IMR Bulletin Dec 1993

I
quarterly 6uCCetin
Disember 1993
No. 30
ISSN : 0127 .0265
KANDUNGAN
fl
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Maklumat perubatan dan kesihatan di tahun 2020 .............................................
1
Tinjauan ke atas perubahan-perubahan ekologi
di kawasan projek hidro-letrik Pergau .............................................................
3
Ringkasan Penerhitan-Penerbitan IMR
4
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6
........................................................................ ..............
8
Tesis-tesis Sarjana Sains
Kursus dm Bengkel
.......................................................
Projek Penyelidikan dalam Penyakit Tropika IMR-JICA
.................................... 11
CONTENTS
/
Medical and Health Informationfor the year 2020 ...........................................
Deoxyribonucleic acid (DNA) analysis by flow cytometry .................................
Medico-ecological studies in the Pergau Hydroelectric Project area ...............
Abstracts of IMR Publications ......................................................................
M . Sc . Theses ....................................................................................................
Courses and Workshops ..................................................................................
IMR-JICA Collaborative Project ....................................................................
Visiting Scientist ..............................................................................................
Obituary ...........................................................................................................
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GAMBAR KULIT
COVER PHOTOS
PROJEK EMPANGAN PERGAU
PERGAU DAM PROJECT
1. Meratakan tanah .
I . Clearing of land .
2.' Penempatan sementara pekerja.pekerja .
2 . 'Iemporary quarters for workers.
3 . Pembinaan terowong .
3. Construction of underground tunnel .
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Artikel Utama
(J.L. F~I-nnnrkrK i t a kini berada di era Teknologi Maklumal
(IT). Setiap individu bercakap tentang IT. Maklumat memberi kelebihan tambahan kepada
seseorang. Setiap negaradan bidang perniagaan
serius tentang IT. Maklumat mengenai produk
baru/barangan keluaran terbaru, pasaran, teknologi terbaru, dll. telah memberi kelebihan
pada sesebuah negara, perniagaan atau untuk
menangdalam persaingannya. Begilujuga halnya
dalam bidang perubatan dan kesihatan.
Sudah tiba masanya para profesional di bidang
perubatan di Malaysia memberi perhatian terhadap IT dan mengambil peluang ini hagi
memenuhi keperluan bidang masing-masing. Para
klinisian, pentadbir, penyelidik, dll. akan
nlendapati bahawa banyak maklumat dalam bidang mereka dengan hanya meluangkan beberapa
rninit untuk mendapatkannya. Terdapat maklumat dalam setiap topik dan maklumat ini adalah
sangat bernilai kepada setiap individu dan tugas
mereka samada dal am bidang diagnosa,
pengendalian penyakit, pentadbiran atau
penyelidikan.
Di sektor perubatan, yang berkaitan dengan
kesihatan dan kesejahteraan hidup setiap
individu, membuat keputusan berdasarkan fakta
adalah amat penting dan keputusan ini dibuat
herdasarkan maklumat yang sedia ada. Maklumat tersebut mungkin sempit, terhad dan
ketinggalan zaman atau juga has, menyeluruh
dan terkini. Bidang kesihatan merupakan aset
Irelr~nd
yarlg arna~yenli~~g
dan pasGnya seliapkeputusan
yang dibuat harus berdasarkan kepada maklumat yang terkini.
Tiada perlu dipertikaikan bahawa setiap
profesional di bidang kesihatan mempunyai
pengetahuan masing-masing dalam menangani
masalah klinikal, pentadbiran atau penyelidikan
yang di hadapi. Bagaimmapun, tidak harus
dilupakan bahawa program pendidikan adalah
dirancang untuk memenuhi keperluan asas bagi
pelajar untuk berfungsi sebagai seorang
profesional dm pengetahuan begini, merupakan
permnlaan kepada proses pembelajaran yang
berterusanke arah kehidupan seorangprofesional.
Sejak Perang Dunia ke-2, penulisan di bidang
sains, termasuk perubatan telah berkembang
denganpesatnya. Fenomenaini sering dirujukkan
sebagai 'ledakan maklumat' . Justeru itu individu
tidak mampu untuk mengemaskini pengetahuan
seiring dengan kepesatan penulisan. IT
berkembang untuk memenuhi keperluan ini, iaitu
pengumpulan dan penyebaran maklumat. Satu
daripada keluaran terkini IT di pasaran ialah
dalam bentuk cakerapadat iaitu CD-ROM (Compact Disc - Read Only Memory). Media ini
berkeupayaan menyimpan maklumat sehingga
270,000 mukasurat teks dalam cakera yang
berukuran 4.7 inci. Kelebihan cakera padat
adalah berkeupay aan membuat pencarian secara cepat, tepat, akses rawak, menggunakan
pelbagai terminologi dan medan.
Artikel Utama
Pengumpulan maklumat di bidang yang khusus,
membina pangkalan data dan menyimpan maklumat dalam satu format yang sama merupakan
satu projek besar dan pihak swasta, juga badan
kerajaan telah pun mengambil peluang ini. Pelbagai pangkalan data boleh diperolehi dalam
bentukcakerapadat (CD-ROM), dari yangkhusus
dalam satu bidang sahaja kepada yang meliputi
seluruh bidang perubatan.
pentadbiran personel, kawalan kualiti,
peraturan, perkhidmatan dan tenaga manusia.
4.
Antara pangkalan data yang popular adalah seperti berikut :MEDLINE - keluaran National Library of
Medicine, USA, yang mengindeks artikel
daripada lebih 3,300 jernal terpilih di
bidang bioperubatan (biomedical). Versi
cetak MEDLINE ialah 'Index Medicus'.
Pangkalan data ini merangkumi penulisan
bioperubatan, termasuk klinikal amali,
penyelidikan, pentadbiran, isu-isu mengenai dasar dan perkhidmatan penjagaan
kesihatan.
2.
3.
EMBASE - keluaran Excerpta Medica,
anak syarikat Elsevier Science Publishing, Amsterdam, The Netherlands. Ia
mempakan pangkalan data bioperubatan
dan farmakologi, meliputi bahan yang
diterbitkan dalam 3,500 jernal daripada
110 negara.
Health Planning & Administration - keluaran National Library of Medicine, USA.
Pangkalan data ini memberikan akses kepada lebih dari 350,000 rekod dalam aspek penjagaan kesihatan....bukan klinikal,
perancangan dan pentadbiran kemudahan
kesihatan, pentadbirdn kewangan, insuran
kesihatan, perlesenan d m pertauliahan,
Drug Information Source - yang menggabungkan kandungan tigapenerbitan oleh
American Society of Hospital Phm-macists,
iaitu AHFS Drug Information, Handbook
of Injectible Drugs dan International Pharmaceutical Abstracts (indeks kepada 700
jernal). Iajuga meliputi tandadan penggunaan ubat, kontraindikasi dan kesan
mudarat, dos dan regimen, kimia dan
kestabilan, penyelidikan ubat, dll.
CANCERLIT - pangkalan data menyeluruh mengenai maklumat penyelidikan
kanser, disusun oleh US National Cancer
Research Institute. Ia menyediakan maklumat terperinci mengenai prosedur diagnostik dan rawatan, epidemiologi (risiko
dan pencegahan), biologi molekul dan sel,
virologi dan irnmunologikanser,karsinogen
dan karsinogenesisdan perkembangan ubat
anti-kanser.
6.
PDQ(Physician DataQuery) - disusun oleh
US National Cancer Institute. PDQ meliputi setiaprawatan yang diperolehi untuk
pesalut kanser. Pangkalan data ini mengandungi Fail Maklumat Kanser dengan
maklumat prognostik dan rawatan, untuk
pesakit dan juga klinisian, Fail Protokol
yang menerangkan lebih dari 1,000 ujian
klinikal yang aktif dan diperakui dan
sejnmlah standard rawatan regimen yang
terhad dan File Direktori yang menyenaraikan alarnat dan nombor telefon lebih
dari 17,000 doktor dan pakar bedah yang
tugas mereka terlibat dengan kanser.
selepas penyiapan empangan. Pada tahun 1992,
pasukan EIA dari IMR beralih ke fasa lain dalarn
projek hidro-letrik dengan mengawasi penyakitpenyakit clan kesihatan mereka yang terlibatdalam
fasa pembinaan empangan tersebut.
Projek EIA ini telah di jalankan di kawasan
Projek Hidro-letrik Pergau dengan bantuan dari
TenagaNasional Berhad. Tujuan kajian ini adalah
untuk menentukan jangkitan biasa yang
berhubungkait dengan perubahan alam sekitar di
kalangan pekerja binaan, menentu perubahan
vektor pen yakit, dan memperolehi maklumat atau
pendapat penduduk-penduduk kampung bagaimana pembangunan baru memberi kesan pada
penghidupan mereka.
