Kanal Pengetahuan | Buku Abstrak Discover, Learn, Share buku abstrak oke
Health Research Expo I
Buku Abstrak
Discover, Learn, Share
Fakultas Kedokteran
Universitas Gadjah Mada
2016
Health Research Expo I, FK UGM
Daftar Isi
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Pengantar
Peta Jalan Penelitian
Featured research
Abstrak Fokus 1 : Kebugaran, Penuaan Dan Gaya Hidup Sehat
Abstrak Fokus 2 : Teknologi Intervensi Medik dan Kesehatan Masyarakat
Daftar Publikasi Jurnal International
TIM PENYUSUN
Penanggung jawab
Ketua Tim Penyusun Buku
Ketua Tim Pameran Poster
Ketua Seminar
Asisten
Editor Buku Abstrak
Layouter
Sekretariat dan Panitia
Email
: Prof. dr. Adi Utarini, M. Sc, MPH, Ph.D
: Harry Freitag LM, S.Gz, M.Sc
: Eri Yanuar Akhmad BS, S.Kep., Ns
: dr. M. Ary Zucha, Ph.D
: dr. Renata Uli Aviola
: dr. Dian Kesumapramudya Nurputra, Ph.D
dr. Junaedy Yunus, M.Sc, Ph.D
Melyza Perdana, S.Kep, MN
Harry Freitag Luglio M, S.Gz, M.Sc, RD
: Ceria Ciptanurani, S.Gz
Muhammad Cahyono Tito Handoyo
Rasyid Herlambang Wicaksono
Dimas Septian Eko Wahyu Sumunar
: Glory Hapsara Suryandari, S.Pd
Rahma Hanggia Iswandi, S.I.Kom
: hre.fkugm@gmail.com
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Health Research Expo I, FK UGM
PENGANTAR
Assalaamu’alaikum Wr Wb,
Penelitian merupakan salah satu pilar Tridharma Perguruan Tinggi yang memberikan
kontribusi nilai yang kompetitif dalam kinerja, baik di tingkat Fakultas maupun
Universitas. Dalam hal ini, fungsi utama Fakultas adalah menciptakan atmosfer
penelitian yang kuat sebagai sistem pendukung bagi para dosen dan peneliti
(termasuk mahasiswa di berbagai tingkatan pendidikan).
Agar kegiatan penelitian dapat berkembang, minimal diperlukan tiga pilar sistem
pendukung, yaitu:
1. Tata kelola penelitian (research governance);
2. Pelaksanaan penelitian (research production); dan
3. Diseminasi hasil-hasil penelitian (research dissemination).
Kegiatan ini digagas bermula dari pertanyaan sederhana dari mahasiswa tingkat
sarjana: “Bagaimana kami dapat mengetahui penelitian-penelitian yang sedang
dikerjakan oleh para dosen di FK UGM?”. Pertanyaan sederhana ini ternyata jauh dari
sederhana untuk menjawabnya. Mahasiswa miskin informasi sekalipun berada di
institusi Fakultas Kedokteran yang kaya akan kegiatan penelitian dan publikasi di
jurnal internasional. Bahkan Fakultas Kedokteran menempati posisi tertinggi di UGM
dalam hal jumlah kegiatan penelitian yang dilakukan, dana penelitian yang dikelola
serta jurnal internasional. Kondisi ini tentu tidak dapat dibiarkan.
Oleh karena itu, dalam rangkaian Dies 70th Fakultas Kedokteran UGM, digagas
kegiatan Health Research Expo I 2016 yang memfokuskan pada diseminasi hasil-hasil
penelitian dari para dosen-peneliti-mahasiswa di lingkungan Fakultas Kedokteran
UGM. Tujuan kegiatan ini adalah memberikan ide-ide kepada mahasiswa dengan
menampilkan penelitian yang sedang ataupun telah berlangsung serta memberikan
informasi kontak email para dosen-peneliti yang dapat dihubungi mahasiswa apabila
mereka tertarik dalam bidang penelitian para dosen-peneliti. Hal ini menjadi pintu
awal bagi mahasiswa untuk memperoleh informasi penelitian yang dikerjakan di
institusi Fakultas Kedokteran UGM. Cara diseminasi yang digunakan terutama adalah
melalui media buku kompilasi abstrak penelitian, seminar untuk mengawali pameran
poster yang akan digelar selama 1 bulan, serta diseminasi melalui website kanal
pengetahuan
dan
informasi
Fakultas
Kedokteran
UGM.
(www.kanalpengetahuan.fk.ugm.ac.id).
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Health Research Expo I, FK UGM
Dengan kegiatan ini, kami berharap minat kegiatan penelitian mahasiswa baik di
tingkat sarjana maupun pascasarjana serta dosen-peneliti menjadi semakin
berkembang. Kami percaya bahwa diantara sekian banyak mahasiswa, akan
bermunculan peneliti-peneliti handal yang dibutuhkan oleh bangsa Indonesia di masa
mendatang. Selain itu, kami berharap pula bahwa kegiatan Health Research Expo
seterusnya akan menjadi bagian dari budaya Fakultas dalam memperingati puncak
acara Dies Fakultas Kedokteran UGM.
Kami mengucapkan terima kasih atas partisipasi seluruh dosen-peneliti dalam
kegiatan ini, serta atas kerja keras para dosen dan staf kependidikan di tim buku
abstrak, tim pameran poster serta tim seminar. Segala kekurangan mohon dapat
disampaikan kepada kami melalui email hre.fkugm@gmail.com, untuk dapat
diperbaiki di masa mendatang. Semoga kegiatan ini memberikan manfaat bagi kita
semua. Amin.
Wassalamu’alaikum Wr. Wb.
