secured to the surgical table in a cranial position. This
position helps later exposure of the ischio-pubic symphysis.
Fig. 4 Pelvic ostectomy has been achieved. Exposure of the pelvic
urethra.
Fig. 2 Ventral exposure of the penis and pelvis. The penis (on the
right) enters cranially under the ischio-pubic symphysis
(short white arrow) whose caudal margin is the curved
dotted line. Adductor muscles are easily identified by their
parallel fibres, forming a large V opening caudally. Ischiourethralis and ischio-cavernosus muscles insertions, and
bulbo-urethral glands are masked by fat at the ischioperineal junction (long white arrow).
Fig. 5 Atraumatic manipulation of the urethral wall with
DeBakey forceps after urethrotomy.
Fig. 3 Ischial ostectomy with bone rongeurs after bilateral elevation
of the adductor muscles from the ischio-pubic symphysis.
Fig. 6 Urethro-cutaneous anastomosis completed.
43
Fig. 7 Urethrostomy diameter is tested. The blunt tip of a 6-Fr
catheter is introduced approximately 1 cm into the stoma
without difficulty.
Fig. 8 The meatus is protected with a copious amount of Vaselinecontaining ointment (Fucidine cream ND, Léo).
Fig. 9 Positive contrast radiography of the urethra postoperatively (case number 3). The arrow points to the
urethrostomy site. Caudally, the ischio-pubic table is lacking.
Fig. 10 Peristomal urine staining in a Persian cat (case number
5). Despite hair being moist and discoloured, there is no
dermatitis.
ostectomy was performed, producing an ostectomy area
approximately 10 mm wide and 12 mm long. Care was taken to
involve no soft tissue within the excision (Fig. 3). After this
ostectomy the pelvic urethra was visualised or, where a catheter
was used, palpated with the catheter inside (Fig. 4).
5. Urethrostomy.
Care was taken to manipulate the urethral wall with non
traumatic De Bakey forceps. The urethral wall was everted
bilaterally (Fig. 5). Suturing of the urethral mucosa to the skin
margins was accomplished without tension via a simple
interrupted pattern of 4-0 or 3-0 monofilament polypropylene
or polyamide sutures, beginning at the 4 cardinal limits of the
urethrotomy. In some overweight cats, some fat tissue
surrounding the stoma site was excised to reduce tension on the
sutures. The part of the penis distal to the bulbo-urethral glands
was amputated, and additional simple interrupted sutures were
placed to achieve the urethro-cutaneous anastomosis (Fig.6).
4. Urethrotomy.
When present, the catheter facilitated identification of the
urethra. Otherwise, the urethral lumen was identified after
transection of the penis at the level of the bulbourethral glands
and a 6 Fr catheter was introduced into the urethra in a cranial
direction. A ventral longitudinal urethral incision was made over
the catheter with a number 15 scalpel blade or with iris scissors,
from the level of the bulbo-urethral glands to a point situated 2
to 3 mm from the cranial margin of the ostectomy. The
urethrotomy was approximately 10 to 12 mm long on the ventral
aspect of the urethra.
6. Skin closure.
Additional skin sutures were used to close the wound cranial
and caudal to the stoma site. The catheter was removed from
the bladder, and introduced into the urethrostomy to test its
diameter (Fig. 7). Bladder wall and coeliotomy wound were
44
closed routinely. The urethrostomy site was protected with a
vaseline containing ointment (Fucidine Leo; Laboratoires Leo,
France) (Fig. 8).
Urethral catheterisation had been performed as initial
management of the obstructive disease in 8 cases only, for 2 to
4 days. For the other 6 cases, urethral catheterisation had been
impossible and a cystostomy tube had been placed for 4 to 7
days. For each of these 14 cats, the urethral obstruction had
been considered non-relievable as the urethral patency did not
recover after placement of the catheter or before the tube
removal. In the remaining 5 cats (3 with a stricture following a
failed PU, 2 with LUTD recurrence) the TPU was conducted
once the bladder was evacuated by cystocentesis.
Post operative care
An Elizabethan collar was placed on each cat immediately after
recovery from anesthesia to prevent self-mutilation of the surgical
site. Positive contrast radiography of the urethra was performed
immediately post surgery in 3 of the first 10 surgical cases
(Fig. 9).
Surgical Technique
All cats received postoperative antibiotic therapy for 5 to 8 days
with either marbofloxacine (Marbocyl; Vetoquinol S.A., France)
at 2 mg/kg intravenously or orally once a day, or cefalexine
(Rilexine; Virbac S.A., France) at 20 mg/kg intravenously or
orally every 12 hours. They also received analgesic drugs with
either morphine (Morphine Chlorhydrate Lavoisier; Laboratoires
Chaix et Du Marais, France) at 0.02 to 0.04 mg/kg
subcutaneously every 4 to 6 hours for 24 to 30 hours, or
meloxicam (Metacam; Boehringer Ingelheim Vetmedica GmbH,
Germany) at 0.15 mg/kg subcutaneously once a day for 1 to 3
days, or a combination of the two. All cats were monitored
postoperatively for urine output. Cats were hospitalised until
voluntary urination had been present for 48 hours. The vaseline
containing ointment was applied to the urethrostomy site 3 to
4 times per day until suture removal at 10 to 12 days
postoperatively. Cats were scheduled for re-examination at 2
weeks, 4 weeks, 3 months and 6 months after surgery. On each
occasion, the stoma diameter was tested as previously described.
Additional follow-up data were collected by phone from the
owners and referring veterinarians. Recommendations for dietary
management of LUTD were made for all cats that had suffered
from this syndrome before presentation.
In all cases, all consecutive steps times of the procedure, (ie.
ventral dissection of the penis, elevation of the adductor muscles
and public ostectomy) were achieved without complication. The
first step of the procedure, i.e. insertion of a bladder catheter,
was done in the first 13 cases only. The pelvic urethra was easily
palpated and identified and the urethrotomy was carried out at
a site such that its proximal opening was situated 15 to 18 mm
below the bulbo-urethral glands. Creation of a definitive
“transpelvic” stoma without undue tension on the urethra or
skin was possible in all cases. In 3 cases, excessive subcutaneous
fat tissue had to be removed before placing the sutures. Once
the stoma was created, it was possible to introduce a 6 French
catheter in all cases, indicating that the diameter of the stoma
was at least 2 mm.
Post-operative findings
All cats tolerated the procedure well and passed urine voluntarily
within 12 hours of surgery. Urinary retention or dysuria were not
seen in the postoperative period. Incontinence was seen in 1
case. Premature suture loosening was seen in 1 case. All cats,
except 2, were discharged between 2 and 4 days postoperatively.
Only 2 cats (15%) received some form of systemic medication
beyond the first 2 weeks postoperatively, which included
antibiotic (1 cat with premature suture loosening), and
corticosteroid (1 cat with urinary incontinence). The case with
suture loosening had dislodged its Elizabethan collar
prematurely. After replacement of the collar, the surgical site was
cleaned twice a day with a sterile isotonic saline solution.
Protection of the stoma site with vaseline ointment was
continued until the wound healed by secondary intentiion after
17 days. The case with urinary incontinence was managed with
prednisolone (Microsolone; Merial, France) given orally at 0.5
mg/kg twice a day from the 10th to the 15th days, and at half
this dosage from the 16th to 20th days postoperatively. The
urinary incontinence was resolved at day 20.
RESULTS
Signalment
Nineteen male cats were considered for inclusion in the study.
All but one were neutered males. The mean age was 6 years
(range, 2 to 9 yr). Their mean body weight was 5.5 kg (3.2 to
7.5 kg). Two-thirds (13 out of 19) were considered overweight.
The breeds represented were mixed breed domestic European
(n=13), Persian (n=3), Siamese (n=2) and Main Coon (n=1).
None of the 19 cats were uremic or hyperkalemic at the time of
presentation. There was no bacterial growth in 4 out of 6 cases
where urine culture was performed. Crystalluria was evidenced
in 13 cases, with predominantly calcium oxalates (n=6), struvites
(n=4), combination of both (n=2), and combination of struvites
and bilirubin (n=1).
Follow-up
All cats were re-examined at 2 weeks for suture removal and at
approximately 4 weeks after the surgery with particular attention
paid to the urethral meatus (Fig. 10). All except one cat had a
patent urethral stoma with no evidence of stricture, as
demonstrated by the easy introduction of a sterile 6 French
catheter into the stoma site. In the case, that had had premature
suture loosening 3 weeks earlier, the introduction of such a
large catheter was not possible, proving the stoma had strictured.
However, the cat was not symptomatic, and the owner of that
Indications for surgery
Indications for TPU were: non relievable urethral obstruction
secondary to a first episode of LUTD (n=4); secondary to
recurrent episodes of LUTD (n=12); and stricture of the stoma
site after a previous failed PU (n=3).
45
Cas
n°
Age
(yr)
Sex
Breed
Indication
Follow-up
(months)
1
2
3
4.5
7
6
NM
NM
NM
European
European
European
OLUTD(2)
OLUTD(3)
OLUTD(2)
48
35
28
4
2
NM
European
OLUTD(1)
25
5
6.5
NM
Persian
OLUTD(2)
23.5
6
7
M
European
Failed PU
(stricture)
22.5
7
8
NM
Persian
OLUTD(1)
20
8
9
4.5
5.5
NM
NM
Siamese
European
OLUTD(2)
OLUTD(2)
20
18
10
11
12
13
6
7.5
4
9
NM
NM
NM
NM
European
European
Siamese
European
17
16.5
16
13
14
15
16
17
5.5
4
8
3.5
NM
NM
NM
NM
European
Main Coon
Persian
European
OLUTD(1)
OLUTD(2)
OLUTD(2)
Failed PU
(stricture)
OLUTD(2)
OLUTD(3)
OLUTD(1)
Failed PU
(stricture)
OLUTD(2)
LUTD(3)
Early complication
(<2 months)
Idiopathic LUTD (4)
at 7,10,14,17 mths
LUTD(1)
Struvite crystalluria
at 17 mths
Permanent peristomal
urine staining
Suture dehiscence at day 2
secondary intention.
healing achieved at day 17
Intermittent urine staining
on the leg
Urinary incontinence
[resolved by day 20]
LUTD(1)
UTI at 5mths
12.5
11
11
8
18
7.5
NM
European
8
19
7
NM
European
7
TOTAL
100%
Table 1. TPU in 19 cats: Signalment, Indications, Complications.
OLUTD (n) : Obstructive LUTD, (n) points out the number of episodes.
cat did not mention any dysuria or stranguria. No other
complication was seen at that time.
Late complication
(<2 months)
Intermittent urine staining
on the leg
10.5%
31.6%
meatus with no evidence of stricture in all cats. Urine staining
(peristomal and permanent for one cat, on the medial aspect of
the feet and intermittent for two others) was unchanged. Three
cats showed late clinical signs of LUTD, manifested by episodes
of hematuria and dysuria, while stoma diameter was unchanged.
Two of them had one single episode of LUTD at 5 months for
one cat and at 17 months for the other. Urine sediments showed
elevated leucocyte counts in one urine specimen collected by
cystocentesis from the first cat. Bacteria were observed
microscopically in this sample. Bacterial culture was positive, and
bacteria were not sensitive to the antibiotic used postoperatively.
Bacterial urinary infection was not demonstrated in the other cat,
but struvite crystalluria was present. The owner had not
continued the dietary treatment, returning to a non-specific
commercial food. These two cats responded well to antibiotic
therapy and dietary management, respectively, and no other
episodes of hematuria and dysuria were noticed during the
follow-up period ranging from 8 to 15 months. The third cat had
several recurrent episodes of hematuria-dysuria at 7, 10, 14 and
17 months, thus approximately once every three months after
the 7th month. Despite two urine cultures at 7 and 14 months,
All cats were re-examined approximately 3 months after the
surgery. At that time, the hair around the stoma site had returned
to its original length. All urethrostomies were patent, with no
difference in diameter from the previous follow-up control. One
continent cat had chronic urine staining of the ventral abdomen
due to retention of urine in the hair surrounding the stoma site
(Fig. 11). Two cats had intermittent urine staining on one of
their feet. According to the owners of these cats, it was
intermittent, depending on their position during micturition. All
other cats seemed to have adopted an altered position during
micturition, and these problems were not noticed. No other
complication were seen at that time.
All cats were re-examined 3 to 5 months later (scheduled 6th
month follow-up examination), and later additional follow-up
data were collected by phone from the owners and referring
veterinarians for all cats except one which died as a result of a
road traffic accident. Urine passed freely through the urethral
46
cats are well documented. Transient, short-term complications
are relatively common and usually transient. They include
dysuria, pollakiuria, hematuria, hemorrhage from erectile tissue
and partial or complete dehiscence of the urethral flap [2,812,14-18] Dehiscence may result from excessive suture tension
(inherent to the surgical technique), or accidental self-mutilation
(non-inherent to the technique) because of an inadequate or
badly-attached Elizabethan collar. Only one cat had partial suture
dehiscence, because of premature loosening of the cervical
collar and excessive leaking of the meatus. This accident had
no severe consequence as the urinary meatus healed well by
secondary intention healing. After this accident, we revised our
method of fixation of the Elizabethan collar, using a hand-made
harness rather than a simple collar. There was no futher
occurence of dehiscence. The lack of spontaneous dehiscence
proves that excessive suture tension is not a particular problem
with TPU.
a bacterial infection was not evidenced. A moderate struvite
crystalluria was seen despite strict adherance to dietary
management. Each episode responded well to an antispasmodic
therapy (Spasmoglucinol, Vétoquinol, France). An anxiolytic
drug (Clomicalm, Novartis,) was also given daily for one month
and every two days subsequently, and no recurrence was seen
up to 28 months postoperatively.
The mean overall follow-up of the nineteen cases was 19
months.
DISCUSSION
Urethrostomy is indicated for the permanent relief of urethral
obstruction in male cats. Obvious but uncommon indications are
irreversible trauma and neoplasia. [2,14] Obstructive LUTD
secondary to matrix crystalline plugs or uroliths that cannot be
managed medically are indications for urethrostomy too, to
circumvent the life-threatening consequences of urethral
obstruction [4,13,14,18].
Long-term complications have also been reported, including
four main types: stricture of the stoma site, urinary incontinence,
urinary tract infection, and chronic urine-scald dermatitis
[8-18,20,21]. The complication rates reported depend on the
technique used: PU is associated mostly with the risks of stricture
and infection whereas PPU is associated with all the above risks.
[7,8-17,19]. Other occasional long-term complications, such as
undetected presurgical or intrasurgical rupture of the urethra
(mostly following catheterization) with later extravasation of
urine into the perineal tissue, rectal prolapse as well as faecal
incontinence, rectourethral fistula and perineal hernia were also
reported after PU [7,14,17]. Stricture or stenosis of the urinary
meatus is a common concern after PU. In one study, urethral
stricture was reported in 37 of 204 cats after PU. All resulted from
incomplete mobilisation and dissection of the penis and its pelvic
attachments with failure to extend properly the urethral incision
to the level of the pelvic urethra [13]. In another study, of 29 cats
referred to a teaching hospital for complications after PU, 22 had
urethral stricture, although the sites of stricture were not specified
[15]. Taking into account past errors, improvements to the
original PU of Wilson and Harisson [5] were proposed. More
recent studies of PU with proper urethral opening 1 cm below
the bulbo-urethral glands reported stricture infrequently
[13,15,18]. This risk is minimal with SPU and PPU as these
techniques involve portions of the urethra respectively pubic and
abdominal, that are 3 to 4 times wider than the perineal portion
[15]. It was therefore expected that the TPU technique reported
here would avoid this complication, as the proximal margin of
the urethrostomy was 15 to 18 mm below the bulbo-urethral
glands. TPU did not result in any symptomatic meatus stricture.
In all cases but one, the diameter of the urinary meatus remained
large enough to accept easily the entrance of a 6 Fr. catheter at
long-term re-examinations.
Indications for the procedure used in this study were
unrelievable obstruction of the perineal urethra secondary to
LUTD (n=16) or stricture following a previous perineal
urethrostomy (n=3). Except in 5 cases (3 post PU meatus
stenosis, 2 recurrent spontaneous obstructive LUTD) , all had
preliminary ineffective attempts to reverse the urethral
obstruction by non surgical means, either by transurethral
catheterisation and reverse flushing (n=8) or by temporary
cystostomy (n=6). Even if these methods should be preferred to
surgical procedures [4,14,19] there is no data in the literature
allowing an assessment of their efficacy. During the inclusion
period of this survey (from January 1997 to April 2002), 13 other
cats that were presented with a urethral obstruction were
managed successfully by either urethral catheterisation (n=13)
or cystostomy (n=2) and were not treated surgically.
All cats selected for TPU were male. All but one had been
neutered with a mean of 3 years between neutering and first
episode of LUTD. No breed predilection was noticed. European
mixed breed cats were over-represented, with a similar ratio to
the overall population of cats presented to our hospitals. Obesity
seemed to represent a predisposing factor for obstructive LUTD
as two-thirds of the selected cats were more than 20% overweight at presentation.
In all cases, the animals tolerated the procedure well. A patent
stoma was created, and voluntary urination occurred within 12
hours of surgery. TPU abolished the clinical signs associated
with urethral obstruction in all cases. No post-operative
hematuria lasted more than 48 hours. No ambulatory disorder
that might have been associated with pubic ostectomy or loss
of adductor muscle attachment was observed.
Urinary incontinence (UI) after urethrostomy techniques is also
a major concern. Different reports indicate UI incidence rates
varying from 0% to 7% after PU and from 35% to 58% after PPU
[4,5,8,10,16,18]. It has been postulated that this may be due to
a partial loss of urethral sphincter capacity [14-17,19,21], and
the effects of PU on urethral sphincter mechanisms have been
investigated using urethral pressure profiles and electro-
Of the 19 cats that underwent a TPU, eight (42.1%) had some
form of minor complications (that were not life-threatening),
10.5% early (before 2 months) and 31.6% later (after 2 months)
(Table 1). Complications related to urethrostomy techniques in
47
myography. One study reported a decrease in maximum urethral
closure pressures one to three weeks after PU, and lack of
urethral electromyographic activity post-surgically [20]. These
findings indicate that perineal dissection during the PU process
may damage the post-prostatic urethral musculature or its
innervation. In half of the cats, however, this loss of function
was reversible. Evaluation of these cats 30 to 96 months after
surgery revealed that 11 out of 24 cats had regained
electromyographic activity of the urethralis muscle in the postprostatic urethra and had normal maximum urethral closure
pressure. Seven cats still had subnormal maximum urethral
closure pressure with little if any electromyographic activity.
Recommendations were made to preserve as well as possible
the somatic (pudendal) and autonomic (hypogastric and pelvic)
nerves during PU including taking care during section of the
ischiocavernosus and ischiourethralis muscles, and blunt
intrapelvic dissection sparing the most dorsal aspect of the
urethra [12,13,14,18]. The benefit of such improved dissection
on cystometrogram variables, electromyographic activity of the
urethralis muscle, and urethral pressure profile after PU has
been demonstrated [14,15]. The incidence of UI is much greater
after PPU. Iatrogenic nerve damage may also occur, with
additional impairment of the prepubic pre-prostatic urethral
sphincter, made of smooth muscle fibres only. This internal
urethral sphincter is more important in urethral competence
than the striated musculature surrounding the post-prostatic
urethra [14,20,21]. In all but one case, there was no UI after
TPU. Our understanding of this result is that the dorsal aspect
of the urethra was neither exposed nor manipulated, avoiding
the risk associated with PU of damage to its innervation.
Additionally, contrary to PPU, the peri-prostatic urethral internal
sphincter was respected. These aspects of the TPU technique
may have decreased the risk of UI. The only cat with transient
UI (cured within 4 weeks) was the smallest in size and had a
temporary 6-Fr catheter inserted into the urethra during the
procedure. We believe that this catheter was oversized for that
cat and may have irritated or distended the urethra leading to
its transient incompetence. The resolution of UI after a short
course of anti-inflammatory drug may corroborate this
hypothesis. This anomaly lead us to stop the systematic use of
a peri-operative catheter (step 1 of the technique) for subsequent
cases in the series.
of those recurrences was demonstrated in 1 case only,
representing 5.2% of UTI after TPU.
Cumulative UI and UTI rates are much higher after PPU than
after PU [7-10]. In one long-term study of PPU in 32 cats, more
than one third (37.5%) of them died or were euthanased because
of complications associated with the procedure. Additionally, in
surviving cats, owners were not satisfied because of the
incidence of chronic dermatitis in the area of the inguinal fat pad
[7]. The potential for postoperative complications after PPU is
so high that this procedure should not be used except as a
salvage procedure.
Subpubic urethrostomy was proposed in 1989 as an alternative
salvage procedure to remedy a failed PU [9]. The authors
indicated that this technique allowed the urethrostomy site to
be placed 3 cm caudal to that in the PPU technique, caudal to
the inguinal fat pad, thereby alleviating the previously-reported
problem of peristomal dermatitis associated with PPU. Some
advantages were obvious with this technique : the portion of the
urethra used for the stoma was effectively the pubic urethra,
wide enough to decrease the risk of late stoma stricture, and it
was far enough caudal to the prostate gland to minimise any
internal urethral sphincter damage. Somehow, the transposition
of the pubic urethra to a subpubic position required a
manipulation of the pelvic urethra with the risk of disruption of
its vascular or nerve supply.
The TPU technique, as we described it originally [22] and in this
paper, reproduced a similar approach to the pelvic urethra, but
with no transposition. This technique placed the urethrostomy
site 15 to 18 mm below the bulbo-urethral glands, 2 to 3 cm
caudal to the inguinal fat pad. There were no major
complications due to the technique itself, such as stoma stricture,
persistent urinary incontinence, or peristomal dermatitis. The
pubic urethra was entered and easily sutured to the skin without
any undue tension, creating a large stoma with little risk of
healing stricture. Urine passed freely through the urethral meatus
with no evidence of symptomatic stricture in all cats, at short and
long-term re-examinations. The dorsal aspect of the urethra was
neither exposed nor manipulated, avoiding the risk associated
with the other urethrostomy techniques of damage to its
innervation. Additionally, contrary to PPU, the peri-prostatic
urethral internal sphincter was respected. These aspects of the
transpelvic technique may have decreased the risk of UI and
possibly UTI.
The incidence of urinary tract infection (UTI) after PU and PPU
seems to be multifactorial in origin. In a study of 18 cats
undergoing PU, six cats had UTI after an average follow-up of
61 months. Two of them had normal urethral pressures whereas
four had low urethral pressures. There was no significant
difference in incidence of bacterial UTI between cats with normal
or low urethral pressures [20]. Finally, factors other than loss of
urethral function may be involved in predisposing cats to
bacterial urinary tract infection after perineal urethrostomy,
such as the underlying uropathy combined with the exposure
to nosocomial contaminants and pre-surgical urethral
catheterisations [14,20,21]. In PPU, the incidence of postoperative
UTI is much higher: infection rates vary from 10% to 35% after
PU, and from 22% to 75% after PPU [8,10,15-18]. In our studied
population, 3 cats presented with late postoperative episodes of
LUTD associated with hematuria and dysuria. The bacterial origin
The feasibility of the TPU technique and its promising longterm outcome may encourage the surgeon to use this technique
in male cats suffering from unrelievable obstructive LUTD. As a
salvage method after a failed PU, TPU should be preferred to a
PPU that is associated invariably with high complication rates.
TPU may also be used as a primary method of urinary diversion,
as an alternative to PU, because it warrants a true approach to
the pubic urethra (needed to generate a large stoma), with no
dorsal peri-urethral tissue manipulation, thus reducing potential
nerve damage.
48
REFERENCES
[12] JOHNSON (D.E.) (1974) - Feline urethrostomy: A critique and
a new method. J Small Anim Pract, 15:421-425.
[13] GREGORY (C.R.), VASSEUR (P.B.) (1983) - Long-term
examination of cats with perineal urethrostomy. Vet Surgery,
12:210-212.
[14] WILSON (G.P.), KUSBA (J.K.) (1983) - Perineal urethrostomy
in the cat. In : Current Techniques in Small Animal Surgery,
Second edition (Bojrab MJ, Edr), Lea & Febiger, Philadelphia,
325-333.
[15] HOSGOOD (G.), HEDLUND (C.S.) (1992) - Perineal
urethrostomy in cats. Comp Cont Educ Pract Vet, 14:1195-1205.
[16] GRIFFIN (D.W.), GREGORY (C.R.) (1992) - Prevalence of
bacterial urinary tract infection after perineal urethrostomy in
cats. J Amer Vet Med Assn, 200:681-684.
[17] SMITH CW, SCHILLER (A.G.) (1978) - Perineal urethrostomy in
the cat: A retrospective study of complications. J Amer Anim
Hosp Assn, 14:225-228.
[18] GRIFFIN (D.W.) et coll (1989) - Preservation of striated-muscle
urethral sphincter function with use of a surgical technique for
perineal urethrostomy in cats. J Amer Vet Med Assn, 194:10571060.
[19] WILLIAMS (J.M.), WHITE (R.A.S.) (1991) - Tube cystostomy in
the dog and cat. J Small Anim Pract, 32:598-602.
[20] GREGORY (C.R.), VASSEUR (P.B.) (1984) - Electromyographic
and urethral pressure profilometry: Long-term assessment of
urethral function after perineal urethrostomy in cats. Am J Vet
Res, 45:1318-1321.
[21] CULLEN (W.C.) et coll (1983) - Morphometry of the male feline
pelvic urethra. J Urol, 129:186-189.
[22] BERNARDÉ (A.), VIGUIER E (2002) - Transpubic urethrostomy
in 11 cats using a caudal pubic ostectomy. Oral communication.
11th annual Scientific meeting ECVS 2002 (abstract), Vet Surgery
31:298.
[1] OSBORNE (C.A.) et coll (1996) - Feline lower urinary tract
disorders: Definition of terms and concepts. Vet Clin N Am,
Small Anim, 26:169-179.
[2] SMITH (C.W.) (1993) - Surgical diseases of the urethra. In:
Textbook of Small Animal Surgery, Second edition (Slatter D,
Edr), WB Saunders, Philadelphia, 462-1473.
[3] CARBONE (M.G.) (1971) - Urethral surgery in the cat. Vet Clin
N Am, Small Anim, 1:281-298.
[4] CAYWOOD (D.D.), RAFFE (M.R.) (1984) - Perspectives on
surgical management of feline urethral obstruction. Vet Clin N
Am, Small Anim, 14: 677-690.
[5] WILSON (G.P.), HARRISON (J.W.) (1971) - Perineal
urethrostomy in cats. J Amer Vet Med Assn, 159:1789-1793.
[6] BLAKE (J.A.) (1968) - Perineal urethrostomy in the cat. J Amer
Vet Med Assn, 152:1499-1506.
[7] MENDHAM (J.H.) (1970) - A description and evaluation of
antepubic urethrostomy in the male cat. J Small Anim Pract,
11:709-721.
[8] Mc CULLY (R.M.) (1955) - Antepubic urethrostomy for the relief
of recurrent urethral obstruction in the male cat. J Amer Vet
Med Assn, 126:173-179.
[9] ELLISON (G.W.) et coll (1989) - Subpubic Urethrostomy to
salvage a failed perineal urethrostomy in a cat. Comp Cont Educ
Pract Vet, 11:946-951.
[10] BAINES (S.J.) et coll (2001) - Prepubic urethrostomy: A long
term study in 16 cats. Vet Surgery, 30:107-113.
[11] KUSBA (J.K.), LIPOWITZ (A.J.) (1981) - Repair of strictures
following perineal urethrostomy in the cat. J Amer Anim Hosp
Assn, 17:422-433.
49
COMMISSIONED PAPER
T he safe use of cytotoxic drugs in
companion animal practice
N. Bexfield(1)
S
U
M
M
A
R
Y
Chemotherapy has become a commonly used and accepted cancer treatment modality in companion animal
practice. Clients are increasingly well informed about treatment options available for their pets, and there is
pressure on veterinary surgeons to use cytotoxic drugs (fig. 1). Yet, to many veterinary surgeons, the use of
cytotoxic drugs remains an unfamiliar and complex subject. Cytotoxic drugs (also known as chemotherapy,
anticancer, antitumour or antineoplastic drugs) are potent and potentially dangerous, not only to the patient,
but to those involved in their administration. This article addresses the safety aspects of storing, preparing
and administering cytotoxic drugs in a companion animal practice setting. Potential side-effects resulting from
the use of cytotoxic drugs are also described.
OVERVIEW
This paper was
commissioned
By FECAVA for
publication
in EJCAP
The main indications for cytotoxic drugs in
veterinary medicine are as first line treatment for
lymphoproliferative and myeloproliferative
disorders including lymphoma (lymphosarcoma), leukaemia and multiple myeloma.
These diseases are systemic in nature and
usually respond favourably to cytotoxic drugs. Cytotoxic drugs
are of limited value as sole agents in the management of large
solid tumours. They do however have a palliative role as adjuncts
to surgery or radiotherapy in the prevention or management of
metastatic disease associated with certain tumours. Cytotoxic
drugs in combination protocols are usually preferred, as
combining different drug classes with differing mechanisms of
action can increase tumour cell kill without
increasing toxicity. Intermittent or pulse dosing
is the usual method of cytotoxic drug delivery,
because continual administration of low doses
will select for tumour resistance.
Risks to those handling cytotoxic drugs
Many of the safety issues discussed in this article should be
considered in respect to individual practice facilities and staff
expertise. A practice policy should be established on cytotoxic
drug administration to enable consistent decision making
Fig. 1: A selection of the cytotoxic drugs used in companion
animal practice, all of which pose a potential risk to
personnel involved in their handling.
NOTE: None of the cytotoxic drugs discussed in this
article are licensed for veterinary use. Owners should be
suitably informed, and appropriate written consent
obtained. All of these agents are potentially hazardous to
the patient and to persons handling them. While every
effort has been made to ensure that the drug selection
and dosages in this article are in accordance with current
recommendations and practice, veterinary surgeons who
prescribe such drugs to patients under their care must
assume responsibility for their use and safe handling.
(1) Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, GB-CB3 0ES. E-mail: [email protected]
51
The safe use of cytotoxic drugs in companion animal practice
Fig. 2: High visibility cytotoxic warning tape.
regarding the use of specific drugs. Some practices may decide
not to administer any cytotoxic drugs, while others may opt for
the safe administration of a select few. Referral to a veterinary
oncologist should also be considered at an early stage.
Cytotoxic drug handling is acknowledged as an occupational
hazard. Many of the cytotoxic drugs used in veterinary medicine
are irritant to the skin and mucous membranes and also have
mutogenic, teratogenic or carcinogenic properties. Human
patients have been shown to develop secondary cancers as a
result of treatment with cytotoxic drugs, and such risks may be
acceptable when patients have a life-threatening illness.
However, these effects are not acceptable to personnel involved
in the reconstruction and administration of cytotoxic drugs. A
number of studies have identified the presence of cytotoxic
drugs and their metabolites in the serum and urine of cytotoxic
drug handlers. The risks associated with occupational exposure
to cytotoxic drugs are small when compared with patients treated
therapeutically, but are far less understood. Exposure to cytotoxic
drugs can occur in several ways:
– Drugs can be absorbed through the skin, although with the
majority of compounds there is little or no absorption. Skin
exposure can also be by contact with contaminated equipment
used in preparing or administering drugs.
– Drugs can be ingested in contaminated food.
– Aerosolised drugs can be inhaled during reconstitution or
administration.
– Accidental inoculation of drugs can occasionally occur,
especially during recapping of used needles.
– Metabolites can be excreted in the faeces or urine for up to
48 hours after administration.
All cytotoxic drugs must therefore be handled with
extreme care and in the full knowledge of their potential
dangers.
such as spill kits. In other European countries, occupational
health and safety issues are addressed by the European Agency
for Safety and Health at Work. They provide good practice
guidelines for the majority of European countries similar to
those of COSHH, and information can be found at
http://agency.osha.eu.int/info.