Kesirnpulan dari kajian ini menunjukkan pertambahan potensi ke atas transrnisi malariadi kawasan
pembinaan disebabkan oleh bertambahnya
kawasanpembiakan nyamuk vektor. Juga terdapat
risiko yang berpotensidalam pembawaan denggi
ke situ kerana terdapat takungan air yang
mengandungi jentik-jentik nyamuk bawaan
vektordi kawasan tersebut. Cacing-cacing tularan
tanah yang biasa terdapat di kalangan pekerja
binaan dan jangkitan cacing kerawit lebih kerap
di dapati di kalangan pekerja yang membina jalan
kerana ketiadaan tandas untuk digunakan pada
masa kerja. Kebanyakan penduduk-penduduk
kampung bersikap berkecuali terhadap empangan
itu dan gembira kerana bertambahnya peluang
perkerjaan dan merekaj uga menjangka mendapat
bekalan air paip dan letnk selepas empangan
dibina.
Ringkasan Penerbitan-Penerbitan IMR
Seroprevalen antibodi terhadap Toxocara
cnnis di kalangan orang asli di Semenanjrmg
Malaysia
Lokman Hakim S, Mak JW, Lam PLW, Nazma S
and Normaznah Y .
Southeast Asian J Trop Med Pub Hlth 1992;
493-496
Assai imunosorben enzim-terungkai menggunakan antigen kemunah-rembes dari
pengkulturan in vitro larva peringkat kedua di-
gunakan untuk menentukan seroprevalen
antibndi Toxocara dikalangan Orang Asli di
Semenanjung Malaysia. Min + 3DS dari 30 subjek
sihat
digunakan sebagai titik perbedaan.
Prevalen keseluruhan adalah 31.9%. Tidak
terdapat perhubungan bermakna d i antara kadar
positif dengan jantina dan kumpulan umur, walaupun kanak-kanak berumur antara 0 -9
tahun mencatatkan kadar positif tertinggi.
Didapati bilangan eosinofil berhubung rapat
dengan proporsi positiviti jangkitan toxocara
dan min densiti optik. Terdapatjugareaktivitisilang dengan sera positif dariTrichuris trichuria.
Penerbitan
Mutasi Gen Ras di pesakit leukemia
Malaysia
Chin YM, Koh CL & Bosco JJ
Acta Haematol1992; 87: 107 - 108
Kajian mutasi gen ras dijalankan secara
sembarangan terhadap 30 pesakit leukemia
mieloid akut (AML) di Hospital Universiti,
Kuala Lumpur, dari Julai 1988 hingga
Oktober 1989. Asid deoksiribonukleik (DNA)
dari sumsum tulang dan darah perifera1 pesakit
diamplifikasikan secarainvitro dengan tindakbalas
rantai polimerase pada kawasan kodon 12, 13,
dan 61 ketiga-tiga gen ras; H-ras, K-ras dan Nras. Hasil yang diamplifikasikan kemudian
dipenghibridan
dengan
perob-perob
oligonukleotid untuk mengesan mutasi titik pada
kodon 12,13, dan 6 1 ketiga-tiga gen ras; H-ras,
K-ras dan N-ras.
Mutasi gen ras dikesan dalam 4 (13.3%) dari 30
pesakit AML. Kekerapan mutasi gen ras dalam
kumpulan kecil AML M3 dan M4adalah 37.5%
dm 8.3%. Keempat-empatpesakitdengan mutasi
ras adalah di bawah 35 tahun. Dalam kajian
tersebut, mutasi gen ras ditemui dalam pesakit
AML M3 dan kumpulan umur yang muda.
Penemuan ini belum dilapurkan di negara barat.
sia Timur pada tahun 1982. Pada tahun 1984,
program pengawalan penyakit bervektor,
Kelantan bersetuju menggunakan pendekatan
penjagaan kesihatan awal sebagai strategi
penambahan dalam usaha-usaha pengawalan
malaria dalam negeri itu, yang kemudiannya
mengalami penambahan kes-kes malaria.
Berbagai-bagai usaha dijalankan untuk
membentukkan kesedaran dan memberangsangkan minat kakitangan kesihatan dan
komuniti untuk menggunakan strategi h i .
Kelantan digunakan sebagai model. Tulisan ini
membentangkan rangka proses yang terbabit
dan ciri-ciri pekerja penjagaan kesihatan awal.
Satu kajian dijalankan di kalangan pekerjapekerja kesihatan, ahli-ahli komuniti dan
kakitangan kesihatan di atas pengetahuan dan
pembabitan penjagaan kesihatan awal dalam
tiga negeri, termasuk Kelantan. Dari pandangan
kejayaan keseluruhan pendekatan ini, dan
kelemahan yang dikesan, beberapa kemun&nan cara penyelesaian telah dicadangkan dan
sepatutnya diberi tindakan.
Kejadian kes rabies manusia di Semenanjung
Malaysia
Ganesan J & Sinniah M.
Med J Malaysia 1993,48: 194-199
Southeast Asia JTrop Med Public Health 1992;
23 Suppl 1:18-22
Kejadian kes rabies manusia di Semenanjung
Malaysia ditinlbulkan. Walaupurlberbagai-bagai
cara kawalan diadakan, kes-kes rabies yang
sporadik masih berlaku di Semenanjung Malaysia terutama di negeri-negeri utara. Tujuan ini
adalah untuk menimbulkan kesedaran dan
kepekaan mengenaipenyakitini supaya profilaksi
yang berkesan selepas jangkitan dapat diambil
secepat mungkin untuk mengelakkan
jangkitannya.
Pendekataan penjagaan kesihatan awal di Malaysia mula-mula dijalankan di Sarawak,Malay-
Ujian makrnal postmortem dari seorang kes rabies dari Hospital Besar Alor Setar dilapurkan.
Menggunakan pendekatan penjagaan
kesihatan awal dalam pengawalan malaria
di Malaysia: Pelajaran dalam penyertaan
komuniti.
Haliza Mohd Riji
Tesis Sarjana
Seorang budak lelaki berbangsa India, berumur
7 tahun telah dimasukkan ke Hospi t d tersebut
kerana gigitan 'anjing gila' yang berkeliaran
sebulan sebelum itu. Pada waktu itu, pesakit
menunjukkan sawan, sentakan otot-otot
mukanya, hidrofobia dan lumpuh flaksid menaik.
Tahap kesedarannya bertukar kepada koma dan
meninggal dunia 10 hari selepas itu. Ujian postmortem dijalankan di Hospital tersebut dan
otaknya dihantar ke Institut Penyelidikan
Perubatan (IPP). Di makmal Virologi IPP, smear
irnpresi dibuat dari otak itu dan didapati positif
kepada antigen rabies yang spesifik melalui ujian
floresen antibodi rabies. Otak itu juga diperiksa
secara histologi.
Potongan darinya menunjukkan gambaran seperti meningoencephalitis viral. Juga, potongan
yang diwarna dengan cam Sellers' menunjukkan
intrasitoplasmik asidofilik badan-badan
rangkuman yang besar serta bujur seperti badan
Negri. Ini dapat memastikan bahawa
meningoencephalitis itu berpunca dari rabies.
Laporan ini diikuti dengan rumusan kaedah
pencegahan terkini dan cara diagnosis rabies.
Ekstrasi Delta-9-THC karbosilik asid dari
urin terkumpul positif kannabis bagi penyediaan piawai
Mohd Isa Wasiman, Mohd Zaini Abd Rahman,
Badrul Amini Abd Rashid &
Zakiah Ismail
Malaysian J Med Lab Sci 1992; 9(1) :26-28
Kaedah ekstraksi delta-9-THC karboksilik asid
dari urin terkumpul positifkannabis untukpenyediaan piawai dibincangkan.Sarnpelurin dijalankan
penyaringan terhadap kannabis menggunakan
"fluoresence polarization immunossay PPIA)".
[Trine terkumpul dilakukan hidrolisis dalam
keadaan alkali pada 50 C untuk 30 rninit, selepas
itu urine diselaraskan kepadapH 2-3 dan diekstrak
menggunakan pelarut sikloheksana : etilasetate.
Karni memperolehi 185ug delta-9-THC-COOH
dari 2 liter urine. Penulenan ekstrak dijalankan
menerusi HPLC persediaan menggunakan turus
fasa terbalik C18 22mm X 25cm. Fraksi
mengandungidelta-9-THC-COOH dikumpulkan
dan dipekatkan dengan pemeruapan di bawah
aliran udara pada 50 C . Jurnlah delta-9-THCCOOH tulen yang diperolehi adalah 98ug.
Kajian Reseptor Molekul Virus Epstein Barr
1
...
...
...
....
...
.>:.:.
.:-
(Abstrak tesis yang diserahkan kepada University of London oleh
Vijayamalar Balasubramaniam bagi Ijazah Sarjana Sains)
Virus s stein ~ a r(EBV)
r
adalah puncapenyakit
Infectious Mononucleosis dan berkait rapat dengan Limfoma Burkitt's (BL) dan karsinoma
nasopharangeal. Ia menjangkiti sel-sel B yang
matang (secaraterpendam) dan sel-sel epitelial di
mana ia melalui proses replikasi ymg aktif.