Prof. dr. Adi Utarini M.Sc, MPH, Ph.D
Wakil Dekan Bidang Penelitian, Pengabdian Masyarakat dan Kerjasama
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Health Research Expo I, FK UGM
PETA JALAN PENELITIAN DI FK UGM
Dokumen peta jalan (road map) penelitian disusun dengan beberapa
pemikiran yang melandasi relevansinya. Secara umum, relevansinya adalah
sebagai berikut:
1. Untuk mengukur pemahaman internal mengenai penelitianpenelitian yang dilakukan oleh institusi serta menggali pemikiran
tentang prioritas penelitian;
2. Mengidentifikasi peluang perbaikan dan memberikan rekomendasi
sistem dan proses penelitian kedepan;
3. Memetakan dan merencanakan pendekatan implementasi peta jalan
penelitian dengan serangkaian inisiatif dan pencapaian kinerja;
4. Meningkatkan komunikasi dengan para peneliti, institusi penelitian
dan pendidikan, serta para pemangku kepentingan;
5. Mendeskripsikan manfaat yang diharapkan dan mengidentifikasi
ukuran keberhasilan dari investasi untuk penelitian.
Tujuan penyusunan peta jalan penelitian ini adalah untuk
menetapkan strategi penelitian FK UGM yang terukur dan
mengkomunikasikannya kepada para peneliti, pemangku kepentingan di
Daerah Istimewa Yogyakarta, nasional, internasional serta kepada lembagalembaga yang memberikan dana penelitian. Dengan tersedianya dokumen
ini, diharapkan pula akan memudahkan para peneliti untuk meningkatkan
daya saing di tingkatnasional dan internasional.
Proses penyusunan dokumen ini diawali dengan studi literatur
mengenai berbagai bentuk dokumen peta jalan riset, bukti-bukti mengenai
masalah kesehatan nasional dan global, sumber pendanaan penelitian serta
serangkaian proses konsultasi dengan para pemangku kepentingan baik
internal maupun eksternal. Proses konsultasi dilaksanakan dalam empat kali
pertemuan uji public draft peta jalan riset. Uji publik pertama dilakukan
dengan mengundang para koordinator penelitian, pusat-pusat dan kelompok
kajian penelitian serta para peneliti di lingkungan FK-UGM. Uji publik kedua
melibatkan para kepala bagian, para peneliti dan komisi 3 Senat Fakultas
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Health Research Expo I, FK UGM
Kedokteran UGM. Uji publik ketiga dan keempat menghadirkan para
pemangku kepentingan eksternal, yaitu dari Daerah Istimewa Yogyakarta
(RSUP dr. Sardjito, RS UGM, DinasKesehatan Daerah Istimewa Yogyakarta,
Kagama Kedokteran, Dewan Riset Daerah Istimewa Yogyakarta) dan nasional
(Kementerian Riset Teknologi dan Pendidikan Tinggi serta Kementerian
Kesehatan).
Melalui serangkaian proses tersebut, maka prioritas riset FK-UGM terdiri
dari dua fokus, yaitu kebugaran, penuaan, dan gaya hidup sehat serta teknologi
intervensi medik dan kesehatan masyarakat. Fokus pertama terkait kebugaran,
penuaan dan gaya hidup sehat merupakan riset yang berfokus pada pemahaman
mekanisme yang mendasari masalah kebugaran, penuaan dan gaya hidup, dan
mencakup topik mengenai genetika dan penyakit, gaya hidup yang
mempengaruhi kesehatan, lingkungan dan gizi, perawatan rehabilitatif dan
paliatif, dan problem kesehatan mental. Sementara fokus kedua terkait
teknologi intervensi medik dan kesehatan masyarakat merupakan riset yang
berfokus pada pasien untuk mengidentifikasi teknologi-cara baru untuk
pembelajaran, pencegahan, diagnosis, pengobatan penyakit, dan intervensi
untuk meningkatkan kesehatan masyarakat. Pada setiap fokus penelitian, dapat
dikembangkan tiga jalur ruang penelitian, yaitu penelitian yang memiliki orientasi
untuk memecahkan masalah kesehatan yang menjadi tantangan sosial,
penelitian yang menghasilkan produk kompetitif, serta penelitian yang
menghasilkan temuan sains baru (Gambar 1).
Peta jalan ini selanjutnya akan digunakan untuk memetakan kekuatan
dosen-peneliti di departemen, laboratorium dan pusat kajian di FK UGM,
penelitian dan publikasi yang telah dihasilkan, serta menetapkan indikator
sebagai ukuran pencapaian kinerja penelitian.
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Health Research Expo I, FK UGM
Gambar 1. Peta Jalan Peneliian FK UGM
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FEATURED RESEARCH
Health Research Expo I, FK UGM
Knowledge and Attitudes Towards Rotavirus Diarrhea And The Vaccine Amongst
Healthcare Providers In Yogyakarta Indonesia
Holly Seale1*, Mei Neni Sitaresmi2, Jarir Atthobari2, Anita E. Heywood1, Rajneesh Kaur1,
Raina C. MacIntyre1, Yati Soenarto2 and Retna Siwi Padmawati2
1
School of Public Health & Community Medicine, Faculty of Medicine, University of New
South Wales, Australia; 2Faculty of Medicine, Universitas Gadjah Mada (UGM),
Yogyakarta, Indonesia
* Correspondence: h.seale@unsw.edu.au
Background
Rotavirus has been identified as the most common pathogen associated with severe
diarrhoea. Two effective vaccines against the pathogen have been licensed. However,
many countries including Indonesia have yet to introduce the vaccine into their national
immunisation programs. This study aimed to examine the attitudes of healthcare
providers (HCPs) and other health stakeholders towards the pathogen and the vaccine.
Methods
Semi-structured in-depth interviews were undertaken in two districts of Yogyakarta
Province, Indonesia with nurses, midwives, primary care providers, pediatricians and
other health stakeholders. Thematic analysis was undertaken.