Individual companion animal practices should perform a risk
assessment, and local rules and standard operating procedures,
similar to those used for radiation protection, should be drawn
up. As well as records in case-notes, separate records of all
cytotoxic drugs administered should be kept. These should
include details of the patient, drug and dose used, method of
administration and staff involved in the procedure. A separate
record book should be kept detailing stock control of cytotoxic
drugs and any incidents such as spillages. Material safety data
sheets of all cytotoxic drugs used in the practice should be
obtained. These provide information on the physical, chemical
and toxicological properties of the drug, as well as storage and
handling instructions, and are distinct from the data sheets
accompanying the product. All staff involved in the handling of
cytotoxic drugs, from stock control to administration should
receive copies of both the local rules and standard operating
procedures and also be provided with suitable training.
Storage
Many of the common oral and injectable preparations require
refrigeration; these agents should ideally be stored in a
designated fridge. If this is not possible they should be kept
well away from food substances in a separate clearly labelled
area of the fridge. The use of high visibility “cytotoxic” warning
tape is recommended (fig. 2). Where practices have multiple
drug dispensing sites, such as in each consultation room,
cytotoxic drugs should be kept in the main pharmacy, ideally
in a separate locked area, and only dispensed by designated
personnel (fig. 3).
Rules and regulations
In general, cytotoxic drugs are hazardous substances, and
guidelines exist on their safe use in the workplace. In Great
Britain, they are defined by the Control of Substances Hazardous
to Health Regulations 2002 (COSHH). Some are also considered
carcinogenic and are therefore subject to Appendix 1 of the
COSHH Approved Code of Practice (ACOP) which provides
additional guidance on the control of carcinogenic substances.
Information on COSHH guidelines can be found at
http://www.hse.gov.uk/coshh/. Under COSHH, employers are
obliged to identify substances which are a hazard to staff, as well
as those who may be exposed, how cytotoxic drugs should be
handled and what to do in the event of a spill or accident. They
also ensure that staff have access to the ideal environment,
protective clothing, policies and procedures, a system of
monitoring and recording effects and any necessary equipment
Protective clothing
Under the Personal Protective Equipment at Work Regulations
1992, personal protective equipment (PPE) should be provided
and used whenever there are risks to health and safety. The
level of protection required depends on the procedure being
undertaken, and when handling cytotoxic drugs should include:
– Gloves: Gloves should be worn at all times. No type of glove
is completely impermeable to every cytotoxic agent, and there
is no consensus as to which glove material offers the best
protection; thicker gloves generally give better protection than
thin ones. Using poor-quality low-cost gloves is neither safe
nor cost effective. The gloves used at the author’s institution
are designed for use with cytotoxic drugs and the thickness
52
N. BEXFIELD
Fig. 3: If possible, cytotoxic drugs should be
kept in a separate locked cabinet.
Fig. 4: Gloves and arm sleeves should be
worn at all times when handling
cytotoxic drugs.
increases from 0.25mm at the cuff to 0.4mm at the fingertips (fig.
4). Powder free gloves should not be used as powder can absorb
cytotoxic drugs. Double gloving is unnecessary and only
required when dealing with a spill.
– Arm sleeves: Non-permeable polyproylene arm sleeves (0.25
– 0.35mm thick) with tight fitting cuffs should be worn at all
times when working with cytotoxic drugs (fig. 4).
– Gowns: Disposable gowns should be worn for both
reconstitution and administration. These should be long
sleeved and water resistant. Alternatively, in some situations,
arm sleeves and plastic aprons can be substituted for longsleeved gowns during drug handling.
– Eye protection: Goggles are used to protect the eyes from
splashes and particles and should fully cover the eyes to
protect the handler (fig. 5). They are not required when work
is being done in a safety cabinet, but should be worn at all
other times.
– Masks: Respiratory protective equipment (RPE) is required if
drugs are to be prepared outside a safety cabinet. These
should also be worn whenever there is a possibility of
inhalation of the drug during administration. Disposable paper
surgical type masks offer no respiratory protection, but may
help avoid mucosal contamination.
Fig. 5: Different types of eye protection
used when handling cytotoxic drugs.
It is unlikely that the majority of practices will have biological
safety cabinets. Preparation of drugs without such equipment is
therefore a compromise on safety, but may be acceptable if only
occasional treatments are given. In this situation drugs should
be prepared in an area away from people and animals, without
doors, windows or draughts, and the maximum possible
personal protection used. This should include gloves, disposable
arm sleeves and a gown, goggles and a mask (see above).
Fig. 6: Drugs should be prepared in a biological safety cabinet
is possible. A disposable absorbent mat protects horizontal
surfaces from accidental spillage.
Drug preparation
Ideally drugs should be prepared in a biological safety cabinet,
which are categorised based on the level of protection they
offer (fig. 6). They offer protection to the operator (class 1), the
operator plus the drug based on airflow (class 2), or are designed
as a complete sealed unit to offer both drug and operator
protection (class 3). In all of these systems, air is filtered through
special particle absorbers before being discharged into the
atmosphere or back into the room. Conventional laminar airflow
cabinets are unsuitable as airflow, hence droplets, is directed
towards the operator. The same is true for fume-hoods which
merely alter local airflow.
53
Fig. 7: Appropriate equipment minimizes Fig. 8: Tablets should be dispensed
in their original containers, or
staff exposure to cytotoxic drugs. Here a
repackaged in child-proof
filtered venting device and leur lok
containers and clearly labelled
syringe are used to prevent aerosol
as cytotoxic drugs.
formation.
Some basic rules when preparing cytotoxic drugs should be
followed. These refer to liquid or powder for reconstitution
cytotoxic drugs:
Fig. 9: Cytotoxic drugs can be formulated as a solution
for injection or powder for reconstitution.
contamination of people or work surfaces. All staff involved in
handling cytotoxic drugs should be familiar with such
procedures, and these should be readily available for emergency
use. The following procedure should be followed when dealing
with a spillage:
1. Put on a double pair of gloves, gown, disposable plastic apron
over the gown, arm sleeves and goggles.
2. If there is visible powder spill, put on a suitable respiratory
mask.
3. If spillage is on the floor, put on overshoes.
4. Wipe up any powder spillage quickly with well damped paper
towels.
5. Mop up liquids that have been spilt on hard surfaces with
paper towels, starting at the outer edge of the spill area and
working in a circular motion towards the middle of the spill.
6. Wash hard surfaces at least twice with copious amounts of
cold, soapy water and dry with paper towel.
7. If there is direct skin contact, the area should be washed
thoroughly with soapy water as soon as possible and for at
least two minutes. Eye wash should be used if necessary.
8. All contaminated materials should be disposed as cytotoxic
waste.
– Drugs should be prepared by trained staff in a designated
area.
– All preparation surfaces, even in a biological safety cabinet
should be covered by a plastic backed-absorbent mat.
– The use of ready-to-use formulations in rubber stoppered
bottles avoids the need for reconstitution.
– Air must never be injected back into the bottle, nor should
syringes containing air be vented into the atmosphere. If it is
necessary to expel air from a filled syringe it should be
exhausted into an absorbent pad.
– The use of commercial filters to prevent the ventilation of
toxic aerosols should be considered (fig. 7). These help
equalise the pressure during reconstitution and as drugs are
being drawn up.
– Regular hypodermic needles placed into the stopper as an air
vent should not be used.
– Leur lok type syringes can be used to prevent accidental
separation of the needle from the syringe or syringe from the
venting device or container (fig. 7).
– All intravenous lines should be primed prior to addition of
cytotoxic drugs to infusion bags.
– After preparation, drugs should be placed in a labelled,
sealable plastic bag to contain any spills during transport to
the area where the drug is to be administered.
Administration of cytotoxic drugs
Cytotoxic drugs are commonly available in two forms:
– Tablets or capsules for oral administration.
– Powder for reconstitution or solution for injection.
The following guidelines should be followed to enable the safe
handling of cytotoxic drugs:
Alternatively, some human hospital pharmacies and private
companies will dispense cytotoxic drugs formulated at the
correct dose and ready for administration. If available, this facility
is a convenient and safer option to drug preparation in some
veterinary practices.
1. ORAL
The oral route of drug administration is convenient, economical,
non-invasive and sometimes less toxic than other routes. Most
oral drugs are well absorbed if the gastrointestinal tract is
functioning normally. However, in some situations drug delivery
by this route is not possible. Several basic recommendations
should be followed when dispensing or administering tablets or
Cytotoxic drug spillages
Veterinary practices should have clear procedures, based on
risk assessment, in place for dealing with spillages or
54
N. BEXFIELD
capsules by the oral route:
– Tablets should NEVER BE CRUSHED OR BROKEN and
capsules should NEVER BE OPENED.
– Safe dosing schedules can be devised for most drugs, by
increasing the inter-dosing interval, sourcing an alternative
formulation or using an injectable preparation.
– It is sometimes possible for drugs to be specially compounded
by a local pharmacy or hospital pharmacy.
– Disposable latex gloves should be worn when handling any
tablet or capsule.
– When tablets or capsules are provided in an individual
wrapper, they should be dispensed in this form.
– Tablets and capsules should be dispensed without altering the
manufacturers’ packaging where possible, but should always
be dispensed in child proof containers.
– Tablets should be counted using a triangle which should be
washed and dried after use.
– In addition to the statutory requirements for the correct
labelling and dispensing of medicinal products, all containers
should be child proof and clearly labelled. The use of highly
visible tape with the “cytotoxic” warning is encouraged (fig.
8).
– If tablets and capsules are given in food, ideally they should
be mixed with a small amount of food to ensure ingestion.
– If administered to the animal directly per os, care should be
taken to avoid accidental spillage or dissolution of the outer
protective covering.
– Hands should always be washed after handling any drugs.
– Staff and owners should receive clear instructions on the
administration of oral medication, and an information leaflet
is useful for this purpose. Owners should be made aware of
the potential hazards when administering these medications,
and also be provided with a supply of gloves.
– Unused medications should be returned to the veterinary
practice for disposal.
cytotoxic’s, some of which are presented as freeze-dried material
or powder, requiring to be mixed with diluents (fig. 9). Potential
dangers in the handling and manipulation of these products
include the creation of aerosols during reconstitution and
accidental spillage.
Intravenous drugs can be administered via a traditional preplaced over-the-needle catheter or butterfly-style catheter (fig.
10). Off the needle administration of any drug, no matter how
small the volume, is strongly discouraged. The following basic
steps should be followed, some of which apply to drugs
administered as an infusion:
– Adequate restraint should be considered if the animal is
fractious or infusion times are long.
– The large veins of the forelimb (cephalic) should be chosen
for i.v. access, as they are the easiest, reduce the risk of
chemical phlebitis and result in fewer problems if
extravasation should occur.
– Butterfly style catheters should not be used when the volume
of drug is greater than 2mls or the drug is given as an infusion
(e.g. doxorubicin as an infusion). Potentially vesicant drugs
should also not be given via butterfly catheters because of the
increased risk of dislodgment over conventional catheters.
– The general rule is to start catheter placement distally and
proceed proximally where possible.
– Alternate the legs to ensure the same veins are not being used
and damaged by chemical and mechanical irritation.
– Patency should be checked by achieving blood return
followed by flushing with 10ml of 0.9% sodium chloride to
ensure there is no resistance, swelling or pain. Heparin saline
should be avoided as it can precipitate some drugs, especially
doxorubicin.
– Catheters should be firmly taped in placed after verification
of patency (fig. 11).
– The catheter site should not be covered.
– During drug administration the catheter site should be
checked periodically and administration of the drug stopped
if resistance is felt, swelling occurs or there are signs of a
local or generalised reaction
– If the drug is given as an infusion, 20mls of saline can be
2. INTRAVENOUS
The main risk for cytotoxic drug exposure to personnel arises
during the preparation and administration of injectable
Fig. 11: Drugs for intravenous injection should be administered
via a securely placed intravenous catheter. (Courtesy of Dr
J Dobson, The University of Cambridge)
Fig. 10: A dog receiving cytotoxic drugs. Note the use of an
absorbent mat and swabs to absorb any leaked drug.
(Courtesy of Dr J Dobson, The University of Cambridge)
55
Disposal
added to the empty bag after the infusion has finished thereby
removing residual drug.
– After the infusion is complete, the catheter and any ports
should be flushed with at least 10mls of saline, and the
catheter removed immediately.
– All materials should be placed into a sealed plastic bag and
discarded as cytotoxic waste.
Suitable containers, clearly labelled and reserved solely for the
use of cytotoxic waste should be available (fig. 12). Waste should
be disposed of by high temperature chemical incineration by a
licensed authority. Practices should consult their waste disposal
provider for more specific details of cytotoxic drug waste
disposal. The following general guidelines apply:
– Sharps should be placed in an impermeable plastic container
specified for cytotoxic waste. Absorbent matting should be
placed in the bottom of the sharps bin to absorb any leakage.
Used needles should never be recapped as this greatly
increases the risk of accidental self injection.
– Solid waste (e.g. contaminated syringes, giving sets, catheters,
fluid bags, absorbent paper, gloves, aprons, e.t.c.) should be
double wrapped and sealed in labelled polythene bags (fig.
13). The sealed bags are then placed in cytotoxic waste bins.
– Empty drug containers and vials containing less than 1ml of
solution may be treated as “solid waste”.
– Excess or out of date drugs, tablets or solutions should be
disposed of in cytotoxic bins for DOOP (Destruction of Old
Pharmaceuticals). They must be double wrapped, sealed in
polythene bags, and clearly labelled with the drug name and
amount remaining.
NB: Peripheral veins should be avoided for routine blood
collection from oncology patients, and the jugular vein used
instead.
3. INTRAMUSCULR AND SUBCUTANEOUS
Only a few cytotoxic drugs can be administered by this route
due to several factors including their irritant nature, incomplete
absorption, bleeding as a result of paraneoplastic
thrombocytopenia and discomfort at the injection site. Drugs
administered in this way include:
– Cytosine arabinoside
– L-asparaginase
– Methotrexate
– Bleomycin
Animals should be adequately restrained for administration of
drugs by this route if the volume administered is large or the
drug is likely to be painful (L-asparaginase). Suitable gloves and
other protective equipment should be worn during the
procedure, as there is greater potential for spillage. After insertion
of the needle, aspiration should be performed to make sure a
blood vessel has not been inadvertently entered.
Animals can excrete potentially harmful drugs or drug
metabolites in their urine, faeces, vomit or saliva for variable time
periods after administration. Steps should be taken to minimise
this exposure:
1. All patients should be clearly identified as receiving or having
received chemotherapy (fig. 14). This is particularly important
for in-patients, which may be cared for by staff who were not
present when cytotoxic drugs were given.
2. Owners should be made aware of the potential risks of
contaminated waste from their pets. Often little more than
normal hygiene precautions are required, but specific
4. INTRACAVITARY ADMINISTRATION
Occasionally some drugs including carboplatin and cisplatin are
administered into a body cavity. Due to the potential hazards
associated with this route of administration, and the specialised
technique required, the clinician is encouraged to consult a
veterinary oncology specialist before undertaking this procedure.
Fig. 12: Containers for cytotoxic waste
should be specific for that purpose and
clearly labelled.
Fig. 13: Solid waste should be sealed in
labelled polythene bags before being
placed in cytotoxic waste bins.
56
Fig. 14: Kennels containing in-patients
receiving cytotoxic drugs should be
clearly marked, as staff providing
ongoing care may have been absent
during drug administration.
N. BEXFIELD
instructions should also be given.
3. Solid waste and small amounts of absorbent material can be
flushed down the toilet.
4. Other waste should be doubled bagged and placed in the
domestic waste.
5. Dogs should be encouraged to urinate on grass, and urine
should be hosed of hard surfaces using care to avoid splashes.
have documented moderate to severe myelosuppression
following single-agent vincristine therapy in occasional patients.
Cells with the shortest life span are most susceptible; therefore
myelosuppression is commonly manifested by a decrease in the
neutrophil count. Mild neutropenia is relatively common and not
often a clinical problem, but severe neutropenia can result in an
increased risk of infections and sepsis. The neutrophil nadir is
usually 7-10 days for the majority of drugs, although there is
some patient variation. Most combination drug protocols are
designed to allow complete bone marrow recovery prior to the
administration of the next round of treatment.
Several factors affect the risk and outcome of infection, the most
important of which are severity and duration of neutropenia.
Animals should be considered at risk of opportunistic infections
when the neutrophil count fall to less than 2.0 x 109/l. Organisms
most frequently isolated are Gram-negative enteric bacteria
followed by Gram-positive cocci. Common sites of infection are
the blood stream (bacteraemia) and the lungs. It is important to
remember that severely neutropenic patients may not show the
classic signs of infection, due to the lack of cells required to
produce an inflammatory response. For instance, neutropenic
animals may exhibit a normal or even subnormal temperature.
Diagnostic tests performed in the symptomatic neutropenic
patient should include a complete blood count (CBC), serum
biochemistry and urinalysis. Other tests such as thoracic
radiography, urine or blood culture may also be required.
COMPLICATIONS OF
CHEMOTHERAPY
Toxicity is the most important and major treatment-limiting factor
in chemotherapy. Cytotoxic drugs are not selective in their
actions on growing or dividing cells, hence organs that contain
a high proportion of dividing cells, for example the bone marrow
or gastrointestinal tract, are particularly susceptible to these toxic
effects. Complications can arise at any time during cytotoxic
drug administration, and some agents can induce immediate
hypersensitivity reactions, while others cause longer term sideeffects. Although potentially life threatening, these toxic effects
are usually reversible on discontinuation of treatment. Some
cytotoxic drugs have other toxic actions that are unfortunately
less reversible. These include doxorubicin (cardiotoxicity),
cyclophosphamide (sterile haemorrhagic cystitis) and cisplatin
(nephrotoxicity).
Discussed below are some of the more common side-effects
applicable to veterinary cancer patients:
There are two main scenarios during cytotoxic drug treatment
when a veterinary surgeon may be faced with a neutropenic
animal:
1. An ill animal presenting several days after administration of
a cytotoxic drug.
2. Routine blood sampling prior to the next dose of a cytotoxic
drug in an otherwise asymptomatic animal.
The response to these two scenarios varies. Withholding
cytotoxic drug administration for 5-7 days, in combination with
1. Bone marrow suppression and infections.
Myelosuppression is the most common and potentially serious
side-effect resulting from the use of cytotoxic drugs, and is the
main dose-limiting factor in veterinary chemotherapy. Most drugs
are myelosuppressive, although there are a couple of exceptions,
namely vincristine and L-asparaginase. Recent reports however
Table 1. Management of cytotoxic drug-induced Neutropenia.
Neutrophil count
(x 109/l)
Status of patient
Recommended action
>3
Asymptomatic/ afebrile
2-3
<2
Continue cytotoxic drugs
Repeat CBC in 3 weeks
Reduce dosage of myelosuppressive drugs by 50%
Repeat CBC in 1-2 weeks
Stop cytotoxic drugs, and repeat CBC in 1 week. If patient has a
potential source of infection, such as an ulcerated tumour,
administer prophylactic antibiotics
Stop cytotoxic drugs. Start antibiotics (oral route usually sufficient).
Monitor patient carefully for deterioration and repeat CBC in several
days
Stop all cytotoxic treatment and monitor carefully. Administer
antibiotics (oral route usually sufficient). Repeat CBC in several days
Hospitalise
Supportive therapy (intravenous fluids, electrolytes etc)
Intravenous antibiotics
Consider sampling patient to identify infective agent
Symptomatic
<1
Symptomatic
57
careful monitoring, is usually all that is required when faced
with an asymptomatic neutropenic animal. An ill neutropenic
animal requires more aggressive management, including the
administration of broad spectrum antibiotics and other
supportive measures. Table 1 outlines the suggested
management of neutropenic patients.
48 hours prior to anticipated chemotherapy induced
neutropenia, and appears to reduce the duration and severity
of neutropenia. Recent evidence suggests it is not beneficial in
the treatment of established afebrile or febrile neutropenia. Only
a human recombinant product is available and there is therefore
the potential for cross-reactive antibody production.
Notes on antibiotic use in the neutropenic patient:
– Antimicrobial therapy is directed at the intestinal flora, with
the principal objective of reducing the Gram-negative and
Gram-positive organisms most often responsible for infections.
The intestinal anaerobic population should be left relatively
undisturbed since it helps prevent colonization by contagious
bacteria, fungi and yeast.
– In most cases the choice of antibiotic is empirical, but should
be bactericidal and broad-spectrum.
– Suitable choices for the treatment of the asymptomatic
neutropenic patient included potentiated sulphonamides or
fluoroquinolones.
– Suitable choices for the treatment of the ill neutropenic animal
include the INTRAVENOUS administration of:
– A penicillin and aminoglycoside.
– A cephalosporin and aminoglycoside.
– A penicillin or cephalosporin and a fluoroquinolone (the
author’s choice).
– A second or third generation cephalosporin alone.
– Impipenem-cilastin or other carbapenems used alone.
NB: Aminoglycosides should not be administered to any animal
with renal compromise, and animals should be adequately
hydrated prior to their use.
NB: Fluoroquinolones should be avoided in skeletally immature
animals because of the possibility of inducing cartilage damage.
2. Gastrointestinal toxicity
The most common problem noted by pet owners following the
administration of cytotoxic drugs is gastrointestinal toxicity,
manifested as anorexia, vomiting and diarrhoea. In most cases
these side-effects are transient and spontaneous recovery occurs
as the gastrointestinal tract epithelium regenerates. Some drugs
including cisplatin and doxorubicin induce nausea and vomiting
within a few hours of drug administration, or these signs may
be delayed, occurring after 48 hours or later. Most other cytotoxic
drugs used in veterinary medicine cause delayed vomiting.
Anti-emetics commonly used in the prevention of cytotoxic drug
induced nausea and vomiting include:
– Metoclopramide (0.5-1.0 mg/kg i.m., s.c., p.o. q6-8hrs) - the
most commonly used anti-emetic, and has both central and
peripheral effects.
– Butorphanol (0.2-0.6mg/kg s.c.)- particularly useful with
cisplatin chemotherapy.
– Chlorpromazine (0.5mg/kg i.m. or s.c. q 6-8hrs) - used for mild
nausea and is centrally acting.
– Ondansetron (0.5mg/kg i.v. loading dose followed by 0.5-1.0
mg/kg p.o. q12-24hrs) - a very effective, although more
expensive anti-emetic.
Treatment of gastrointestinal complications is symptomatic and
includes intravenous fluid therapy, anti-ulcer and anti-emetic
drugs:
– Mild signs can usually be managed by withholding food and
water, and if the animal is vomiting, by providing an antiemetic.
– Severe gastrointestinal toxicity lasting for more than 36 hours
and not responding to oral anti-emetic therapy should be
treated aggressively.
– Severe gastrointestinal mucosal injury can predispose to
bacterial translocation, and parenteral antibiotics may be
required.
Notes on the use of prophylactic antibiotics:
– Antimicrobial prophylaxis use is controversial in both human
and veterinary oncology.
– Routine prophylactic therapy during cytotoxic drug use is not
recommended if the owner can closely observe the animal,
and if the anticipated neutropenia is of short duration.
– Prophylactic antibiotics should be considered in the
asymptomatic patient whenever a neutrophils count is less
than 1.0 x109/l.
– Prophylactic antibiosis is most likely to be beneficial during
severe, prolonged neutropenia.
– Animals that have had a previous episode of cytotoxic drug
induced sepsis should be given prophylactic antibiotics during
additional treatment (in combinations with a reduced dose of
cytotoxic drugs).
– Prophylactic antibiotics have the potential to induce
gastrointestinal side-effects and the development of resistant
organisms. Prophylactic antibiosis is particularly discouraged
in cats which are less at risk of infections secondary to
neutropenia than are dogs, but are more at risk of antibioticinduced gastrointestinal disorders.
3. Extravasation
Some cytotoxic drugs are vesicants and can induce serious sideeffects if they leak out of the vein or are extravasated (fig. 15).
In veterinary medicine the most common drugs to cause this
reaction are vincristine, vinblastine and doxorubicin. The severity
of the reaction is dependant on the agent and the volume that
leaks into the surrounding tissues. Clinical signs range from
pain, erythema, swelling and moist dermatitis, to severe skin
sloughing. Signs tend to be delayed occurring after
approximately 1-7 days (vincristine/vinblastine) or 7-10 days
(doxorubicin).
In the event of perivascular leakage of a vesicant drug, the
following general guidelines should be followed:
– Stop the infusion.
– Leave the catheter in place.
Notes on Granulocyte colony stimulating factor (GCSF).
GCSF is a haematopoietic cytokine, which acts primarily to
stimulate the proliferation and maturation of neutrophil
precursors. It is most beneficial when given prophylactically 24-
58
N. BEXFIELD
Fig. 17: Cats rarely develop severe
Fig. 15: Early tissue necrosis following
alopecia but may lose their
perivascular administration of
whiskers after cytotoxic drugs.
doxorubicin in a dog. (Courtesy
(Courtesy of Dr J Dobson, The
of Dr J Dobson, The University of Fig. 16: Owners should be warned about the possibility of
University of Cambridge)
Cambridge)
alopecia following the use of certain cytotoxic drugs.
– Try to aspirate any remaining drug and blood from the
catheter, although this is often not possible.
– Remove the catheter.
– Administer soluble corticosteroids systemically (intravenous),
locally (subcutaneous) and topically (cream) around the site
of extravasation.
Specialist help from a veterinary oncologist should also be
sought as early as possible.
– Doxorubicin can induce mast cell degranulation, therefore
slowing the infusion and pre-treating with anti-histamines and
glucocorticoids can eliminate or lessen the effects.
Treatment of hypersensitivity reactions is the same for any drug
and includes the following:
– Discontinue the infusion.
– Administer anti-histamines and glucocorticoids intravenously.
– Give intravenous fluids and adrenalin (epinephrine) if
necessary.
Specific recommendations for two of the most frequently used
drugs are given below, although these guidelines are based on
experience from human medicine:
5. Effects on hair coat
Doxorubicin/epirubicin:
– Infiltrate the area with 2 to 5 ml of 2.1% sodium bicarbonate,
leave for 2 minutes and aspirate off.
– Apply dimethylsulfoxide (dimethylsulphoxide, DMSO)
topically to the area every 2 hours.
– Apply hydrocortisone cream (or equivalent).
– Apply COLD compresses.
Poor hair growth or alopecia may occur, but is breed-dependent
and typically occurs in breeds with growing hair such as Poodles,
Old English sheepdogs and some terriers (fig. 16). Hair usually
grows back when chemotherapy is discontinued, but
occasionally may return with an altered consistency or colour.
Cats rarely develop alopecia but may lose their whiskers (fig.
17). Owners of susceptible breeds should always be warned
about these potential side-effects.
Vincristine/vinblastine:
– Infiltrate area with 1500 units of hyaluronidase.
– Apply HEAT and compression.
Several side-effects are drug specific and include:
1. Cardiac toxicity- doxorubicin
Cardiotoxicity is a widely recognised side-effect of doxorubicin
and can occur with short and long-term therapy. The acute form
manifests as tachycardia and arrhythmias occurring during or
soon after administration of the drug. The chronic form is more
common and results in dilated cardiomyopathy leading to
congestive heart failure (fig. 18). The mechanism of
cardiotoxicity associated with doxorubicin administration is due
to free radical production and subsequent oxidative damage to
myocytes. Diagnosing doxorubicin associated cardiotoxicity can
be difficult and unfortunately is often only performed when
clinical signs of congestive heart failure are apparent.
Tachyarrhythmias are the first sign to be noted, followed by
echocardiographic evidence of decreased fractional shortening.
There are several potential biochemical markers of ensuing
cardiotoxicity under trial, and the author has preliminary data
to suggest one of these, cardiac troponin-I, may be of use.
Treatment of doxorubicin-induced cardiomyopathy is the same
as that employed for any other type of cardiomyopathy, and the
reader is referred elsewhere.
4. Allergic reactions
The agents most commonly associated with hypersensitivity or
allergic reactions include L-asparaginase and doxorubicin. Signs
of hypersensitivity reactions include urticaria, erythema,
vocalisation, restlessness, vomiting, and oedema of the head.
Severe reactions can also lead to hypotension. Cats tend to
exhibit similar signs, but respiratory signs such as dyspnoea or
open-mouth breathing are also relatively common. Certain
precautions can be employed to reduce the occurrence of
hypersensitivity reactions. These include:
– Administering L-asparaginase intramuscularly rather than
intravenously.
– Attempting to avoid repeated doses of L-asparaginase as the
likelihood of hypersensitivity reactions increases after repeat
treatment (due to the formation of antibodies against Lasparaginase).
– Administering an anti-histamine or combination of an antihistamine and glucocorticoid prior to administration of drugs
that can potentially cause hypersensitivity reactions.
59
Fig. 18: Four-chamber echocardiographic image demonstrating
dilated cardiomyopathy which may result from doxorubicin
therapy.
Fig. 19: Sterile haemorrhagic cystitis resulting from the use of
cyclophosphamide in a dog. Owners can be provided with
urine dipsticks and instructed to perform urinalysis to help
prevent its occurrence. (Courtesy of Dr J Dobson, The
University of Cambridge)
Doxorubicin-induced cardiotoxicity can be prevented by:
– Using doses no higher than the maximum cumulative dose
(240mg/m2 for dogs).
– Avoiding the drug in breeds with a predisposition to
cardiomyopathy.
– Avoiding the drug in dogs with concurrent heart disease.
– Periodic monitoring for cardiotoxicity by echocardiography;
at the authors institution, this is performed prior to the initial
treatment and subsequently before every second or third
treatment.
– Monitoring pulse rate and character during doxorubicin
administration and immediately afterwards. If abnormalities
are detected, the infusion should be stopped or the rate
decreased.
– Increasing the infusion time thereby reducing peak plasma
levels and cardiotoxic effects.
– The concurrent use of the cardioprotective agent dexrazoxane,
which chelates iron thereby preventing doxorubicin
interaction and subsequent free radical formation. It is given
30 minutes prior to doxorubicin. The author does not use this
drug as its availability is limited and other methods are
employed to minimise cardiotoxicity.
– By using alternative drugs to doxorubicin such as epirubicin.
Cardiotoxicity appears to be less of a problem with this drug,
although can still occur.
rather than having the toxic metabolite accumulate in the
bladder overnight.
Ensuring a good fluid intake.
Encouraging frequent emptying of the bladder.
Administering prednisolone for its diuretic and antiinflammatory effects; some animals may however already be
receiving prednisolone therapy as part of a multidrug protocol.
Administering frusemide concurrently with cyclophosphamide
has shown some benefit.
Administer the bladder protective drug mesna (2mercaptoethanesulfonate). It is beneficial in the treatment of
sterile haemorrhagic cystitis in humans, but its use in
veterinary oncology is infrequently reported.
Owners can be provided with urine dipsticks and instructed
to test their animal’s urine at least once a week while on
cyclophosphamide therapy. Owners should be instructed to
stop cyclophosphamide if there is persistent haematuria or
proteinuria. Owners should be discouraged from collecting
urine in the 48 hours immediately after administration of any
cytotoxic drug however.
–
–
–
–
–
–
Clinical signs of sterile haemorrhagic cystitis are non-specific of
lower urinary tract disease, and include haematuria, dysuria and
pollakuria. Urinalysis typically reveals red blood cells, proteinuria
and mild to moderate numbers of white cells. Urine culture at
least during the early part of the disease is negative.
2. Sterile haemorrhagic cystitis- cyclophosphamide
Sterile haemorrhagic cystitis is a potential side-effect of
cyclophosphamide treatment in the dog and cat (fig. 19). This
toxicity is more common during chronic therapy but has been
reported to occur after only one treatment. Cystitis results from
the toxic effects of a metabolite of cyclophosphamide, acrolein,
on the bladder mucosa.
There are no specific treatments for cyclophosphamide induced
cystitis, although the following measures should be followed:
– Discontinue the drug.
– Prophylactic antibiotics to treat any secondary infections.
– Anti-inflammatory drugs such as glucocorticoids or nonsteroidal anti-inflammatory drugs (the latter should not be
administered to any animal already receiving glucocorticoids).
– Intravesicular administration of 1% formalin or 25% DMSO
has been advocated, but author has no experience with either
of these treatments. Studies in large groups of dogs are also
lacking, and both drugs have the potential to worsen the
disease so are probably best avoided.
Several measures can be taken to decrease the likelihood of
sterile cystitis developing:
– Administering cyclophosphamide in the morning, thereby
allowing the patient to urinate frequently during the day,
60
N. BEXFIELD
3. Hepatotoxicity- methotrexate or lomustine
Ensure the giving set is primed and contains no air bubbles.