Reseptor virus EB di dalam sel B telah dikesan
sebagai molekul CD21lCR2. Lirnfoma Burkitt's
wujud dalam bentuk epidemik dan sporadik.
Bentuk sporadik selalunya virus EB yang tidak
mempunyai genom (Virus EB genom negatlf).
Virus EB genom negatif dari keturunan sejurai
kanser ini tidak mempunyai atau mempunyai
kadarekspirasi CD21 yang terlalurendah. Walau
bagaimana pun, sel-sel ini boleh dijangkiti dengan virus EB. Tujuan kajian ini adalah :
Tesis Sarjana
1)
Untuk melihat hubungan tahap infeksi
EBV dari EBV negatif sel dari keturunan
sejurai
2)
Untuk cuba menghalang infeksi EBV
dari negatif sel dari keturunan sejurai
dengan menggunakan antihodi
monoklonal terhadap CD21.
Kami berjaya menj angkitkan BL2 dari keturunan
sejurai walaupun, tahap ekspresi CD21 < 2%.
BL30 sel dari keturunan sejuraijuga telah berjaya
dijangluti. (20% ekspresiCD21). Kamijugadapat
membuktikan bahawaantibodi monoklonal OKB7
menghalang infeksi EBV sel keturunan sejurai
secara separa dan pcnyatuan B2 dapat
menggalakkan penyerapan dan infeksi EBV.
Dari hasilnya, kami percaya bahawa kemungkinan wujudnya reseptor alternatif di EBV negatif
BL sel keturunan sejurai : BL02 dan BL30. Ia
juga telah menunjukkan B2. berkemunglunan
mempunyai penggalak penyerapan EBV dan
EBNA protin sintesis. Dari awal1970penyelidikpen ye1 idik percaya bahawa wujudnya reseptor
alternatif kerana sel-sel epitelial (semasa itu)
tidak mempunyai kadar reseptor seperti mana
reseptor CD21 yang dapat dikesani.
Maka hasilnya yang diperolehidapat menimbulkan
rninat dalam reseptor alternatif ini. Tangpngjawab B2 dalam sebagai penggalak penyerapan
virus haruslah disiasati kerana ia mungkin dapat
mcnunjukkan jalan cara penyerapan dan
pengambilan EBV di samping mengesanreseptor
alternatif ini.
Penghasilan antibodi monoklonal terhadap
Haemophilus ducreyi
(Abstrak tesis yang diserahkan kepada Universiti Malaya oleh
Rohani Md Yasin bagi Ijazah Sarjana Pathologi)
Chancroid adalah penyakit jangkitan sex yang
disebabkan oleh bacteria Haemophilus decreyi
yang menyebabkan luka atau ulser. Penyakit ini
sering terjadi di negara-negara yang sedang
membangun di rnana herpes genitaljarang ditemui.
Ia juga hendaklah dibezakan dari penyakit sifilis
dm 'lymphogranuloma venereum'. Diagnosis
boleh dibuat berdasarkan salah satu dari yang
berikut : Pengasingan bacteria penyebab;
Pengesanan bacteria penyebab di dalam nanah
dari bisul atau biopsi tisu; Gambaran klinikal.
Diagnosis biasanya dibuat berdasarkan
persembahan klinikal dan disahkan dengan
demonstrasi H. ducreyi melalui palitan dan
pengasingan organisma itu dari ulser atau nanah
bisul.
Interpritasi palitan ulser agak sukar dibuat walaupun oleh orang yang telah mahir kerana
mofologi yang khusus 'school of fish' yang
dlbentuk oleh H. ducreyi tidak selalu ditemui dan
bacteria lain yang sering terdapat di dalam ulser
itu sering memberikan gambaran yang serupa.
Beberapa penyelidlk yang terdahulu mendapati
kepekaan pencelupan Gram berbeza-beza dari
27 - 50% dengan ketepatan dan 'positive predictive value' yang rendah. Pengasingan bacteria ini
mahal dan sukar kerana ia memerlukan media
Kursus & Bengkel
yangkhusus. Kejayaan pengasingan tidakpernah
melebihi 60%. Deny s dan rakan-rakan telah membentuk asai imunofloresen tak langsung untuk
mengesan chancroid tetapi penggunaan serum
polivalen memberikan reaktiviti bersilang yang
tinggi. h i dapat diatasi dengan penggunaan
antibodi monoclonal (MAB).
MAB telah dibentuk terhadap H. ducreyi 'ibu'
menggunakan teknik Kohler dan Milstein (1975).
Saringan telah dilakukan menggunakan teknik
imunofloresen dan kelas imunoglobulin
dite,ntuka menggunakan asai 'captures enzymelinkedimmunoabsorbance'.MAB yang dihasilkan
telah diuji terhadap beberapa H. ducreyi strain
dan lain-lain spesis hacmophilus juga lain-lain
organisma untuk menentukan ketepatan dan
reaktiviti bersilang mereka.
Kejayaan percanturnan adalah dalam lingkungan
75% dan hanya 8 klon telahdipelihara seterusnya.
Dari 8 MABs itu, 5 adaldh IgG, 2 adalah IgM
sementara satu bertindak balas dengan keduadua IgM dan IgG. MABs dari klon-klon F62, F41
dan D3 1 tidak memberikan reaktiviti bersilang
dengan H. injluenzae, H. parainfluenzae, H.
aphrophilus,
N. gonorrheae, E. coli and
P. aeruginosa. MAB dari klon D31 bertindak
balas dengan kesemua 21 H. ducreyi strain yang
diuji tetapi memberikan reaktiviti bersilang yang
tertinggi dengan lain-lain spesis haemophilus dan
lain-lain organisma (7125). MAB dari klon F42
tidak dapat mengesan 2 dari 21 H. ducreyi strain
tetapi mengesan 2 dari 19 lain-lain spesis
haemophilus dan 2 dari 25 organisma lain.
Penentuan awal ciri-ciri MABS yang dihasilkan
menunjukkan hibridF42 adalah klon yang terbaik.
Apabila MAB dari klon ini digunakan dalam ujian
irnunofloresen tak langsung ia memberikan peratus ketepatan sebanyak 88.6% dan kepekaan
sebanyak 90.5%. Ini masih tidak memuaskan
kerana peratus kepekaan adalah di bahagian yang
rendah dan ketepatannya adalah amat rendah.
Satu MAB yang baik mestilah spesifik di mana ia
mempunyai ketepatan yang tinggi walaupun
kepekaannya tidak begitu tinggi. Sebagai contoh
MAB terhadap Chlamydia trachomatis yang
dihasilkan oleh Kallestad Diagnostic untuk
pengesanan antigen C. trachomatis mempunyai
kepekaan setinggi 86% dan ketepatan setinggi
98 - 100%. Untuk r~ierirlayatkarlMAB yang
spesifik lebih banyak klon hendaklah dievaluasi
dan MABs yang terpilih hendaklah disaring lebih
lanjut untuk menentukan Liridak balas
merekaterhadap fokus penentu antigen yang
spesifik seperti sebahagian dari protin membran
luar dari H. ducreyi, sebelum evaluasi bagi menentukan kepekaan dan ketepatan diteruskan.
Kursus dan Bengkel
Perayaan Ulangtahun ke 90 IPP
IPPtelah ditubuhkan dalam tahun
1900, telah
menyambut ulangtahunnya yang ke 90 dalam
tahm 1992 dengan mengadakan Seminar
Saintifik, Hari Terbuka dan Hari Keluarga.
Kemuncak dari perayaan tersebut ialah Seminar
Saintifik yang diadakan pada 23-25 Jun. Tema
Seminar tersebut ialah 'Penyelidikan Kesihatan:
Pencapaian, Cabaran dan Arah Tujuan Masa
Depan'. Objektif Seminar adalah untuk menilai
semula hasil kerja Institut selama 90 tahun, dan
mencadangkan arah tujuan masa depan. Seminar
tersebut telah dibuka dengan rasminya oleh
Yang Berhormat Dato' Lee Kim Sai, Menteri
Kesihatan.
Kursus & Bengkel
Gambaran keseluruhan penyelidikan yang telah
dijalankan di IPP telah diberikan oleh Dato'
(Dr) M. Jegathesan, Pengarah IPP dan ini dituruti
oleh Ucapan Dasar bertajuk 'Arah Tujuan Masa
Depan Penyelidikan Kesihatan di Malaysia' yang
disampaikan oleh Ketua Pengarah Kesihatan,
Tan Sri Dato' @r) Abu Bakar Suleiman. Beberapa orang penyelidik-penyelidik kanan IPP
telah diberi tanggungjawab untuk menilai
pencapaian-pencapaian penyelidikan dalarn bidang-bidang tertentu dan menjelaskan bagaimana
ia telah menyumbang ke arah penjagaan dan
perawatan pesakit serta pengawalan penyakit.