Results
Fourteen interviews were conducted between August and October 2013. We identified
that while participants do not consider diarrhea to be an important problem in Indonesia,
they do acknowledge that it can be serious if not properly treated. While the majority
had some level of knowledge about rotavirus, not all participants knew that a vaccine
was available. There were mixed feelings towards the need for the vaccine. Some felt
that the vaccine is not ranked as a priority as it is not listed on the national program.
However, others agreed there is a rationale for its use in Indonesia. The cost of the
vaccine (when sold in the private sector) was perceived to be the primary barrier
impacting on its use.
Conclusions
The high cost and the low priority given to this vaccine by the public health authorities
are the biggest obstacles impacting on the acceptance of this vaccine in Indonesia. HCPs
need to be reminded of the burden of disease associated with rotavirus. In addition,
reminding providers about the costs associated with treating severe cases versus the
costs associated with prevention may assist with improving the acceptance of HCPs
towards the vaccine. Promotion campaigns need to target the range of HCPs involved in
the provision of care to infants and pregnant women.
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Health Research Expo I, FK UGM
The Importance of Molecular Genetic Analysis for Diagnosis of Disease
Gunadi1, Rochadi1, Akhmad Makhmudi1, Kristy Iskandar2, Hisahide Nishio3, Aravinda
Chakravarti4
1
Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, UGM/Dr.
Sardjito Hospital; 2Faculty of Medicine, UGM/UGM Hospital; 3Kobe University
Graduate School of Medicine, Kobe, Japan; 4Johns Hopkins University School of
Medicine, Baltimore, MD, USA.
Contact: drgunadi@ugm.ac.id
Background
Molecular diagnosis of genetic disease is detection of various changes in DNA, RNA,
chromosome, or protein related to an inheritable disorder.We have performed
molecular analysis of the following genetic disorders: 1) Hirschsprung disease; 2)
Hypohidrotic ectodermal dysplasia; and 3) Spinal Muscular Atrophy.
Method
Three genetic markers (RET rs2435357, NRG1 rs16879552 and rs7835688) were
examined using TaqMan assays for association with Hirschsprung disease. To screen
an ED1 mutation, DHPLC and direct sequencing were performed in genomic DNA of
hypohidrotic ectodermal dysplasia patients. To investigate p.G381R could alter EDA
overall structure, electrostatic surface and molecular structure were analyzed. The
adenine number in SMN intron 3 in spinal muscular atrophy patients were
determined by GeneScan.
Result
Hirschsprung disease (HSCR): RET rs2435357 showed strongest association with HSCR
both by case-control analysis (p=2.5x10-8) and transmission disequillibrium test
(p=4.2x10-6). NRG1 rs7835688 was modestly associated with HSCR only by casecontrol analysis (p=4.3x10-3), whereas rs16879552 demonstrated no association
(p>0.097).
Hypohidrotic ectodermal dysplasia (HED): We identified two novel mutations,
p.L40fsX100 and p.G381R, in ED1 of HED patients. Simulation analysis suggested that
the p.G381R mutation hampers binding of EDA to its receptor via alteration of overall
EDA structure.
Spinal muscular atrophy (SMA): Almost all individuals, including healthy individuals,
SMA patients and SMA-like patients, carried only alleles with a normal polyadenine
tract. Hypomutability of the polyadenine tract in SMN intron 3 suggests the existence
of transcriptional mechanisms preventing alterations to open reading frame of
axonal SMN and not allowing variability in the protein structure of a-SMN.
Conclusion
Molecular genetic analysis may have a beneficial effect on early diagnosis of
inheritable disease, then, decrease its morbidity and mortality.
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Health Research Expo I, FK UGM
Multiple Markers for Early Identification of Nasopharyngeal Carcinoma
Susanna Hilda Hutajulu,1 Luh Putu Lusy Indrawati,2 Camelia Herdini,2 Jajah Fachiroh,3
Sagung Rai Indrasari,2 Bambang Hariwiyanto,2 Harijadi,4 Hesti Gunarti,5 Retno Dwi
Danarti,5 Sofia Mubarika Haryana,3 Astrid E. Greijer,6 I. Bing Tan,2,7 Jaap M.
Middeldorp6
1
Department of Internal Medicine, 2Department of Ear, Nose and Throat,
3
Department of Histology and Cell Biology, 4Department of Pathology, and
5
Department of Radiodiagnostic and Radiotherapy, Faculty of Medicine/Dr Sardjito
Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, 6Department of Pathology,
VU University Medical Center, Amsterdam, The Netherlands, 7Department of Ear,
Nose and Throat, The Netherlands Cancer Institute/Antoni van Leeuwenhoek
Hospital, Amsterdam, The Netherlands
Background
Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck cancer in
Indonesia and closely linked to active Epstein-Barr virus (EBV) infection. EBV-based
markers are proposed for identifying early stage of NPC allowing aberrant antibodies
against EBV and viral DNA load as screening tools. We performed a clinical,
serological and viral load study in subjects presenting with chronic symptoms in head
and neck to define the serologic response to EBV antigens and EBV DNA load and find
early onset NPC. Besides those markers, methylation analysis in the promoter of
tumor suppressor genes (TSGs) may serve as a complementary marker for identifying
early cases. This study also determined methylation status of multiple TSGs and
evaluated whether it may improve early detection.
Methods
A total of 217 individuals were recruited and underwent clinical examination. Blood
samples were taken from all subjects and nasopharyngeal brushing was collected
from the majority of individuals. Initial serology analysis was done by peptide-based
EBV IgA ELISA and confirmed with IgG immunoblot. Furthermore, nasopharyngeal
brushings from 53 NPC patients, 22 high risk subjects and 25 healthy EBV
carrierswere tested for analysis of methylation-specific PCR (MSP) using primers
targeting ten TSGs.