– Add the required dose of drug to the bag of saline.
– Place an intravenous catheter into a suitable peripheral vein,
and connect a three way tap. Ensure correct placement of
the catheter by flushing with a least 10mls of saline. NB do
not use heparin saline as this can result in precipitation of the
drug.
– Tape the catheter securely in place.
– Premedicate the animal with an antihistamine given by slow
intravenous injection over one minute.
– Connect the giving set to the three-way tap, and administer
the diluted doxorubicin in the saline drip over approximately
20-30 minutes.
– Monitor the animal’s heart rate, rhythm and catheter site. Stop
the infusion if there are signs of anaphylaxis, arrhythmias or
problems with the catheter site.
– When the infusion is complete, 20mls of fresh saline can be
added into the empty saline bag, and this administered to the
patient to remove remaining drug residues from the infusion
set.
– Close off the giving set and disconnect it from the three-way
tap.
– Flush the catheter with approximately 10 mls of fresh saline
prior to removal.
– Dispose of the catheter, giving set and empty saline bag as
contaminated cytotoxic waste.
NB: Appropriate protective clothing should be worn during the
preparation and administration of this drug (see earlier).
Hepatotoxicity associated with cytotoxic drug use is rare. In
human oncology patients, liver damage is most frequently
associated with the use of methotrexate or lomustine. Severe
hepatotoxicity has also been reported in dogs receiving
lomustine chemotherapy, and it would therefore be prudent to
measure liver enzymes and monitor liver function periodically
during treatment with this drug.
4. Neurotoxicity- vincristine, cisplatin and 5-fluorouracil
Neurotoxicity is rarely observed in small animal patients
receiving cytotoxic drugs. Vincristine is reported to cause a
peripheral neuropathy in dogs, manifested by hindlimb
weakness. In humans, vincristine can cause a variety of nervous
system effects including peripheral, central or autonomic effects,
which most often occur with high, repetitive dose therapy.
5. Nephrotoxicity- cisplatin
Cisplatin is the drug most associated with nephrotoxicity,
although both doxorubicin and methotrexate can also cause
renal damage. There is an increased incidence of clinically
evident cisplatin-induced nephrotoxicity in patients with preexisting urinary tract disease. A minimum data base prior to the
administration of cisplatin should therefore include a CBC, BUN
and creatinine measurement and urinalysis. Various means of
preventing cisplatin induced nephrotoxicity are described below.
By comparison, carboplatin is not reported to be nephrotoxic
in humans at normal doses, and the same is expected in small
animal patients.
As the kidneys are the elimination pathway for a variety of
cytotoxic drugs, reduced renal function can lead to prolonged
exposure of normal tissues to cytotoxic drug, thereby potentially
increasing side-effects. Specific formulae, such as the CockroftGault conversion formulae are employed in human medicine to
allow the dose of a wide variety of drugs to be adjusted based
on renal function. Similar formulae however do not exist for
small animal patients.
Carboplatin:
– Calculate the required dose of the drug. The usual dose is
300mg/m2.
– Reconstitute the drug according to the manufactures
instructions.
and connect a three-way tap. Ensure correct placement of the
catheter by flushing with a least 10mls of saline.
– Connect an intravenous giving set to a 500ml bag of 0.9%
saline. NB: do not use needles or giving sets containing
aluminium as precipitation of the drug may occur.
– Connect the giving set to the three-way tap and allow the
saline to run in at a moderate rate.
– Inject the carboplatin through the side port of the giving set
over about 10 minutes while the saline is running.
– Leave the saline running for several minutes after carboplatin
administration.
– Disconnect the giving set and remove the catheter.
– Dispose of the catheter, giving set and saline bag as
contaminated cytotoxic waste.
NB: Some texts recommend the use of 5% glucose saline instead
of 0.9% saline to reduce the risk of carboplatin being converted
to cisplatin. This is more likely to be a problem however if
carboplatin is mixed with saline for a prolonged period of time.
CONCLUSIONS
By adhering to these guidelines, the safe use of cytotoxic drugs
should be possible for the majority of companion animal
practices, with minimal risk to all staff involved. Practices and
personnel should not become complacent with cytotoxic drug
administration, and regular risk assessment and updates to local
rules should be performed. Careful administration of cytotoxic
drugs and subsequent monitoring is also required to avoid the
many potential complications resulting from the use of these
drugs.
Procedures for the administration of specific drugs:
Doxorubicin:
– Calculate the required dose of drug. The usual dose is
30mg/m2.
– Reconstitute the drug according to the manufacture’s
instructions.
– Connect a conventional intravenous giving set to a 500ml bag
of 0.9% saline and discard approximately 200-300mls of fluid.
61
Cisplatin:
NB: cisplatin should never be administered to cats as its use
results in fatal pulmonary oedema.
Six hour infusion with saline diuresis:
– Prehydration: Intravenous 0.9% saline at 25ml/kg/hour for 3
hours.
– Cisplatin: 50-70mg/m2 given as a slow intravenous infusion
over approximately 20 minutes.
– Anti-emetic: metoclopramide at 1mg/kg intravenously.
Alternatively butorphanol or a 5HT-3 antagonist such as
ondansetron can be used.
– Further diuresis: Intravenous 0.9% saline at 15ml/kg/hour for
3 hours.
Infusion with mannitol diuresis:
– Prehydration: Intravenous 0.9% saline at 10ml/kg/hour for 4
hours.
– Mannitol: 0.5g/kg given intravenously in saline over 30
minutes.
– Cisplatin: 50-70mg/m2 given as a slow intravenous infusion
over approximately 20 minutes.
– Anti-emetic: as above.
– Further diuresis: Intravenous 0.9% saline at 10ml/kg/hour for
4 hours.
Vincristine:
– Calculate the required dose of drug. The usual dose is
between 0.3 and 0.75 mg/m2.
and connect to a three-way tap.
– Ensure correct placement of the catheter by flushing with a
least 10mls of saline.
– Inject vincristine slowly over approximately one minute.
– Flush the catheter with approximately 10mls of saline.
– Remove the catheter and dispose all materials as contaminated
cytotoxic waste.
FURTHER READING
ABRAMS-OGG (A.C.G.), KRUTH (S.A.) – Antimicrobial Therapy for
the Neutropenic dog and Cat. In: Bonagura JD, editor. Kirk’s
Current Veterinary Therapy. Philadelphia: W.B. Saunders Co.,
2000: p.267-272.
New Product Information
CAN YOU HANDLE LIQUID AND POWDER
CYTOTOXIC SPILLS?
Helapet announces two firsts in one! Berner’s NEW Spill Kit
XP is the first kit suitable to safely clean up both liquid and
powder Cytotoxic spills and it is the first kit to comply with
European PPE guidelines for handling cytotoxics.
Every kit contains appropriate safety apparel, absorbent
mats, distilled water and scoop and tongs for glass and sharp
fragments, as well as packaging for disposal. With easy to
follow instructions, units can rest assured that spills can be
dealt with quickly and efficiently whilst offering maximum
protection to the operator.
For more information, contact our friendly sales team on
0800 0328 428, or visit our website at www.helapet.co.uk
ALLWOOD (M.), STANLEY (A.), WRIGHT (P.) – The Cytotoxics
Handbook. 4th edition, Ratcliffe Medical Press, 2002.
CHUNN (R.), GARRETT (L.), MACEWEN (E.G.) - Cancer
chemotherapy. In: Withrow SJ and MacEwen EG, editors. Small
Animal Clinical Oncology. Philadelphia: W.B.Saunders Co.,
2001:p.92-118.
DOBSON (J.M.), GORMAN (N.T.) - Cancer Chemotherapy in Small
Animal Practice. Blackwell Scientific publications, 1993.
HANN (K.A.), RICHARDSON (R.C.) – Cancer Chemotherapy. A
Veterinary Handbook. Baltimore, Williams and Wilkins, 1995.
LANA (S.E.) – Chemotherapy. In: Dobson JM and Lascelles BD,
editors. BSAVA Manual of Canine and Feline Oncology. BSAVA
Publications, 2003: p. 86-103.
NEWMAN (M.A.), VALANIS (B.G.), SCHOENY (R.S.) HEE (S.Q.) –
Urinary biological monitoring markers of anticancer drug
exposure in oncology nurses. Am J Public Health, 1994, 84:852855.
VALANIS (B.), VOLLMER (W.M.), STELE (P.) – Occupational
exposure to antineoplastic agents: self-reported miscarriages
and still births among nurses and pharmacists. J Occup Environ
Med, 1999, 41:632-638.
COSHH. Control of Substances Hazardous to Health Regulations
2002. Approved Code of Practice and Guidance (fourth Edition
HSE books ISBN 0 7176 2534 6).
Safe Handling of cytotoxic drugs. HSE information Sheet MISC615.
Some of the many manufacturers supplying protective
equipment for the safe use of cytotoxic drugs:
Helapet Limited, Circle Business Centre, Blackburn Road, Houghton
Regis, Bedfordshire, LU5 5DD, UK.
Chemoprotect® protection system, supplied by Codan Limited,
Eastheath Avenue, Wokingham, Berkshire, RG41 2PR, UK.
COMMISSIONED PAPER
T he future of Biomarkers and
Personalised Medicine in Companion
Animal Practice
S. Mian(1)( 2), K. Slater(1), T.Cave(3)
S
U
M
M
A
R
Y
The ability to utilise a patient’s own genetic expression information to detect the onset of disease, monitor
its progression and even suggest possible treatment modalities which have the highest probability of success
would undoubtedly provide a mechanism in which to enhance the quality of care and treatment for companion
animals. As with all clinical situations, veterinarian decision making is made on a case by case scenario and
is based upon an individual’s medical history and current disease diagnostic indicators. Having tools available
that could help increase the rationalisation process for choosing a particular course of action at the individual
level would not only aid the clinical management of these patients but result in enhanced patient care.
Tailored or “personalised medicine” as it is referred to, is receiving considerable interest from the human
clinical field. New technologies are becoming increasingly available to the medical arena having highthroughput capabilities to perform rapid bio-profiling of individuals. These molecular fingerprints, or
biomarkers as they are more commonly known, provide an extremely powerful mechanism in which to exploit
diagnostic and prognostic information regarding disease course and therapeutic outcomes for individual
patients. The potential of these technologies to detect individualised molecular fingerprints are not restricted
to only human medicine. Biomarker technologies are now being translated into the veterinary arena and offer
the same potential to the veterinary practitioner as they do to their counterparts within human clinical
medicine – that is the ability to personalise the treatment of individual patients resulting in enhanced patient
care to unprecedented levels.
Keywords: Biomarker; Proteomic; SELDI; Oncology; Personalised medicine
INTRODUCTION
Phenotypic signature patterns - biomarkers
This paper was
commissioned
by FECAVA for
publication in EJCAP
activated is one of the primary mechanisms in
which an animal may control its normal
physiological function. The products of gene
expression (RNA, protein, carbohydrate, lipid
etc) can be considered as an organism’s
phenotype and the ability to monitor these
signature patterns during normal physiological
processes would provide a useful mechanism in which to
monitor overall functional status [1]. Deviation in the expression
of these molecular fingerprints could therefore represent the
first sign in the development of a pathological state. The
production of diagnostic tools which have the ability to profile
The genome represents the total genetic
composition of a biological organism and
through co-ordinated temporal (time) and
spatial (location) gene expression the development of cells and
tissues with specialised function occurs. The overall result is the
production of an organism with defined attributes and accounts
for both species differences and individual breed characteristics.
Enabling subsets of genes to be specifically activated and de-
(1) Shahid Mian BSc (Hons) Phd., K. Slater BSc (Hons) Phd., PetScreen Ltd, Biocity, Pennyfoot St., Nottingham, GB-NG1 1GF.
(2) Correspondence should be addressed to Email: [email protected]
(3) Tom Cave BVSc MSc (Clinical Oncology) DSAM MRCVS Cave Referrals, Sandwell, 7 Hector Stones,Woolalvington Somerset GB-TA7 8EG
Email: [email protected]
63
Biomarkers and Personalised Medicine
Single versus multiple biomarkers
a patient’s molecular fingerprint to monitor pathological changes
would provide a novel mechanism in which to monitor disease
onset and its progression [2].
Phenotypic differences within an individual companion animal
are not restricted to species, age, sex, breed, single nucleotide
polymorphisms (SNPs) but also within an individual’s metabolic
state, disease and immune status etc [8]. While certain expression
patterns within an organism are relatively constrained (e.g.
proteins associated with the differentiation status of a specialised
cell such as a cardiomyocyte) the temporal and spatial pattern
of other genes need to be co-ordinately activated, repressed
and their gene products modified and turned over in response
to meet the daily physiological changes required to maintain
homeostasis. Environmental factors can also influence
phenotypic expression patterns throughout the life of an animal
[9]. A patient therefore represents a mixture of conserved and
dynamic subsets of gene expression patterns. How is it possible
with such biological heterogeneity therefore to identify
biomarkers that will be of clinical relevance? The answer is
believed to reside in the use of multiple rather than single
biomarkers [10]. Multiple biomarkers represent a composite
pattern populated by several key differentiators which indicate
the normal versus the pathological state. This approach is
expected to achieve the levels of diagnostic redundancy needed
for personalised veterinary care. Unless a marker is specifically
associated with a diseased state and is not expressed in any
other tissue type, it is unlikely that clear demarcation between
normal and diseased states will ensue using a simple
presence/absence diagnostic tool. Diagnostic assays that can
accurately distinguish between the number of true positive cases
for a disease indication (sensitivity) and true negative cases
(specificity) will be essential if the field of veterinary medicine
is to move towards personalised healthcare. Given the nature
of genetic variation not only from species to species but from
breed to breed, it is likely that multiple biomarkers will be
essential to deal with inter and intra group variation.
Biomarkers can be described as phenotypic signature patterns
of a given physiological state(s). As such, they have the potential
to represent a variety of biological processes which may include,
for example, normal or diseased conditions. In principle these
molecular fingerprints can be elicited from any biomolecule
which is expressed from an organism’s genome (e.g. RNA,
protein) and by extrapolation therefore, exist within any tissue
type implicated to a particular physiological process. Biomarkers
are receiving considerable attention by clinical practitioners of
human medicine due to their translational application as
diagnostic or prognostic indicators [3]. They have been used as
phenotypic indicators for early disease detection and progression
in a wide range of pathologies extending over several medical
disciplines e.g. oncology, renal, cardiac, immunological,
neurodegeneration etc [4].
New technologies have arisen to meet this growing demand for
rapid biomarker identification. It is envisaged that they will be
able to provide greater levels of sensitivity and specificity than
is currently afforded by conventional disease markers [5]. An
ability to identify biomarker patterns from specific patients with
defined pathologies could therefore, offer the promise of a
personalised approach to healthcare [6]. There would be many
advantages of adopting such a strategy to clinical practice. It
could for example facilitate the selection of treatment regimes
in which a patient may possess a high probability of responding
whilst avoiding therapeutics that are likely to be ineffectual
and/or likely to show significant toxicity to non-target tissues [7].
Providing such tools to clinical practitioners would provide a
mechanism in which to rationalise the clinical decision making
process for a given patient using data derived from diagnostic
biomarker patterns.
Biomarker identification – the post genome technologies
Owners of companion animals and the veterinarians who treat
them are now demanding ever increasing standards of quality
care administered to pets. Translating biomarker technologies
with diagnostic/predictive capability to the veterinary field would
provide one such mechanism in which to facilitate this process.
The rationale for such a directed approach is simple. Each patient
which is presented clinically to a veterinarian will be assessed
at an individual level, i.e. on a case by case scenario. Factors
such as previous medical history, current clinical manifestations,
type of animal, and risk to particular pathologies will then set
in motion a series of diagnostic investigations. Integration of all
of these factors would facilitate the initiation of a course of
clinical action with concomitant patient monitoring for suitable
therapeutic response. Such a dynamic situation represents a
highly challenging environment for clinical practitioners,
especially veterinarians who unlike their clinical counterparts
within human medicine, have to deal with a variety of animal
species with their predisposition for particular diseases.
Biomarkers may offer the potential therefore to identify key
disease indicators at the individualised level for a particular
species of animal.
In 2004 the International Human Genome Sequencing
Consortium published a highly accurate sequence annotation of
the human genome from approximately 3 billion base pairs of
genetic code with 99% sequence coverage [11]. It is believed that
the human genome encodes for some 20,000-25,000 genes and
taking into consideration such events as alternative splice
variants and post-translational modifications there may be
somewhere in the order of 500,000 to 1 million gene products
in total. In 2003 an initial publication regarding the genomic
sequencing of canine was reported [12]. With approximately 2.4
billion base pairs and an estimated 20,000 genes, it is likely that
the total number of gene products will be similar to that found
in humans. Identifying biomarkers with clinical relevance to the
veterinary field will be extremely challenging given not only
the number of biological products with biomarker potential for
a given animal species with, but also the different separation and
isolation characteristics which will be associated with different
classes of biomolecule (e.g. RNA, protein, lipid). In order to
make the problem tractable, several areas have emerged to
analyse each subclass of major molecule in this post-genomic
area. For example the study of RNA transcript expression is
referred to as transcriptomics [13], while the analysis of
64
S. MIAN, K. SLATER, T.CAVE
Figure 1: A Time-of-Flight (ToF) mass spectrometer. A laser is fired
at the target support containing the clinical sample and the
proteins are ablated from the surface (red spot). The molecules
are then accelerated in a flight chamber and hit the detector
at rates which are inversely proportional to their mass.
Figure 2a: Proteomic profiling derived via the mass spectrometric
analysis of proteins from a biological sample. The y-axis
represents relative intensity value while the x-axis denotes
the mass:charge value for each peak.
metabolite expression is known as metabolomics [14]. The study
of protein expression patterns whether in single cells or complex
tissues such as blood plasma, is known as the field of proteomics
[15, 16, 17]. While several technologies have been developed to
deal with the complex biological diversity of protein populations
(e.g. antibody/antigen microarrays; surface plasmon resonance),
one approach using mass spectrometry is proving to be an
extremely powerful tool in the search for diagnostic biomarkers
with clinical relevance [18, 19, 20, 21].
proportional to their mass and as such small molecules arrive
at the detector faster than larger molecules. In this manner, a
relative intensity spectrum can be produced from a clinical
specimen in which intensity is represented on the y-axis and m/z
(mass:charge) is denoted on the x-axis (Figure 2a). A simple
comparison of two mass spectra e.g. one derived from a serum
sample taken from a dog without cancer and one taken from
an animal with cancer may enable differences in protein
expression patterns to be rapidly identified (Figure 2b). These
proteomic based biomarkers may therefore form the basis of a
diagnostic test. Different methodologies can be adopted to
introduce biological specimens into mass spectrometers for
proteomic analysis and one key approach which has received
considerable interest is where the biological sample is prepared
as a mixture with an energy absorbing molecule called matrix.
The biological sample and matrix are co-crystallised on a solid
support surface (the process is referred to as MALDI (Matrix
Assisted Laser Desorption/Ionisation)) and the mixture analysed
by ToF mass spectrometry. The advantage of such an approach
Seldi
Mass spectrometry is an analytical tool which has the ability to
accurately measure the mass of a molecule and the time-offlight instruments (ToF) have been proving to be extremely
useful in the search for disease related biomarkers (Figure 1) [22,
23, 24, 25]. Proteins entering the mass spectrometer are ionised
and accelerated down a field free flight chamber where they hit
a detector. The speed at which molecules “fly” is inversely
A
Peak X
B
Figure 2b: A serum biomarker profile
taken from a dog with no
pathology (A) and a dog with
confirmed cancer (B). In Figure
2A peak X is noted to have a
higher relative intensity value
than the animal with cancer.
Figure 2B shows the presence of
peak Y which is absent from the
animal without disease.
Peak Y
Mass/Charge
65
clinically is that high throughput automated procedures can
facilitate the screening of hundreds to thousands of patient
samples in a relatively short time.
Identification of potential markers necessitates the use of
hundreds of specimens in order to develop statistically confident
biomarkers which could form the basis of novel assays.
Originally this was extremely difficult as many of the proteomic
platforms did not lend themselves immediately to high
throughput analysis. However, the drive to identify disease
related biomarkers has resulted in the emergence of new
technologies with high throughput capability and integrated
workflow processes. The result was no longer a constraint on
sample processing and data generation, but an ability to process
the large volumes of proteomic data which are necessary for the
identification of clinical biomarkers. One mechanism to deal
with this issue was to implement the use of computer
programmes which have an ability to recognise expression
patterns associated with particular phenotypes e.g. normal or
disease conditions [31, 32]. To date a variety of approaches have
been implemented in order to “mine” data for biomarker
expression patterns. Data mining, as it is referred to, assists in
rapidly identifying the most important protein candidates having
diagnostic /prognostic potential. Methodologies such as CART
(Classification and Regression Tree analysis), PCA (principal
components analysis), and artificial neural networks have been
used to assist in biomarker identification [33, 34]. The power
of computational analysis for clinical biomarkers lies in the fact
that they can analyse literally millions of data points in a
relatively short time providing a cohort of proteins which may
be useful as predictive indicators. Once key biomarkers have
been identified, these algorithms have been utilised to predict
the pathological status of additional blind clinical samples with
high degrees of accuracy.
In MALDI based applications the biological sample is prepared
for mass spectrometric analysis prior to deposition on the MALDI
target plate through a series of clean-up processes enabling the
complexity of the clinical specimen to be reduced and mass
spectrometric analysis greatly simplified. An alternative approach
is to use a solid support which has a chemically modified surface
(e.g. possessing antibody coating for the selection of particular
epitopes or having biochemical modifications for the preferential
selection of particular classes of proteins/peptides (e.g.
hydrophobic, hydrophilic, cationic, anionic etc)). The use of
this type of modified solid support or “protein chip” is known
as SELDI (Surface Enhanced Laser Desorption/Ionisation) and
it has a number of advantages over conventional MALDI. These
include both rapid sample clean-up (as it occurs on chip rather
than off) and mass spectral reproducibility. As with conventional
MALDI, matrix is applied to the protein chip to form a protein
crystalline structure and the biological sample is analysed directly
using ToF mass spectrometry. The SELDI protein chip
technology has been used to characterise biological material
from a variety of sources in the search for biomarkers with
clinical relevance 26, 27, 28, 29]. Clinical precursor material
which has been analysed includes serum, plasma, solid tissue,
urine, cerebral spinal fluid etc. The versatility and adaptability
of the system makes it highly suitable for clinical applications
where the types of biological material being presented for
diagnostic analysis are varied and a requirement to process large
sample numbers in relatively short time periods is necessitated
[30]. As such the potential for developing novel diagnostic tools
for veterinary medicine is significant using this type of approach.
CLINICAL APPLICATIONS OF
SELDI PROTEIN CHIP
TECHNOLOGY TOWARDS
BIOMARKER IDENTIFICATION
Bioinformatics – computer algorithms for biomarker
identification
In the search for biomarkers with clinical diagnostic/prognostic
capability, bottlenecks were originally confined to the lack of
reproducible throughput of hundreds of patient samples.
Ovarian cancer represents a highly aggressive gynaecological
tumour which is normally innocuous to the patient until
presentation at late stages. Clinical manifestation is likely to
coincide with metastasis and increased biological aggressiveness,
making surgical resection and therapeutic intervention extremely
difficult. Early detection of ovarian cancer results in high rates
of patient cure. The need for diagnostic biomarker assays with
greater sensitivity for detecting true positive cases is therefore
justified. In 2002 a seminal paper published in the Lancet by
Petricoin et al [35] presented data to show how proteomic
profiling using SELDI protein chip technology followed by
analysis by ToF mass spectrometry could be utilised to produce
a “protein fingerprint” of serum. Initial molecular profiling was
performed upon 50 patients with ovarian cancer and 50 control
individuals who where either disease free or had benign
conditions. Using a “supervised” learning algorithm (a computer
program in which the user informs the algorithm which profiles
are derived from cancer patients and which are not; in this
manner the programme has a basis upon which to identify
biomarker peaks associated with each diagnostic class “cancer”
Squamous cell carcinoma in a cat.
66
Figure 3: A schematic of how different peaks can be detected using mass spectrometric analysis on SELDI chips using anion exchange
chromatography in order to fractionate. The mass:charge value is presented on the x-axis while relative intensity and elution phase
are shown on the y-axis.
and “non-cancer”) to train an iterative searching program, 116
blind serum sample proteomic profiles (50 cancer and 66 noncancer) were then presented to the trained architecture. From
this study 100% of ovarian cancer patients and 95% of noncancer individuals were correctly classified. While flaws were
identified in this original study [36] it proved that serum
biomarkers could be used as basis for classifying patients
diagnostically. Since then, biomarker profiling of serum has
been used to discriminate patients with cancer from those
without in a number of oncological indications including prostate
[37], breast [38], ovarian [5] and lung [39].
as patients who either do or do not progress to stage IV. The
potential of identifying at risk individuals for disease progression
using biomarkers was shown to be feasible using this
technological approach.
Biomarker identification using SELDI protein chip technology for
disease identification has not been restricted to the use of serum.
It has been applied to tissue sections e.g. for grading tumours
[41] or identification of biomarkers associated with disease, cell
lines for chemo-response [42], urine for biomarkers associated
with bladder cancer [43] and cerebral spinal fluid. The potential
for human personalised medicine using these types of novel
approaches to assess risk of disease onset, its progression and
even therapeutic response for individuals is promising. By
analogy their implementation into veterinary practice has the
potential to aid clinical decision making processes for patients
to an equal degree.
Mian et al have used a similar profiling methodology in
conjunction with supervised training algorithms to classify serum
samples taken from melanoma patients with either stage I or
stage IV disease [40]. Two hundred and five serum samples from
101 early-stage (American Joint Committee on Cancer [AJCC]
stage I) and 104 advanced stage (AJCC stage IV) melanoma
patients were profiled using SELDI protein chip technology and
linear ToF mass spectrometry. 109 samples (representing
approximately equal distribution of both stages) were used as
a training set for an artificial neural network (ANN) computer
algorithm. ANNs mimic animal brains in that they learn through
an iterative process of trial and error. Once training was
completed the algorithm was then used to classify 96 blind
proteomic profiles derived from the remaining group of stage I
and stage IV patients. It was found that 88% of samples were
correctly classified. Extending the study further, these authors
profiled the serum taken from 55 patients with stage III disease
and one year clinical follow-up. 28 patients were known to have
progressed to stage IV disease whereas 27 did not. Using
biomarker analysis, patterns of expression could be identified
by the ANN enabling 80% of the patients to be correctly classified
Application of SELDI protein chip to canine cancer serum
fingerprinting
In order to ascertain the potential of SELDI proteomic profiling
for biomarker discovery in veterinary clinical samples, these
authors conducted a proof of principle study using serum taken
from dogs with a variety of cancers (mast cell/lymphoma) versus
dogs without disease. Each serum sample was fractionated
initially using anionic exchange chromatography (enriching for
proteins which possess negative regions) and eluted with
sequential buffers of increasing pH (pH3, pH4, pH7, pH9 and
organic). Fractionation of any complex biological sample
(tissue/serum etc) is critical if clinically important biomarkers of
low concentration are to be detected. It has been widely reported
that high abundant molecules e.g. serum albumin, IgG may
67
A
Biomarker
Intensity
B
C
Mass/charge
Figure 4a: Mean intensity values for a highly significant serum biomarker are presented for the cancer and normal populations.
Figure 4b: Visualisation of the reduction in relative intensity value for the biomarker between normal and cancerous serum.
Figure 4c: A receiver operating characteristic (ROC) plot showing the ability to detect true positives (sensitivity) from false positives
(1- specificity).
Figure 5: Separation of cancer and normal populations using PCA (principal components analysis) for peaks identified in each of the
fractions indicated. Three components have been applied to account for the majority of variation in the proteomic profiles.
68
mask the detection of disease associated biomarker proteins.
The removal of these molecules by reducing sample complexity
may therefore facilitate the detection of novel disease related
biomarkers which are present in very low amounts. Figure 3
shows how a serum sample can be fractionated into alternative
protein components using only a single type of SELDI
chromatography (anionic exchange). A comparative analysis
between fractionated and un-fractionated serum indicated that
a greater number of peaks could be detected in the fractionated
serum compared to the non-fractionated sample (321 versus 134
peaks respectively – data not shown). The greater the number
of protein peaks detected the higher the probability that one or
more may provide the basis of a diagnostic biomarker pattern
with disease association.
Epitheliotrophic cutaneous T-cell lymphoma (mycosis fungoides)
in a dog.
In order to identify peaks having potential utility as biomarkers
for cancer, statistical analysis using t-testing was performed to
select candidates which had significant differences (P<0.05 level)
between normal and cancer patient serum samples. Initial data
passing revealed that 81 peaks had statistically significant pvalues at the P<0.05 level (data not shown). An example of one
of the significant peaks is presented in Figure 4. A scatter plot
of intensity values for the biomarker in both normal and cancer
associated serum samples is provided in Figure 4a. This peak is
significantly down-regulated in cancer serum samples (P<0.001)
compared to non-diseased animals. Figure 4b shows the
biomarker which has been identified via automated peak
detection software. Figure 4c presents data in the form of a ROC
(Receiver Operating Characteristic) curve which produces a
measure of the ability of a biomarker to discriminate between
true positives i.e. cancer patients (also referred to as sensitivity)
and false positive i.e. negative patients which are classified as
positive (this is calculated as 1-specificity). The AUC (Area Under
the Curve) value was calculated to be 0.99 indicating good
demarcation of this biomarker peak to identify true positives
from false positives within the cohort of samples tested. As
biological variation increases e.g. breed, sex, tumour type then
it is likely that single markers which show extremely good
promise within the early stages of diagnostic evaluation do not
have sufficient power to deal with the complexity seen clinically.
identification are far reaching and include the possibility of
choosing the most appropriate form of therapy for a given
individual, developing novel therapeutics and ultimately
understanding the cause of disease onset and progression.
CONCLUSIONS
Human clinical medicine is moving towards the exploitation of
genetic information via post-genome technologies. Biomarker
assays represent one key evolutionary product from this era.
Veterinary medicine is also capitalising upon these advances as
the profession moves rapidly to exploit post-genome information
and facilitate its translation into a clinical setting. The results for
companion animal practice both in the short and medium/longterm will be the production of significantly improved diagnostic
assays for a wide range of clinical pathologies. Additionally, it
should facilitate production of novel therapeutics with greater
specificity and less toxicity. This will ultimately translate to a
more directed approach to patient care than can be afforded with
current veterinary medical practice and aid veterinarians in their
decision making processes.
Additional data analysis using principal components analysis
(PCA) (a statistical approach to identify principal components
which can account for as much of the variation in data between
the two populations) is presented for each of the fractions
(Figure 5). The data would suggest that all fractions can be
separated extremely well (with the exception of pH 7) into
cancer and normal populations using this type of approach
using candidate biomarker ions which were initially identified
as having statistically significant p-values.
REFERENCES
[1] GO (V.L.), NGUYEN (C.T.), HARRIS (D.M.), PAUL LEE (W.N.) “Nutrient-gene interaction: metabolic genotype-phenotype
relationship”. J Nutr., 2005 Dec;135(12):3016S-20S.
[2] BAST (R.C.) Jr, LILJA (H.), URBAN (N.), RIMM (D.L.), FRITSCHE
(H.), GRAY (J.), VELTRI (R.), KLEE (G.), ALLEN (A.), KIM (N.),
GUTMAN (S.), RUBIN (M.A.), HRUSZKEWYCZ (A.) Translational crossroads for biomarkers. Clin Cancer Res., 2005
Sep 1;11(17):6103-8.
[3]SENZER (N.), SHEN (Y.), HILL (C.), NEMUNAITIS (J.) “Individualised cancer therapeutics: dream or reality?” Expert
Opin Ther Targets., 2005 Dec;9(6):1189-201.
[4]O’RIORDAN (E.), GOLIGORSKY (M.S.) - “Emerging studies of the
urinary proteome: the end of the beginning?” Curr Opin Nephrol
Hypertens., 2005 Nov;14(6):579-85.