Tajuk-tajuk yang telah diliputi ialah penyakit
berjanglut, penyakit tidak berjangkit,pemakanan
manusia, d a m sekitar dan kesihatan. Berapa
orang saintis tempatan dan luar yang terkenal
telah juga dijemput untuk membentangkan kertas
kerja mengenai perkembangan semasa isu-isu
tropika seperti biologi molekular dan
bioteknologi, alam sekitar dan kesihatan,
penyelidikan dalam penyakit parasitik dan
pemakanan manusia.
Komponen penting dari Seminar tersebut ialah
sessi dialog di antara pengarah-pengarah Program Kementerian Kesihatan dan penyelidikpenyelidik dari IMR, di mana pihak terdahulu
mengemukakan pemasalahan yang a a d a p i
dalam perlaksanaan program masing-masing
yang memerlukan penyelesaian. Beberapa isu
yang sangat penting telah dibangkitkan dan
beberapa projek penyelidikan telah dikenalpasti
untuk perhatian segera. Kedua-kedua belah
pihak ber-yendayal sessi tersebut sangat berfaedah
dan cadangan supaya ianya diadakan secara
tetap dan lebih kerap disuarakan. Prosiding serninartersebut telah diterbitkan dan boleh dipmulehi
dari IMR.
Sutnbangan Mak Joon Wah
Seminar SEAMEO-TROPMED mengenai
filariasis
Seminar SEAMEO-TROPMED ke 34 mengenai
'Status S e m a w Filariasis di Asia Tenggera7
telah diadakan diInstitut Penyelidikan Perubatan,
Kuala Lumpur dari 26-27 Jun 1992. Seminar
tersebut telah dibuka secara rasrni oleh Ketua
Pengarah Kesihatan, Tan Sri Dato' @r) Abu
Bakar Suleiman dan telah dihadiri oleh peserta
dari Indonesia, Filipina. Thailand, Malaysia,
Jerman, U.S.A. dan Pertubuhan Kesihatan
Sedunia. Objektif Seminar tersebut ialah untuk
membincangkan keadaan semasa filariasis di
negara-negara dari rantau ini, membentangkan
penemuan semasa penyelidikan dan menilai semula kemajuan dalam filariasis. Tajuk-tajuk yang
dikaji semula ialah kemajuan dalam teknik
epidemilogi dan diagnostik, kemoterapi, biologi
molekular dan imunologi, genetik, biologi dan
ekologi nyamuk, kawalan vektor dan aspek sosial
penyakitfilariasis. Perbincangan am juga telah
diadakan tentang perkaitan kemajuan-kemajuan ini dengan perawatan pesakit dan
pengawalan filariasis limfatik. Adalah
dicadangkan bagi negara-negara di rantau ini
supaya mengambillangkah segera untuk meningkatkan bilangan kakitangan yang dilatih dalam
penyelidikan dan kawalan filariasis lirnfatik.
SEAMEO-TROPMED boleh memainkan peranan positif dalam aspek ini melalui seminarseminar seperti yang diadakan, dan bertindak
sebagai satu forum bagi penyebaran maklumat
mengenaiperkembangan semasa. Prosiding serninar akan diterbitkan sebagai terbitan tarnbahan
dari jurnal 'Southeast Asian Journal of Tropical
Medicine and Public Health'.
Sumbangan Mak Joon Wah
Kursus asas mikroskupi eleklron trans~nisi
Unit Mlkroskopi Elektron di Institut Penyelidkin
Perubatui idah rritmgcridalikiui "Kcll.sus Asas
Mikroskopi Elektron Transmisi" untukpegawaipegawai yang menjalankanpenyelidikan dihstitut
ini. Dr Dcborah J. Stcnzcl dari Queensland
University of Technology adalah pakar perunding
anjuran WHO. Lapan orang peserta dan tiga
Kursus & Bengkel
orang pemerhati menghadiri ktwsus ini yang
dijalankan pada 12 - 28 Oktober 1992.
Syarahan-syarahan dan latihan amali dijalankan
bagi memenuhi keperluan pegawai-pegawai yang
tidak mempunyai pengalaman dalam bidang
rnikroskopi elektron. Peserta-peserta diajar mengenai mikroskop elektron transmisi,teknik imunolabel, sitokimia, dan pengendalian peralatanperalatan sepertipenyejat vakum, pembuatpisaugelas dan ultramikrotom. Kemahiran lain yang
diajar termasuk pemeriksaan contoh-contoh
ultrakeratan di bawah mikroskop elektron
transmisi, fotomikrografi, memperoses filem dan
mencetak cetakan lekap. Perhatian lebih
ditumpukan kepada pemeriksaan fotomikrograf
bagi mengenal pasti ultrastruktur-ultrastruktur
sel dan membezakannya dari artifak-artifak yang
rnengelirukan, juga beberapakelemahan teknikal
pemprosesan contoh dan kualiti foto mikrograf.
Pakar perunding menggunakan pengalamannya
sendiri dalam setiap langkah dari peringkat awal
pemprosesan hingga ke produk terakhir, iaitu
fotornikrograf. Peserta-peserta telah diberi
penerangan tentang kegunaan mikroskopi
elektron transmisi dalam bidangpatologi, virologi,
bakteriologi, parasitologi dan entomologi. Dalam
kursus ini, peserta juga telah membincangkan
kemungkinan penggunaan mikroskopi elektron
transrnisi dalam penyelidikan mereka.
Sumbangan Karen Lai Peng Foon
Pemastian kualiti bagi perkhidmatan
makmal palulugi
Program Kepastian mutu (QAP) KKM bertujuan
untuk mempastikan kualiti dalam rriernberikan
khidmat rawatan kesihatan. Ia merupakan satu
dari enam jawatankuasa bagi pelbagai bahagian
Kcmcn tcrian. Jawatankuasa Perkhidmatan
Makmal Patologi telah ditubuhkan pada akhir
1990. Ia dianggoti oleh Jawatankuasa Kecil
Patologi Kimin, Mikrobiologi Perubatan,
Haematologi & Penabungan darah dan
Histopatologi & Sitopatologi yang akan ber-
tanggungjawah ke atas tugas mengenalkan
penunjuk QA yang sesuai untuk pelbagai disiplin
makmal patologi dan penerapan penggunaannya.
QAP Perkhidmatan Makmal Patologi telah
dilancarkan dengan rasminya pada 12 Februari
1993 dan ia telah diikuti dengan bengkel yang
ke 2 dimana penemuan dan kajian perintis yang
dijalankan pada tahun lalu dibincangkan. Ia
bertujuan bagi membincangkan kebolihlaksanaan pelbagaipenunjuk dan penetapan piawaian.
Pengawasan penunjuk kualiti perkhidmatan
rnakrnal sedang dijalankan. Ini termasuklah
penunjuk 'pencapaian' dalam Skim Penilaian
Mum Luaran Kebangsaan (EQAS) yang mesti
dijalankan bersesuaian dengan prinsip dan kaedah
EQAS Antarabangsa WHO, dan 'turn around
times' bagi pelbagai khidrnat yang diberikan.
Disamping itu kadar penolakan spesimen dan
peratus ujian segera, adalah sebagai penunjuk
kesesuaian penggunaan makmal. Kesemua
penunjuk ini cukup merangkurni aspek-aspek
penting yang mempengaruhi hasil dari perkhidmatan makmal.
Perkhidmatan makmal patologi adalah sebahagian dari khidmat dalam rawatan pesakit.
Keputusan makmal selalu penting bagi menentukan diagnosis dan pengurusan pesakit.
Pengawasan berkala menggunakan penunjuk
membolihkan makmal yang gagal mencapai
piawaian dikenalpasti. Satu proses bertujuan
memperbaikinya rnelibatkan pencarian sebab bagi
kegagalan tersebut dan diikuti dengan langkah
susulan yang sesuai dan seterusnya pengawasan
semula dibuat bagi melihat perubahan
kedudukannya. Berdasarkan matlamat QA yang
bertujuan pembaikan berterusan satu piawaian
baru (yang berdasarkan kriteria minima dapat
diterima dan bukan yang ideal) akan diambil. Ini
bcrlcpalan dengarr pcrubahan rnasa yarlg
mengakibatkan kualiti yang semakin tinggi dapat
dicapai dirnasa akan datang.
Sumbangan Lim How Hin
Usahasama
Projek Penyelidikan dalam Penyakit Tropika
IMR - JICA
Sejarah penyelidlkan perubatan kolaboratif
antara Malaysia dan Jepun terhasil apabila satu
perjanjian dicapai di antara Institut Penyelidikan
Perubatan, Kuala Lumpur dengan Agensi
Kerjasama Antarabangsa Jepun (JICA) pada 23
Jun 1992,dalam kerjasama teknikal penyelidikan
mengenai penyakit-penyakit tropika tertentu.