Results
As many as 75 (34.6%) subjects demonstrated positive EBV IgA ELISA with 23 (10.6%)
showing high response. Sixteen individuals (7.4%) had high IgG immunoblot score.
EBV DNA load was determined by real-time PCR in 65 seropositive patients and 28
(43.1%) of them showed a high level. Seropositive individuals with high viral load
were sent for diagnostic work-up. Seven cases revealed a nasopharyngeal mass by
CT-scan and three of them (1.4%) were histologically confimed as NPC, two of which
were early stage. Another case showed hyperplasia positive for EBV-encoded small
RNA (EBER). For methylation analysis, NPC samples showed high frequency of
methylation for individual TSGs (range from 29.2%-79.2%). A combination of five
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Health Research Expo I, FK UGM
methylation markers (RASSF1A, p16, WIF1, CHFR and RIZ1) gave best result to
discriminate NPC from healthy individuals with detection rate of 98%.
Conclusions
These results indicated that elevated EBV antibody combined with high viral load can
identify early NPC cases. Periodic follow-up is suggested for individuals revealing EBV
seropositivity and high viral DNA load to anticipate another new early case. Multiple
marker MSP was proposed as a complementary test in combination with EBV-based
markers.
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Health Research Expo I, FK UGM
The incremental cost-effectiveness of engaging private practitioners to refer
tuberculosis suspects to DOTS services in Jogjakarta, Indonesia
Yodi Mahendradhata, Ari Probandari, Riris A. Ahmad, Adi Utarini, Laksono
Trisnantoro, Lars Lindholm, Marieke J. van der Werf, Michael Kimerling, Marleen
Boelaert, Benjamin Johns, Patrick Van der Stuyft
Department of Public Health, Faculty of Medicine, Gadjah Mada University,
Jogjakarta, Indonesia; Centre for Health Service Management, Faculty of Medicine,
Gadjah Mada University, Jogjakarta, Indonesia; Epidemiology and Disease Control
Unit, Public Health Department, Institute of Tropical Medicine, Antwerp, Belgium;
Department of Public Health, Faculty of Medicine, Sebelas Maret University,
Surakarta, Indonesia; Epidemiology and Public Health Sciences, Public Health and
Clinical Medicine, Umeå University, Umeå, Sweden; KNCV Tuberculosis Foundation,
The Hague, The Netherlands; Department of Infectious Diseases, Tropical Medicine &
AIDS, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical
Center, University of Amsterdam, The Netherlands; Gorgas TB Initiative, UAB School
of Medicine, Division of Infectious Diseases, Birmingham, Alabama; WHO Country
Office for Indonesia, Jakarta, Indonesia
Background
We aimed to evaluate the incremental cost-effectiveness of engaging private
practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in
Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between
May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which
57.5% failed to reach a health center. The smear-positive rate among patients
reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306
(21.4%) new smear-positive cases were enrolled through the PPs strategy. The
incremental cost-effectiveness ratio per smear-positive case successfully treated for
the PPs strategy was US$351.66 (95% CI 322.84–601.33). On the basis of an
acceptability curve using the National TB control program's willingness-to-pay
threshold (US$448.61), we estimate the probability that the PPs strategy is costeffective at 66.8%. The strategy of engaging PPs was incrementally cost-effective,
although under specific conditions, most importantly a well-functioning public
directly observed treatment, short-course (DOTS) program.
Methods
We launched, in May 2004, an intervention to involve the PPs in Jogjakarta in TB
control. Private practitioners were encouraged to refer TB suspects to HCs for
diagnosis and treatment, but could also opt for treating their TB patients themselves
in accordance with national guidelines, using free drugs supplied by the National TB
control program. We identified the probability that a strategy is cost-effective using
the cost-effectiveness acceptability curve (CEAC). The CEAC was plotted as the
proportion ofthe Incremental Cost Effectiveness Ratio (ICER) estimates judged to be
cost-effective over the range of values of willingness-to-pay for an additional smear-
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Health Research Expo I, FK UGM
positive case successfully treated.We set a hypothetical willingness-to-pay threshold
based on the National TB control program's estimated marginal cost. We further
analyzed the sensitivity of total costs to input values that are likely to be under the
control of program managers. To do this, we assessed possible scenarios to the
CEACs:
Results
Eventually, only 410 PPs referred suspects during the study intake period. The
number of suspects (1,064) notified by the 410 PPs was much lower than the number
of suspects (10,878) notified through the HCs (Figure 1). Most of the suspects (57.5%)
notified and referred by PPs never reached a health center. The PPs strategy allowed
registering an additional 280 new smear-positive cases over 12 months.
• Sensitivity analysis on the total patient cost ratio between the two strategies
indicates that our estimate is robust to changes across a number of key variables
(Figure 2). Only when the cost for laboratory and consultation before DOT in
patients referred by PPs is at the lower bound of the 95% CI, costs to patients
notified by PPs are not substantially higher than to those notified by HCs.
• Average Cost-Effectiveness Ratio per smear-positive case successfully treated for
the HCs strategy was US$321.66 (95% CI 190.71–342.99), whereas Incremental
Cost-Effectiveness Ratio per smear-positive case successfully treated for the PPs
strategy was US$351.66 (95% CI 322.84–601.33)
• At a willingness-to-pay threshold for a smear-positive case successfully treated of
US$448.61 (the estimated National TB control program's marginal cost in 2004–
2005), the PPs strategy was incrementally cost-effective in 66.8% of simulation
iterations (Figure 3). Adjusting the DOT consultation cost in HCs to the most
efficient observed value (US$1.04) increased this percentage to 83.1%, whereas
lowering the smear-positive rate to 20% and increasing the proportion of suspects
who reached the HCs to 62% reduced the percentage to 63.1%. Lowering the
willingness-to-pay threshold obviously reduces all the above percentages and at,
for instance, US$400 the PPs strategy is less than 50% likely to be cost-effective in
most scenarios.