[5]ZHANG (Z.), BAST (R.C). Jr, YU (Y.), LI (J.), SOKOLL (L.J.), RAI
(A.J.), ROSENZWEIG (J.M.), CAMERON (B.), WANG (Y.Y.),
The data presented in this initial analysis has indicated that
serum biomarkers can be rapidly identified which are capable
of distinguishing animal patients which either do or do not have
cancer. The ability to develop novel biomarker assays for
companion animal diseases such as cancer is likely to afford the
same clinical benefits to the veterinary field as will be seen in
the human field. Biomarkers do not simply represent a paradigm
in which to manage patients clinically. The benefits of biomarker
69
MENG (X.Y.), BERCHUCK (A.), VAN HAAFTEN-DAY (C.),
HACKER (N.F.), DE BRUIJN (H.W.), VAN DER ZEE (A.G.),
JACOBS (IJ.), FUNG (E.T.), CHAN (D.W.) - “Three biomarkers
identified from serum proteomic analysis for the detection of
early stage ovarian cancer.” Cancer Res., 2004 Aug
15;64(16):5882-90.
[6]KIRKWOOD (S.C.), HOCKETT (R.D.) Jr. - “Pharmacogenomic
biomarkers.” Dis Markers, 2002;18(2):63-71.
[7]DARE (T.O.), DAVIES (H.A.), TURTON (J.A.), LOMAS (L.),
WILLIAMS (T.C.), YORK (M.J.) - “Application of surfaceenhanced laser desorption/ionization technology to the
detection and identification of urinary parvalbumin-alpha: a
biomarker of compound-induced skeletal muscle toxicity in
the rat.” Electrophoresis, 2002 Sep;23(18):3241-51.
[8]GERMAN (J.B.), WATKINS (S.M.), FAY (L.B.) - “Metabolomics in
practice: emerging knowledge to guide future dietetic advice
toward individualized health.” J Am Diet Assoc., 2005
Sep;105(9):1425-32.
[9]KIMMEL (G.L.) - “An overview of children as a special population- relevance to predictive biomarkers.” Toxicol Appl Pharmacol.,
2005 Aug 7;206(2):215-8.
[10] BELKOWSKI (S.M.), POLKOVITCH (D.), D’ANDREA (M.R.) “Synergistic approaches to clinical oncology biomarker
discovery”. Curr Top Med Chem., 2005;5(11):1047-51.
[11] International Human Genome Sequencing Consortium.
“Finishing the euchromatic sequence of the human genome”.
Nature, 2004 Oct 21;431(7011):931-45.
[12] KIRKNESS (E.F.), BAFNA (V.), HALPERN (A.L.), LEVY (S.),
REMINGTON (K.), RUSCH (D.B.), DELCHER (A.L.), POP (M.),
WANG (W.), FRASER (C.M.), VENTER (J.C.) - “The dog genome:
survey sequencing and comparative analysis”. Science, 2003
Sep 26;301(5641):1898-903.
[13] HU (Y.F.), KAPLOW (J.), HE (Y.) - “From traditional biomarkers
to transcriptome analysis in drug development”. Curr Mol Med.,
2005 Feb;5(1):29-38.
[14] GERMAN (J.B.), WATKINS (S.M.), FAY (L.B.) - “Metabolomics
in practice: emerging knowledge to guide future dietetic advice
toward individualized health”. J Am Diet Assoc., 2005
Sep;105(9):1425-32.
[15] CONRADS (T.P.), HOOD (B.L.), PETRICOIN (E.F.) 3rd, LIOTTA
(L.A.), VEENSTRA (T.D.) - “Cancer proteomics: many
technologies, one goal.” Expert Rev Proteomics, 2005
Oct;2(5):693-703.
[16] THADIKKARAN (L.), SIEGENTHALER (M.A.), CRETTAZ (D.),
QUELOZ (P.A.), SCHNEIDER (P.), TISSOT (J.D.) - “ Recent
advances in blood-related proteomics.” Proteomics, 2005
Aug;5(12):3019-34.
[17] COLANTONIO (D.A.), CHAN (D.W.) - “The clinical application
of proteomics.” Clin Chim Acta., 2005 Jul 24;357(2):151-8.
[18] REYZER (M.L.), CAPRIOLI (R.M.) - “MALDI mass spectrometry
for direct tissue analysis: a new tool for biomarker discovery.”
J Proteome Res., 2005 Jul-Aug;4(4):1138-42.
[19] Zhou (M.), Conrads (T.P.), Veenstra (T.D.) - “Proteomics
approaches to biomarker detection.” Brief Funct Genomic
Proteomic, 2005 May;4(1):69-75.
[20] Wright (M.E.), Han (D.K.), Aebersold (R.) - “Mass spectrometrybased expression profiling of clinical prostate cancer.” Mol Cell
Proteomics, 2005 Apr;4(4):545-54.
[21] Xiao (Z.), Prieto (D.), Conrads (T.P.), Veenstra (T.D.), Issaq
(H.J.) - “Proteomic patterns: their potential for disease
diagnosis.” Mol Cell Endocrinol., 2005 Jan 31;230(1-2):95-106.
[22] LE NAOUR (F.), CHARRIN (S.), LABAS (V.), LE CAER (J.P.),
BOUCHEIX (C.), RUBINSTEIN (E.) - “Tetraspanins connect
several types of Ig proteins: IgM is a novel component of the
tetraspanin web on B-lymphoid cells.” Cancer Immunol
Immunother., 2004 Mar;53(3):148-52.
[23] WULFKUHLE (J.D.), PAWELETZ (C.P.), STEEG (P.S.),
PETRICOIN (E.F.) 3rd, LIOTTA (L.) - “Proteomic approaches to
the diagnosis, treatment, and monitoring of cancer.” Adv Exp
Med Biol., 2003;532:59-68.
[24] MERCHANT (M.), WEINBERGER (S.R.) - “Recent advancements
in surface-enhanced laser desorption/ionization-time of flightmass spectrometry.” Electrophoresis, 2000 Apr;21(6):1164-77.
[25] STANLEY (B.A.), GUNDRY (R.L.), COTTER (R.J.), VAN EYK
(J.E.) - “Heart disease, clinical proteomics and mass
spectrometry.” Dis Marker, 2004;20(3):167-78.
[26] MUKHOPADHYAY (T.K.), HALLIWELL (D.), ODWYER (C.),
SHAMLOU (P.A.), LEVY (M.S.) - “Rapid characterisation of outer
membrane proteins in Neisseria lactamica by surface enhanced
laser desorption and ionisation - time of flight mass
spectroscopy for use in a meningococcal vaccine”. Biotechnol
Appl Biochem., 2005 Apr;41(Pt 2):175-82.
[27] PAPADOPOULOS (M.C.), ABEL (P.M.), AGRANOFF (D.), STICH
(A.), TARELLI (E.), BELL (B.A.), PLANCHE (T.), LOOSEMORE
(A.), SAADOUN (S.), WILKINS (P.), KRISHNA (S.) - “A novel
and accurate diagnostic test for human African trypanosomiasis.”
Lancet, 2004 Apr 24;363(9418):1358-63.
[28] GOLDSTEIN (L.E.), MUFFAT (J.A.), CHERNY (R.A.), MOIR
(R.D.), ERICSSON (M.H.), HUANG (X.), MAVROS (C.), COCCIA
(J.A.), FAGET (K.Y.), FITCH (K.A.), MASTERS (C.L.), TANZI
(R.E.), CHYLACK (L.T.) Jr, BUSH (A.I.) - “Cytosolic beta-amyloid
deposition and supranuclear cataracts in lenses from people
with Alzheimer’s disease.” Lancet, 2003 Apr 12;361(9365):125865.
[29] XIAO (Z.), LUKE (B.T.), IZMIRLIAN (G.), UMAR (A.), LYNCH
(P.M.), PHILLIPS (R.K.), PATTERSON (S.), CONRADS (T.P.),
VEENSTRA (T.D.), GREENWALD (P.), HAWK (E.T.), ALI (I.U.)
- “Serum proteomic profiles suggest celecoxib-modulated targets
and response predictors.” Cancer Res., 2004 Apr 15;64(8):29049.
[30] WIESNER (A.) -“Detection of tumor markers with ProteinChip
technology.” Curr Pharm Biotechnol., 2004 Feb;5(1):45-67.
[31] XU (X.Q.), LEOW (C.K.), LU (X.), ZHANG (X.), LIU (J.S.),
WONG (W.H.), ASPERGER (A.) - “Molecular classification of
liver cirrhosis in a rat model by proteomics and bioinformatics.”
Proteomics, 2004 Aug 11;4(10):3235-3245.
[32] YU (U.), LEE (S.H.), KIM (Y.J.), KIM (S.) - “Bioinformatics in the
post-genome era.” J Biochem Mol Biol., 2004 Jan 31;37(1):75-82.
[33] LILIEN (R.H.), FARID (H.), DONALD (B.R.) - “Probabilistic
disease classification of expression-dependent proteomic data
from mass spectrometry of human serum.” J Comput Biol.,
2003;10(6):925-46.
[34] LI (L.), TANG (H.), WU (Z.), GONG (J.), GRUIDL (M.), ZOU (J.),
TOCKMAN (M.), CLARK (R.A.) - “Data mining techniques for
cancer detection using serum proteomic profiling.” Artif Intell
Med., 2004 Oct;32(2):71-83.
[35] PETRICOIN (E.F.), ARDEKANI (A.M.), HITT (B.A.), LEVINE
(P.J.), FUSARO (V.A.), STEINBERG (S.M.), MILLS (G.B.),
SIMONE (C.), FISHMAN (D.A.), KOHN (E.C.), LIOTTA (L.A.) “Use of proteomic patterns in serum to identify ovarian cancer.”
Lancet, 2002 Feb 16;359(9306):572-7.
[36] BAGGERLY (K.A.), MORRIS (J.S.), COOMBES (K.R.) “Reproducibility of SELDI-TOF protein patterns in serum:
comparing datasets from different experiments.” Bioinformatics,
2004 Mar 22;20(5):777-85.
[37] ADAM (B.L.), QU (Y.)., DAVIS (J.W.), WARD (M.D.), CLEMENTS
(M.A.), CAZARES (L.H.), SEMMES (O.J.), SCHELLHAMMER
(P.F.), YASUI (Y.), FENG (Z.), WRIGHT (G.L.) Jr. - “Serum
protein fingerprinting coupled with a pattern-matching
algorithm distinguishes prostate cancer from benign prostate
hyperplasia and healthy men.” Cancer Res., 2002 Jul
1;62(13):3609-14.
[38] GONCALVES (A.), ESTERNI (B.), BERTUCCI (F.), SAUVAN (R.),
CHABANNON (C.), CUBIZOLLES (M.), BARDOU (V.J.),
70
HOUVENAEGEL (G.), JACQUEMIER (J.), GRANJEAUD (S.),
MENG (X.Y.), FUNG (E.T.), BIRNBAUM (D.), MARANINCHI
D.), VEINS (P.) AND BORG (J.P). - “Postoperative serum
proteomic profiles may predict metastatic relapse in high-risk
primary breast cancer patients receiving adjuvant
chemotherapy.” Oncogene advance online publication 26,
September 2005; doi: 10.1038/sj.onc.1209131.
[39] YANG (S.Y.), XIAO (X.Y.), ZHANG (W.G.), ZHANG (L.J.),
ZHANG (W.), ZHOU (B.), CHEN (G.), HE (D.C.) - “Application
of serum SELDI proteomic patterns in diagnosis of lung cancer.”
BMC Cancer, 2005 Jul 20;5:83.
[40] MIAN (S.), UGUREL (S.), PARKINSON (E.), SCHLENZKA (I.),
DRYDEN (I.), LANCASHIRE (L.), BALL (G.), CREASER (C.),
REES (R.), SCHADENDORF (D.) - “Serum proteomic
fingerprinting discriminates between clinical stages and predicts
disease progression in melanoma patients.” J Clin Oncol., 2005
Aug 1;23(22):5088-93.
[41] BALL (G.), MIAN (S.), HOLDING (F.), ALLIBONE (R.O.), LOWE
(J.), ALI (S.), LI (G.), MCCARDLE (S.), ELLIS (I.O.), CREASER
(C.), REES (R.C.) - “An integrated approach utilizing artificial
neural networks and SELDI mass spectrometry for the
classification of human tumours and rapid identification of
potential biomarkers.” Bioinformatics, 2002 Mar;18(3):395-404.
[42] MIAN (S.), BALL (G.), HORNBUCKLE (J.), HOLDING (F.),
CARMICHAEL (J.), ELLIS (I.), ALI (S.), LI (G.), MCARDLE (S.),
CREASER (C.), REES (R.) - “A prototype methodology combining
surface-enhanced laser desorption/ionization protein chip
technology and artificial neural network algorithms to predict
the chemoresponsiveness of breast cancer cell lines exposed
to Paclitaxel and Doxorubicin under in vitro conditions.”
Proteomics, 2003 Sep;3(9):1725-37.
[43] ZHANG (Y.F.), WU (D.L.), GUAN (M.), LIU (W.W.), WU (Z.),
CHEN (Y.M.), ZHANG (W.Z.), LU (Y.) - “Tree analysis of mass
spectral urine profiles discriminates transitional cell carcinoma
of the bladder from noncancer patient.” Clin Biochem., 2004
Sep;37(9):772-9.
REPRINT PAPER (D)
M andibulectomy and maxillectomy
as a treatment for bone invasive oral
neoplasia in the dog – a retrospective
analysis of 31 patients
Martin Kessler (1)
S
U
M
M
A
R
Y
From 1999 to 2001, 31 dogs with bone invasive tumours of the jaws were treated by maxillectomy or
mandibulectomy at the Hofheim Small Animal Clinic (Germany). In addition to surgery, 3 dogs received
chemotherapy, two due to metastatic spread and one after marginal resection of an extensive tumour. The
goal of this study was to describe epidemiology and pathology of the various tumours, review the rate of
postoperative complications and determine postoperative jaw function with regard to food and water uptake
and grasping of sticks or balls. Patient survival times were evaluated and compared to published data. Medium
and large sized dogs were overrepresented in this study; the average age was 9.9 years, 20 (65%) of the animals
were male and 11 (35%) were female. Of the 31 tumours, 23 (74%) were malignant, 8 (26%) were benign; 21
(68%) were located in the mandible, 10 (32%) in the maxilla. The histologic diagnoses were as follows:
squamous cell carcinoma (n = 10, 32%), malignant melanoma (n = 8, 26%), acanthomatous epulides (n = 7;
23%), fibrosarcoma (n = 3; 10%) and one each of osteosarcoma, atypical histiocytoma and central ameloblastoma.
Only one dog suffered major postoperative complications resulting in euthanasia. Follow up was available
for 23 patients using an owner questionnaire to evaluate function of the jaws after resection. One dog
experienced problems that were felt to result in a significant reduction in quality of life. Three other patients
had difficulties grasping hard objects but had no problems with food or water uptake. In the remaining dogs
no significant functional deficits were reported by the owners. Functional deficits were not associated with
the extent or location of jaw resection. Survival times were available from 26 patients, of these 18 were still
alive with an average survival time of 14 months.
Maxillectomy or mandibulectomy is an appropriate method for treatment of bone invasive tumours of the
jaws and has a low complication rate. In most cases postoperative function of the jaws is undisturbed.
INTRODUCTION
This paper was originally
published in:
Kleintierpraxis* (2003)
48(5), p.289-300
In small animals the oral mucosa is a frequent
primary location for the development of
neoplasia. The most common canine tumours
of the oral cavity, listed in decreasing frequency
are malignant melanoma, squamous-cell carcinoma, and
fibrosarcoma. Epulides are the most relevant benign neoplasia
of the oral cavity (TODOROFF und BRODEY,
1979; KESSLER und V. BOMHARD, 1997;
HORSTIG et al., 1998).
Oral tumours have a tendency to invade the
surrounding bone, which explains the inevitable
and quick recurrence when they are locally excised without the
removal of adjacent bone (TODOROFF und BRODEY, 1979).
(1) Hofheim Small Animal Clinic, Im Langgewann 9, D-65719 Hofheim E-Mail :[email protected]
* Presented by DGK-DVG (Germany)
73
Maxillectomy or mandibulectomy have been described in the
literature as therapy of invasive oral tumours with good long
term results (TODOROFF und BRODEY, 1979; BRADLEYet al.,
1984; KOSOVSKY et al., 1991; SCHWARZ et al., 1991a and b;
WALLACE et al., 1992). Until now in the German literature, only
a few case reports have been published. This publication
describes the most common bone invasive canine oral tumours
and retrospectively examines clinical results of 31 patients
undergoing maxillectomy or mandibulectomy due to such
tumours. Statistical evaluation was performed for the most
important types of tumours and their locations, type and extent
of maxillectomy or mandibulectomy, postoperative
complications and the patients’ survival times. With the aid of
an owner’s questionnaire, postoperative jaw function such as
biting ability and food and water uptake was examined.
Oral Malignant Melanoma (Fig. 1)
Oral melanomas occur more frequently in dachshunds, cocker
spaniels and poodles. In one study, these three breeds alone
accounted for almost 50% of patients with oral malignant
melanoma (KESSLER, 1999). Although the tumour is usually
partly or completely pigmented, occurrences of ‘amelanotic
(pigmentless) melanoma’ in the oral cavity are not uncommon.
Melanomas are characterised by their aggressive biologic
behaviour leading to both local infiltration and swift metastatic
spread. Metastases are rarely present at the time of diagnosis,
however they develop in the majority of patients mainly in the
lymph nodes and lungs during the course of the disease. The
time between diagnosis and metastatic spread differs greatly
between individuals. Even with obvious macrometastases, it has
been reported that the survival rate can be up to two years
(HAHN et al., 1994).
Fig. 2: Squamous-cell carcinoma of the gingiva in a 4 year old
mixed breed dog (patient number 10). The maxillectomy
extended from the left canine to and including Pm3
(compare Fig. 9).
Squamous-Cell Carcinoma of the gingiva (Fig. 2)
Oral squamous-cell carcinomas are light red, often ulcerated
growths that at an early stage could be misdiagnosed as
gingivitis. The surrounding bone is inevitably infiltrated, leading
to osteolysis resulting in the loosening or falling out of the
adjacent teeth. This type of tumour seldom metastasises, if so
then very late in the course of the disease. If metastasis does
occur the lymph nodes are most often affected and only
seldomly the lungs or other organs (TODOROFF und BRODEY,
1979; SCHWARZ et al., 1991a). The prognosis is good when,
through radical treatment, complete resection of the tumour is
achieved.
Oral Fibrosarcoma (Fig. 3)
Oral fibrosarcomas can affect dogs at any age but large and
middle sized dogs are predisposed (KESSLER und BOMHARD,
1997; KESSLER, 1999). This tumour occurs most often in the
mucosa of the gums and on the hard palate. These tumours
have a hard consistency and are contiguous with the surrounding
tissue. They are extremely invasive and therefore a macroscopic
differentiation between diseased and healthy tissue is not
possible. Invasion of the surrounding bone is imminent, as seen
in most cases through the presence of osteolysis. The rate of
metastatic spread is about 30%.
Acanthomatous epulides (Fig. 4)
Epulides comprise ca. 30% of all canine oral neoplasia and are
the most common benign tumours of the canine oral cavity.
The term epulides is only a descriptive clinical expression.
Nomenclature and classification varies greatly in the literature.
Most often 3 types are distinguished: (1) fibromatous epulides
Fig. 1: Malignant melanoma in the maxilla of a mixed breed dog
(patient number 18). The ensuing maxillectomy of the right
side included Pm1 and extended to just rostral of M3.
74
MARTIN KESSLER
Fig. 4: Acanthomatous epulis of the mandible in a Belgian
shepherd (Patient number 27). A mandibulectomy including
Pm3 to M1 was performed.
Fig. 3: Fibrosarcoma of the maxilla located around the canine
of a 6 year old Labrador Retriever (patient number 20). A
maxillectomy was performed from I1 to Pm2 spanning the
midline of the hard palate and continuing to the
contralateral side.
Fig. 5: Ameloblastoma of the mandible in a Swiss Mountain dog
(patient number 30). A bilateral rostral mandibulectomy
was performed from and including the left Pm3 to the right
Pm2.
(or E. fibropapillomatosa); (2) ossifying epulides; (3)
acanthomatous epulides. The last group has been more recently
termed “peripheral” or “acanthomatous ameloblastoma” and in
publications from the UK as “basal cell carcinoma”. This type is
characterised by quick and invasive growth. Invasion and
destruction of the surrounding jaw bone is evident in most cases,
resulting in the impression, both clinically and radiographically,
of a malignant tumour. Metastatic spread however does not
occur. The authors have found that acanthomatous epulides
make up about 20% of all epulides (KESSLER and v. BOMHARD,
1997). Medium and large sized dogs are more often affected.
predilection. The tumour is locally destructive, as seen
radiographically through the presence of osteolysis, however
does not metastasise.
This study retrospectively examined 31 dogs of different breeds
presented with oral bone invasive tumours at the Hofheim Small
Animal Clinic from 1999 to 2001. Before surgery, every patient
underwent a complete diagnostic workup including a
histopathological biopsy. The extent of invasiveness into the
surrounding bone was determined with the help of computed
tomography (CT). Radiography of the thorax was performed in
every patient with a malignant tumour to determine the presence
or absence of metastases.
Ameloblastoma (Fig. 5)
Ameloblastoma, also referred to as adamantinoma, belongs to
the family of tumours originating from the dental lamina
(‘odontogenic tumour’) and is the least differentiated, non
inductive tumour in this group. Different schools of thought
exist on the differentiation between (‘central’) ameloblastomas
originating in bone and acanthomatous epulides (‘peripheral
ameloblastoma’) (VERSTRAETE et al., 1992). The ameloblastoma
is the most common odontogenic tumour and has been
described in dogs ranging in age from 3 to 13 years. This tumour
can arise from any part of the gingival with no specific site
Chemotherapy was performed postoperatively on four patients.
Three of the four were diagnosed with a squamous-cell
carcinoma (two of these with metastases, one with very
extensive growth), and the fourth patient was diagnosed with
a metastasised malignant melanoma. The two patients with
metastasised squamous-cell carcinoma were treated with an
75
mandibulectomy in 6 cases and a partial or complete lateral
mandibulectomy in 14 cases was performed. In one case a
resection of 75% of the mandible was necessary. Of the maxillary
tumours, 3 were removed by a rostral and 7 by a lateral
maxillectomy.
Administration protocol for cisplatin
1. Diuresis with 0.9 % NaCl, 18 ml/kg/h for 6 h
2. Odansetron (Zofran®) 2-4 mg/dog per os 3 h after
beginning diuresis
3. Cisplatin (55-60 mg/m2 BSA) as continuous
intravenous drip infusion over 20 minutes
4. Diuresis with 0.9 % NaCl, 18 ml/kg/h for 2 h
Three patients suffered complications directly after completion
of the surgery. After rostral mandibulectomy (from and including
the right M1 to the left PM2), one patient (Table 3 No. 13)
experienced the temporary presence of a ranula, which
spontaneously disappeared after two weeks. In two patients
healing of the surgical wound was compromised due to
dehiscence with infection. The first patient (Table 3, No. 18;
resection PM1 to M3 reaching past the midline) suffered
dehiscence after a caudal maxillectomy, which was successfully
repaired by revision surgery. The second patient (Table 2 No.
4) also experienced dehiscence after a caudal mandibulectomy
(complete mandible caudal from PM2). After a revision,
dehiscence occurred again, which led the owner to opt for
euthanasia.
Administration protocol for Carboplatin
1. Odansetron (Zofran®) 2-4 mg/dog i.v. just before
beginning chemotherapy
2
2. Carboplatin 290-300 mg/m BSA over 20 minutes i.v.
Table 1: Administration protocol for Platinum derivatives
alternating application of cisplatin or carboplatin (treatment and
dosage see Table 1) with bleomycin (12000 IU/m2 body surface
area (BSA) s.c. every 2 weeks after the platin application). Patient
number 8 with the aforementioned extensive squamous cell
carcinoma of the maxilla was treated with a cisplatin
monotherapy (5 applications of 55-60 mg/m2 BSA i.v. every four
weeks). The treatment of the dog with the metastasised
malignant melanoma consisted of a combination preparation of
Carboplatin (290 mg/m2 BSA over 20 min i.v.) and human
interferon (interferon-a 2a – Roferon-A “, Roche; 3 million IU/m2
BSA s.c. weekly for 3 months).
In the cases of 23 patients, information could be obtained from
the owners about water and food uptake, as well as the ability
of the dogs to fetch sticks or balls. Of the remaining 8 patients,
owners of seven could not be contacted, and in one dog, as
already mentioned, euthanasia had been performed due to
recurring suture breakdown. From evaluation of the 23 dogs,
only one (Tab. 3, No. 12, partial mandibulectomy PM4-M1) was
reported by the owner to experience a handicap that reduced
quality of life. This patient experienced problems with food
uptake and therefore had to be hand fed. The owner stated that
the ‘lower jaw repeatedly caught on the canines’. Three patients
(mandibulectomies No. 3 and 13, maxillectomy No. 29) did not
have problems with food uptake, but had difficulties taking hard
objects between the jaws (chew-bones, sticks, balls). Patient
Patient follow up occurred either through a physical examination
at the clinic or telephone conversation with the owner. Special
emphasis was placed on judging the ability of the patient to eat
or drink and to play with balls or sticks.
RESULTS (TABLES 2 TO 5)
Of the 31 bone invasive tumours of the jaws included in this
study, 23 (74%) were malignant; 8 (26%) were diagnosed as
benign by histopathological examination. A total of 21 tumours
(68%) were located in the mandible, 10 (32%) in the maxilla. The
following tumours occurred in decreasing frequency: squamouscell carcinoma (n=10, 32%), malignant melanoma (n=8, 26%),
acanthomatous epulides (n=7, 23%), and fibrosarcoma (n=3,
10%). One each of the following tumours occurred:
osteosarcoma, atypical histiocytoma and ameloblastoma. Male
dogs were more often affected: in this study 20 (65%) of the
patients were male (entire or castrated), whereas only 11 (35%)
were female (entire or spayed). The average age of the patients
was 9.9 years (range 4-16 years). Dogs of different breeds as well
as mixed dogs were affected, however most of the patients were
middle to large breeds. Breed predispositions could not be
determined due to the small number of cases included in the
study.
The extent of jaw resection was determined by location and
size of the affected area. Additional computed tomographic
examination was performed for tumours of the maxilla to
optimise the planning of the operation (Fig. 6). Bone was
removed either with an oscillating saw and/or an osteotome
and mallet. Of the cases with a tumour of the mandible, a rostral
Fig. 6: CT used in the surgical planning of a maxillectomy to
remove an extensive squamous cell carcinoma located far
caudal in the oral cavity (patient number 8). Notice the
almost complete osteolysis of the right maxillary bone and
parts of the zygomatic arch. CT is essential for the planning
and preparation of this type of surgery.
76
MARTIN KESSLER
No Description
1
2
3
Retriever,
7y, fn
Small Munsterland
dog; 12y, m
Spitz-mix
14y, m
Mn
/Mx
Mn
Mn
ST
(mo)
18
L canine – R
PM2
R PM1-M3
outcome
alive
Fu/Wu/St/Ba
no further contact
German Shepherd
9y, mn
Mn
Mixed breed,
medium 11y, m
Ballonaise
13y, mn
Mn
Mn
R M1-L PM4
17
alive
no problems
7
Fox Terrier mix
12y, fn
Mn
PM2-joint
13
alive
no problems
8
German Shepherd
mix 10y, f
5
6
comments
no problems
complete
mandible
from PM1
caudally
complete
mandible
from L PM2
caudally
L PM3-M2
4
Mn
resection
21
alive
not possible to
chew bones,
jaw “crooked”
0,5
Eutha
19
alive
no problems
Dehiscence
Lnn metastasis,
Chemo: 4xCarbo +
4x Bleomycin
4 mo post OP: Lnn.
followed by resection
and Chemo: 6x
both Cisplatin and
Bleomycin
Chemotherapy:
5xcisplatin
Mx
R PM3-M3,
11
alive
no problems
zygomatic
arch, lateral
maxillary bone
9
Airedale Terrier
Mx
L PM3-M1,
24
alive
no problems
8y, fn
1/3 of hard palate
10 Bernese Mountain
Mx
L canine15
alive
no problems
dog - Mix 4y, m
PM3, over
palatine midline
y= age in years - Mn=mandible - Mx=maxilla – fn=female neutered – mn=male neutered – m=male – f=female - Resection:
start of segment including tooth mentioned – L=left – R=right - complete=including Ramus of mandible – ST=survival time –
Fu/Wu= food-/water uptake – St/Ba – playing with stick or ball - Eutha = euthanasia
Table 2: Squamous-cell carcinoma of the jaw
Significant side effects did not occur. Patients with malignant
melanoma experienced the worst survival rates (Table 3). Of
the 7 patients whose information was available, only two were
still alive (survival time 7 and 9 months postoperatively) at the
time of original publication in 2003. Five patients required
euthanasia due to recurrence (2 patients) and recurrence and
metastasis (3 patients) of the tumour. The survival times were
2, 3.5, 6, 6 and 16 months respectively. The patient (Tabl. 3,
number 12) with lymph node metastasis at the time of the
operation was treated postoperatively with a chemoimmunotherapy and had the longest survival time of all
melanoma patients (16 months). As above, no significant side
effects occurred as a result of the chemotherapy. Survival times
could be determined for 3 of the 4 patients with oral sarcomas
(Tabl. 4). One patient died 7 months after surgery due to illness
not associated with neoplasia and without evidence of
recurrence. The remaining two patients with sarcoma were still
living in 2003 without tumour recurrence (6 and 20 months). Of
the eight patients with acanthomatous epulides, information
number 13 was always wet in the ventral neck due to salivation.
The remaining 19 patients were not reported by the owners to
experience any type of difficulties.
Of the 31 patients, information on the survival times of 26
patients could be gathered. Eighteen were still alive at the time
of this manuscript’s original publication in 2003 with an average
survival rate of 14 months (compare tables 2 to 5). Of the 10
patients with squamous-cell carcinomas, as stated above,
euthanasia was performed in one due to repeated suture
dehiscence and one other patient was not available for follow
up. The remaining 8 patients were still alive at the original
publication in 2003, with a remission time of 11-24 months
(average 17.25 months, table 2). All 3 patients treated
postoperatively with chemotherapy were still alive in 2003: two
patients with metastasis (patients 6 and 7) lived without further
spread for 13 and 17 months, respectively, and one patient
(number 8) with a large affected area of the maxilla has lived
11 months without signs of tumour recurrence (Fig. 7).
77
No Description
11 Spitz mix
13y, fn
12 Yorkshire
Terrier mix
10y, m
Mn/Mx
Mn
resection
R PM4-M2
ST (mo)
6
Outcome
Eutha
Fu/Wu/St/Ba
no problems
Mn
L PM4-M1
16
Eutha
7
alive
difficulty Fu;
St/Ba impossible;
jaw “catches
on canines”
difficulty eating
large pieces,
drooling
13
Dachshund
12y, f
Mn
R M1- L PM2
14
Poodle mix,
14y, m
Bearded Collie;
10y, m
Poodle
13y, m
Mix-breed
14y, m
Mn
Mx
bilateral rostral
to PM1
L PM2-M3
9
alive
no problems
Mx
R canine – L I3
2
Eutha
no problems
15
16
17
comments
recurrence and
metastasis
LN mets, Chemo:
6x Carbo &
Interferon
temporary
ranula
no further
contact
tumour
recurrence
Mx
Size of an egg,
6
Eutha
no problems
tumour
extending to
recurrence
soft palate
18 Small mixed
Mx
R PM1-M3
3.5
Eutha
no problems
dehiscence, 2nd
breed
extending
OP; tumour
12y, fn
across midline
recurrence & mets
y= age in years - Mn=mandible - Mx=maxilla – fn=female neutered – mn=male neutered – m=male – f=female - Resection: start
of segment including tooth mentioned – L=left – R=right - complete=including Ramus mandibulae – ST=survival time – Fu/Wu=
food-/water uptake – St/Ba – playing with stick or ball - Eutha = euthanasia
Table 3: Malignant melanoma of the canine jaw
about the survival times is available from 7 (Tabl. 5). One of the
7 dogs required euthanasia 12 months postoperatively not
caused by tumour associated illness. The remaining patients
were still alive in 2003 with a remission time of 3 to 35 months
(average 15.5).