Projek penyelidikan dalam penyakit-penyakit
tropikaIMR-JICA bermula secararasminyadengan ketibaan Professor Hiroshi 'I'anaka sebagai
ketua penasihat dan Cik Izumi Ota sebagai
penyelaras, pada 13 Januari 1993 di IMR.
Objektif projek tennasuklah pemindahan kepakaran dalarn bidang bioteknologi dari pakarpakar Jepun kepada rakan sejawat dari Malaysia
dan membangunkan asai-asai diagnostik yang
lebih sensitif d m cepat bagi ppenjagaari pesakit
serta pengawalan penyakit malaria, denggi,
demam denggi berdarah dan ensefalitis Japanese.
Selain daripada pakar-pakar perunding jangkapanjang yang ditempatkan d i Bahagian
Entnmologi Peruhatan, Virologi dan Pusat Bioteknologi, beberapaorangpakar-pakarperunding
jangka-pendek akan dltempatkan di IMR. Rakan
sejawatdariBahagian-bahagianyang terlibat &an
diberi latihan di Jepun. Peralatan bioteknologi
bagi meningkatkan kemudahan akan chsediakan
oleh JICA.
Sumbangan Mak Joon Wah
Leading Article
( Medical and Health Information for the year 2020
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J.L. Fernandez - Irelan
I t is the Information Technology (IT) Age.
Everyone is tallcing about IT. It is information
that gives one the added advantage. Every
country and every business is serious about IT.
Information on new products, new technology,
new markets, etc. is what gives a country or
business, advantage or the winning edge over its
competitors. This should also be the case in
medicine and health.
Itis time that the medical professionalin Malaysia
pay more attention to IT, and take advantage of
i t to meet his own needs. Clinicians,
administrators, researchers, etc will find that
there is a vast amount of untappedinformation in
their own individual fields only if they care to
spend a few minutes searching for it. There is
information on every topic, and information can
be very valuable in each and everyone's work, be
it in the diagnosis, management of diseases,
administration or research.
In the medical sector which deals with the health
and well-being of the individual, informed
decision-making is of dire importance, and
informed decision-making is the making of
decisions based on information available.
Available information can be narrow, limited and
out-dated or can be wide, detailed and current. In
dealing with health, which is our greatest asset, it
goes without saying that decisions should be
based on the latter.
No doubt it can be argued that each health
professional has his own individual store of
knowledge upon which he draws to solve the
clinical, administrative or research problems that
face him. However it must not be forgotten that
educational programmes are designed to provide
the basic knowledge with which the student can
start functioning as a professional, and this
knowledge is meant to be the beginning of a
continuous process of life-long professional
learning.
SinceWorld WarU, scientific literature, including
medical literature, has been growing
exponentially. This phenomenon is often referred
to as the information explosion. Thus the
individual is faced with an ever increasing body
of literature that he can never hope to keep up
with. ITgrew out of this need to organize the vast
amount of information that one is faced with.
One of the most recent IT products in the market
to meet this need is the CD-ROM, Compact Disc
- ReadOnly Memory. This mass storage medium
allows up to 275,000 pages of text to be stored
on a single 4.7 inch silver disc. The advantages
of the CD are almostinstantaneous direct, random
access and multi-term, multi-field searching
capability.
Gathering together information in a specific field
andcreating databases by putting this information
into a common format is big business, andprivate
firms as well as government departments have
taken advantage of this. A whole range of
databases are available on CD-ROM, and some
of these are specialised databases covering only
one subject while others span the whole field of
medicine.
Some of the better known databases are as
follows:
Leading Article
i. MEDLINE, produced by the National Library
of Medicine, USA. It indexes articles from more
than 3,300 selected leading biomedical journals.
The printed version of MEDLINE is Index
Medicus. This database covers biomedical
literature, including clinical practice, research,
administration, policy issues and health care
services.
ii. EMBASE, produced Excerpta Medica, a
subsidary of Elsevier Science Publishing,
Amsterdam,TheNetherlands. This is a biomedical
and pharmacological database covering material
published in 3,500 journals from 110 countries.
The printed version is called Excerpta Medica
and is divided into 52 separate sections, e.g.
Excerpta Medica - Immunology and Excerpta
Medica - Radiology and Nuclear Medicine.
iii. Health Planning & Administration, produced
by the National Library of Medicine, USA. This
datahase provides access to more than 350,000
records on the non-clinical aspects of health care
delivery, planning and administration of health
facilities,financialmanagement, healthinsurance,
licensure and accreditation, personnel
administration, quality assurance, regulations,
and services and manpower.
iv. Drug Information Source, which incorporates
the contents of three publications by the American
Society of HospitalPharmacists, i.e. AHFS Drug
Information, Handbook on Injectable Drugs, and
InternationalPharrnaceutical Abstracts (ildexing
some 700 journals). Its coverage includes
indications and uses, contraindications and
adverse ellecls, dosages andregimens, chemistry
and stability, investigational drugs, etc.
v. CANCERLIT, a comprehensive database of
cancer research information compiled by the US
National Cancer Research Institute. It presents
detailed information on diagnostic and treatment
procedures, epidemiology (risk and prevention),
molecular and cell biology, cancer virology and
immunology, carcinogens and carcinogenesis,
andanti-cancer drug development.
vi. PDQ (Physician Data Query) compiled by the
US National Cancer Institute. PDQ covers every
therapeutic option available to cancer patients.
This database includes a Cancer Information File
with prognostic and treatment information for
patients as well as clinicians, a Protocol File
describing over 1,000 active or approved clinical
trials and a limited number of standard treatment
regimens, and a Directory File listing addresses
and telephone numbers of over 17,OOOphysicians
and surgeons who work with cancer.
vii. AIDS Compact Library, produced by
Macmillan New Media, USA. It includes
treatment databases such as AIDSTRIALS and
AIDSDRUGS, full-text articles from 10 leading
medical journals such as JAMA and BMJ,
AIDSLINE from the US National Library of
Medicine, International AIDS Database from the
Bureau of Hygiene and Tropical Diseases in
London, and clinical newsletters such as AIDS
Clinical Care and AIDS Newsletter.
viii. Life Sciences Collection, produced by
Cambridge Scientific Abstracts, USA. This
contains abstracts from journals, books,
monographs, conference papers, US patents and
reports, covering a whole range of subjects
incuding animal behaviour, biochemistry,
biotechnology, calcified tissue, chemoreception,
ecology, entomolugy, genetics,'human genome,
immunology, microbiology, neurosciences,
oncogenes, toxicology, virology, and AIDS.
CD-ROM technology has, no doubt, brought
information to our door-step. Every medical and
health personnel who is vested with the care of
individual or groups of people or the nation as a
whole must attempt to keep abreast with the
latest developmentsin this field. How can anyone
hope to choose the best available option if helshe
does not know what the options themselves are?
Tecltnique
It goes without saying that medicalprofessionals,
particularly clinicians, are extremely busy people.
However, with the heavy responsibility thrust
upon them, it is all the more necessary that they
spare a few minutes a week updating themselves.
Sitting in front of a computer and browsing
through articles of interest to them will not only
be a form of relaxation to the doctors' busy
schedule, and it will also add zest to their work,
and even serve as a force propelling them to write
case reports and undertake research in their own
fields. After allif Malaysians are looking towards
being a fully industrialized nation by the year
2020, the health and medical professionals must
not be left behind by their counterparts in the
advanced nations.
Deoxyribonucleic acid (DNA) analysis
by flow cytometry
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( Chin Yuer Meng
T h e study of cell kinetics has been facilitated by
the use of flow cytometry to determine cellular
DNA content. A single-cell suspensionis prepared
andcells are stained with afluorescent dye whose
binding is proportional to the DNA content of the
cell. Cells are then directed in single file through
a laser beam to excite the DNA-specific dye, and
the fluorescence emission is collected and
displayed as a fluorescence distribution as shown
in Fig. 1. By integrating the areas under the curve
(Fig. 1) the percentage of cells in each phase of
the cell cycle, GOIG1, S, and G2+M can be
determined.
Cell cycle analysis by flow cytometry can be used
to study the biochemistry of cell growth, kinetic
properties of cell population and the proliferative
activity of a tumour. During the S-phase of the
cell cycle, DNA synthesis occurs. The proliferalivt: activity of a turrivur is indicated by the Sphase fraction.
1x
DNA
2x
Content
Fig. 1 : DNA distribution of a population of singk
cells produced byjlo w cytometry.
Technique
DNAploidy analysis is usedin clinical research to
predict the outcome of certain malignancies. For
the solid tumours, an aneuploid neuroblastoma
is associated with a favourahle prognosis while
an aneuploid colon carcinoma is associated with
an unfavourableprognosis. In acutelymphoblastic
leukemia (ALL) hyperdiploidy shows a good
prognosis while hypodiploidy indicates a bad
prognosis. To determine the ploidy status of a
tumour, the DNA index is calculated by dividing
the GO/Gl DNA peak channel of the tumour cell
by the GO/G1 DNA peak channel of a normal
population of cells. A diploid tumour will givc a
DNA index of one. A hyperdiploid population
will have a DNA index greater than one while
that of a hypodiploid population will be less than
one.