Conclusions
We have shown that an intervention to engage PPs to refer TB suspects to DOTS
services can be introduced relatively successfully, that this led to detecting or at least
notifying many additional smear-positive cases, and that it formed a path for a
significant number of such cases into the National TB control program, where they
had excellent treatment outcomes. Most importantly, we have showed that our
intervention was cost-effective, albeit under specific conditions and given high
commitment for intensive dialogue and supervision. Before scaling up or replicating
our intervention, one should consider these enabling factors, but also ways to ensure
better screening by PPs and referral effectiveness, possible alternative strategies
(e.g., community participation, involvement of hospitals), and the need for
strengthening of the public sector.
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Health Research Expo I, FK UGM
Frequent Deregulation Of Rb1 Expression By Loss Of Imprinting In Human
Hepatocellular Carcinoma
Sumadi Lukman Anwar1,3, Till Krech1, Britta Hasemeier1, Elisa Schipper1, Nora
Schweitzer2, Arndt Vogel2, Hans Kreipe1, Ulrich Lehmann1
1Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany;
2Department of Gastroenterology, Hepatology and Endocrinology, Medizinische
Hochschule Hannover, Hannover, Germany; 3Department of Surgery, Faculty of
Medicine Universitas Gadjah Mada, Yogyakarta, Indonesia,
Contact: sl.anwar@ugm.ac.id
Background
The tumour suppressor gene RB1 is frequently silenced in many different types of
human cancer including hepatocellular carcinoma (HCC). However, mutations of the
RB1 gene are relatively rare in HCC.
Method
A systematic screen for the identification of imprinted genes deregulated in human
HCC revealed that RB1 shows imprint abnormalities in a high proportion of primary
patient samples. Quantitative DNA methylation analysis and allele specific
methylation were performed as well as expression of main RB1 and alternative
transcript were performed in HCC cell lines and primary HCC tissues.
Results
Altogether 40% of the HCC specimens (16/40) showed hyper -or hypomethylation at
the CpG island in intron 2 of the RB1 gene. Demethylation at the intron 2 CpG island
by DNMT1 knockdown or aza-deoxycytidine (DAC) treatment stimulated expression
of RB1-E2B transcript accompanied by diminished RB1 main transcript expression. No
aberrant DNA methylation was found at the RB1 locus in hepatocellular adenoma
(HCA, n=10), focal nodular hyperplasia (FNH, n=5) and their corresponding adjacent
liver tissue specimens. Deregulated RB1 expression due to hyper- or
hypomethylation in intron 2 of the RB1 gene is found in tumours without loss of
heterozygosity and is associated with a decrease in overall survival (p = 0.032) if
caused by hypermethylation of CpG85.
Conclusion
This unequivocally demonstrates that loss of imprinting represents an important
additional mechanism for RB1 pathway inactivation in human HCC complementing
well-described molecular defects.
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Fokus #1
Kebugaran, Penuaan Dan Gaya Hidup Sehat
A.
B.
C.
D.
E.
Genetika dan penyakit
Gaya hidup yang mempengaruhi kesehatan
Lingkungan dan gizi
Rehabilitative and palliative care
Mental health problems
Health Research Expo I, FK UGM
A. Genetika dan penyakit
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Discrepancy of acetylation status prediction using genetic polymorphism
in the NAT-2 Coding region examination with acetylsulphadimidine
measurement.
Mammograohic density thresholding method, estradiol, and estrogen
receptor a gen polymorphism (ESR 1) as breast cancer predictor.
Clinical characteristics and gene mutation of tuberculosis sclerosis
patients in Indonesia.
Neurofibromatosis tipe 1: karakteristik gambaran klinis dan indentifikasi
mutasi gen.
Hubungan polimorfisme gen ACE dengan keparahan dan luaran stroke
iskemik.
Association of ondansetron serum concentration and polimorphisms of
CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of
chemoterapy induced nausea and vomiting.
Hubungan antara interaksi polimorfisme gen UCP2, KCNJ11 dan TCF7L2
dengan asupan tinggi lemak dan karbohidrat sederhana dalam kaitannya
dengan kejadian obesitas.
Polymorphism of the DATI and DRD4 genes are not associated with ADHD
in Indonesia children.
Hubungan polimorfisme alel CYP2A6*4 dan CYP2A6*9 dengan kadar
dihydroartemisinin-piperakuin pada penderita malaria falciparum.
Pengaruh polimorfisme reseptor Fc gamma IIIA (FcJRIIIA) dan jumlah sel
efektor terhadap respon kemoterapi trastuzumab pada pasien kanker
payudara lokal lanjut dan metastasis dengan HER2/NEU positif.
Polimorfisme gen p53Arg72Pro, MDM2SNP309, HER2Ile655Val, ER594
A>G, p21 Ser31Arg dan FGFR2 rs2981582; studi risiko kanker payudara
onset dini di Yogyakarta.
Hubungan antara mutasi gen filaggrin dengan dermatiti atopik. Kajian
mutasi gena filaggrin tipe asia di suku Jawa.
Distribusi dan dinamika genotype serta analisis gen vp4, vp7, nsp2, nsp4
dan nsp5 rotavirus penyebab diare anak balita di indonesia.
Korelasi Polimorfisme Genetik Sitokrom P450 2A6 dan 2B6 dengan
Kuantitas Merokok di Kota Yogyakarta
Cytoarchitecture of the olfactory bulb in the laggard mutant mouse.