KESSLER and v. BOMHARD, 1997). In this study, 21 patients
were affected with tumours of the mandible compared to only
10 of the maxilla. Reported in the literature is a disproportionately
higher incidence of squamous-cell carcinoma (TODOROFF und
BRODEY, 1979) and acanthomatous epulides (WHITE, et al.,
1985) in the mandible compared to in the maxilla.
DISCUSSION
Partial Maxillectomy/Partial Mandibulectomy
A mandibulectomy or maxillectomy is performed to resect a
malignant jaw tumour or a bone invasive benign neoplasm
(BERG, 1998). Conservative ‘excisions’ of the tumours, such as
Epidemiology
In this study, the tumours malignant melanoma, squamous-cell
carcinoma, fibrosarcoma, and acanthomatous epulis were
identified as the most common bone invasive tumours occurring
in dogs, confirming results observed in other publications
(TODOROFF and BRODEY, 1979; KESSLER and v. BOMHARD,
1997; HORSTIG et al., 1998). The age and breed range were
similar to those in other publications, older dogs being more
often affected (COHEN et al., 1964; TODOROFF and BRODEY,
1979; EVANS and SHOFER, 1988; WALLACE et al., 1992).
According to other studies oral sarcomas also affect younger
individuals (COHEN et al., 1964; TODOROFF and BRODEY,
1979). However, statistically this could not be supported in this
study due to the small number of cases. For the same reason,
determining breed disposition was also impossible, however
middle and larger breed dogs seem to make up the majority of
affected individuals, as is the case in this and other studies
(TODOROFF und BRODEY, 1979; SCHWARZ et al., 1991a;
Fig. 7: Cosmetic result after extensive maxillectomy 11 months
after surgery (Patient number 8, see also Fig. 6). Jaw function
is completely preserved.
78
MARTIN KESSLER
Tumour
histology
FS
Mn/MX
resection
Mn
R PM4-joint
Labrador Retriever
6y, fn.
FS
Mx
Fox Terrier
9y, f
Mixed breed
12y, m
FS
Mx
OS
Mn
L I1-PM2
2/3 width of
palatine
R PM1 –
L PM2
both rostral
to PM1
No
Description
19
German shepherd,
20
21
22
ST
(mo)
20
outcome
alive
comments
no further
contact
no problems
no further
contact
6
alive
no problems
y= age in years - Mn=mandible - Mx=maxilla – fn=female neutered – mn=male neutered – m=male – f=female – FS=fibrosarcoma –
OS=osteosarcoma - Resection: start of segment including tooth mentioned – L=left – R=right – ST=survival time – Fu/Wu= food-/water
uptake – St/Ba – playing with stick or ball
Table 4: Sarcomas of the canine jaw
local removal or scraping, leads almost inevitably to a swift
recurrence (TODOROFF und BRODEY, 1979; HARVEY et al.,
1981; SCHWARZ et al., 1991a and b). The resection involves
the removal of the affected jaw segment including the teeth.
When performing a mandibulectomy, it is not necessary to
stabilise or connect the remaining jaw segments (WITHROW
and HOLBERG 1981). The reconstruction is achieved by suturing
the lingual and labial mucosa as well as their anchoring to the
remaining segment(s) of the lower jaw (Fig. 8a and b). During
mandibulectomy, special care must be taken to avoid damaging
the nerves of the tongue or excretory ducts of the sublingual
salivary glands. The operation is more demanding the further
caudal the mandibulectomy. When performing disarticulation of
the temporomandibular joint, care must be taken not to injure
the mandibular alveolar artery, vein and lingual nerve, which run
directly medial to this joint. Resection of the maxilla requires the
closure of the ensuing oronasal defect. This can be accomplished
by elevating a buccal mucosal flap originating from the adjacent
upper lip (Fig. 9). A maxillectomy is also invariably more difficult
with increasing amount of bone/tissue removal or the further
caudal the tumour is located or resected. The most demanding
resections are those requiring either a complete reconstruction
of the tempero-mandibular joint region or incorporating the
rostral soft palate. Depending on the type of tumour, a certain
amount of invasive growth is expected and should be considered
when planning the resection. The tumour mass, determined
using CT and gross appearance, as well as a safety margin of
normal soft tissue and bone should be excised. For this reason
it is imperative to determine the tumour type. In addition to
determining the invasive growth of the tumour (radiographs,
CT) and the metastatic spread (fine needle aspirate or biopsy of
the regional lymph nodes, thoracic radiographs), a biopsy of the
tumour itself using fine needle aspirates or a bone punch is
necessary to plan the surgery correctly. According to the
experience of the author, the following sufficient distances for
the safety margin around the mass should be observed: gingival
squamous cell carcinoma approx. 1 cm, malignant melanoma 2
cm, and fibrosarcoma 3 cm (Fig. 10). Acanthomatous epulides
can be resected with a safety margin of 0,5-1 cm.
Partial maxillectomy or partial mandibulectomy show good
cosmetic and functional results (FOX et al., 1997). Also in this
study, even after extensive resection, only one patient
experienced difficulty with food uptake. Most dogs retained the
ability to take unwieldy or hard objects (chew-bones, balls,
sticks) between the jaws. In all, 22 of the 23 owners were
satisfied with the functional results of the jaw resection.
COMPLICATIONS
The most common complications after maxillectomy or
mandibulectomy are dehiscence, wound infection, disturbance
of the salivary gland ducts, difficulty with food uptake, pain,
tongue dysfunction and abnormal salivation (WHITE, 1987;
MATTHIESEN and MARRETTA, 1990; SCHWARZ et al., 1991a
and b; MUIR and ROSIN, 1995). Complications also occurred in
this study, however, the overall rate was low. The results were
not satisfactory with two patients: euthanasia of one patient due
to repeated dehiscence, and food uptake problems of another
patient. Both patients with fatal complications underwent
extensive resection of the caudal jaw segment. Caudal tumours,
as stated also in the literature, are known to have a poor
prognosis due to the limited surgical possibilities (SCHWARZ et
al., 1991a).
Biological behaviour, Therapy and Prognosis
The results of this study support what has previously been
published about the biological behaviour of oral tumours. Two
of the ten patients with squamous-cell carcinoma exhibited
metastasis to the mandibular lymph nodes, whereas lung
metastases were not evident. In published literature 8 out of 58
animals had lymph node metastases (EVANS and SHOFER, 1998;
SCHWARZ et al., 1991a and b; MILLER et al., 1994) and only 1
of 35 dogs had pulmonary metastases (TODOROFF and
BRODEY, 1979). Apparently this tumour metastasises at an
advanced stage of the disease. At post mortem examination of
11 dogs, metastasis was evident in the lymph nodes of 5 animals
and in the organs of 4 animals (TODOROFF and BRODEY,
79
Fig. 9: Closure of the resection defect resulting from maxillectomy
with a mucosal flap from the upper lip (patient number 10).
The pre-operative appearance is shown in figure 2.
Fig. 8: Hemimandibulectomy due to fibrosarcoma of the lower
jaw (a) post-operative and (b) the resected jaw segment.
During soft tissue reconstruction, care is taken to protect the
excretory ducts of the sublingual salivary glands
Fig. 10: Mandibulectomy due to fibrosarcoma. Because of the
severe invasive growth of this tumour, the aim is to excise an
additional 3 cm of healthy tissue around the mass.
1979). It can be inferred that this tumour most likely initially
metastasises to the lymph nodes, necessitating their histological
examination. According to literature reports, squamous-cell
carcinomas that develop caudally in the oral cavity have a poorer
prognosis. This may be due to the occult growth of this tumour,
which causes the animal to be presented for examination at an
already advanced stage of the disease. Neither a stronger
tendency to metastasise nor an inherent malignant biological
behaviour of the caudally located gingival squamous-cell
carcinoma has been proven.
in veterinary medicine. The authors applied a protocol derived
from those in human medicine using a platinum derivative
(Cisplatin or Carboplatin) combined in 2 cases with the antitumour antibiotic Bleomycin. The effectiveness of both platinum
derivatives is similar, however the method of administration and
the costs involved differ. Carboplatin is a newer generation of
platinum derivative that is not nephrotoxic and as a result can
be administered intravenously over a short time period without
diuresis. However, the cost of carboplatin is much higher than
that of cisplatin, which makes it economically challenging for
Few cases of concurrent chemotherapy in the treatment of
metastasised oral tumours or of those with a high metastasis
rate are described in the literature. Chemotherapy to treat
gingival squamous-cell carcinoma has not yet been established
80
MARTIN KESSLER
No
23
24
25
26
27
28
29
30
Description
large mixed breed,
10y, m
Collie,
9y, f
Beagle Crossbred
16y, m
Retriever
6y, m
Belg. SH
11y, m
West Highl. Terrier
9y, f
Schnauzer
8y, m
Swiss Mountain dog
8y, m
Tumour
histology
AE
ST
outcome
Fu/Wu/St/Ba
(mo)
3
Mn
AE
Mn
L complete - R
Canine
R I3 - Canine
alive
no problems
5
alive
no problems
AE
Mn
R I1 - PM1
20
alive
no problems
AE
Mn
R I1 - Canine
24
alive
no problems
AE
Mn
R PM3 - M1
12
no problems
AE
Mn
R PM1 - M1
35
Eutha (not
tumour
associated)
alive
AE
Mx
L PM2 – R
Canine
6
alive
AM
Mn
L PM3 – R PM2
20
alive
no problems
but no bones
or balls
no problems
Mn/MX
resection
no problems
y= age in years - Mn=mandible - Mx=maxilla – fn=female neutered – mn=male neutered – m=male – f=female – AE=acanthomatous
epulis – AM=ameloblastoma - Resection: start of segment including tooth mentioned – L=left – R=right - complete=including Ramus
mandibulae – ST=survival time – Fu/Wu= food-/water uptake – St/Ba – playing with stick or ball – Eutha = euthanasia
Table 5: Acanthomatous epulides/ ameloblastoma of the canine jaw
use in larger animals. When treating with cisplatin, an extensive
diuresis protocol is necessary to prevent kidney damage (Table
1). The main side effect of both medications is emesis during
application through a direct stimulation of the chemoreceptor
trigger zone in the brain. To prevent emesis, odansetron
(Zofran®, 4-8 mg/animal p.o.) combined with metoclopramide
(0.2 mg/kg i.v.) should be given approximately 2 hours before
initiating chemotherapy. Bleomycin does not yet have many
applications in veterinary medicine. In this case, Bleomycin was
given subcutaneously twice a week. Side effects are rare, but the
development of pulmonary fibrosis and a hypersensitivity
reaction have been reported, and in individual cases the
development of paw pad ulcers occurred. No side effects were
observed in the patients in this study undergoing treatment. The
survival times of dogs with squamous-cell carcinoma with
concurrent chemotherapy are encouraging. Both animals
(patients 6 and 7) with extensive metastasis to the lymph nodes
survived postoperatively 13 and 17 months, respectively. Patient
number 8, who was additionally treated with cisplatin because
of the size of the lesion, was still in remission at the time of
publication, 11 months postoperatively.
difficult to interpret. Even so, in this study the one patient who
was treated additionally with chemotherapy and immunotherapy
(patient 12) had the best survival time of 16 months.
One explanation for the variable survival times of malignant
melanomas could lie in their immunogenetic properties, in which
the presence of the tumour causes an immunological response.
The course of the disease is for this reason dependent on the
effectiveness of the patient’s immune system. This property of
melanomas can be exploited therapeutically. Various studies
involving different immune modulators have been published, for
example C. Parvum (MacEWEN et al., 1986), L-MTP-PE
(MacEwen et al., 1994), Interleukin, and tumour necrosis factor
(MOORE et al., 1991). The authors used human recombinant
interferon-α 2a (Roferon-A“, Roche), which was given twice
weekly subcutaneously by the owner at a dose of 3 Mio. IU/m2
BSA. This dosage results in serum values of a therapeutic value,
however it is known that some patients build neutralising
antibodies against the human interferon. Further studies are
necessary to determine recommended clinical uses of
immunotherapy. The recent introduction of a feline recombinant
interferon opens new possibilities in veterinary medicine,
however until now no publication has provided data on the
best melanoma tumour immunotherapy.
Similar to reports in the literature, patients in this study with oral
melanoma suffered the shortest survival times. Of over 200
patients reported in the literature undergoing mandibulectomy
or maxillectomy, there was a mean survival time of 7.5 to 9
months. However, it is striking that the survival time for oral
melanoma varies greatly (1-46 months) (HARVEY et al., 1981;
MacEWEN et al., 1986; KOSOVSKY et al., 1991; SCHWARZ et
al., 1991a and b). Because of the high rate of metastasis, it seems
wise to augment the surgical treatment of malignant melanomas
systemically. However, due to the wide range in survival time
a comparative study evaluating concurrent therapies would be
Oral fibrosarcomas affect both the lower and upper jaw with
almost equal incidence and are characterised by local invasive
growth into surrounding tissue. The rate of metastasis is lower
compared to other oral tumours but higher compared to
fibrosarcomas occurring elsewhere. Tumours localised to the
maxilla or hard palate have the worst prognosis due to operative
restrictions. Even after radical resection, fibrosarcomas have the
highest recurrence rate of all oral tumours (SCHWARZ et al.,
81
BRADLEY (R.L.), (D.P.) SPONENBERG AND (R.A.) MARTIN (1986):
- Oral neoplasia in 15 dogs and 4 cats. Sm. Anim. Vet. Med. Surg.
1, 33–42.
BURACCO (P.), (A.) BONIOLI, (G.) ROMANELLI et al. 1994: Surgery / chemotherapy in 43 canine and feline oral tumours.
Proc. 14th Ann. Conf. Vet. Canc. Soc. 51–52.
COHEN (D.), (R.S.) BRODEY AND (S.M.) CHEN (1964): Epidemiologic aspects of oral and pharyngeal neoplasms of
the dog. Am. J. Vet. Res. 25, 1776–1779.
DUBIELZIG (R.R.) AND (D.E.) THRALL (1982): - Ameloblastoma and
keratinizing ameloblastoma in dogs. Vet. Pathol. 19, 596–607.
EVANS (S.M.) AND (F.) SHOFER (1988): Canine oral nontonsillar
squamous cell carcinoma: prognostic factors for recurrence and
survival following orthovoltage radiation therapy. Vet. Radiol.
29, 133–137.
FOX (L.E.), GEOGHEGAN, (S.L.), (L.H.) DAVIS et al. (1997): Owner satisfaction with partial mandibulectomy or
maxillectomy for treatment of oral tumours in 27 dogs. J. Am.
Anim. Hosp. Assoc. 33, 25-31.
GARDNER (D.G.) AND (D.C.) BAKER (1993): - The relationship of
canine acanthomatous epulis to ameloblastoma. J. Comp. Path.
108, 47–55.
GARDNER (D.G.) (1996): - Epulides in the dog: a review. J. Oral
Pathol. Med. 25, 32-37.
HAHN (K.A.), (D.B.) DENICOLA, (R.C.) RICHARDSON et al. (1994):
- Canine oral malignant melanoma: prognostic utility of an
alternative staging system. J. Sm. Anim. Pract. 35, 251–256.
HARVEY (H.J.), (E.G.) MACEWEN, (D.) BRAUN et al. (1981):
Prognostic criteria for dogs with oral melanoma. J. Am. Vet.
Med. Assoc. 178, 580–582.
HORSTING (N.), (A.) VON REISWITZ, (P.) WOHLSEIN et al. (1998):
- Oropharyngeale Tumoren des Hundes - Eine klinische Studie
über 79 Fälle. Berl. Münch. Tierärztl. Wschr. 111, 242–247.
KESSLER (M.) AND (D.) VON BOMHARD (1997): Tumoren der
Maulhöhle beim Hund: Epidemiologische Untersuchungen bei
491 Fällen. In: Kessler, M. (Hrsg.): Kleintieronkologie, Paul
Parey, Berlin 1999; 278.
KOSOVSKY (J.K.), (D.T.) MATTHIESEN, (S.M.) MARRETTA et al.
(1991): - Results of partial mandibulectomy for the treatment of
oral tumours in 142 dogs. Vet. Surg. 20, 397–401.
LAMONT (E.B.) AND (E.E.) VOKES (2001): Chemotherapy in the
management of squamous-cell carcinomas of the head and
neck. Lancet Oncol. 2, 261-269.
MACEWEN (E.G.), (A.K.) PATNAIK, (H.J.) HARVEY et al. (1986):
- Canine oral melanoma: comparison of surgery versus
surgery plus Corynebacterium parvum. Cancer Invest. 4,
397–402.
MACEWEN (E.G.), (I.D.) KURZMAN, (S.C.) HELFAND et al.
(1994): Combined L-MTP-PE and surgery for canine oral
melanoma. Proc. 14th Ann. Conf. Vet. Cancer Soc. 109–110.
MATTHIESEN (D.T.) AND (S.M.) MARRETTA (1990): - Results and
complications associated with partial mandibulectomy and
maxillectomy techniques. Probl. Vet. Med. 2, 248–275.
MILLER (T.L.), (G.S.) PRICE, (R.L.) PAGE et al. (1994): - Radiotherapy
of canine non-tonsillar squamous cell carcinoma. Proc. 14th
Ann. Conf. Vet. Cancer Soc. 20–21.
MOORE (A.S.), (G.H.) THEILEN, (A.D.) NEWELL et al. (1991): Preclinical study of sequential tumour necrosis factor and
interleukin-2 in the treatment of spontaneous canine neoplasms.
Cancer Res. 51, 233–238.
MUIR (P.) AND (E.) ROSIN (1995): - Parotid duct obstruction after
caudal maxillectomy in a dog. Vet. Rec. 46.
1991a and b). Local recurrence of this tumour is the most
common cause of death or euthanasia. Of 104 cases described
in the literature, 45% suffered a recurrence (WITHROW and
HOLBERG 1981; WHITE et al., 1985; BRADLEY et al., 1986;
SALISBURY et al., 1986; KOSOVSKY et al., 1991; SCHWARZ et
al., 1991a and b; WHITE, 1991; WALLACE et al., 1992; BURACCO
et al., 1994). The mean survival time was approximately 11
months and, depending on the study, only 25 to 50% of the
patients survived the first year following surgery. The results of
this study are comparable to those already published, although
the case number is too small for statistical analysis.
Acanthomatous epulides frequently infiltrate bone causing
lysis, which clinically and radiographically resembles a malignant
tumour. Because they do not undergo metastasis, they are
classified as benign or semimalignant. Surgical resection of the
mass is normally curative (WHITE et al., 1985; BJORLING et al.,
1987; KOSOVSKY et al., 1991; WHITE, 1991). In this study, over
an average of 15.5 months there were no cases of recurrence.
CONCLUSION
This study confirms that the therapy of oral invasive tumours
through mandibulectomy or maxillectomy is well tolerated by
the patient and the functional and cosmetic results are
satisfactory. The prognosis of animals with malignant neoplasia
of the oral cavity depends on many factors. They are as follows:
(1) the histological tumour type, (2) the duration of disease, (3)
the site of the tumour, and (4) the extent of surgical resection.
A satisfactory prognosis seems to be possible also in cases where
the tumour has already metastasised when adjuvant
chemotherapy is performed.
In closing it should be stated that oral neoplasia respond well
to radiation therapy. Because of the limited availability of this
treatment option, no patient in this study underwent such
therapy. Fundamentally, radiation therapy is suitable as an
adjuvant therapy (squamous-cell carcinoma and oral sarcoma)
or as a primary therapy (malignant melanoma, acanthomatous
epulides). As this therapy option becomes more and more
available to animals, it will play an increasing role in therapy
protocols for patients with oral neoplasia. It is to be expected
that through the use of all available therapies (surgical resection,
radiation therapy, chemotherapy), the survival times of affected
patients can be greatly improved.
REFERENCES
BERG (J.) (1998): - Principles of oncologic orofacial surgery. Clin.
Tech. Small Anim. Pract. 13, 38-41.
BJORLING (D.E.), (J.N.) CHAMBERS AND (E.A.) MAHAFFEY (1987):
- Surgical treatment of epulides in dogs: 25 cases (1974–1984).
J. Am. Vet. Med. Assoc. 190, 131–138.
BRADLEY (R.L.), (E.G.) MACEWEN AND (A.S.) LOAR (1984): Mandibular resection for removal of oral tumours in 30 dogs
and 6 cats. J. Am. Vet. Med. Assoc. 184, 460–463.
82
FECAVA SPONSERED PAPER
F eline paediatric medicine
Kit Sturgess (1)
S
U
M
M
A
R
Y
This article aims to look at three important areas of kitten medicine; nutrition, investigation of the stunted
kitten and managing the collapsed kitten. The latter two scenarios are common reasons for presenting a kitten
for further veterinary advice and investigation.
CLINICAL NUTRITION
IN KITTENS
This paper is based on
the FECAVA sponsored
lecture given at the
PSAVA Annual
Congress* Krakow
19-20th
November 2005
Choice of supplement
– An appropriate supplement should have
adequate nutritional density at the
recommended dilution (Table 2); too low
and it is difficult for a kitten to take in
sufficient volume to meet its nutritional
needs (stomach volume approximately
70ml/kg).
– Hydration is important and concentrated formulae may
predispose to dehydration.
– Fluid requirements in neonatal kittens are up to 180ml/kg/day
hence frequent feeding is required to deliver an appropriate
volume of fluid.
Cats have unique nutritional needs. Nutritional
problems are most likely to occur under periods
of maximum demand such as rapid growth,
when any dietary deficiencies or toxicities can result in significant
disease. Key areas for consideration of nutrition include
– Nutritional requirements of orphan kittens
– Diets for growing kittens
– Nutritional pitfalls
Nutritional requirements of orphaned kittens
Kittens can require supplementary feeding for a variety of
reasons, most commonly due to
– Death of the queen during parturition
– Failure of the queen’s milk supply
– Rejection of one or more kittens by the queen
– Litter size is too great for the queen to supply adequate
nutrition
– Attempts to reduce the risk of infection from a queen known
to be FIV or FeLV positive
Whilst the ideal substitute is to foster the kitten on to another
lactating queen who will accept the kitten this is rarely possible.
Queen’s milk is substantially different from bovidae milk (Table
1) and this can not be used as a straight substitute. Home-made
and commercial formulae are available (Table 2 and 3).
Dry Matter %
Protein (%)
Fat (%)
Sugar (%)
Ash (%)
Calcium (mg/100g)
Phosphorus (mg/100g)
Iron (mg/100g)
Kcal/100ml
Queen Bitch
Cow
Goat
21
7.5
8.5
4.0
0.6
180
162
0.35
121
13
3.3
3.7
5.0
0.7
115
95
0.2.-0.6
74
12
2.9
3.8
4.7
0.8
0.3-0.4
22.7
7.5
9.5
3.8
1.2
240
180
0.7
146
Table 1 – Comparison of queen’s milk with other milk sources
(1)Vet Freedom, Brockenhurst, Hampshire, GB - S042 7QT. E-Mail: [email protected]
* Hosted by PSAVA(Poland)
83
– High osmolality fluids may delay gastric emptying e.g. KMR
powder.
– Arginine levels can be too low in some formulae and
predispose to cataracts (queen’s milk arginine = 430mg/100g
or 355mg/100kcal).
– Taurine levels need to be sufficient (queen’s milk taurine =
10mg/100g or 8.3mg/100kcal); if the taurine content is
unknown, oral supplementation can be given (Figure 2).
– All home made recipes should be kept refrigerated and used
within 24 hours.
– Cream contains high levels of short and medium chain fatty
acids and is relatively deficient in linoleic acid.
– Queen’s milk is high in albumin compared to casein;
however, curd can be used as this contains coagulated casein
and not micelles (which are larger in bovine milk than
queen’s milk and risks hard coagula forming in the stomach).
– Egg whites can cause diarrhoea but are a good source of
albumin.
– Even the best replacers have potential problems so kittens
should be weaned as early as is practicable (from 3-4 weeks).
Figure 2 – Echocardiogram of a cat with dilated cardiomyopathy.
Queen
Dry Matter %
Protein (%)
Fat (%)
Sugar (%)
Ash (%)
Calcium (mg/100g)
Phosphorus (mg/100g)
Iron (mg/100g)
Kcal/100ml
Volume (ml/100kcal)
Recipe 1
21
7.5
8.5
4.0
0.6
180
162
0.35
6.25
7.1
3.3
0.5
150
135
0.29
121
83
7.1
4.4
4.7
0.8
96.2
126
0.6
16.9
8.9
5.5
5.9
1.0
120
158
0.75
80
125
Recipe 2
6.4
3.4
2.9
0.7
109
109
3.5
13.6
10.3
5.5
4.7
1.1
176
176
5.6
62
161
KMR powder*
www.aah-pets.com
32.6
14.5
9.5
13.3
6.0
6.8 (5.4) 4.5 (3.6)
2.1
1.2
370
244
290
192
1.3
0.8
151
66
Cimicat*
www.vetbed.co.uk
5.9
3.9
(5.6)
1.0
175
131
NR
17.5
6.4
4.2
(6.1)
1.1
189
141
NR
92
108
Vital Milk
Royal Canin
11
13
(6.2)
2
366
266
NR
33.3
5.9
7
(3.3)
1.1
198
144
NR
186
54
Figures in italics are per 100kcal of metabolisable energy; figures in brackets are % lactulose;
* - values are as fed according to manufacturers recommendations
Table 2 – Comparison of queen’s milk with milk replacers
Recipe 1
Skimmed milk
Low fat curd (not cottage cheese)
Lean minced beef
Egg yolk
Vegetable oil
Lactulose
Vitamin/mineral mix
Total
Recipe 2
70g
15g
8g
3g
3g
0.8g
0.2g
100g
One whole fresh egg
Protein supplement*
Milk, sweetened, condensed
Corn oil
Water 250ml
15g
25g
17ml
7ml
Total
310g
* Protein supplement used was ProBalance Feline (available via www.calvetsupply.com ) – analysis - 47% crude protein,
1% crude fibre and 17% crude fat. The supplement has essential vitamins and minerals, additional nutrients and digestive enzymes.
Table 3 - Homemade milk substitutes for kittens
84
KIT STURGESS
activity than dogs as well as lower levels of diassacharidases
making the feeding of a low fat diet more difficult in terms
of an alternate source of calories.
3. Cats tend to be more selective eaters and therefore dietary
manipulation that results in reduced palatability such as the
addition of fibre can have a low acceptance.
4. Carbohydrates are not the major secretagogues of insulin in
cats.
5. Cats have an essential requirement for taurine. Taurine
deficiency is usually associated with attempts to feed a
vegetarian/vegan diet. Taurine deficiency can lead to central
retinal degeneration, dilated cardiomyopathy and reproductive
failure. In the early stages these changes are reversible.
6. Cats are more sensitive to oxidants in their food which can
cause Heinz body anaemia. Such changes have been
associated with feeding some baby foods which use onion
powder as a base.
7. Cats require a source of preformed vitamin A.
8. Cats have an essential requirement for arachidonic acid in
their diet.
Feeding orphaned kittens
– Attention should be paid to the environment as kittens are
unable to thermoregulate (ambient temperature 30-32oC;
humidity 55-60%).
– Caloric need for kittens is 22-26kcal/100g (most kittens weigh
100-120g at birth)
– i.e. a new born kitten needs 18-23ml of queen’s milk per
day.
– Weight gain of 10-15g/day is ideal.
– Feed warm formula (37.8oC) at least 4 times daily depending
on the age of the kitten.
– Under feed for first feeds gradually increase to full amount
over 2-3 days.
– Feed using a nipple bottle, dosing syringe or stomach tube.
– When using a nipple bottle, milk should slowly ooze from
the teat when the bottle is inverted. A drop of milk should
be on the teat before inserting into the kitten’s mouth. The
milk should be allowed to flow under gravity, squeezing the
bottle to increase the flow rate risks aspiration.
– Feeding tubes are faster; a 5 FG tube should be used if the
kitten is less than 300g. Measure from the nose to the last rib
and insert the tube to this length.
– After feeding it is vital to stimulate micturition and defecation,
this can be done by massaging the anogenital area with
moistened cotton wool.
– Handling before feeding stimulates exercise promoting
muscular and circulatory development.
Vegetarian/vegan diets for kittens
– It is not possible to formulate vegetarian/vegan diets for cats
without careful addition of essential ingredients that are
usually animal derived such as taurine and arachidonic acid.
– Even when produced, balanced vegetarian/vegan diets do
not seem to have the same health benefits as meat-based
diets.
– Kittens are particularly vulnerable to nutritional deficiencies.
Diets for growing kittens
Feeding a raw meat diet
Once kittens have been weaned they need to be fed a diet
suitable for growth. A variety of proprietary diets are available.
Kitten diets have higher energy density, protein and vitamin
levels than adult maintenance diets. They are usually designed
for kitten up until 6 months of age. There are a variety of reasons
for making a dietary change at around 6 months as this often
coincides with neutering that results in a 20-30% reduction in
caloric need. When feeding or formulating a kitten diet, the
unique nutritional requirements of cats should be born in mind.
Kittens have a higher caloric need than adults although the total
volume fed can be small (Table 4).
1. Cats have a higher protein requirement; arginine deficient
diets such as some baby foods can rapidly cause hepatic
encephalopathy.
2. Cats have significantly lower (about 1/3rd the level) amylase
Physiological state
< 3 months (growth)
3 - 6 months (growth)
6 - 12 months
It has been argued that raw diets are better than cooked diets
for cats. No good clinical studies have been performed to address
this point. Even raw food is not the same as a freshly killed
rodent or bird particularly as it is likely to have been refrigerated
or frozen. The greatest risk of feeding raw food is infection
whether this is preformed toxins in spoiled foods, bacteria such
as Salmonella or parasites such as Toxoplasma. Appropriate
sourcing, storage and preparation of raw food are crucial. When
feeding raw food, the possibility of cross contamination of
human food should also be considered.
Nutritional pitfalls
Because of their unique nutritional needs some foods are best
avoided or given in strict moderation to kittens, these include:
Energy requirements
(kcal / kg bodyweight)
Weight of food required g/kg body weight*
Canned diet
Dry diet
250
130
80 (neutered) -100 (entire)
* 190
* 100
** 70-90
* based on typical kitten diet - canned (130kcal/100g); dry diet (425kcal/100g)
** based on typical adult diet - canned (110kcal/100g); dry diet (400kcal/100g)
Table 4 - Estimated energy requirements in healthy kittens
85
60
30
20-25
Figure 3- Radiograph showing a marked reduction in bone density in a kitten with nutritional secondary hyperparathyroidism associated
with feeding an exclusive lean chicken diet.
contain preformed histamine. Ingestion results in reddening of
the skin, most noticeably the nose, nausea, vomiting, diarrhoea,
abdominal pain and pruritus that develops within 15-60 minutes
of ingestion
Liver
Liver contains excessively high levels of vitamin A leading to
painful bone deformities which do not resolve even if the diet
is corrected (Figure 4).
Milk products
Cats generally do love milk but they may lack the enzymes to
digest it resulting in large quantities of fermentable sugars
reaching the colon leading to osmotic diarrhoea.
N.B. Milk is a balanced diet; calcium is NOT in excess hence milk
can not be used to balance diets which have excessive
phosphorus such as an all meat diet.
Figure 4 – Radiograph of the stifle of a cat showing calcification
of the soft tissues associated with hypervitaminosis A.
Onion-based foods
Cats are sensitive to oxidant intoxicants such as onions that are
used as a base in some baby foods for example.
Table scraps
Feeding less than 10% of calories as table scraps is unlikely to
cause nutritional imbalance but can lead to obesity if not taken
into account when calculating the daily ration. Feeding table
scraps can lead to behavioural problems - begging, refusing to
eat regular food etc.
Pharmacological activity
Some foods have pharmacological activity e.g. chocolate but
these are rarely consumed by kittens
Figure 5 – Severely stunted and septic kitten (on the table) caused
by an umbilical infection. This kitten did not survive.
Meat and poultry
Carnivores in the wild eat the majority of the carcase and not
just lean meat which has excessive amounts of phosphorus
relative to calcium and is deficient in sodium, iron, copper,
iodine and vitamins. An all meat diet can lead to severe and
potentially fatal skeletal abnormalities, nutritional secondary
hyperparathyroidism (Figure 3) and joint malformations.
Fish
Raw fish can contain thiaminase which destroys vitamin B1
(thiamine) as well as potentially containing parasites.
Excessive amounts of fish can cause a relative deficiency of
vitamin E especially if the fish is packed in oil.