The disadvantage of flo w cylu~nclricmeasurement
is that it requires cells to be in a single cell
suspension. Single cells can be prepared from
fresh solid tissues by solubilization in detergent,
enzymatic digestion and mechanical
dsaggregation. Flow cytometric analysis of a
tissue should always beinterpreted in conjunction
with Wright-Giemsa andlor Haematoxylin-eosinstained cytocentrifuge preparation of the cell
suspension f o r morphological studies.
Morphologic correlation must be made to confirm
that the cellular population of interest was present
in the cell suspension studied.
Flow cytometry can be applied to the study of
fixed tissue that is stored in paraffin blocks. A
technique fordissolving the paraffin, followed by
dispersion and 'staining of the cells has been
developed (1).This technique is useful for relating kinetic parameters of human tumours to
subsequent outcome of treatment of the patients,
since it can be applied retrospectively to tumours
from patients where complete followup is available. Compared to fresh tissue, DNA analysis by
flow cytometry using paraffin blocks is very time
consuming and gives histograms which show
wider coefficient of variation.
Several fluorescent dyes have been used to stain
DNA, including ethidium bromide, propidium
iodide, acridine orange, mithramycin and Hoechst
33312. Acridine orange can be used to separate
and sort cells on the basis of both DNA content
(green fluorescence, from staining doublestraricled DNA) and RNA content (red
fluoresence, from staining single-stranded RNA),
and has been used to discriminate between G1
cells and non-proliferating subpopulations.
In solid tumours such as breast, ovarian,
colorectal, pulmonary, and cervical carcinoma,
the frequency of aneuploidy increases with the
advancement of the tumour stage. The survival
rate of these patients with aneuploid tumours are
worse than those with diploid tumours. Tumours
with a low S-phase fraction (less than 5%) have
a better prognosis than those with a high S-phase
fraction. Aneuploid tumours have a higher Sphase fraction than diploid tumours, thus
indicating a higher proliferative rate than diploid
tumours (2, 3).
At the Institute for Medical Research, DNA
ploidy studies by flow cytometry is being carried
out in acute myeloid leukemia (AML), ALL and
breast cancer. Of the 50 ALLpatients, 10% were
hyperdiploid. All the 50 AML patients studied
were diploid. In our preliminary studies of breast
cancer patients, aneuploidy was detected in 40%
of the patients. There is also an association of
aneuploidy with the histopathological staging of
the breast cancer. Followup studies are being
done on the prognosis of the ALL and breast
cancer patients with and without aneuploidy.
Using DNA analysis by flow cytometry cell cycle
distribution and ploidy status of a tumour can be
determined. Flow cytometry plays an important
role in the diagnosis, prognosis and histological
classification of the tumour.
References
1. Hedley DW. Flow cytometry using paraffinembedded tissue: five years on. Cytometry 1987;
8: 377-385.
2. Seckinger D, Sugarbaker E & Frankfurt 0.
DNA content in human cancer. Arch Path01 Lab
Med 1989; 113: 619-626.
3. Hatfty BG, Tith M, Flynn S, Fischer D &
Carter D. Prognostic value of DNA flow
cytometry in the locally recurrent, conservatively treated breast cancer patient. J Clin Oncol
1992; 10: 1839-1847.
Medico-ecological studies in the
Pergau Hydroelectric Project area
T h e Institute for Medical Research (IMR) has
for some years been involved in the medicoecological environmental impact assessment
(EIA) of hydroell=c~icprojects. Mrasl of the
studies were aim at obtaining base-line information and assessingpotential disease hazards which
may be brought about by ecological changes.
Two studies have been on completed hydroelectric projecls. In 1992, the EIA team of the
IMR began monitoring the health of people at the
site of the dam during its construction.
The last mentioned study was conducted in the
Pergau Hydroelectric Project area. The objectives were to determine the common infections
related to environmental changes among construction workers and to study presence of vectors of diseases, as well as to obtain information
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from the villagers on how the project affected
their lives.
The findings showed that there was a potential
increase in transmission of malaria in the construction area owing to the increase in suitable
breeding sites for the mosquito vectors. There
was the potential risk of introduction of dengue
into the area as many containers were found to
have larvae of the dengue vectors. Soil-transmitted helrninth infections were common among the
workers, and it appeared that hookworm infection was more common among roadconstruction
workers who had no access to toilets during
working hours. Most villagers were neutral in
their feelings towards the construction of the dam
though they were pleased with the increase in job
opportunities and anticipated being supplied with
electricity once the dam became operational.
ZMR Publicutions
Abstracts of IMR Publications
Seroprevalence of Toxocara canis antibodies
among Orang Asli (aborigines) in Peninsular
Malaysia
Lokman Hakim S, Mak JW, Lam PLW, Nazma S
and Normaznah Y .
Southeast Asian J Trop Med Public Health
1992; 23: 493-496.
A n enzyme-linked immunosorbent assay using
excretory-secretory antigens of the second stage
larvae maintained in vitro was used to determine
the seroprevalence of Toxocara antibodies in
Orang Asli (aborigines) of Peninsular Malaysia.
The mean + 3SD optical density of 30 healthy
subjects was used as the cutoff point. Overall
prevalence was foundto be 3 1.9%. No significant
relationship was found between positive rates
with sex and age groups, though children between
0 and 9 years recorded the highest positive rate.
Eosinophil counts were found to beclosely related
to the proportion of positivity to Toxocora
infection and mean optical densities. There was
some degree of cross-reaction with Trichuris
trichuria positive sera.
Kuala Lumpur, from July 1988 to October 1989.
The deoxyribonucleic acid (DNA) isolated from
the bone marrow or peripheral blood of the
leukemia patients were subjected to in vitro
amplification at regions around codons 12, 13,
and 61 of the three ras genes; the H-ras, Km s , and N-)-asby thepolyn~erasechain reaction.
The amplified products were then hybridized
with oligonucleotide probes to detect point
~r~ulalions
at codons 12, 13, and 61 of the three
ras genes; the H-ras, K-ras, and N-ras.
Ras gene mutations were detected in 4 (13.3%)
of the 30 AML patients. The incidence of ras
gene mutations in the M3 and M4 subgroups of
AML were 37.5% and 8.3% respectively. All the
four patients with ras mutations were below 35
years. In the present study, ras gene mutations
was mainly found in M3 AML patients and a
young age group. These findings have not been
reported in Western countries before.
Adopting the primary health care approach
in Malaria control in Malaysia: Lessons in
community participation
Haliza Mohd Riji
Ras Gene Mutations in Malaysian leukemia
patients
Southeast Asian J Trop Med Public Health
1992; 23 Suppl. 1: 18 - 22
Chin Y M , Koh CL & Bosco JJ
R a s gene mutation studies was performed at
random on 30 acute myeloid leukemia (AML)
patients, admitted to the University Hospital,
T h e Primary Health Care (PHC) approach in
Malaysia was first tried out in Sarawak, East
Malaysia in 1982. In 1984, the Vector Borne
Disease Control Programme in Kelantan decided
to adopt the PHC approach as an additional
strategy in its effort to control malaria in the state,
ZMR Publications
which then experienced an increase in malaria
cases. Effort was directed at creating awareness
and stimulating the interest of health staff and
communities to adopt the strategy. Kelantan was
made the model state. The paper gives an outline
of the process involved and some characteristics
of PHC workers. A study was carried out among
health workers, community members and health
staff on their knowledge and involvement in PHC
in three states, including Kelantan. Tn view of the
overall success of this approach, and the
weaknesses which have been identified, possible
solutions have been suggested and should be
acted upon.
Occurence of human rabies in Peninsular
Malaysia
Ganesan J & Sinniah M.
Med. J. Malaysia 1993; 48: 194-199
T h e occurence of a case of human rabies in
Peninsular Malaysia is highlighted. Despite the
various control measures taken sporadic cases of
rabies have continued to occur in Peninsular
Malaysia especially in the northern states. The
purpose of this paper is to create awareness of the
occurence ofrabies so that effective post-exposure
prophylaxis will be instituted as soon as possible
to prevent the possible occurence of this dreaded
disease.
The postmortem laboratory findings from a human case of rabies from the Alor Setar Hospital
are reported. A.7-year old Indian boy had been
admitted to the Alor Setar Hospital with a
history of having been bitten by a stray 'mad
dog'one month prior to admission. On admission
the patient had fits, twitching of facial muscles,
hydrophobia and ascending flaccid paralysis.
Consciousness deteriorated into coma and the
patient died 10 days after admission. A
postmortem was performed at the Alor Setar
Hospital and the brain sent to the IMR. At the
Virology laboratory of the IMR impression smears
were made from the brain and these were positive
for specific rabies antigen by the fluorescent
rabies antibody technique. The brain was also
examined histologically. The sections showed
features consistent with those of viral
meningoencephalitis. In addition sections stained
by the Sellers' method showed largely oval
intracytoplasmic acidophilic inclusion bodies
having features consistent with Negri bodies and
hence further confirming that the meningoencephalitis was caused by rabies.