Prognostic Impact Of Metastatic Status In Patients With
Nasopharyngeal Carcinoma
Factors Influencing Treatment Adherence Of Nasopharyngeal
Cancer And The Clinical Outcomes: A Hospital-Based Study
Differential expression of microRNA-21 on nasopharyngeal
carcinoma plasma patient
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Health Research Expo I, FK UGM
19. Case report on pediatric nasopharyngeal carcinoma at Dr. Sardjito
Hospital, Yogyakarta
20. Results of Treatment With Neoadjuvant Cisplatin-5fu In Locally
Advanced Nasopharyngeal Carcinoma: A Local Experience
21. Geriatrics with Nasopharyngeal Cancer
22. The Expression of miR-141 in Patients with Nasopharyngeal Cancer
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Health Research Expo I, FK UGM
Discrepancy of acetylation status prediction using genetic polymorphisms in the
NAT-2 coding region examination with acetylsulphadimidine measurement
Erna Kristin, Dwi Aris Agung Nugrahaningsih, Mustofa
Department of Pharmacology and Therapy, Faculty of Medicine, UGM
Contact: erna_kristin@yahoo.co.uk
Background
N-acetyltransferase2 (NAT2) gene polymorphism is known to be associated with the
isoniazid hepatotoxicity. NAT2 polymorphism results in slow and fast acetylator
phenotype. Using NAT2 polymorphism to predict acetylator status is a future project
to individualized isoniazid therapy.
Methods
The aim of our study is to investigate the NAT2 genotype in Javanese, one of
dominant ethnics in Indonesia, to predict hepatotoxicity in tuberculosis (TB) patients
receiving isoniazid in combination with other TB drugs. We examined NAT2
polymorphisms on coding region using PCR direct sequencing. We also determined
the acetylation status by measuring acetyl sulphadimidine.
Results
Nineteen subjects were enrolled in this study. Most of them were male. The age
average was 43.58 ± 15.43 years old. Their average body mass index and serum
transaminase were within normal range. In this study, we identified 11 different
NAT2 genotypes. We found that the major NAT2 genotypes were NAT2*4/*4
(31.58%) and NAT2*6A/*6A (21.05%). Based on the genotype prediction, most of the
subjects were slow acetylator (63.16%). Meanwhile based on acetylation status
determination using acetylsulphadimidine measurement in the urine, 52.63% were
fast acetylator and 47.37% were slow acetylator. The serum transaminase increase
also tended to be higher on slow acetylator group compared with those on fast
acetylator group, even though the different was not statistically significant.
Interestingly, we found discrepancy between acetylation status prediction using
NAT2 genotype and acetylsulphadimidine examination.
Conclusions
We find that NAT2 gene polymorphism on coding region do not predict the
acetylator status accurately. We suggest that NAT2 gene polymorphism might have
to be examined on promoter region for better prediction of acetylation status.
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Health Research Expo I, FK UGM
Mammographic density thresholding method, estradiol level and estrogen
receptorɲ gene polymorphism (ESR1) as breast cancer predictor
Lina Choridah1, Teguh Aryandono2, Arif Faisal1, Ahmad Hamim Sadewa3
Department of Radiology. 2Department of Surgery, Faculty of Medicine, Universitas
Gadjah Mada. 3Department of Biochemistry, Faculty of Medicine, Universitas Gadjah
Mada.
Contact:linachoridah@ugm.ac.id
1
Background
Estrogen is believed to play an important role in the development and progression of
breast cancer. Mammographic densities equivalent to the cell proliferation, estradiol
and ESR 1 Gene Polymorfism allegedly acted as a predictor of breast cancer.
Methods
We performed an observational study, data were collected prospectively using a
cohort study design. Subjects were women who came to oncologic clinic for
mammographic screening, with either high or low breast density. Subjects were then
grouped into two, with and without breast cancer. The data were analyzed using
relative risk and multivariate logistic regression.
Results
Women with PMD 25-34% , 35-49%, 50-64% and >65% had relative risk of 1.67 (95%
CI, 0.47 to 5.89), 3.4 (95% CI, 1.16 to 9.97), 3.43 (95% CI, 31.19 to 9.88) and 3.45 (95%
CI, 1.174 to 10.14%) times, respectively, compared to PMD
Buku Abstrak
Discover, Learn, Share
Fakultas Kedokteran
Universitas Gadjah Mada
2016
Health Research Expo I, FK UGM
Daftar Isi
1.
2.
3.
4.
5.
6.
Pengantar
Peta Jalan Penelitian
Featured research
Abstrak Fokus 1 : Kebugaran, Penuaan Dan Gaya Hidup Sehat
Abstrak Fokus 2 : Teknologi Intervensi Medik dan Kesehatan Masyarakat
Daftar Publikasi Jurnal International
TIM PENYUSUN
Penanggung jawab
Ketua Tim Penyusun Buku
Ketua Tim Pameran Poster
Ketua Seminar
Asisten
Editor Buku Abstrak
Layouter
Sekretariat dan Panitia
: Prof. dr. Adi Utarini, M. Sc, MPH, Ph.D
: Harry Freitag LM, S.Gz, M.Sc
: Eri Yanuar Akhmad BS, S.Kep., Ns
: dr. M. Ary Zucha, Ph.D
: dr. Renata Uli Aviola
: dr. Dian Kesumapramudya Nurputra, Ph.D
dr. Junaedy Yunus, M.Sc, Ph.D
Melyza Perdana, S.Kep, MN
Harry Freitag Luglio M, S.Gz, M.Sc, RD
: Ceria Ciptanurani, S.Gz
Muhammad Cahyono Tito Handoyo
Rasyid Herlambang Wicaksono
Dimas Septian Eko Wahyu Sumunar
: Glory Hapsara Suryandari, S.Pd
Rahma Hanggia Iswandi, S.I.Kom
: hre.fkugm@gmail.com
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Health Research Expo I, FK UGM
PENGANTAR
Assalaamu’alaikum Wr Wb,
Penelitian merupakan salah satu pilar Tridharma Perguruan Tinggi yang memberikan
kontribusi nilai yang kompetitif dalam kinerja, baik di tingkat Fakultas maupun
Universitas. Dalam hal ini, fungsi utama Fakultas adalah menciptakan atmosfer
penelitian yang kuat sebagai sistem pendukung bagi para dosen dan peneliti
(termasuk mahasiswa di berbagai tingkatan pendidikan).