Fish that has been improperly preserved or inadequately
refrigerated, particularly the tuna and mackerel family, can
86
KIT STURGESS
INVESTIGATION OF THE
STUNTED KITTEN
Kittens are frequently presented to veterinary surgeons because
they are poorly grown (Figure 5). Based on the DAMNIT-V
system, the most likely causes of stunted growth are highlighted.
D Degenerative; developmental, demented (psychological)
A Anomaly (congenital); allergic, autoimmune
M Metabolic
N Neoplastic, nutritional
I Infectious; inflammatory; idiopathic; immune mediated;
iatrogenic
T Traumatic, toxicity
V Vascular
Figure 6 – An under grown kitten with an abscess on its head
secondary to feline infectious peritonitis.
Causes
Abnormality of bone growth
– Chondrodystrophy
Deficient nutrient intake
– Inadequate or inappropriate diet
– Gastrointestinal parasitism
– Persistent vomiting or regurgitation e.g. vascular ring anomaly
– Maldigestion / malabsorption
Increased caloric demand
– Fever
– Chronic infectious or inflammatory disease (Figure 6)
– Major trauma
– Increased caloric loss
– Protein losing enteropathy
– Protein losing nephropathy
– Urine nutrient loss e.g. juvenile onset diabetes mellitus, renal
glycosuria
Major organ defect
– Hepatic - portosystemic shunt, glycogen storage disease
(Figure 7)
– Renal - dysplasia, pyelonephritis
– Congenital cardiac anomaly
– Lysosomal storage disease
– Endocrinopathy
– Hypothyroidism (Figure 8)
– Hyposomatotrophism
Figure 7 – Six month old male, Havana kitten weighing less
1.7kg and showing neurological signs associated with a
portosystemic shunt.
Key history
– Did the queen have a normal, pregnancy and parturition?
– When was the problem first noticed?
– Has the kitten been slow and poorly grown since birth?
Suggests a congenital defect.
– Was the kitten showing normal development (i.e.
indistinguishable from the other members of the litter) and
then suddenly stopped? Suggests an acquired disease.
– Are any other members of the litter similarly affected?
– Have kittens in previous litters shown similar signs?
– What is the kitten’s diet, appetite and food intake?
– Are there signs, other than failure to grow, that indicates
major organ disease?
– Is the kitten’s body proportionate or disproportionate?
– Is the kitten’s body condition good or poor?
Figure 8 – Hypothyroidism causing severe reduction in growth
rate and skeletal malformation.
Physical examination
Examination of kittens can be difficult as they rarely stay still and
can be aggressive if from a feral background. Neonates tend to
show limited responses to disease, initially becoming agitated
and crying, progressing to inactivity, hypothermia and loss of the
suckling reflex. As with all young animals, changes in their status
can be very rapid. Weight gain can be a sensitive indicator of
developing problems and can be easily measured by the owner
(Figure 9). Failure to gain weight over any 24 hour period is
worthy of further investigation.
87
Daily weight of kittens
Weight (grams)
FCK
Age (days)
Figure 9 – Growth curves for a litter of kittens, one kitten’s growth rate began to slow.
A few days later this kitten developed a flat chest (Figure 12).
– Respiration 15-35 per minute.
– Regular rhythm.
– Heart murmurs may be innocent, associated with non-cardiac
disease (e.g. anaemia, portosystemic shunt) or associated
with congenital cardiac disease (Table 5).
– Lung sounds difficult to distinguish but should be present;
check for symmetry or malformation of the thoracic cavity.
External features
– Body weight
– Hair coat (amount, condition, parasites, persistence of kitten
coat)
– State of hydration
– Signs of injury
– Appearance of umbilicus
– Discharge from nose/eyes/ears
– Urine staining (patent urachus)
– Diarrhoea / rectal patency
– Congenital malformation
Eyes
– Kitten’s eyes open between day 5 and day 14.
– Pupillary light response is present within 24 hours of opening.
– Mild cloudiness of cornea is usually evident at opening but
should resolve rapidly.
– Swelling under the eyelids indicates pus formation (often
staphylococcus spp.), very rarely Chlamydophila felis
(Chlamydia psittaci) (Figure 10).
Ears
– External auditory meatus is closed at birth and opens between
6 and 14 days; check for mites.
– Middle ear infection indicated by a bulging tympanum.
Mouth
– Colour of mucous membrane.
– Evidence of cleft palate (Figure 11).
Abdomen
– Should feel full but not swollen or tight.
– Liver and spleen not palpable.
– Intestines soft, mobile and non-painful.
– Urinary bladder freely movable.
Figure 10 – Kitten with serous ocular discharge associated with
C.felis infection.
Thorax
– Shape of thorax - flat chest (Figure 12), pectus excavatum
– Heart rate around 200-220 beats per minute.
88
KIT STURGESS
Figure 11 – Cleft palate.
Figure 12 – Flat-chested kitten – this condition develops shortly after birth and particularly
affects Burmese kittens.
– Acquired diseases tend to be infectious or toxic and therefore
other members of the litter are likely to be showing signs.
Neurological assessment
– Alertness
– Response to stimulation
– Suckle reflex
– Other reflexes appropriate to age
– Gait (walking from around 4 weeks old)
– Posture
– Flexor and extensor dominance appears more variable in
kittens than puppies.
Diagnostic approach
– Is the nutritional and caloric intake adequate?
– Is trauma a realistic possibility – if so how is it affecting
growth?
– Is the problem likely to be a congenital abnormality (if so
which organ) or an acquired disease?
– Is an endocrinopathy likely – kittens tend to be stunted but
otherwise clinically well?
– Ensure adequate and appropriate nutrition.
– Ensure adequate worming and ectoparasite control.
– Haematology, biochemistry and urinalysis to assess major
organ disease
– Include hepatic function tests (bile acids).
– Retrovirus serology.
– Survey radiographs - thorax, abdomen, and appendicular
skeleton.
– Ultrasound and echocardiography
– Hormonal tests – growth hormone, thyroid function
– Endoscopy and biopsy of the stomach and small intestine.
– Fibroblast culture or urinalysis for lysosomal storage disease
(Figure 13).
– Specific DNA-based genetic tests.
Innocent murmurs
Congenital murmur
Usually I-III/VI, craniodorsal, ejection type
Variable with heart rate and body position
Often musical
Typically diminishing with age & resolving by 16 weeks
Usually loud unless
– large defect
– tricuspid valve dysplasia
– mild semilunar valve stenosis
May be associated with clinical signs
– failure to grow
– cyanosis,
– exhaustion after brief periods of play
– weakness
– collapse
– Source of congenital murmurs can be difficult to identify
in some cats
Decision making
Table 5 – Characteristics of innocent cardiac murmurs and murmurs associated with congenital heart disease
89
MANAGING THE COLLAPSED
KITTEN
History should be focused on
– Health of other members of the litter – infectious disease is
likely to affect more than one kitten in the litter.
– Environment to assess the likelihood of trauma or access to
potentially toxic compounds.
– Internal or external parasitism is very common.
– What parasite control has been used?
– Is there a possibility that the parasiticide is causing the
problem e.g. piperazine, organophosphates, permethrins?
Neonatal responses are relatively limited and body reserves are
low so kittens can rapidly change from being bright and well
to collapsed and seriously ill. This section will focus on the
initial management of the collapsed kitten including physical
examination, history taking, basic diagnostics and rational
therapy.
Physical examination
History
A thorough physical examination is essential both in order to
try and achieve a diagnosis as well as identify urgent problems
that require therapy. Normal physiological values for kittens are
given in Table 6.
Many of the historical questions will be similar to those for the
stunted kitten. Congenital diseases can present acutely such as
the kitten with a cardiac defect that goes into congestive heart
failure or the kitten with a portosystemic shunt that becomes
encephalopathic. However, in the majority of cases, trauma,
intoxication or infectious disease will be the most likely causes.
In such cases, the kitten will have been normally developed,
growing and eating well up until the very recent past.
Age
Rectal
Heart rate
(days) temperature (bpm)
(oF)
Respiratory
rate (/min)
Environmental
temperature
(oF)
0-7
8-14
15-28
29-35
>35
15-35
15-35
15-35
15-35
Adult
85-90
80
80
70-75
70
96 ± 1.5
100
Adult
Adult
200-250
70-220
70-220
70-220
70-220
Investigation of neonatal disease
– Routine haematology (Table 7) and biochemistry (Table 8)
can be performed from a very early age on blood obtained
by jugular puncture (Figure 14).
Parameter
Kittens (mean or range)
Age
0-3 days 2 weeks
4 weeks
6 weeks
PCV (%)
Haemoglobin (g/dl)
RBC (x1012/l)
MCV (fl)
MCH (pg)
MCHC (g/dl)
WBC (x109/l)
41.7
11.3
5.11
81.6
24.6
27.3
7.55
25.7-27.3
8.5-8.9
4.57-4.77
52.7-55.1
18.0-19.6
32.5-33.5
14.1-16.5
26.2-27.9
8.3-8.9
5.66-6.12
44.3-46.9
14.2-15.4
31.3-32.5
16.1-18.8
33.6-37.0
11.5-12.7
5.05-5.53
65.5-69.3
22.4-23.6
33.7-35.3
9.1-10.2
Table 6 - Physiological values in young kittens
Table 7 - Haematological values in young kittens
Parameter
Kitten age (weeks)
2
4
7-12
Total protein (g/l)
Albumin (g/l)
Sodium (mmol/l)
Potassium (mmol/l)
Chloride (mmol/l)
Inorganic phosphate (mmol/l)
Calcium (mmol/l)
Urea (mmol/l)
Creatinine (µmol/l)
Cholesterol (mmol/l)
ALK-P (U/l)
ALT(U/l)
Glucose (mmol/l)
Bilirubin (µmol/l)
Bile acids (µmol/l)
40-52
20-24
<5
4.3-11.6
68-269
11-24
6.08-10.32
1.7-16.9
<10
46-52
22-24
149-153
4.0-4.8
120-124
2.0-2.4
2.4-3.2
<5
36-54
4.6-11.4
90-135
14-26
7.92-8.96
1.7-3.4
<10
51-57
24-32
147-152
5.0-6.2
113-128
2.5-3.1
2.2-2.8
4.2-6.3
36-91
-
Table 8 - Serum biochemistry values in young kittens
90
KIT STURGESS
Figure 13 – An under grown kitten with skeletal abnormalities
associated with a lysosomal storage disease.
Figure 14 – Jugular venipuncture in a week old kitten.
– Many infectious diseases develop too rapidly to obtain results
quickly enough (especially bacterial culture and sensitivity or
paired serum samples) to be of value to that individual but
a knowledge of cause may be beneficial to the rest of the litter
or subsequent litters.
– To minimise the amount of blood required, glucose can be
estimated on a glucometer and 0.5ml EDTA tubes used
making a total bleed of 1.5ml in the smallest of kittens
sufficient for most tests to be carried out.
a lengthening of the interval between doses.
– Great care should be taken when administering broadspectrum antimicrobials orally because of their potentially
adverse effects on the developing gut microflora.
– Subcutaneous and intramuscular absorption of drugs is slower
and less reliable than in adults particularly if the kitten is
dehydrated.
– Antimicrobials administered to the dam do not reach
therapeutic concentrations in the milk.
– Ensuring adequate nutritional support either by nasooesophageal or gastric intubation is a vital part of therapy
particularly in the face of sepsis.
Blood volume in cats is estimated at 75ml/kg. A week-old
kitten will weigh around 200g and have 15ml of blood
– Radiographs can be difficult to evaluate in young kittens as
mineralization of the skeleton is poor and the film can be
easily over exposed. Reducing the kV to half that used for
an adult of similar body thickness should produce
radiographs that will provide valuable diagnostic information.
– Faecal examinations can be easily performed and are of
particular value where protozoan parasites are suspected.
Despite aggressive therapy, acutely sick kittens will die and it
is important to try and encourage the owner to allow a post
mortem examination. Maximum information can be obtained if
the carcass is fresh. If a post-mortem can not immediately be
performed, the body should be stored in the fridge and not the
freezer. A systematic approach should be adopted and all details
should be recorded including sex, colour, body weight, amount
of body fat, presence of ingesta in the stomach, faeces in the
colon and urine in the bladder.
Figure 15 – Fluid warmer that can be attached to the giving set
line.
Consideration affecting the treatment of neonatal disease
Special consideration needs to be given when giving drugs or
fluids to paediatric patients as they have an immature
metabolism, small total body weight but relatively high body
surface area.
Drugs
– Absorption, distribution, metabolism and excretion of drugs
can be significantly different from adults.
– Few drugs have had dose rates calculated for use in young
kittens.
– Generally, an increase in the initial dose (/kg) is required with
91
Fluid therapy
Fluid requirements (/kg) are higher in neonates than adults BUT
total volumes are low. Young kittens have immature kidneys and
lack the ability to concentrate their urine in the face of
dehydration and therefore will become dehydrated very quickly
especially if there is increased fluid loss such as vomiting or
diarrhoea.
– Maintenance fluid requirements of very young kittens (less
than 2 weeks) are around 180ml/kg/day. By weaning fluid
requirements are around 120ml/kg/day. Adult maintenance
requirements (50ml/kg/day) are appropriate in kittens over
6 months old.
Intravenous
– 23g or 25g catheter can be placed in the cephalic vein of
many small kittens.
– Larger catheters can be placed in the jugular vein but this can
be difficult in kittens that are dehydrated. Placing a jugular
catheter may required sedation/anaesthesia and cut down.
The benefits of jugular access have to be balanced with the
risks of placement.
– The kitten’s short legs can make the catheter very positional
and flow difficult to maintain in gravity fed fluid systems.
Forced flow in the absence of syringe or fluid pumps can be
achieved using
– Battery operated, fixed-rate (0.5 or 1.0ml/hr), single use
fluid reservoirs (Figure 16).
– Spring-driven, refillable, syringe pumps, flow rate variation
is limited and achieved using variable diameter tubing
connected to the patient.
– Single patient use, refillable balloon infusion devices that
use the elastic recoil of the balloon to push the fluid. Flow
rate variation is limited and achieved using variable
diameter tubing connected to the patient.
Example
A week old kitten weighing 200g will therefore require 36ml
of fluid at maintenance over 24 hours i.e. 1.5ml per hour.
Even using a paediatric giving set, this is equivalent to 1 drop
every 40 seconds.
Increased fluid rates are necessary if the kitten is dehydrated
or has increased fluid loss (diarrhoea or vomiting). Fluid
should be given at approximately 4ml/kg per episode of
vomiting or diarrhoea
Intraperitoneal
– This route is not ideal as absorption can be relatively slow
especially in the face of hypovolaemia and is poorly suited
to long-term fluid therapy. However, in the hypovolaemic,
collapsed kitten this may be the fastest way of delivering
therapy in the short term.
– The risks of puncturing viscera are low.
– Aseptic technique is mandatory.
– Daily fluid requirements should be calculated and the volume
divided to be given 2-3 times daily.
If the kitten is 8% dehydrated and having episodes of
vomiting and diarrhoea every 4 hours then
– Maintenance at 1.5ml/hr
Fluid deficit is 16ml – replace 50% in the first 6 hours (=
1.3ml/hr) and the remainder over 18 hours (= 0.5 ml/hr)
– Increased need associated with GIT signs is 24ml/kg/day
= 5ml/day = 0.2ml/hr
Fluid rate for first 6 hours is then 3ml/hour (1 drop per 20
seconds) reducing to 2.2ml/hour (1 drop every 27 seconds)
These calculations are approximations and it is vital
that the state of hydration and urine output is
monitored.
Intraosseus
– Useful where venous access not possible due to vein size or
hypotension causing the veins to collapse.
– The cortical bone is sufficiently soft in kittens such that a
hypodermic needle (18-19g) can be used.
– The area should be surgically prepared and the needle placed
in either the proximal tibia or proximal femur. Only one
attempt should be made at each site since, if the bone cortex
– Syringe pumps can be of great value and are significantly
cheaper than fluid pumps; otherwise a burette with a
paediatric giving set (60 drops per ml) will ensure that the
kitten is not over-hydrated.
– Kittens will tend to become acidotic associated with many
disease states but reduced hepatic function can mean that
they are less able to metabolise lactate into bicarbonate.
– For most kittens Ringers solution is appropriate. If the
kitten is significantly acidotic, bicarbonate can be given
separately at 1mmol/kg over 20 minutes.
– Glucose can be replaced using a 5% dextrose solution mixed
50:50 with lactated ringers or by giving 1-2ml of 10-25%
glucose i/v to profoundly depressed kittens.
Figure 16 – Mechanical, low
flow rate devices (available
from Mila International:
www.milaint.com).
Methods of drug and fluid administration
Kittens are particularly prone to hypothermia so fluids should
be warmed before administration. Because the rate of
administration of fluids is slow, warming the whole bag of fluid
is not effective. Fluid needs to be warmed as it passes through
the giving set using a proprietary fluid warmer (Figure 15),
heated pads or warm water that is regularly replaced.
92
KIT STURGESS
is already punctured, it will result in fluid leaking out.
– Fluids, drugs or whole blood can be given at the same rates
as for i/v therapy.
–
–
–
–
–
Neonatal isoerythrolysis
Blood group A kittens are at risk of neonatal isoerythrolysis if
they are born to a B group queen. B group cats have naturally
occurring, high affinity, anti-A antibodies that are passed to the
kitten in the colostrum resulting in immune-mediated haemolytic
anaemia.
Inadequate colostrum
Low birth weight
Trauma
Neonatal isoerythrolysis
Infectious disease
Key history
– Breeding history of household.
– Disease status of household.
– Individual breeding history of queen.
– Number of kittens born alive and dead.
– Health of queen now and during pregnancy.
– Status of other litter members.
– Status of other kittens in the household.
– Recent arrivals / showing / mating.
– Pattern of illness to-date.
– Health parameters noted by breeder e.g. weight gain.
– Hygiene, worming, vaccination and flea control regimes.
– Has the kitten ever appeared normal?
– Did the kitten ever suckle normally?
– Has supplementary feeding been provided (risk aspiration)?
– Blood group of queen and stud cat (if known).
Clinical signs
Kittens start to fade when they are a few days of age. Owners
first notice discoloration of the urine due to haemoglobinuria.
Kittens will become jaundiced. Tail and ear tip necrosis will also
occur.
Blood group distribution by breed in the UK
NB – blood group distribution in other areas of Europe may be
different from this
Breeds with no type B cats
– Siamese, Burmese, Tonkinese, Oriental short hair, Ocicat
Breeds with <5% type B cats
– DSH, DLH, Maine Coon, Norwegian Forest Cat
Breeds with 10-20% type B cats
– Abyssinian, Birman, Himalayan/Persians, Scottish fold ear,
Somali, Sphinx
Breeds with >20% type B cats
– British and exotic short hairs, Cornish and Devon rex
Investigation
A full physical examination should be performed including a
neurologic assessment for alertness, suckle reflex, response to
noxious stimuli and reflex responses (not fully developed until
12 weeks).
Decision making
– Level of problem - household, litter or individual.
– Congenital vs. hereditary?
– Infectious vs. anatomic?
– Likelihood of trauma?
– Possibility of neonatal isoerythrolysis?
Therapy
Aggressive therapy needs to be given at an early stage and blood
transfusion with group A blood is necessary. Mortality rates can
be high.
Prevention
Subsequent matings of the queen should with a B group stud
cat. If this is not possible then the kittens should be blood
grouped (jugular sample or umbilical blood) at birth before they
are allowed to suckle and A or AB group kittens given A group
colostrum (usually requires fostering onto an A group queen)
or milk replacer until after gut closure (24 hours). In kittens
given milk replacer, the lack of colostrum will, however, make
them vulnerable to other infectious diseases. This risk can be
reduced by feeding 1-3ml of serum from a type A cat.
Ideally queens and stud cats should be blood typed prior to
mating.
Diagnostic investigation
– Routine haematology and biochemistry
– Faecal and urinalysis
– Bacterial culture
– Serology
– A positive FIV test can not be interpreted in a neonate
because of passive transfer of antibodies from the queen.
A kitten born to an FIV antibody negative queen is highly
unlikely to have FIV.
– Imaging studies
– Biopsy / post mortem
Fading kittens
Blood transfusions
Definition
These are typically kittens born apparently healthy that either
fail to suckle (or lose their suckle reflex) and die with no organspecific clinical signs. Fading kittens may occur as single cases;
affect multiple or all kittens in the litter.
Kittens can survive with a very low haematocrit and can present
with a PCV as low as 6-8%. These kittens are very vulnerable to
stress and need to be handled carefully and pre-oxygenated
before attempting to take blood or place an i/v line. Where
severe anaemia is suspected, a small amount of blood is required
to blood type the kitten and measure their PCV. If the kitten is
symptomatic or has a PCV of less than 12%, blood transfusion
is appropriate and can be very rewarding. Only small volumes
of blood are required but can result in dramatic clinical
improvement.
Common causes
– Congenital abnormality
– Exposure to teratogens in utero
– Inadequate nutrition
93
Blood volume required
REFERENCES AND FURTHER
READING
Example
A 200g kitten (7 day old) presents with a PCV of 8%.
A group matched blood donor is available whose PCV is 30%.
Target PCV is 25% for the kitten
Volume required =
Desired PCV (L/L) – Actual PCV (L/L) x 100 x bodyweight (kg)
PCV of donor (L/L)
HOSGOOD (G.), HOSKINS (J.D.) (1998) - Small Animal Paediatric
Medicine and Surgery, Butterworth Heinemann, Oxford.
IHLE (S.L.) (2005) - Failure to Grow in Textbook of Veterinary
Internal Medicine [6th edition]; Ettinger, S.J. & Feldman, E.C. eds.
Elsevier Saunders, Missouri, pg. 80-82.
JACOBS (R.N.), PAPICH (M.G.) (2000) - in Kirk’s Current Veterinary
Therapy XIII; Bonugura, J. ed. W.B.Saunders, Philadelphia, pg.
1211-1212.
KIRK (C.A.), DEBRAEKELEER, (J.), ARMSTRONG (P.J.) (2000) Normal Cats in Small Animal Clinical Nutrition [4th edition];
Hand, M.S., Thatcher, C.D., Remillard, R.L. & Roudebush, P. eds.
Walsworth Publishing Company, Missouri, pg. 329-334.
STURGESS (C.P.) - (1998) Infectious Disease Of Neonates, Young
Puppies & Kittens in BSAVA Manual of Small Animal
Reproduction & Periparturient Care, pg.159-166.
STURGESS (C.P.) (2003) - Feline Internal Medicine, Blackwells,
Oxford, pg 27-28, 35-36, 313-319.
= 0.25 – 0.08 x 100 x 0.2 = 11ml
0.30
Blood collection
Blood can be collected in 10-20ml syringes pre wetted with acid
citrate dextrose solution (1ml/10ml of blood collected) via a 21g
butterfly catheter placed in the jugular vein of a donor cat. In
some cases mild sedation of the donor [e.g. ketamine (5mg/kg)
and midazolam (0.25mg/kg)] may be necessary. Alpha2adrenergic agonists such as medetomidine should be avoided
due to their hypotensive effects making venipuncture difficult.
Donor cats should be clinically healthy, less than 8 years old and
ideally have been tested negative for FeLV, FIV and FIA (feline
infectious anaemia).
Performing the transfusion
Blood should be administered via an intravenous or intraosseus
route using a T-connector or low volume extension tubing (23ml) to minimise dead space. Blood should be given at an initial
transfusion rate of half maintenance for the first half hour in the
non-emergency situation. In reality, for most kittens this means
a bolus of 0.5 ml and waiting for half an hour to see whether
there is an adverse reaction. Thereafter blood can be given at
twice maintenance. In an emergency, blood can be given at
shock rates (70ml/kg/hour) – for the kitten in the example
above, this means giving the 11ml needed over about 45
minutes.
CONCLUSIONS
Kitten medicine is a truly challenging but very rewarding area
for the veterinarian. The small size of the patient, speed with
which they deteriorate and lack of localising clinical signs makes
investigation and treatment difficult. The value of success,
however, is great in the hope that your patient will survive and
enjoy the next 15 year or so of life.
ACKNOWLEDGMENTS
Professor T.J. Gruffydd-Jones for Figures 8 and 11
Dr D. Gunn-Moore for Figures 6 and 13
Mrs R. Giles for Figure 1
94
REPRINT PAPER (CH)
A utochthonous infections with
Angiostrongylus vasorum in dogs in
Switzerland and Germany
S. Staebler(1), H. Ochs(1), F. Steffen(3), F. Naegeli(4), N. Borel(2), N. Sieber-Ruckstuhl(3), P. Deplazes(1)
S
U
M
M
A
R
Y
Angiostrongylus vasorum is endemic in foxes and other carnivores in the south and south east of France,
Denmark and Great Britain. The reddish nematode is present in the pulmonary arteries and the right side of
the heart and causes respiratory and cardiovascular signs. From 1999 to 2004, A. vasorum was diagnosed in
three dogs from southern Switzerland, five dogs from northern Switzerland and in one dog from southern
Germany. There were variable clinical signs in the affected dogs including coughing, tachypnoea and
dyspnoea. Two of the dogs had neurological signs. Four of these dogs died and diagnosis was confirmed
by necropsy. Diagnosis in the other five dogs was achieved by detecting the larvae in faeces. Based on the
case history at the time of presentation, these nine dogs were probably autochthonous cases.
Key words: Angiostrongylus vasorum – epidemiology – central Europe
INTRODUCTION
appeared in:
Schweiz.Arch.Tierheilk*
2005 147(3) p121-p127
up to 5 years (Eckert and Lämmler, 1972).
Occasionally, the larvae can be found in the left
side of the heart, the kidneys, the anterior
chamber of the eyes and in the brain (Bolt et
al., 1994). Infected dogs develop various
respiratory and cardiovascular signs such as
coughing, tachypnoea, dyspnoea, cardiac
dilatation, ascites and hydrothorax (Bolt et al., 1994). Often a
consumptive coagulopathy can be observed which results in
anaemia and subcutaneous haematomas. In rare cases,
neurological manifestations such as depression, ataxia, paralysis
and epileptiform seizures have been described (Capdebielle and
Hussenet, 1911; Patteson et al., 1993; Perry et al., 1991; Reifinger
and Greszl, 1994; Tinapp, 1969). Severe clinical manifestations
occur mostly in animals in their first year of life (Eckert and
Lämmler, 1972). Without treatment the infection can be fatal.
Angiostrongylus vasorum is a parasitic
nematode with an indirect life cycle. Foxes and
dogs are final hosts and gastropods (snails and
slugs) obligatory intermediate hosts (Guilhon,
1963; Guilhon, 1965; Guilhon and Bressou,
1960). After ingestion of an infected intermediate host, the third
stage larvae migrate via the abdominal visceral lymph nodes
into the blood. The adults lodge within the pulmonary arteries
and the right side of the heart and start to produce eggs (Rosen
et al., 1970). The eggs reach the pulmonary arterioles via the
bloodstream and develop into first stage larvae. These penetrate
the alveoli, are coughed up into the pharynx, swallowed and
shed in the faeces of the final host. The prepatent period is
between 40 and 49 days. Infected dogs can remain patent for
(1) Institute of Parasitology, (2) Institute of Veterinary Pathology, (3) Clinic for Small Animals, University of Zurich, Winterthurstrasse 266a, CH-8057, Zurich,
(4) Studio Veterinario, Balerna. E-mail: [email protected] (Dr Staebler), [email protected](Prof Deplazes)
* Presented by SVK/ASMPA (Switzerland)
95
Autochthonous infections with Angiostrongylus vasorum in dogs
ANIMALS, MATERIALS AND
METHODS
A. vasorum is mainly transmitted in wildlife using the fox as its
final host. The geographical distribution in both foxes and dogs
is sporadic and focal. In Europe, endemic foci exist in Italy,
south-west France, Ireland, south-west England (Bolt et al., 1994)
and Denmark (Bolt et al., 1992). Of 509 foxes investigated in
Italy, 39% were infected with A. vasorum (Poli et al., 1991). A
similar prevalence (36%) was demonstrated in 39 foxes in
Denmark (Willingham et al., 1996). Sporadic autochthonous
cases have been reported from France, south-east England,
Switzerland, Spain and the former Soviet Union (Bolt et al.,
1994).
Faeces and/or nematodes found during necropsy and formalinfixed tissues from nine dogs were examined for the presence of
A. vasorum. The first stage larvae were extracted from faeces by
the Baermann technique (Eckert, 2000). Identity was confirmed
by the larval length (310-400 μm) and the typical structure of the
tail with a dorsal cuticular spine (Deplazes, 2005). Adult
nematodes found in the heart were confirmed as A. vasorum by
their typical morphology (male: 14-18 mm long, slightly reddish,
terminal end slightly enrolled with a small bursa and two long
spicules (360-400 μm); female: 18-25 mm long, vulva shortly
before the anal opening, red intestines) (Deplazes, 2005).
There are only a few reports of autochthonous cases of
angiostrongylosis in central Europe. Wolff (1969) diagnosed A.
vasorum in a dog breeding establishment near Zurich with up
to 51% of slugs (Arion rufus) infected with larvae of A. vasorum.
Recently, two infected foxes were detected in Basel (Gottstein,
2001; [email protected]).
Tissues taken during necropsy and fixed in 10% formalin were
processed for routine histology. In three cases the larvae could
be demonstrated by HCl-pepsin digestion (modified Trichinella
technique) (Eckert, 2000) of formalin-fixed tissues. In brief,
tissues (5g/l) were minced mechanically and digested in an HCl
solution (1% v/v) with pepsin (5g/l) in a water bath at 45°C
with shaking. After four to eight hours of incubation (time
depending on the kind of tissue and its fixation in formalin) the
suspension was sieved and sedimented two times for 20 mins.
The sediment was carefully examined microscopically for the
presence of adults and larvae.
Canine angiostrongylosis has also occurred sporadically in
imported dogs (Ribière et al., 2001). In addition, larvae of A.
vasorum were detected in nine out of 8438 samples in a private
laboratory near Freiburg i. Br. (Barutzki and Schaper, 2003). In
7 cases the dogs originated from different parts of Germany
(Nordrhein-Westfalen, Hessen, Saarland, Bayern and BadenWürttemberg) (Dr. D. Barutzki, personal communication). In
this article we report nine presumably autochthonous cases of
angiostrongylosis in southern and northern Switzerland and the
adjacent German border area.
Table 1: Clinical data, necropsy- and histological findings as well as parasitological results
Case
nr
Breed, age and sex
(diagnosis)
1
Sheep dog, 5 years old,
Cough after effort
m (11.1999)
Dogo Argentino,
Inappetence, apathy, ataxia
10 months old, f (01.2000)
2
Clinical symptoms
-
First larvae in faeces (MT)
Interstitial pneumonia, arteritis,
meningitis, encephalitis
Bleeding into thorax, lung, thymus,
pericard, mediastinum;
granulomas in the lung
-
Adults in heart (N),
A. pulmonalis (N), lung
(H); larvae in the brain (H)
Adults and first larvae in
lung (D), third larvae in
thymus (D)
Cough, slightly pneumonia
Bronchointerstitial pneumonia with
bleedings, interstitial nephritis,
bleedings and malacia in the brain
-
First larvae in lung and
kidney (D); first larvae in
the intestine (SF)
Cough, tachypnœa
-
Clearing throat after activity
-
Cough, dyspnea
Pneumonia with sections of adults
First larvae in lung (D)
3
Labrador, 1 year old,
f (01.2002)
Cough, nose bleeding
4
Poodle, 1 year old,
f (02.2002)
Labrador, 1 year old,
f (06.2002)
Cough
5
6
7
8
9
Lagotto Romagnolo,
6 months old, m (11.2002)
Scottish Terrier,
2 years old, m (09.2003)
Labrador, 9 years old,
m (12.2003)
Maltese, 8 months old,
f (01.2004)
necropsy and histological results Parasitological proof
Swollen eyes, ataxia, cramps
m: male; f: female; -: not done, N: necropsy; H: histology; D: digestion; MT: migration technique; SF: sedimentation/flotation
96
S. STAEBLER
7
8
4
2
6
1
5
9
3
Figure 1: Geographical distribution of dogs (cases 1-9) with Angiostrongylus vasorum-infections.