The case report is followed by a summary of
currently available preventive measures and
diagnostic methods for rabies.
Extraction of Delta-9-THC Carboxylic Acid
from pooled cannabis positive urine for
preparation of standard.
Mohd Isa Wasiman, Mohd Zaini Abd Rahman,
Badrul Amini Abd Rashid and Zakiah Ismail.
Malaysian J Med Lab Sci 1992; 9(1): 26-28
r
1
1he procedure
for extraction of delta-9-THC
Carboxylic acid from pooled cannabis positive
urine for preparation of standard is discussed.
The urine samples were screened for cannabis
using fluorescence polarization irnrnunoassay
(FPIA). The pooled urine was subjected to alkaline
hydrolysis at 50°C for 30 min, after which the
urine were adjusted to pH 2-3 and extracted with
cyc1ohexane:ethylacetate solvent. 185 ug of delta9-THC-COOH was recovered from 2 liters of
urine. Purification of the extract was carried out
by preparative HPLC using a reverse phase 22mm
x 25 cm C18 column. The fraction containing
delta-9-THC-COOH was pooled, and
concentrated by evaporation under an air stream
at 50°C. The amount of pure delta-9-THCCOOH recovered was 98 ug.
M. Sc. Theses
f
Study of the Epstein Barr virus
receptor molecules
i
(Abstract of thesis submitted to the University of London by Vijayamalar Balasubramaniam
for the degree of Masters of Science)
T h e Epstein Barr virus (EBV) is the causative
agent of infectious mononucleosis and is closely
associated with Burkitt's lymphoma (BL) and
nasopharyngeal carcinoma. It primarily infects
matureB cells (latently) andepithelial cells where
it undergoes active replication. The receptor for
EBV in theB cell has been identified as the CD211
CR2 molecule. BL exists as an epidemic and
sporadic form. The sporadic form is usually EBV
genome negative. EBV negative cell lines raised
from this tumour have no or very low levels of
expression of CD21. However these cells can be
infected withEBV. The aims of this project were:
1)
To correlate the level of EBV infection in
EBV negative cell lines
2)
To attempt to block EBV infection of
EBV negative cell lines with monoclonal
antibodies to CD21.
We were successful in infecting the BL2 cell line
although the level of expression of CD21 was less
than 2%. BL30 cell line was successfully infected
(20% expression of CD21). We also showed that
monoclonal antibody OKB7 partially blocked
EBV infection of these ccll lines and that I32
binding appeared to enhance the uptake and
infection of EBV.
The results of this small project has led us to
believe that there is a likely possibility of the
existence of anotherlalternative receptor present
in EBV negative BL cell lines: BL2 and BL3O. It
has also showed that B2 probably has an enhancing EBV uptake andEBNA protein synthesis. As
early as the 1970's researchers had believed in the
existence of an alternative receptor especially
since epithelial cells (at that time) did not have
detectable levels of CD21-like receptors.
Thus the results obtained should stimulate a
modicum of interest in the quest for an alternative
receptor. The role of B2 in enhancing virus
uptake should be investigated too as it may throw
some light on the mode of uptake and
internalisation of the EBV as well as the identification of alternative receptor.
Courses and Workshops
Courses and Workshops
IMR celebrates its 90th Anniversary
T h e IMR, founded in 1901, celebrated its 90th
anniversary in 1992 with a Scientific Seminar,
Open Day and a Family Day. The theme of the
Scientific Seminar, held from 23 to 25 June, was
Health Research: Achievements, Challenges and
Future Directions. The objectives of the Seminar
were to review the 90 years of work of the
Institute, with special emphasis on the last 15
years, and to consider its future direction. The
Seminar was opened by the Minister of Health,
the Honourable Dato' Lee Kim Sai.
where the former identified problems encountered in the implementation of their respective
programmes. Some extremely important issues
were raised and a number of research projects
were identified for urgent action. Both sides
found the exercise extremely useful and it was
suggested that the dialogue sessions be held
frequently. The proceedings of the Seminar has
been published and is available from the IMR.
Contributed by Mak Joon Wah
Workshop on Flow Cytometry in Clinical
Medicine
An overview of research carried out in the IMR
was given by Dato' (Dr) M. Jegathesan, Director,
IMR, andthis was followed by aKeynote Address
on Future Directions on Health Research in
Malaysia by the Director-General of Health, Tan
Sri Dato' (Dr) Abu Bakar Suleiman. Some senior
IMRresearchers were given the task of reviewing
the research achievements on selected topics and
relating these to patient care and management
and control of diseases. The topics covered were
infectious diseases, non-communicablediseases,
human nutrition; environment and health. Some
prominent local and foreign scientists were also
invited to present papers on recent developments
in topics such as molecular biology,
biotechnology, environment and health, research
in parasitic diseases, and human nutrition.
An important component of the Seminar was a
dialogue session between programme directors
of the Ministry of Health and IMR researchers,
T h e first flow cytometer (Facscan system) in
Malaysia was installed at the Institute for Medical
Rescarch in 1988. Since then interest has been
shown by staff members in using the flow
cytometer for research projects. The Flow
Cytometry Workshop in Clinical Medicine was
therefore organised by the Division of
Haematology, IMR with the help of the Division
of I~ii~nunology
and sponsorcd by the Training
Division of the Ministry of Health.
Prior to the workshop, pi-e-workshop lectures
were conducted from 10 to 21 August 1993 by
lecturers from University Hospital, Universiti
Kebangsaan Malaysia, National University of
Singapore and IMR. The lectures included basics
of immunology, experiences with the flow
cylorneler and cell cycle kinetics. These lectures
were useful adjuncts to the workshop proper.
Courses and Workshops
Purtic~ipanisand or~inizing
c~otnrniliec~
ofihr workshop
Participa
at one of the lec
The workshop proper which was held from 6 to
15 September 1993 was officially opened by the
Director of IMR, Dato' Dr M. Jegathesan. The
consultant for the workshop, Ms Melinda Leong
was from Singapore, and the 10 participants
included officers and medical laboratory
technologists from the IMR and a specialist from
Hospital Kuala Lumpur. The objectives of the
workshop were to provide an overview of the
Facscan system and how it works, and familiarize
the participants with system operation, maintenance and quality control. Techniques for
sample preparation, irnrnunophenotyping and
DNA content analysis of cells from leukemias
and cancers were taught. The workshop also
gave the participants information on the usefulness
of the Facscan system in routine diagnostic work
and its potential in the field of research. It is
hoped that the participants will utilise this newly
gained knowledge to improve on their research.
Participants were given certificates of attendance
by the Ministry of Health, Malaysia.
Contributed by Rahimah Ahmad
Courses and Workshops
Quality Assurance for the Pathology
Laboratory Services
Thc Ministry of Health Quality Assurance (QA)
Programme is aimed at ensuring quality in the
provision of the health care services. One of six
committees of the Ministry, the Laboratory Committee was set up in late 1990. It comprises the
Chemical Pathology, Medical Microbiology,
Haematology, & Blood Banking and
Histopathology & Cytopathology sub-committees which arc given the task of developing
practical QA indicators for the respective medical laboratory disciplines and implementing them.
The laboratory QA Programme was officially
launched on 12 February 1993. In the second
workshop the findings of pilot studies, conducted the previous year to determine feasibility
of using the various indicators and standards
established, were discussed.
The monitoring of nine laboratory qualityindicators is in progress, These include the performance indicators from existing national external
quality assessment schemes (EQAS), turnaround
times, specimen rejection rate and the percentage
of urgent laboratory tests. These indicators cover
key aspects of the laboratory process which
affect outcome of the services.
The pathology laboratory services are an integral
component of the overall patient-care services as
laboratory results are often necessary for diagnosis of disease and patient management. Periohc
monitoring of the quality indicators is to identify
laboratories which fail to comply with desired
standards. Improvement involves identifying the
reasons for failure to comply with desired standards and instituting proper remedial actions. In
accordance with QA7s goal of continuous im-
provement, realistic standards (based on minimum acceptable criteria rather than the ideal) are
adopted, and these will be raised in future to
improve quality.
Contributed by Lim How Hin
SEAMEO-TROPMEDSeminar on Filariasis
T h e 34th SEAMEO-TROPMED Seminar on
Current Status of Filariasis in SoutheastAsia was
held at the Institute for Medical Research, Kuala
Lumpur, from 26 to 27 June 1992. The Seminar
was officially opened by the Director-General of
Health, Tan Sri Dato' (Dr) Abu Bakar Suleiman
and attended by delegates from Indonesia, Philippines, Thailand, Malaysia, Germany, U.S.A.
and the World Health Organization. The objectives of the Seminar were to discuss the current
situation of filariasis in countries of the region,
present recent findings, and review advances in
the study of filariasis. The topics reviewed were
advances in epidemiological and diagnostic techniques, chemotherapy, molecular biology and
immunology, genetics, biology and ecology of
mosquitoes, vector control, socio-behavioural
aspects of filariasis. General discussions were
held on how these advances relate to patient
managementand the control of lymphaticfilariasis.