Agar kegiatan penelitian dapat berkembang, minimal diperlukan tiga pilar sistem
pendukung, yaitu:
1. Tata kelola penelitian (research governance);
2. Pelaksanaan penelitian (research production); dan
3. Diseminasi hasil-hasil penelitian (research dissemination).
Kegiatan ini digagas bermula dari pertanyaan sederhana dari mahasiswa tingkat
sarjana: “Bagaimana kami dapat mengetahui penelitian-penelitian yang sedang
dikerjakan oleh para dosen di FK UGM?”. Pertanyaan sederhana ini ternyata jauh dari
sederhana untuk menjawabnya. Mahasiswa miskin informasi sekalipun berada di
institusi Fakultas Kedokteran yang kaya akan kegiatan penelitian dan publikasi di
jurnal internasional. Bahkan Fakultas Kedokteran menempati posisi tertinggi di UGM
dalam hal jumlah kegiatan penelitian yang dilakukan, dana penelitian yang dikelola
serta jurnal internasional. Kondisi ini tentu tidak dapat dibiarkan.
Oleh karena itu, dalam rangkaian Dies 70th Fakultas Kedokteran UGM, digagas
kegiatan Health Research Expo I 2016 yang memfokuskan pada diseminasi hasil-hasil
penelitian dari para dosen-peneliti-mahasiswa di lingkungan Fakultas Kedokteran
UGM. Tujuan kegiatan ini adalah memberikan ide-ide kepada mahasiswa dengan
menampilkan penelitian yang sedang ataupun telah berlangsung serta memberikan
informasi kontak email para dosen-peneliti yang dapat dihubungi mahasiswa apabila
mereka tertarik dalam bidang penelitian para dosen-peneliti. Hal ini menjadi pintu
awal bagi mahasiswa untuk memperoleh informasi penelitian yang dikerjakan di
institusi Fakultas Kedokteran UGM. Cara diseminasi yang digunakan terutama adalah
melalui media buku kompilasi abstrak penelitian, seminar untuk mengawali pameran
poster yang akan digelar selama 1 bulan, serta diseminasi melalui website kanal
pengetahuan
dan
informasi
Fakultas
Kedokteran
UGM.
(www.kanalpengetahuan.fk.ugm.ac.id).
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Health Research Expo I, FK UGM
Dengan kegiatan ini, kami berharap minat kegiatan penelitian mahasiswa baik di
tingkat sarjana maupun pascasarjana serta dosen-peneliti menjadi semakin
berkembang. Kami percaya bahwa diantara sekian banyak mahasiswa, akan
bermunculan peneliti-peneliti handal yang dibutuhkan oleh bangsa Indonesia di masa
mendatang. Selain itu, kami berharap pula bahwa kegiatan Health Research Expo
seterusnya akan menjadi bagian dari budaya Fakultas dalam memperingati puncak
acara Dies Fakultas Kedokteran UGM.
Kami mengucapkan terima kasih atas partisipasi seluruh dosen-peneliti dalam
kegiatan ini, serta atas kerja keras para dosen dan staf kependidikan di tim buku
abstrak, tim pameran poster serta tim seminar. Segala kekurangan mohon dapat
disampaikan kepada kami melalui email hre.fkugm@gmail.com, untuk dapat
diperbaiki di masa mendatang. Semoga kegiatan ini memberikan manfaat bagi kita
semua. Amin.
Wassalamu’alaikum Wr. Wb.
Prof. dr. Adi Utarini M.Sc, MPH, Ph.D
Wakil Dekan Bidang Penelitian, Pengabdian Masyarakat dan Kerjasama
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Health Research Expo I, FK UGM
PETA JALAN PENELITIAN DI FK UGM
Dokumen peta jalan (road map) penelitian disusun dengan beberapa
pemikiran yang melandasi relevansinya. Secara umum, relevansinya adalah
sebagai berikut:
1. Untuk mengukur pemahaman internal mengenai penelitianpenelitian yang dilakukan oleh institusi serta menggali pemikiran
tentang prioritas penelitian;
2. Mengidentifikasi peluang perbaikan dan memberikan rekomendasi
sistem dan proses penelitian kedepan;
3. Memetakan dan merencanakan pendekatan implementasi peta jalan
penelitian dengan serangkaian inisiatif dan pencapaian kinerja;
4. Meningkatkan komunikasi dengan para peneliti, institusi penelitian
dan pendidikan, serta para pemangku kepentingan;
5. Mendeskripsikan manfaat yang diharapkan dan mengidentifikasi
ukuran keberhasilan dari investasi untuk penelitian.
Tujuan penyusunan peta jalan penelitian ini adalah untuk
menetapkan strategi penelitian FK UGM yang terukur dan
mengkomunikasikannya kepada para peneliti, pemangku kepentingan di
Daerah Istimewa Yogyakarta, nasional, internasional serta kepada lembagalembaga yang memberikan dana penelitian. Dengan tersedianya dokumen
ini, diharapkan pula akan memudahkan para peneliti untuk meningkatkan
daya saing di tingkatnasional dan internasional.