RESULTS
With the exception of dog 9, which died before treatment
commenced, cases 1, 4, 6 and 7 were successfully treated either
with fenbendazole (Panacur®) whilst case 8 was treated with
milbemycin and praziquantel (Milbemax®). Faecal examination
two weeks after treatment was negative in all dogs. Only dog 8
had a history of travel outside the area. This animal had been
to southern France, Burgundy and Alsace. Three of the six
presented dogs were known to eat snails or slugs. One dog,
which did not have a history of eating snails or slugs, was known
to eat fallen fruit.
During the past five years, A. vasorum infection was diagnosed
in five dogs from northern Switzerland, in one dog from the
Swiss-German border region and in three dogs from southern
Ticino close to the Italian border (Figure 1). In five dogs
angiostrongylosis was diagnosed by faecal examination and the
animals were treated. Four dogs died and the diagnosis was
confirmed by necropsy. In three of these dogs the digestion of
formalin-fixed tissues was required. We present six cases with
similar clinical signs and three further cases separately. Detailed
data for the individual dogs, including the breed and age, clinical
signs, necropsy, histological and parasitological results are
summarised in Table 1.
Case 2:
A 10 month old entire Dogo Argentino bitch presented with
innappetence, salivation and retching followed by disorientation.
This progressed to impaired consciousness with apathy and
general ataxia. There was no improvement despite fluid therapy,
antibiotics and non-steroidal anti-inflammatory drugs. The animal
became comatosed and died after four days. At necropsy, masses
of dark red, adult A. vasorum up to 2 cm long could be found
in the right side of the heart and the larger branches of the
pulmonary arteries. Histology revealed a high degree of diffuse,
chronic to active and interstitial pneumonia with necrotising
arteritis, caused by parasitic thrombosis. In the larger pulmonary
arteries, adults were found and masses of eggs in the alveoli.
The changes in the brain consisted of diffuse, purulent meningitis
and perivascular encephalitis. In the brain there were multiple
small foci of haemorrhage and necrosis. Larvae were visible in
the neuropil.
Cases 1, 4, 6, 7, 8 and 9:
These dogs had respiratory signs (Table 1), which varied
between cases only in duration and intensity. In addition, dog
8 had thrombocytopenia and prolonged bleeding after a tooth
extraction. In five of these animals diagnosis was confirmed by
demonstrating larvae in the faeces. Dog 9 died and larvae were
demonstrated at post mortem by digestion and histology of lung
tissue.
In addition to angiostrongylosis, three dogs (cases 1, 4 and 7)
had a co-infection with Crenosoma vulpis. Dog 7 was also
infected with Ancylostoma and Taenia spp. Echinococcus
multilocularis was excluded by PCR examination of the taeniid
eggs (Mathis et al., 1996).
97
Autochthonous infections with Angiostrongylus vasorum in dogs
This animal belonged to a dog breeding unit, had a history of
eating slugs and snails and had never left Switzerland. Faecal
samples from the remaining dogs on the unit tested negative for
the presence of A. vasorum.
The experimental infection of dogs with A. vasorum with
infested snails has been demonstrated (Bolt et al., 1992). The
parasite can be introduced into new areas by the importation
of infected dogs. It is believed that the introduction of the
parasite into Denmark was by dogs originating from France
(Bolt et al., 1992). In a parasitological investigation of 100 red
foxes in Denmark in 1973, A. vasorum was not detected (Guildal
and Clausen, 1973). Twenty years later this parasite had become
established in the fox population around Copenhagen (C.M.
Kapel, personal communication). Cases of angiostrongylosis are
now frequently diagnosed (Bolt et al., 1992).
Case 3:
A one year old neutered Labrador bitch from southern Ticino
was presented with a cough and was treated with antibiotics.
Two weeks later, the dog presented with peracute shock,
coughing and nasal haemorrhage. Haematologically the bitch
had a slightly regenerative anaemia. Despite treatment with
antibiotics and corticosteroids the animal died 12 hours later.
Post mortem findings included pulmonary, pericardial,
mediastinal and thymic haemorrhage. Histology revealed a
granulomatous pneumonia with masses of giant cells and
isolated sections of A. vasorum larvae.
In the present report, six dogs were from the region of
Basel/Aargau (Fricktal) and the adjacent region of southern
Germany (Figure 1). In this area (Basel-Stadt) A. vasorum was
demonstrated in two foxes, which suggests the parasite is
endemic (Gottstein, 2001, [email protected]). Because
the fox population is increasing, especially in urban areas of
central Europe (Chautan et al., 2000; Deplazes et al., 2004), the
distribution of the parasite could increase. The slug Arion rufus
is a known intermediate host in central Europe (Eckert and
Lämmler, 1972), but other snail or slug species as well as the
common frog (Rana temporaria) are potential intermediate hosts
(Bolt et al., 1993; Eckert and Lämmler, 1972; Guilhon and Cens,
1973). Among our nine dogs, three were known to eat slugs.
In digested lung and thymic tissue one first and two third stage
larvae of A. vasorum were found respectively. In the brain, liver
and kidneys as well as in the coagulum from the heart no larvae
could be detected. The dog originated from southern Ticino
and had briefly visited the adjacent area in northern Italy.
Case 5:
A one year old entire Labrador retriever bitch was presented with
lameness and weakness of the hind legs. Additionally, the bitch
salivated and had swollen eyelids. The rear left tarsus was
swollen with a small wound. A day later the bitch showed
generalised ataxia, muscular spasms and anal bleeding.
Haematology revealed a slight anaemia and leucocytosis. Despite
fluid therapy, antibiotics, spasmolytics, anti-tetanus serum and
corticosteroids the animal died within two days.
The clinical presentation of the nine dogs varied. Older dogs had
a slight cough, especially after exercise. In contrast, dogs one
year old or less had severe clinical signs and some died. Bolt
(1994) suggested that slugs are eaten especially by young dogs
and fox puppies, and this could explain the severe course of the
disease. Two dogs died within a few days showing neurological
signs. Such an acute presentation, together with neurological
signs, is unusual (Bolt et al., 1994).
The histological changes consisted of an extensive, diffuse,
broncho-interstitial pneumonia, diffuse haemorrhage and
numerous larvae. In the kidneys, parasite sections were present
together with mild, patchy interstitial nephritis. Changes in the
brain and meninges consisted of small foci of acute haemorrhage
and malacia.
Two other dogs died due to parasitic infection after coughing
for two weeks. These animals were not diagnosed clinically and
consequently were treated with antibiotics only. This
demonstrates the importance of a correct diagnosis and
appropriate anti-parasitic therapy.
In the intestinal contents, first stage larvae of A. vasorum and
Trichuris eggs were recovered by sedimentation/flotation
technique. The digestion of lung tissue demonstrated large
numbers of first stage larvae of A. vasorum. In digested kidney
tissue only two first stage larvae were recovered. No larvae
could be found in digested heart, brain and liver tissue or in the
anterior chamber of the eye.
In individual cases coagulation abnormalities with consumptive
coagulopathy and thrombocytopenia occurred leading to a
haemorrhagic diathesis manifested by anaemia, haemoptysis,
melaena and subcutaneous haematomas (Bolt et al., 1994).
Excessive bleeding after the excision of a tooth, epistaxis and
bleeding into the thorax was reported in two of the dogs.
The diagnosis of A. vasorum is made by the demonstration of
first stage larvae in faeces or in washings from bronchoalveolar
lavage. As the larvae are not shed continuously, negative dogs
should be retested. Larvae of Crenosoma vulpis can be clearly
distinguished morphologically. Capillaria aerophilia also causes
respiratory signs, but can be distinguished by the characteristic
eggs using sedimentation/flotation techniques (Deplazes, 2006).
A serological test for angiostrongylosis is not presently available.
As in case 3 this animal originated from southern Ticino but
had visited northern Italy.
DISCUSSION
The distribution of A. vasorum in central Europe has been
incompletely investigated, but several case reports from
Germany and Switzerland document its existence. From different
endemic regions it is known that foxes are the most important
final hosts (Bolt et al., 1992; Poli et al., 1991).
Angiostrongylosis can be treated with fenbendazole 50 mg/kg
daily for five days or 20 mg/kg two times daily for 2-3 weeks
98
S. STAEBLER
(Deplazes, 2006). Mebendazole at a dose of 50-100 mg/kg orally
two times daily over five to 10 days is also effective (Bolt et al.,
1994). Milbemycin, 0.5 mg/kg orally once a week for four weeks,
was effective in 14 out of 16 dogs (Conboy, 2004). Antigens
released during therapy (anaphylactic shock) and dead adult
stages (emboli) can cause side effects.
REFERENCES
BARUTZKI (D.), SCHAPER (R.) - Endoparasites in dogs and cats in
Germany 1999-2002. Parasitol. Res. 2003, 90:148-150.
BOLT (G.), MONRAD (J.), FRANDSEN (F.), HENRIKSEN (P.), DIETZ
(H.H.) - The common frog (Rana temporaria) as a potential
paratenic and intermediate host for Angiostrongylus vasorum.
Parasitol. Res. 1993, 79:428-30.
BOLT (G.), MONRAD (J.), HENRIKSEN (P.), DIETZ (H.H.), KOCH
(J.), BINDSEIL (E.), JENSEN (A.L.) - The fox (Vulpes vulpes) as
a reservoir for canine angiostrongylosis in Denmark. Field
survey and experimental infections. Acta. vet. scand. 1992,
33:357-62.
BOLT (G.), MONRAD (J.), KOCH (J.), JENSEN (A.L.) - Canine
angiostrongylosis: a review. Vet. Rec. 1994, 135:447-52.
CAPDEBIELLE, HUSSENET: Embolie cérébrale produit par
Strongylus vasorum. Rev. Vét. 1911, 36:144-147.
CHAUTAN (M.), PONTIER (D.), ARTOIS (M.) - Role of rabies in
recent demographic changes in Red Fox (Vulpes vulpes)
populations in Europe. Mammalia. 2000, 64:391-410.
CONBOY (G.) - Natural infections of Crenosoma vulpis and
Angiostrongylus vasorum in dogs in Atlantic Canada and their
treatment with milbemycin oxime. Vet. Rec. 2004, 155:16-18.
DEPLAZES (P.) - Helminthosen von Hund und Katze. In:
Veterinärmedizinische Parasitologie. Hrsg. T. Schnieder, Parey
Buchverlag Berlin, 2006.
DEPLAZES (P.), HEGGLIN (D.), GLOOR (S.), ROMIG (T.) Wilderness in the city: the urbanization of Echinococcus
multilocularis. Trends. Parasitol. 2004, 20:77-84.
ECKERT (J.) - Helminthologische Methoden. In: Veterinärmedizinische Parasitologie. Hrsg. M. Rommel, J. Eckert, E.
Kutzer, W. Körting und T. Schnieder, Parey Buchverlag Berlin,
2000, 69-84.
ECKERT (J.), LÄMMLER (G.) - Angiostrongylose bei Mensch und
Tier. Z. Parasitenkd. 1972, 39:303-322.
GOTTSTEIN (B.) - Lungenwurm Angiostrongylus vasorum bei einem
Fuchs in der Schweiz. BVET-Magazin. 2001, 1:22.
GUILDAL (J.A.), CLAUSEN (B.) - Endoparasites from one hundred
Danish red foxes (Vulpes vulpes (L.)). Norweg. J. Zool. 1973,
21:329-330.
GUILHON (J.) - Recherches sur le cycle évolutif du Strongle des
vaisseaux du chien. Bull. Acad. Vét. 1963, 36:431-442.
GUILHON (J.) - [Larval development of Angiostrongylus vasorum
(Baillet, 1866) in the Arionidae organism]. C. R. Acad. Sc. 1965,
261:4225-7.
GUILHON (J.), BRESSOU (C.) - Rôle des limacidés dans le cycle
évolutif d’Angiostrongylus vasorum (Baillet, 1866). C. R. Acad.
Sc. 1960, 251:2252-2253.
GUILHON (J.), CENS (B.) - Angiostrongylus vasorum (Baillet, 1866):
Étude biologique et morphologique. Ann. Parasitol. Hum.
Comp. 1973, 48:567-596.
MATHIS (A.), DEPLAZES (P.), ECKERT (J.) - An improved test
system for PCR-based specific detection of Echinococcus
multilocularis eggs. J. Helminthol. 1996, 70:219-222.
PATTESON (M.W.), GIBBS (C.), WOTTON (P.R.), DAY (M.J.) Angiostrongylus vasorum infection in seven dogs. Vet. Rec.
1993, 133:565-70.
PERRY (A.W.), HERTLING (R.), KENNEDY (M.J.) - Angiostrongylosis
with disseminated larval infection associated with signs of ocular
and nervous disease in an imported dog. Can. Vet. J. 1991,
32:430-431.
POLI (A.), ARISPICI (M.), MANCIANTI (F.), ABRAMO (F.) Pathology of naturally acquired Angiostrongylus vasorum
infection in the red fox (Vulpes vulpes). Angew. Parasitol. 1991,
32:121-6.
REIFINGER (M.), GRESZL (J.) - Pulmonale Angiostrongylose mit
systemischer Ausbreitung und zentralnervaler Manifestation bei
einem Hund. J. Vet. Med. B. 1994, 41:391-398.
RIBIERE (T.), GOTTSTEIN (B.), HUBER (E.), WELLE (M.), FORSTER
(J.L.), GROSCLAUDE (P.) - A propos d’un cas d’angiostrongylose
canine. Schweiz. Arch. Tierheilkd. 2001, 143:313-318.
ROSEN (L.), ASH (L.R.), WALLACE (G.D.) - Life history of the canine
lungworm Angiostrongylus vasorum (Baillet). Am. J. Vet. Res.
1970, 31:131-43.
TINAPP (D.) - Über das Wirt-Parasit-Verhältnis bei der experimentellen Infektion des Hundes mit Angiostrongylus raillieti
(Travassos, 1927). Dissertation. Justus Liebig-Universität,
Giessen, 1969.
WILLINGHAM (A.L.), OCKENS (N.W.), KAPEL (C.M.), MONRAD
(J.) - A helminthological survey of wild red foxes (Vulpes vulpes)
from the metropolitan area of Copenhagen. J. Helminthol. 1996,
70:259-63.
WOLFF (K.), ECKERT (J.), LEEMANN (W.) - Beitrag zur
Angiostrongylose des Hundes. In: Vortrag Tagung Fachgr.
”Kleintierkrankheiten”, Dtsch. Vet.-med. Ges, Zürich, 1969.
AVEPA (Spain) leads the way
AVEPA and the IVEE (Institute for Veterinary Economic Studies) develop the first
MBA Programme for Veterinary Practices Managers in Europe
For the first time in Europe, small animal Veterinariarians will be able to obtain an official MBA degree specifically designed for
Veterinary Practice Managers. This MBA Programme, which started its first course in the city Barcelona in October 2005, is a joint initiative
of AVEPA and the Universitat Autònoma de Barcelona (home of the College of Veterinary Medicine).The course language will be Spanish,
but Practice Managers and Veterinarians from all over Europe will be welcome to enrol.
This two year programme is composed of eight modules with
the following structure:
First Year: Introduction courses in Human Resources), Finance,
Marketing and Strategy.
Second Year: Advance courses in Human Resources, Finance,
Marketing, and Strategy.
After the completion of the first four modules successful
participants receive an official Diploma of Veterinary Practice
Management. When all of the eight modules in the programme
have been completed qualifying students will receive their
official Masters in Veterinary Practice Management (an official
title from the Universitat Autònoma de Barcelona).
Classes will take place on a “one day per week – six hours per
day” basis (Wednesdays in Barcelona, Thursdays in Madrid)
over the period October-May for two consecutive years.
This initiative is the result of AVEPA’s follow-up from the findings
of the 2004 Practice Management Report, where the lack of
managerial resources and capabilities among practicing
veterinarians was identified as one of the factors limiting the
profitability of veterinary businesses.
The Programme will combine academic rigour with relevant
professional experience in the veterinary industry. The teaching
methods will be predominantly practical, combining lectures
with cases and practical exercises specifically designed for
circumstances pertaining in small animal veterinary practices.
A brief description of the outline of the syllabus is detailed
below:
1) Human Resources:
– Practice Team management
– Self-Appraisal as a leader, and leadership capabilities
development
– Emotional Intelligence in the context of a Veterinary Hospital
– Performance Appraisal systems in a Veterinary Hospital
– Compensation Policies in a Veterinary Hospital
– Staff recruitment, training, motivation and retention in a
Veterinary Hospital
– Conflict resolution, negotiation, meeting management...
– Delegation
2) Finance:
– Financial Accounting Statements (Balance Sheet, Profit and
Loss, Cash Flow statement)
– Management Accounting: profitability analysis, cost analysis,
pricing techniques
– Financial Analysis: financial diagnostics, financial and
operating ratios, treasury management, budgeting
– Financing sources
– Investment Analysis
– Practice Valuations
– Value Creation for a Veterinary Hospital
3) Marketing:
–
–
–
–
–
–
–
–
–
–
Local Scope Marketing
Health Services Marketing
Pricing Policies and Marketing Implications for a Vet Hospital
Customer Service (phone, reception, in the consultation
room...)
Personal communication technques for the veterinarian
Merchanding at the vet hospital
Complaint management at the vet hospital
CRM: relational marketing at the vet hospital
Client Satisfaction: measurement, tracking and interpretation
in the vet hospital
Advertising in the vet hospital
4) Strategy and Planning
– Business Plan for a Vet Hospital
– Balanced Score Card for a Vet Hospital
– Financial and Operating Ratios (AVEPA Practice Management
Report 2004)
– The role of the Practice Manager
– Organizational Architecture at the Vet Hospital
– Management Information Services in the Vet Hospital
– Process definition and standarization
– Competitive Strategies for Veterinary Hospitals
– Growth Strategies for Veterinary Hospitals
– Succession, retirement, selling-out...
– Business Ethics for veterinarians
For further information contact AVEPA
E-mail: [email protected]
Editors note
The use of the words ‘Veterinary Hospital’ in the above report encompasses Veterinary Practices employing a manager.
COMMISSIONED PAPER
P atterns in Practice ownership:
a UK perspective
F. J. Marshall(1)
B
A
C
K
G
R
O
U
N
D
Veterinary practices in the United Kingdom were formerly often based in market towns in agricultural areas.
Companion animal practice was usually carried out as an adjunct to agricultural practice. With the increase
in pet ownership during the second half of the twentieth century some genuinely mixed practices, whilst
remaining as agricultural practices, began to provide more specialised companion animal services often with
veterinary surgeons dedicated to the latter. In addition many new practices developed devoted solely to
companion animals. Some of these became very sophisticated in the services offered.
The concept of the Veterinary Hospital developed throughout the latter half of the century with practices
offering highest quality services with round the clock availability of such quality services, using resident nursing
staff employed to care for in-patients and who could summon veterinary surgeons when required.
Many other practices offered at their central site a high level of daytime service equalling the level of service
of Veterinary Hospitals but did not provide resident night-time care. Some offered services during limited
hours at branch surgery sites with any in-patient services provided at the central surgery. Some Veterinary
Hospitals equally offered centralised hospital standard care for their transferred branch-surgery patients.
OWNERSHIP
This paper was commissioned
by FECAVA for publication
in EJCAP
Ownership of practices in Great Britain has
traditionally varied from one veterinary surgeon,
often employing others, to partnerships of
several veterinary surgeons, again often
employing other veterinary surgeons. Whatever
the pattern, ownership of practices always
remained in the hands of veterinary surgeons as the regulations
of the governing (statutory) body, the Royal College of
Veterinary Surgeons (RCVS), forbade any alternative.
Management of practices was generally carried out by one or
more of the partners. They were seldom (with a few exceptions)
experienced in management, either in respect of financial or
personnel (staff) matters. As long as the practice appeared to be
profitable and sufficient income was obtained to enable the
partners to enjoy whatever lifestyle they wished, the practice was
assumed to be successful, to be ‘doing OK’.
During the sixties and seventies there grew a
greater awareness of commercial business
realities. No longer could services be provided
without an appreciation of the need for
commercial success of a veterinary practice as
a business. Practices could not continue to give
indefinite free credit to local farmers just because his family had
been clients for many years.
Some practices responded to these pressures by recruiting
‘Practice Managers’ who had management experience but,
initially, little knowledge of the realities of veterinary practice.
Others enabled partners (or employees) to learn and then
implemrnt management practises whilst remaining employed
within the practice. From this concept has developed the, now
very well founded, Veterinary Practice Management Association.
(1) F. J. Marshall B.V.M.S. M.R.C.V.S. 2 Lake View, Wakefield , GB-WF27SN
101
REGULATORY CHANGES
Whilst taxation issues impinged on the owners of some larger
practices or groups, leading them to look at other options of
ownership, the RCVS continued to maintain that ownership of
a practice could only be by individual veterinary surgeons, either
singly or in partnership. As far as the RCVS was concerned, any
disciplinary action by RCVS for infringement of rules of
professional conduct could only be taken against an individual
veterinary surgeon and not against a partnership or against any
company which owned a veterinary practice.
During the last decade of the century, commercial pressures
upon some practices led to their wishing to become
incorporated as Limited Companies. The RCVS, having taken
legal advice, relaxed its regulations to allow companies and nonveterinary surgeons to own practices. Whilst many practices
remain in traditional veterinary ownership a number of new
models have emerged.
Picture 2: ‘A neutering and vaccination Clinic’
which, whilst containing veterinary practices, offer what is
conceived as a one-stop shop for pet owners (Picture 1). These
premises provide a wide range of food products, pet accessories
and related items but also offer grooming, boarding and dogtraining along with meeting and lecture rooms which are used,
amongst other groups, by a leading provider of Veterinary Nurse
training. In the Veterinary Clinic work up protocols and pricing
are rigidly controlled by the management. As yet, the writer is
not aware of plans for further similar sites.
NEW MODELS
Large Group Practices
Various alternatives of practice ownership and management
have developed. There are some large groups of practices under
single veterinary ownership with multiple premises and many
employed veterinary surgeons. Such groups exist mostly in areas
of dense population. Many of these large groups, and even
some under single ownership, have incorporated as ‘limited
companies’ for taxation purposes.
(There are lower tax rates on Companies than on individuals plus
other fiscal and legal advantages)
Vaccination and Neutering Clinics
There is a small number of practices, usually in areas of dense
population, which style themselves as Vaccination and
Neutering Clinics. These offer basic services in, as the name
The ‘One stop concept’ – all Petcare onder one roof
A company which owns 400 premises in the United
States has opened two sites in the north of England
Picture 1: The One stop Pet care resort
suggests, vaccination and neutering, plus microchipping and
worm and flea control, often at prices lower than at conventional
practices. (Picture 2). They do not offer any general veterinary
treatment, clients being directed to neighbouring onventional
practices for this pupose. In general, these neighbouring
102
F. J. MARSHALL
CORPORATE GROUPS
practices also have to provide any necessary emergency
treatment for post-surgical complications.
In the UK there are two main companies operating as corporate
groups. One was started by a veterinary surgeon, the other by
people with great experience of the veterinary profession
through working in the pharmaceutical industry. Each obtained
finance through venture capital and gradually purchased new
practices as existing owners sought to sell. In some cases the
sale was prompted by the inability of the vendor to find other
veterinary surgeons willing to take on the responsibity of practice
ownership.
Relationships with such neighbouring conventional practices
can be troubled but in most cases initial resentment has soon
settled. The main claim of such clinics is that they encourage
responsible ownership by increasing the numbers of vaccinated
animals and decreasing the pool of unwanted puppies and
kittens without competing with conventional practices for
mainstream veterinary services. The clinic shown in picture 1
is owned by a group with several conventional clinics within a
ten-kilometre radius so it can provide its own out-of-hours
service.
In each case the practice continues to operate under its previous
identity and is reponsible for local management, working to
agreed budgets for both income and expenditure and with
specific profit targets. The clinical director in each practice
reports to managers who take overall responsibility for a number
of practices and who may, or may not, be either veterinary
surgeons or other directors of the company.
Out of hours clinics
Out of hours services in many areas of the country are now
provided by specialist clinics, some of them operating from
purpose-built premises and others using premises occupied
during the day by conventional practices. Some of these out of
hours clinics are owned by existing practitioners whilst others
are groups under the ownership of companies set up specifically
for the purpose (Picture 3).
The central office takes decisions on company policy in relation
to suppliers of pharmaceuticals, IT services, stationery etc. It also
supplies support services in matters of human resources,
discipline, payroll management, payments to suppliers,
VAT(TVA/IVA) etc. A committee comprising a number of
clinical directors agrees policy towards choice of
pharmaceuticals, diet products and other supplies. The central
office then negotiates best rates with suppliers in order to
maximise profit margins.
Two additional but especially important new models of
ownership are gradually spreading throughout the UK. These are
corporate groups and joint-venture partnerships. As stated
above, veterinary surgeons are seldom trained in business
practices and each of these new models removes the
responsibility for business management from the veterinary
surgeon, allowing them to concentrate on doing what they do
best – to be a veterinary surgeon.
Because the practices which have been purchased have mostly
been well-established multi-vet practices there has been little
evidence to clients of any change, especially when the former
owners have remained working in the practice to ensure
continuity. This continuity has also been facilitated by the
premises remaining as they were, without changes being made
to show the transfer of ownership. Thus branding of the group
is usually evident only on stationery and on client-related items
Picture 4:‘There is no evidence that the practice is part of a
Corporate Group’
103
Picture 5:‘There is a stong branding of design and décor’
initial financial outlay than is likely to be required by those
choosing to ‘put up their plate’* or to buy a share in an existing
partnership. In addition, anyone choosing to start a new practice
has to take the risk that the location chosen may not be ideal,
whereas , in the case of JVP’s the company chooses sites only
after extensive research into the demographics of the proposed
location.
such as vaccination certificates. Picture 4. shows such a practice
where there is no evidence on the frontage that it is one of
more than thirty premises around Britain owned by the same
company.
Virtually all these JVP practices are new. In consequence they
tend to have only one or two veterinary surgeons initially
although some have now been established long enough to
become multi-vet practices. One of the groups operates from
stand alone premises, sometimes adaptations of existing
buildings but in other cases using newly-built commercial
premises (Picture 5). The other group has several veterinary
surgeries within pet superstores on large retail parks and, in
addition, a few stand alone sites.
JOINT-VENTURE
PARTNERSHIPS
As with the corporate groups, in the UK there are two main
joint-venture partnership groups. In contrast to the former,
however, there is a strong branding which extends from décor
of premises to stationery to uniforms and even to special
promotional offers. Picture 5 shows two separate premises of
one of the groups and the strong branding can be seen in direct
contrast to the premises in Picture 4.
Each group seeks to capture clients from the existing client base
of other practices by offering a more personalised approach
(easy when you are the only veterinary surgeon in a clinic and
thus the only one the client ever sees), and also by offering a
more comprehensive service. Special offers are made in order
to encourage clients to move from other practices. Many existing
practices have been resentful of the opening of JVP practices in
their areas but there is evidence that market extension occurs,
as with the limited service clinics, with clients who had never
previously visited a veterinary practice beginning to do so and
free to transfer their patronage to those existing practices.
Ownership of the practice is, as the term Joint-Venture
Partnership (JVP) suggests, jointly between the company and the
partner or partners who manage the practice. The company
seeks sites which it then equips so that the practice is presented
to the partners in a key in hand situation. The partners introduce
capital which entitles them to work in the practice but also have
a certain amount of debt towards the company. The aim is that
this debt is repaid over a period of time out of the retained
profits of the partner(s).
CONCLUSION
As with the corporately-owned practices, management aspects
are organised centrally. Only individual promotional decisions
are be taken locally, often with central control over policy even
when budgetary aspects relate to the local practice. A number
of promotional offers are determined centrally are valid in any
practice in the group. The central company is paid a percentage
of practice profit for these management services and the JVP
retains the remainder after redemption of the initial loan from
the company.
Many different new types of practice have been descibed above.
The most significant are the final two viz. corporate groups and
joint-venture partnerships.
These two emergent styles of practice are growing but do not
have the momentum which might suggest that they will entirely
replace the older patterns. In particular it remains to be seen how
long Joint-Venture Partners will remain within such JVP
arrangements rather than opting to establish their own
independant practices without the need to pay part of their
profit for a centralised management service.
The main attraction of a JVP practice to the young veterinary
surgeon is the opportunity to own a practice with much lower
*start a practice totally independantly.
104
BOOK REVIEWS
opinion. Finally there are significant differences between the
colour reproduction of the haematology pictures that was
probably not apparent in the original smears.
I would recommend this book as a colour atlas of the
diagnosis of diseases of falcons. However it would not be a
good choice if a veterinarian wanted a single book for
treating birds of prey: look at the book before you buy it.
Colour Atlas of Falcon Medicine
Renate Wernery, Ulrich Wernery, Jörg Kinne and Jaime
Samour
Published by Schlütersche,
(www.schhlueterche.de) 144 pages,
378 illustrations, Hardback,
ISBN 3-89993-007-X €94, £76
Dr. N. H. Harcourt Brown (UK)
Ear, Nose, Throat and Tracheobronchial Diseases in
Dogs and Cats.
The title ‘A colour atlas of falcon
medicine’ gives a guide to the
contents of this book. The vast
majority of the book is about a
single family: Falco, although there
is a small amount concerning species that these birds eat or
hunt. The atlas contains a huge number of good quality
pictures illustrating many aspects of falcon disease.
The book is divided into several sections: Falcons and
falconry in the Middle East; haematology and blood
biochemistry; then viral, bacterial fungal and parasitic diseases
followed by two sections concerned with miscellaneous and
unknown diseases. Lastly there is a section about vaccination
of these birds which has been used in an attempt to prevent a
number of serious diseases.
The falconry section is an interesting overview of falconry in
the Middle East. It is not quite the same as falconry in Europe
especially regarding the use of live pigeons to ‘train’ the
falcons to kill their prey.
The haematology section will prove extremely useful to
anyone wishing to learn about or carrying out falcon
haematology. Much of the information can be extrapolated to
other avian genera. There is useful information for novices
about blood collection and blood film preparation techniques.
There is a description of automated counting systems that
explains the pitfalls of these techniques. There are a lot of
useful tables of normal falcon haematology values which are
followed by many excellent pictures of the normal and
abnormal blood cells. This is complemented by sections on
abnormal haematology throughout the rest of the book. A
similar approach is made with blood biochemistry. This
section would certainly encourage clinicians to examine
blood smears, a procedure which every avian veterinarian
should perform.
The rest of the book is devoted to the diseases seen in falcons
in the Middle East, which are shown as clinical cases, gross
post-mortem specimens, and as histology slides. Worm eggs
and blood parasites are all well illustrated
This is a most interesting book that will be of great use to
anyone that has to deal with a significant number of falcons
(Falco spp.). Veterinarians and technicians studying for further
qualifications would also find this atlas helpful. However I
think that there is a downside: although the book is entitled
‘falcon medicine’ there is no discussion of treatment or
prognosis of the conditions illustrated. Another complaint is
that there are many useful and interesting comments that
would have been even more valuable if they were referenced.
It is difficult for the reader to know what is fact and what is
Anjop Venker van Haagen
Published by Schlütersche,
( www.schluetersche.de) 248 pages,
182 illustrations, Hardback,
ISBN 3-87706-635-6 €89, £71
Ear, Nose and Throat symptoms are
common among the clinical
problems found in the daily caseload
of veterinary surgeons dealing with
companion animals. Inflammatory,
degenerative and neoplastic diseases are common diagnoses.
Although the symptoms may be very easy to detect, it is often
very difficult however to reach a proper evaluation of the
problem and reach a precise final diagnosis. In fact to achieve
this, a detailed knowledge of the anatomy and the
physiopathology is required and this has to be supported by
adequate equipment and diagnostic techniques.
This book provides precise and detailed information
concerning the anatomy, the functions, and the way to
approach the physical examination. It continues with the
diagnostic techniques, the classification of the disease, the
differential diagnosis and eventually the correct treatment of
each case. An ENT workup is usually a complex mixture of
both clinical and surgical approaches and a good knowledge
of both these aspects of the patient is necessary.
The book is divided into six sections covering the ear, the
nose and nasal sinuses, the pharynx, the larynx, the trachea
and bronchi and ending with an interesting chapter on cranial
neuralgias and paralysis. The pictures, tables and drawings
are presented in an exquisite way, being detailed, perfectly
printed and easy to interpret. Every topic is comprehensively
covered with pictures detailing clinical signs, diagnostic
imaging examples and histopathology features. It is a book
that will help both the student in the study of these diseases
and the experienced practitioner in approaching cases which
are difficult to treat.