It was recommended that countries in the Region
should take urgent steps to increase the pool of
personnel trained in research and control of
lymphatic filariasis, and that SEAMEOTROPMED play a positive role in this respect
through Seminars such as the present one, to
serve as forums to disseminate recent advances.
The proceedings of the Seminar will be published
as a supplementary issue of the Southeast Asian
Journal of Tropical Medicine and Public Health.
Contributed by Mak Joon Wah
Collaboration
Basic Course on Transmission Electron
Microscopy
T h e IMR Electron Microscopy Unit conducted
a Basic Course on Transmission Electron Microscopy for researchers of the Institute. Dr.
Deborah J. Stenzel from Qutxnslarid University
of Technology was the WHO consultant for the
course. Eight participants and 3 observers attended the course which was held from 12 to 28
October 1992.
The lectures and practicals were designed for
those without any previous experience in electron microscopy. The participants were taught
the mechanics of the transmission electron microscope (TEM), processing of biological speci-
mens, immuno-labelling and cytochemistry, and
use of supportequipment such as vacuumevaporator, knife maker and ultra-microtome, exarnination of ultra-sections under the TEM, taking of
photo-micrographs, development of film and
making of contact prints. Emphasis was placed
on the examinatinn nf photo-micrographs tn
identify ultra structures and artifacts, defects in
the processed specimens and quality of photomicrographs. The group was briefed on the
applicationsof transmission electronmicroscopy
inpathology,virology, bacteriology, parasitology,
and entomology. During the course, the
participantsalso discussedthepossibilityof using
transmission electron microscopy in their research work.
Contributed by Karen P.F. Lai
IMR-JICA Collaborative Project
A milestone in collaborative medical research
between Malaysia and Japan was reached when
an agreement was signed between the Institute
for Medical Research, Kuala Lumpur and the
Japan International Cooperation Agency (JICA)
on 22 June 1992, on technical cooperation in
research of selected tropical diseases. The IMRJICA research project on tropical diseases
officially began with the arrival in the IMR of
Professor Hiroshi Tanaka, Chief Advisor andMs
Izurni Ota, Coordinator, on 13 January 1993.
The objectives of the project include the transfer
of expertise in biotechnology from Japanese
experts to their Malaysian counterparts and the
development of more rapid and sensitive diagnostic assays for patient care and control of
malaria, dengue, dengue haemorrhagic fever and
Japanese encephalitis. In addition to long term
consultants being attached to the Divisions of
Medical Entomology, Virology and the
Biotechnology Centre, a number of short-term
consultants are also posted in the M R . The
counterparts from the Divisions concerned will
receive further training in Japan. In addition,
equipment for upgrading facilities will be supplied by JICA.
Contributed by Mak Joon Wah
Visiting Scientist
Rama C. Nair
Professor Rama Chandran Nair, Director of
Epidemiology and Community Medicine at the
University of Ottawa (U of 0 ) , Canada has spent
part of his sabbatical leave from January to June
1993at theInstitute for Medical Research (IMR).
Professor Nair is a biostatiscian and epidemiologist, with primary interests in epidemiologic research methods. He has over 40 publications in
refeered journals and numerous presentations to
learned societies. Apart from his regular teaching
activities at the Faculty of Medicine at U of 0 ,he
has conducted several workshops on Research
Methodology for students of various disciplines.
He has assisted severall-esearchersin Carlaclaand
abroad in developing research proposals and
carrying out research.
His visit to the IMR was sponsored partly by the
SEAMEO-TROPMED institutional linkage
agreement, which he was instrumental in negotiating, between IMR and U of 0. Under this
activity, Professor Nair held a workshop on
Research Methodology at the IMR in March
1993, and this was attended by more than 50
researchers. Dr. Amal Nasir b, Mustaffa of the
Division of Epidemiology and Biostatistics at
IMR is currently doing research for his M.Sc.
degree, under the guidance of Professor Nair.
Several researchers from IMR and HKL have
taken advantage of his presence in Malaysia to
obtain statistical advice on their research. He has
also initiated and helped in setting up an electronic linkage (E-mail) between IMR and U of 0
as well as other national and international agencies.
As part of his research activities, Professor Nair
has collaborated with Dr. Lye Munn Sann of the
Division of Epidemiology and Biostatistics on
various research projects. This resulted in the
submission of several articles for publications
(one of which has already been accepted).
In addition to the above, Professor Nair has
organized the National Workshop on Clinical
Epidemiology, sponsored by the World Health
Organisation and IMR (held in May 1993). He
has also been the joint coordinator for the National Workshop on Research Methodology in
Vietnam, held under the sponsorship of WHO
and the Government of Vietnam. He conducted
a one-week workshop in April 1993 on Advanced Statistical Methods for the Faculty of the
Department of Community Medicine at Universiti
Sains Malaysia, Kubang Kerian, and is planning
a two day workshop on Clinical Trials forphysicians in Kuching, Sarawak in June 1993.
Professor Nair's visit to IMR has been a catalyst
in promoting better linkage between IMR and U
of 0 and it is anticipated that similar collaboration
between other staff memhers of both instit~~tions
will take place during the coming years for the
mutual benefit of the two institutions.
Obituary
[
Obituary
......
Arthur Anantharaj Sandosham
L.M.S., Ph.D., M.D., A.M.
9 June 1905 - 28 November 1992
Professor Sandosham was born in Karur, India
on 9 June 1905. He came to Malaya with his
family in 1913. He married Emily in 1931 and
they had three children, two sons and a daughter.
Professor Sandosham passed away at the age of
87 on 28 November 1992 in Trichur, India.
Professor Sandosham completed his secondary
education at the Penang Free School and was
awarded an Entrancc Scholarship to King Edward VII College of Medicine, Singapore. He
graduated in 1930 with prizes in Medicine and
Public Health. Tn 1948,he was awarderlaQue~n's
Scholarship to pursue a Ph. D. degree at the
London School of Tropical Medicine and Hygiene.
Upon graduation, Professor Sandosham joined
the Department of Biology at his alma mater. He
was appointed to the chair of parasitology. In
1959, he was appointed Vice-Chancellor of both
&visions (Singapore and Kuala Lumpur) of the
University of Malaya. Professor Sandosham left
the University in 1960 to work at the WHO
Western Pacific Regional Office in Manila as the
coordinator of malaria studies. He joined the
Institute for Medical Research in 1961as a senior
research officer in malaria and filariasis. In 1963,
he was appointed Director of IMR and served in
the post until 1965. He remained in the IMR as
research consultant and advisor to the Division of
Malaria and Filariasis and was the first Dean of
the Dipluma in Applied Parasitology and Entomology course in 196811969. He retired from the
IMR in 1970.
Although Professor Sandosham's early work
was in classical parasitology, his major and
enduring interest was malaria. He wrote his first
book on malaria entitled 'Malaria in Malai' during the war when he was headof the Anti-Malaria
Laboratory in Singapore. When he joined the
IMR he collaborated with Dr. J.W. Field and Yap
Loy Fong in producing a new edition of the book
on the microscopical diagnosis of malaria. While
at the IMR, Professor Sandosham's work was
focused on two problems, the transmission of
simian malaria to man and on the emergence of
drug resistant Plasmodium falciparum strains.
The simian malaria work led to the discovery of
many new species of malaria parasites. One of
these, Plasmodium sandoshimi, found in the
flying lemur, was named after Professor
Sandosham.
Professor Sandosham was a very active member
of society. He served on many committees and
organizations. It was Prufessur Sandusham whu
suggested the formation of the 'Malaysian Society of Parasitology' and later became its first
president. In addition, he was editor of the Medical Journal of Malaysia and the SEA Journal of
Tropical Medicine and Public Health. Throughout his working life, this kind and approachable
man, used his good offices to encourage and help
the younger members of the scientific community. Sandy, as he was affectionately known, was
famous for his special brand of humour which
laced his after-dinner speeches and the 'Sandy's
Spices' column which he wrote for the MMA
newsletter.
With Professor Sandosham's demise, the scientific and medical community has lost a leader, a
mentor and a very dear friend.
Contributed by Harvinder Kaur Gill
Pengerusi
:
Dr. lsmail Mohd. Nor
Penasihat
Penyunting
:
Penolong
:
J.L. Fernandez - Ireland
Chin Yuet Meng
Azizah Mohd. Radzi
Mohd. Fo'ad b. Kastamam
:
Bangunan IMR - 1977
Bangunan IMR - 1901
lnstitut Penyelidikan
Peru batan
(Institute for Medical
Research)
Jalan Pahang
50588 Kuala Lumpur
Malaysia