The high level of experience of the author, an internationally
recognised authority in this field for many years, guarantees
the quality of the information contained in this book. Dr
Venker van Haagen also chairs the Scienific Advisory
Committee of the World Small Animal Veterinary Association
(WSAVA).
Dr. Claudio Brovida (I)
106
BOOK REVIEWS
My overall impression is of a useful and accessible guide with
up to date information on canine and feline behaviour
problems; extended with features like ‘summary textboxes’
and ‘immediate action’ boxes that provide key information for
problem cases and behavioural emergencies. To conclude,
this book will be a helpful tool in everyday practice and is
highly recommended for veterinary practices with interest in
behaviour.
Dr. Tiny De Keuster (B)
Behaviour problems in small animals – Practical
advice for the veterinary team
Jon Bowen and Sarah Heath.
.
Published by Elsevier Saunders,
(http://intl.elsevierhealth.com.vet)
283 pages, Paperback (2005),
ISBN 0702027677 €39,95, £26.99
Notes on rabbit internal medicine
This book is an excellent and
practical guide for the veterinary
practitioner. The content covers
behaviour problems in cats and
dogs, and is divided into 4 Parts and
16 Chapters.
Part one contains a range of practice tips on how to provide a
behavioural service as well as preventive behavioural care
such as how to run puppy & kitten classes. Part two contains
the basic tools used in behavioural medicine: an introduction
to canine and feline social behaviour and communication,
followed by an excellent chapter on learning theory and
behaviour modification. In the next chapter the authors clarify
the role of pharmacology in behavioural medicine: the classes
of psychoactive drugs, management of drug therapy, case
selection, monitoring and the termination of treatment, are
tackled in a comprehensive way. I was particulary pleased to
see that the authors repeatedly explain the limitations and
pitfalls of drug therapy, for example that drugs are not a
substitute for a behavioural work up. The last chapter of part
two describes the management of ageing dogs and cats, the
diagnostic tools to recognize cognitive impairment and
dementia, as well as treatment and prognosis options.
Part three covers canine behavioural problems: canine fear,
anxiety and phobia related disorders, canine compulsive
disorders, canine elimination problems and canine aggression
problems. Part four covers feline behavioural problems: feline
fear, anxiety and phobia; feline compulsive disorders, feline
house soiling, marking and feline aggression problems.
Each of these chapters take into consideration the physiological and neurochemical underlying mechanisms, diagnosis,
prognosis, summary of treatment methods as well as
comprehensive counselling advice. On top of the excellent
guidelines on behavioural problem solving, the book is
illustrated with beautiful drawings and pictures. The book
concludes with suggestions for further reading which is
unfortunately quite short, and appendices containing referral
forms and very useful cat and dog handouts.
However, a few minor shortcomings of this book need to be
mentioned. In the preface the authors explain the reason why
no references at all are cited in the text (to keep it readable).
In my opinion, the book would benefit from adding scientific
references in order to allow the practitioner to read more in
depth and to clarify the origin of provided information.
Further, there are some discrepancies between the
information provided in different chapters (chapter 6 and 8)
concerning the indication of SSRI’s in canine aggression and
the SSRI’s anticholinergic side effects.
Richard Saunders and Ron Rees Davies
Blackwell Publishing Ltd.
(www.blackwellpublishing.com)
240 pages, Paperbck (2005),
ISBN 1405115149 € 44 (approx),
£29.99
Rabbits are the third most popular
animal kept as pets, and in recent
years both the interest from
veterinary surgeons and the
expectations of rabbit owners has increased considerably. A
number of texts on rabbits have been published, either as a
section within a book or as a book devoted completely to
rabbits. However whilst some of these books have been
excellent there has been little attempt to approach rabbit
medicine from the point of view of differential diagnoses,
which this book does. It leads the reader through the
possibilities for various clinical signs in a systematic way,
rather than taking an individual disease approach. It is written
in note form, which helps to make the information readily
available, and is therefore intended as an accessible reference
text.
As well as the section on differential diagnoses, there is a
major section on organ systems, which complements this
approach. This section includes information on the feeding
and nutrition of rabbits, as well as listing the causes of
disease, clinical signs and treatment within each organ system.
In addition there is a comprehensive section on laboratory
findings, with lists of conditions that cause an alteration in the
normal parameters of blood cells and biochemistry. The small
section on therapeutics concentrates on the areas of treatment
that differ from the more common species in small animal
practice.
Some diseases, especially infectious ones, do not readily fall
within a single organ system, and these receive individual
attention in a separate section of this book. There is an
extensive bibliography that will allow additional information
to be found if required. A thorough contents and index are
helpful in locating the information contained within these
notes, although it is all laid out in a logical way.
This book would certainly find a useful place in any practice
treating rabbits, although being a medicine text it may need to
be complemented by other information sources for
anaesthesia and surgery.
Dr. Owen Davies (UK)
107
BOOK REVIEWS
up-most quality and in black and white, which allows the
reader to interpret them with his/her own colour references,
depending of the laboratory techniques and nuances. Last but
not least the most appropriate references are listed at the end
of each subchapter.
The second part of the book describes in detail all the
epithelial and mesenchymal neoplasms of the skin (in 5 and
11 subchapters respectively). The classification and
terminology are based on World Health Organization
standards. Clinical and histopathological characteristics of
tumours are described, often with a comparison of their
human counterpart. There are beautiful histopathological
illustrations in black and white and in colour for
immunohistochemical stainings, indispensable in many
instances. Most appropriate references appear at the end of
each subchapter.
This book offers a magnificent clinical and histopathological
description of all the non-neoplastic skin diseases and
neoplastic skin tumours of dogs and cats known at the
beginning of the 21st century! Furthermore it gives additional
information on pathogenesis, epidemiology, and comparative
dermatology and dermatopathology. The 944 page text is
exhaustive, perfectly written and in total there are 1250
superb clinical and histopathological illustrations.
Diagnosis is an art in both dermatology and dermatopathology, a discipline by itself. When biopsies are done, this art
establishes the link between clinical signs and microscopic
signs through the indispensable “anatomo-clinical relation”.
This book is all about it.
Charles Leblois (1892-1955), the founder of the French School
of veterinary dermatology, wrote in 1926 “Diagnosis is an art I
pursue with passion”*. There is no doubt that the authors also
have this deep passion!
Indeed, every general practitioner interested in dermatology,
every histopathologist interested in the skin and a fortiori
every dermatologist and dermatopathologist should have this
book, a masterpiece, permanently to hand.
Skin Diseases of the Dog and Cat
Clinical and histopathologic diagnosis- Second edition.
Thelma Lee Gross, Peter J. Ihrke, Emily J. Walder,
Verena K. Affolter.
Blackwell Publishing Ltd.
(www.blackwellpublishing.com) 944
pages, Hardback (2005), ISBN:
0632064528, €215, £149.50,
Approx
This is the second edition of what is
already a remarkable work, i.e. the
first edition published in 1992 by the
first 3 authors.
The first impression is as follows: this is a big heavy book,
with a good hard cover; you do not have in your hand
another small dermatology manual or colour atlas. In
addition the quality of the paper is extremely good and the
layout is very nice. This renders the book easily readable, i.e.
to be open for studying as well as when you need it in a
particular clinical situation. Furthermore, the contents at the
front and index at the back are both highly comprehensive.
The first part covers inflammatory, dysplastic and
degenerative diseases, and is divided in chapters about the
epidermis, the dermis, the adnexa and the panniculus. In
each chapter, patterns are envisaged systematically in
subchapters: 8 for the epidermis, 7 for the dermis, 5 for the
adnexa, 1 for the panniculus. This is a morphological
classification. For all the diseases however, the authors have
put together the pathogenesis, predilections, clinical features
including updated nomenclature, comparison to human
diseases, and cutaneous histopathology of these diseases,
including biopsy site selection. Inevitably, some diseases are
divided in two chapters e. g. pemphigus foliaceous, discoid
lupus erythematosus, feline eosinophilic plaque and ulcer,
dermatomyositis, etc, but this had to be expected as many
diseases affect several components of the cutaneous tissue.
Clinical pictures, all in colour, illustrate ideally the typical
aspects of the diseases. Histopathological pictures are of the
*‘Diagnostiquer est un art que je sers avec passion’, in ‘DOCUMENTS
pour servir à l’Edification d’une DERMATOLOGIE ANIMALE (Chien
et Chat)’ Vigot Frères, Paris, 1926
Dr. Didier-Noel Carlotti Dip ECVD (F)
108
BOOK REVIEWS
veterinary practice such as “Demodex canis is a prostigmatid
mite” (“prostigmatid” describes a subclass of mites) contribute
to the enormous volume covered. The reader may thus get
the impression that the book was composed for veterinary
practitioners and students instead of veterinary nurses and
technicians.
The first edition has still a number of errors, such as in
spelling (e.g. “Demodex follicuarium” instead of the correct
term “Demodex folliculorum”) or in a figure where the reader
has to understand that A, B, C in the text corresponds to 1, 2
and 3 in the drawing. The light microscope expandeded for a
better perception of its parts shows among others a reflecting
mirror. Today such types of microscopes are usually found in
museums and are not used in practice.
Taken as a whole, the manual is very promising. It is hoped
that the second edition will correct the errors.
Veterinary Dermatology
A manual for nurses and technicians
Francis Gaudiano, Cathy Curtis
Published by Elsevier Saunders
(http://intl.elsevierhealth.com.vet)
241 pages, Paperback.
ISBN 0750 8804 1, €39,95, £26.99,
Skin problems are the most common
disorders seen by veterinarians in
small animal practice. Veterinary
nurses and technicians are regularly
involved in the management of
dermatological conditions including
diagnostic and therapeutic procedures.
A manual on veterinary dermatology for nurses and
technicians has been needed for a long time as a source of
reference and as a guide to nurses and technicians entering
the field of dermatology. This book is published in
paperback binding and has 241 pages.
After an overview on the structure and function of the skin 12
chapters cover dermatology clinics, diagnostic tests, skin
diseases caused by ectoparasites, bacteria and fungi, skin
allergies, endocrine, metabolic and paraneoplastic disorders,
keratinisation and pigmentation disorders, ear diseases,
autoimmune skin diseases, tumours, wounds, and
dermatological conditions in exotic pets (13 chapters in total).
The chapters are well structured and the text is overall easy to
read. Glossaries of terms and case studies are very helpful in
the understanding of complex contents. Exceedingly rare skin
diseases such as Lichenoid psoriasis in English Springer
Spaniels and information beyond the normal scope of daily
Hans-Joachim Koch Dip ECVD (D)
VÖK CONTINUING EDUCATION SEMINARS 2006
INDEX OF ADVERTISERS
Company
Page
AFFINITY PETCARE................ 7
AVID ..................................... 99
BLACKWELL PUBLISHING ..108
CSAVA/FECAVA/ESFM ........ 50
CPD SOLUTIONS ................105
DATAMARS .......................... 94
ECVIM-CA.............................. 20
ELSEVIER SCIENCE ............. 109
ESFM..Inserts in some countries
ESVOT ................................... 49
EVDS ................................... 72
HELAPET ............................. 62
Advertorial ............................. 62
HILL’S PET NURTITION.............
Inside front Cover and page 26
Company
All to be held in Austria in the German Language
Page
22 - 23 April
Seminar on Practice Management/
Marketing “Optimization of the
Veterinary Practice”
20 - 21 May Vienna Seminar „Clinical Update for Practising
Vets - From Practitioners for
Practitioners“
27 May
Steyr VÖK Intensive Seminars on
03 June
ULTRASOUND. Each Seminar has a
30 September
maximum number of 10 participants –
07 October
Early reservation essential!
06 June
Vienna 13th ROYAL CANIN/Waltham® Seminar
on DIETETICS Gastrointestinal diseases
in the dog and cat”
28 – 29 Oct. Vienna VÖK Seminar on ONCOLOGY (Part 1)
04-05 Nov. Vienna Seminar on Practice Management/
Marketing “Optimization of the
Veterinary Practice”
11- 12 Nov. Steyr
19th VÖK Seminar on ULTRASOUND
“Abdomen – Special Cases”
25 - 26 Nov. Krems 31st VÖK Seminar on X-RAY
04- 05 March Salzburg Bavarian Ethological Seminars “Dog
01- 02 April
education and behaviour”. Reduced fee
13- 14 May
for VÖK and VTÖ members
For further information visit: www.voek.at
or contact: [email protected]
IAMS EUKANUBA .................. 4
IMEX .....................................32
INTERVET ............................ 3
KRUUSE ............................... 71
LIFELEARN ........................... 72
MERIAL....... Inside back Cover
FECAVA/WSAVA/CSAVA....... 6
ROYAL CANIN /WALTHAM ......
.................................Back cover
SVK /ASMPA ..................... 100
SHOR-LINE .........................105
TECKNIK TECHNOLOGY .. 31
WOODLEY EQUIPMENT ...... 9
109
Wels
CALENDAR OF MAIN EUROPEAN NATIONAL MEETINGS
AND OTHER CONTINUING EDUCATION OPPORTUNITIES
A list of the addresses and telephone numbers of the Secretariat or person holding information is attached.
WSAVA & FECAVA Congresses (Red)
National meetings (blue)
2006
8-9 April
19-22 April
20-23 April
22-23 April
AIVPA-FE
NACAM
BSAVA
AVEPA
Pisa
Amsterdam
Birmingham
Seville
Mallorca
Las Palmas
Cremona
Scivac HQ
Verona
Zaragoza
Gijón
Tallinn
2-5 May
SCIVAC
7 May
13-14 May
AIVPA
AVEPA
13-14 May
ESAVA
18-20 May
19-20 May
19-21 May
20-21 May
20-21 May
SVK/ASMPA
SCIVAC
AFVAC/GEDAC
AVEPA
AIVPA-FE
20-21 May
8-10 June
29 June -1 July
7-9 September
7-10 September
14-16 September
16-17 September
21 September
22 September
23-24 September
SAVAB
ESVD
ECVS
ESVD-ECVD
ESVOT
ECVIM-CA
VÖK
ECVBM-CA
ESVCE
WDWE
21-24 September
23-24 September
GSAVA
AVEPA
7-8 October
AIVPA
11-14 October
27-29 October
21-22 October
3-5 November
9 - 10 November
10-11 November
10-11 November
18-19 November
19 November
23-24 November
25-26 November
FECAVA/WSAVA/
CSAVA
AVEPA
AIVPA-FE
SCIVAC
SSAVA
DSAVA
TSAVA
AVEPA
AIVPA-FE
AVEPA
AVEPA
3 December
7-9 Dec
AIVPA
AFVAC
CE course “Feline Radiology”
Voorjaarsdagen
Annual Congress
CE Ophthalmology
CE Trauma
CE Neurology
Practical Course on Rehabilitative
Physiotherapy in dogs
Round Table “Psycho-physical Stress in working dogs”
CE Oncology
CE Cardiology
Annual Congress Ear, nose, throat
diseases-FECAVA supported CE
Interlaken
Annual Congress
Rimini
52nd SCIVAC Congress
Paris (F)
Annual Congress
Santiago
CE Trauma
Parma
CE course “Feline Ultrasonography and
Echography” Theory and practice
Antwerp
Zoonotic diseases
Spa (B)
Workshop (Dermato-endocrinology)
Sevilla (E)
15th Annual Scientific Meeting
Lisbon (P)
Annual Congress
Munich(D)
Annual Congress
Amsterdam
Annual Congress
Salzburg
21st.Annual-Meeting “Ear, Nose and Throat”
Ghent(B)
Current research in behaviour and welfare
Ghent(B)
Welfare and Behaviour: The Science behind the Art
Ghent(B)
10th Anniversary Conference of the Flemish
Working Group on Ethology # Welfare and
behaviour: the science behind the art)
Dusseldorf
52 Annual Congress
Alicante
CE Trauma
Mallorca
CE Ophthalmology
Modena
National Congress “Gastroenterology
surgery updating”
Prague
12th FECAVA/30th
WSAVA/CSAVA Congress
Madrid
National congress
Perugia
CE “Cats and dogs Haematology and Cytology”
Perugia
53rd SCIVAC Congress
Uppsala
Annual meeting
Aarhus
Annual Congress
Istanbul
1st Anadolum Congress
Barcelona
CE Oncology
Messina
Study Day “Feline Dermatology”
Sevilla
CE Trauma
Madrid
CE Oncology
Bilbao
CE Cardiology
Las Palmas
CE Emergency Care
Agnano (Napoli) Seminar “Endocrinology”
Bordeaux
Annual Congress
28 March- 1 April
FECAVA/CSAVS
Dubrovnik
★
★ ★
★
★
★
★
★
★
★ ★ ★
Italian
Dutch, English & Others
English *
Spanish
Spanish
Spanish
English / Italian
Italian
Spanish
Spanish
English
German/French/English
Italian, English
French
Spanish
Italian
Dutch
English
English
English
English
English
German, English
English
English
English
German
Spanish
Spanish
Italian, English
English &
Others
Spanish, English
Italian
Italian, English
Swedish
English/Danish
English, Turkish
Spanish
Italian
Spanish
Spanish
Spanish
Spanish
Italian
French
2007
13-17 April
27-29 April
3-5 May
26-27 May
26-29 August
19-20 October
Last Weekend
November
BSAVA
NACAM
SVK/ASMPA
SAVAB
WSAVA
AVEPA
Birmingham
Amsterdam
Montreux
Antwerp
Sydney (Aust)
AFVAC
FECAVA/CSAVS/ESFM
European Congress
Annual Congress
Voorjaarsdagen
Annual Congress
Obesity Seminar
World Congress
National Congress
★
★ ★
★
★
★
★
★
Annual Congress
* 60 Veterinary surgeons or 70 Nurse Registrants are required for simultaneous translation to be provided
# WDWE Contact: www.behaviour2006ghent.be
110
English and others
★
★ ★ ★
English*
Dutch English and others
German French and English
English Dutch
English and others
Spanish English
French
BSAVA CONTINUING EDUCATION COURSES 2006
All to be held in the UK, in the English Language. When at Gloucester in the BSAVA HQ
11th May
Warrington
Which Bag Do I Chose? Fluid Therapy and Transfusion Medicine
30th May
Hinckley
Feline Modular - Looking through cats eyes: feline ophthalmology made easy
31st May
Gloucester
Small Animal Medicine Modular - Endocrinology II
10th - 11th June
Beaconsfield
Challenges in Emergency Medicine and Critical Care (Medical Bias)
16th-17th June
Oxford
Critical Care and Emergency Surgery - Check Your Own Pulse First
19th-20th June
Bromsgrove
Urinary Tract Surgery: Can’t Go, Won’t Stop: Regulating The Flow
22nd June
Gloucester
"Disorders of the South End of the Dog – Some Surgical Solutions"
27th June
Hinckley
Feline Modular - The Jaundiced Cat
28th June
Gloucester
Small Animal Medicine Modular - Cancer: Presentation to Palliation
2nd-3rd September
Buxton
Spinal Surgery oops!
5th September
Knutsford
Brain cases ? Intracranial localisation makes my head hurt!
7th September
Leicester
"Image is everything, Darling!"
13th - 14th September
Beaconsfield
Amazons to zebra finches: A modern, practitioner approach to exotic avian medicine
28th September
Warrington
This pet has travelled abroad - the risk of exposure to exotic infectious agents
30th Sept -1st Oct
Melton Mowbray The Beginners Guide to Small Animal Diagnostic Ultrasonography
3rd October
Gloucester
Therapeutics Modular - Antimicrobial and Fluid Therapy
4th October
Gloucester
Small Animal Medicine Modular - Upper Urinary Tract
5th October
Gloucester
Small Animal Medicine Modular - Lower Urinary Tract
7th November
Gloucester
Therapeutics Modular - Analgesia
8th November
Gloucester
Small Animal Medicine Modular - Antimicrobial Therapeutics
9th November
Basingstoke
A cavity with a view - Advances in endoscopic surgery
10th November
Basingstoke
Wounds That Make Your Skin Crawl
13th November
Kettering
Understanding Joint Disease
14th November
Kettering
Fixing the Fractured Feline
5th December
Gloucester
Therapeutics Modular - Cytotoxics and Chemotherapeutics
6th December
Gloucester
Therapeutics Modular - Cardiovascular Therapeutics
For Information visit: www.bsava.com or contact: [email protected]
ESAVS CONTINTUING EDUCATION COURSES 2006
All courses to be held in the English language.
Advanced Veterinary Studies
11 - 15 September
2 - 7 October
19 - 24 June
24 July - 4 August
7 - 18 August
5 - 9 July
10 - 14 July
10 - 14 July
13 - 17 September
4 - 8 September
13 - 24 November
21 - 25 October
30 September - 4 October
14 - 18 October
28 August - 8 September
26 June - 1 July
10 - 15 September
Milano / Italy
Salzburg / Austria
Luxembourg
Vienna / Austria
Vienna / Austria
Berne / Switzerland
Berne / Switzerland
Brno / Czech Republic
Brno / Czech Republic
Zurich / Switzerland
Utrecht / Netherlands
Berne / Switzerland
Berne / Switzerland
Berne / Switzerland
London / United Kingdom
Luxembourg
Zurich / Switzerland
Behavioural Medicine II
Cardiology III / Advanced Cardiology
Dentistry II
Dermatology I
Dermatology II
Diagnostic Ultrasound I
Emergency Care I
Endoscopy Intensive Course
Exotic Pets Medicine & Surgery
Feline Medicine & Surgery II
Internal Medicine II
Neurology I,
Neurology II
Neurology III / Advanced Neurology / Neurosurgery
Ophthalmology I
Oral Surgery
Small Animal Reproduction II
Excellence in Veterinary Therapy
1 - 5 November
Palma de Mallorca / Spain
24 - 28 April
Shanghai / China
Small Animal Therapy: Cardiology and Orthopaedics
Optimizing the Management of Clinical Disorders in
Companion Animals: Internal Medicine and Emergency Care
For Information visit: www.esavs.org
ADVANCE NOTICE
2007
2008
2009
BSAVA 13 – 17 April
Voorjaarsdagen 27-29 April
FECAVA/CSAVS 30/3-1/4
AFVAC Last weekend November
SVK/ASMPA 22-24 May (Interlaken)
WSAVA 26 – 29 August(Sydney Aust.)
AVEPA 19 – 20 October
BSAVA 3-6 April
BSAVA 2-5 April
111
AFVAC Last weekend November
FECAVA/WSAVA/ VICAS 23-26 August
SECRETARIAT OR ADDRESS TO CONTACT FOR INFORMATION
(Full Association names are given at the front of the Journal)
AFVAC/
CNVSPA
AIVPA
APMVEAC
AVEPA
BASAV
BHSAVA
BSAVA
CSAVA
CSAVS
DSAVA
ESAVA
FAVP
GSAVA
HSAVA
HVMS
LAK
LSAPS
LSAVA
MSAVA
MVA
NACAM
NSAVA
PSAVA
RSAVA
SAVAB
Secretariat: 40 rue de Berri – F-75008 Paris
Tel: (33) 1 53 83 91 60 – Fax: (33) 1 53 83 91 69
Contact: Dr Giuseppe Tranchese
Via G. Marconi 107 - I-800030
I-800030 Mariglianella (Naples) Italy
Website: www.seltravet.it
Tel: (39) 081 8856776 – Fax: (39) 081 8856622
Contact: Dr. Vieira Lopes
Rua Américo Durao No 18-D/as Olaias
P-1900 Lisboa
Tel: (351) 1 840 41 79 – fax: (351) 1 840 41 80
Secretariat: Paseo San Gervasio 46-48, E7
E-08022 Barcelona
Tel: (34) 93 2531522 – Fax: (34) 93 4183979
www. avepa.es
Director: Dr. Boyko Georgiev
Tzarigradsko shausse 73
Sofia 1113, Bulgaria
Tel: (359) 88 927160 – Fax: (359) 66 44 50
Contact: Dr. Josip Krasni-Alipasina St. 37
7100 Sarajeva – Bosnia and Herzegovina
Secretariat: Woodrow House
1 Telford Way, Waterwells Business Park
Quedgeley, Gloucester GB-GL2 4AB
Tel: (44) 1452 726700 – Fax: (44) 1452 726701
www.bsava.com
Contact: Dr. Jiri Beranek
University of Veterinary and Pharmaceutical
Sciences – Palackého 1/3 – 612 Brno
Czech Republic
Tel: (420) 603 272 796 – Fax: (420) 549246974 *
E-mail: MED.PROD@worldonline .cz
Contact: Dr. Davorin Lukman
Specijalizirana Ambulanta Varazdin
Trnovecka 6,
42000 Varazdin, Croatia
Tel/Fax: (385) 42 331 895
Secretariat: Emdrupvej 28 A, DK 2100 Copenhagen
Tel: (45) 38 71 08 88 – Fax: (45) 38 71 03 22
Contact: Dr. Tiina Toomet
Kopli 4A Tallinn, EE-0004 Estonia
Tel: (372) 6413 11 – Fax: (372) 641 3110
Contact: Dr. Kaj Sittnikow
Ykskoivuntie 32, FIN-23500
Uusikaupunki
Tel: (358) 2 844 2580 Fax: (358) 2 844 2589
E-mail: [email protected] *
Contact: Dr. Angelika Drensler
Gerberstr. 26 – D-25335 – Elmshorn
Tel: (49) 4121 266 369 Fax: (49) 4121 265 895
Contact: Dr. Zsolt Kendik
Isvan u. 2 Budapest H-1078
Tel: (36) 305950750
Contact: Dr. Katerina Loukaki
Protopapa 29, Helioupolis, GR- 163 43 Athens
Tel/Fax: (30) 2109932295
Secretary: Tom Angel
28, rue de Syren – L-5870 Alzingen
Tel: (352) 36 9807– Fax: (352) 36 9807
Contact: Dr. Lita Konopore
Zvaigznáju Gatve 2 Riga, LV-1082
Tel: (371) 7546 366 – Fax: (371) 7606 202
President: Dr. Saulius Laurusevicius
Tilzes 18 – LT-3022 Kaunas
Tel & Fax: (370 37) 363 490
Contact: Dr. S. Cokrevski,
Ul. Lazar Ppo Trajkov 5-7 Skopje, Fyrom
Tel: (389) 91 115 125 – Fax: (389) 91 114 619
Contact: Dr. C.L. Vella
Blue Cross Veterinary Clinic
Msida Road, Birkirkera, Malta
Tel: (356) 225 363 – Fax: (356) 238 105
Director: Dr. Leen den Otter
Dorpsdijk 16 - NL - 3161 KE Rhoon Holland
Tel: (31) 10 5012414
Contact: Kjetip Dahl
PO Box 6781 St. Olavs Plass N-0130 Oslo
Tel: (47) 22 994600 – Fax: (47) 22 994601
Contact: Dr. Jerzy Gawor
UI Chlopska 2a 30-806 Kracow
Tel/Fax: (48) 12 658 8365
Contact: Dr. A. Tkachov-Kuzmin
V-Kojinoi, 23 – 121096 Moscow, Russia
Tel/Fax: (7) 095 921 6376
Contact: Dr. J van Tilburg
Ernest Claeslaan 14 B-2500 Lier
Tel: (32) 3 489 2309 – Fax: (32) 3 480 1942
Contact: SAVAB Flanders: Dr. Leen Verhart
G. Van der Lindenlaan 15 B-2570 Duffell
Fax: (32) 15 31 73 90
SCIVAC
Secretariat: Palazzo Trecchi
Via Trecchi 20 – I-26100 Cremona
Tel: (39) 0 372 460440 – Fax: (39) 0 372 457091
www.scivac.it
SkSAVA Contact: Tibor Brauner
Uhrova 1
831 01 Bratislava
Slovak Republic
Tel/Fax: (421) 7 54 78 80 93
SMASAP Director: Denis Novak
Dr Ivana Ribara 186/30, 11070 Belgrade, Serbia
Tel/fax: (381) 11 2851 923; (381) 11 382 17 12;
(381) 11 2604 289
E- mail: [email protected]
SSAVA
Contact: Dr. Anne Carlswärd
Jönköping Small Animal Hospital
Oskarshallsgatan 6 – 8-553 03 Jönköping
Tel: (46) 36 34 18 80
Fax: (46) 36 34 18 85
SVK/
Contact: Dr. Peter Sterchi
ASMPA Mühlegrund – CH-3807 Iseltwald
Tel: (33) 845 11 45
SZVMZ Contact: Dr. Zorko Bojan
Veterinary Faculty, Gerbiceva 60,
SLO-1000 Ljubljana, Slovenija
Tel: (386) 14779277 – Fax: (386) 647007111
TSAVA
Director: Prof. Mustafa Aktas
University of Istanbul- Faculty of Veterinary
Medecine, Dept. of surgery. Avcilar Campus.
34320-Avcilar/Istanbul-Turkey
Tel: 0212-4737070/17297 – Fax: 0212-4737240
USAVA
Contact: Dr. Vladlen Mykhaylovich USHAKOV
8 Filatova str., Apartement 24,
Odessa 65000, Ukraine
Tel.: (380) 503369810 Fax: (380) 482 606726
VICAS
Contact: Dr. Peter A. Murphy
Summerhill Veterinary Hospital, Wexford,
Co. Wexford Ireland
Tel: (353) 53 43185 – Fax: (353) 53 43185 by request
www.veterinary-ireland.org
VÖK
Contact: Silvia Leugner
Royal Canin Österreich GmBH Hietzinger
Hauptstrasse 119, A-1130 Wien
Tel: (43) 1879 1669 DWI8 - Fax: (43) 18791669-11
Associate members
ESAVS
ECVD
ECVS
ESFM
ESVC
ESVCE
ESVD
ESVIM
ESVN
ESVOT
EVDS
EVSSAR
Contact: EAVS Office Birkenfeld, Schadtengasse 2
D-55765 Birkenfeld
Tel: (49) 6782 980650 – Fax: (49) 6782 4314
Contact: Dr. Dominique Héripret
Clinique Vétérinaire Frégis
43, avenue Aristide-Briand F-94110 Arcueil
Tel: (33) 149 85 83 00 – Fax: (33) 149 85 83 01
Contact: Executive Secretary – ECVS Office
Winterthurerstrasse 260, CH-8057 Zürich
Tel: (41) 44 635 84 08 – Fax: (41) 44 313 03 84
Contact: Claire Bessant
Taeselbury, Highstreet, Tisbury, Wiltshire,
GB - SP3 6LD, UK
Tel: (44) 1747 871872 - Fax: (44) 1747 871873
E-mail: [email protected] or [email protected]
Contact: Dr. Chris Amberger
96, rue de la Servette CH-1202, Geneve
Contact: Dr. Sarah Heath
11 Cotebrook Drive, Upton, Chester GB-CH2 1RA
Tel: (44) 1244 377365 – Fax: (44) 1244 399288
E-mail: [email protected] or:
[email protected]
President: Chiara Noli E-mail: [email protected]
Tel: (33) 149 85 83 00 – Fax: (33) 149 85 83 01
Contact: Prof. Jean-Pierre Cotard
Ecole Nationale Vétérinaire d’Alfort
7 avenue du Général de Gaulle
F-94700 Maisons-Alfort
Tel: (33) 1 439 67162 – Fax: (33) 1 489 38761
www. vet.uu.nl/esvim/www.ecvimcongress.org
www.ecvimcongress.org
Contact: Dr. Gualtiero Gandini
Dipartimento Clinico veterinario
Facoltà di Medicina Veterinaria
Università degli Studi di Bologna
I-Via Tolara di Sopra 50
I-40064 Ozzano Emilia (Bologna)
[email protected]
Contact: Dr. Aldo Vezzoni, SCIVAC
Palazzo Trecchi 20 – I-26100 Cremona
Tel: (39) 0 372 23451 Fax: (39) 0 372 20074
www.esvot.org
Contact: Dr. Margerita Gracis
Piazza del Carmine 2 I-20121 Milano
Tel: (39) 2 338 187 4498 – Fax: (39) 02 878 353
E-mail:: [email protected]
Contact: Dr. Catherina Linde-Forsberg
Department of Obstetrics and Gynaecology
PO Box 7039
Swedish University of Agricultural Sciences
SE – 750 07 Uppsala

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