Proses penyusunan dokumen ini diawali dengan studi literatur
mengenai berbagai bentuk dokumen peta jalan riset, bukti-bukti mengenai
masalah kesehatan nasional dan global, sumber pendanaan penelitian serta
serangkaian proses konsultasi dengan para pemangku kepentingan baik
internal maupun eksternal. Proses konsultasi dilaksanakan dalam empat kali
pertemuan uji public draft peta jalan riset. Uji publik pertama dilakukan
dengan mengundang para koordinator penelitian, pusat-pusat dan kelompok
kajian penelitian serta para peneliti di lingkungan FK-UGM. Uji publik kedua
melibatkan para kepala bagian, para peneliti dan komisi 3 Senat Fakultas
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Health Research Expo I, FK UGM
Kedokteran UGM. Uji publik ketiga dan keempat menghadirkan para
pemangku kepentingan eksternal, yaitu dari Daerah Istimewa Yogyakarta
(RSUP dr. Sardjito, RS UGM, DinasKesehatan Daerah Istimewa Yogyakarta,
Kagama Kedokteran, Dewan Riset Daerah Istimewa Yogyakarta) dan nasional
(Kementerian Riset Teknologi dan Pendidikan Tinggi serta Kementerian
Kesehatan).
Melalui serangkaian proses tersebut, maka prioritas riset FK-UGM terdiri
dari dua fokus, yaitu kebugaran, penuaan, dan gaya hidup sehat serta teknologi
intervensi medik dan kesehatan masyarakat. Fokus pertama terkait kebugaran,
penuaan dan gaya hidup sehat merupakan riset yang berfokus pada pemahaman
mekanisme yang mendasari masalah kebugaran, penuaan dan gaya hidup, dan
mencakup topik mengenai genetika dan penyakit, gaya hidup yang
mempengaruhi kesehatan, lingkungan dan gizi, perawatan rehabilitatif dan
paliatif, dan problem kesehatan mental. Sementara fokus kedua terkait
teknologi intervensi medik dan kesehatan masyarakat merupakan riset yang
berfokus pada pasien untuk mengidentifikasi teknologi-cara baru untuk
pembelajaran, pencegahan, diagnosis, pengobatan penyakit, dan intervensi
untuk meningkatkan kesehatan masyarakat. Pada setiap fokus penelitian, dapat
dikembangkan tiga jalur ruang penelitian, yaitu penelitian yang memiliki orientasi
untuk memecahkan masalah kesehatan yang menjadi tantangan sosial,
penelitian yang menghasilkan produk kompetitif, serta penelitian yang
menghasilkan temuan sains baru (Gambar 1).
Peta jalan ini selanjutnya akan digunakan untuk memetakan kekuatan
dosen-peneliti di departemen, laboratorium dan pusat kajian di FK UGM,
penelitian dan publikasi yang telah dihasilkan, serta menetapkan indikator
sebagai ukuran pencapaian kinerja penelitian.
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Health Research Expo I, FK UGM
Gambar 1. Peta Jalan Peneliian FK UGM
vii
FEATURED RESEARCH
Health Research Expo I, FK UGM
Knowledge and Attitudes Towards Rotavirus Diarrhea And The Vaccine Amongst
Healthcare Providers In Yogyakarta Indonesia
Holly Seale1*, Mei Neni Sitaresmi2, Jarir Atthobari2, Anita E. Heywood1, Rajneesh Kaur1,
Raina C. MacIntyre1, Yati Soenarto2 and Retna Siwi Padmawati2
1
School of Public Health & Community Medicine, Faculty of Medicine, University of New
South Wales, Australia; 2Faculty of Medicine, Universitas Gadjah Mada (UGM),
Yogyakarta, Indonesia
* Correspondence: h.seale@unsw.edu.au
Background
Rotavirus has been identified as the most common pathogen associated with severe
diarrhoea. Two effective vaccines against the pathogen have been licensed. However,
many countries including Indonesia have yet to introduce the vaccine into their national
immunisation programs. This study aimed to examine the attitudes of healthcare
providers (HCPs) and other health stakeholders towards the pathogen and the vaccine.
Methods
Semi-structured in-depth interviews were undertaken in two districts of Yogyakarta
Province, Indonesia with nurses, midwives, primary care providers, pediatricians and
other health stakeholders. Thematic analysis was undertaken.
Results
Fourteen interviews were conducted between August and October 2013. We identified
that while participants do not consider diarrhea to be an important problem in Indonesia,
they do acknowledge that it can be serious if not properly treated. While the majority
had some level of knowledge about rotavirus, not all participants knew that a vaccine
was available. There were mixed feelings towards the need for the vaccine. Some felt
that the vaccine is not ranked as a priority as it is not listed on the national program.
However, others agreed there is a rationale for its use in Indonesia. The cost of the
vaccine (when sold in the private sector) was perceived to be the primary barrier
impacting on its use.
Conclusions
The high cost and the low priority given to this vaccine by the public health authorities
are the biggest obstacles impacting on the acceptance of this vaccine in Indonesia. HCPs
need to be reminded of the burden of disease associated with rotavirus. In addition,
reminding providers about the costs associated with treating severe cases versus the
costs associated with prevention may assist with improving the acceptance of HCPs
towards the vaccine. Promotion campaigns need to target the range of HCPs involved in
the provision of care to infants and pregnant women.
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Health Research Expo I, FK UGM
The Importance of Molecular Genetic Analysis for Diagnosis of Disease
Gunadi1, Rochadi1, Akhmad Makhmudi1, Kristy Iskandar2, Hisahide Nishio3, Aravinda
Chakravarti4
1
Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, UGM/Dr.
Sardjito Hospital; 2Faculty of Medicine, UGM/UGM Hospital; 3Kobe University
Graduate School of Medicine, Kobe, Japan; 4Johns Hopkins University School of
Medicine, Baltimore, MD, USA.
Contact: drgunadi@ugm.ac.id
Background
Molecular diagnosis of genetic disease is detection of various changes in DNA, RNA,
chromosome, or protein related to an inheritable disorder.We have performed
molecular analysis of the following genetic disorders: 1) Hirschsprung disease; 2)
Hypohidrotic ectodermal dysplasia; and 3) Spinal Muscular Atrophy.
Method
Three genetic markers (RET rs2435357, NRG1 rs16879552 and rs7835688) were
examined using TaqMan assays for association with Hirschsprung disease. To screen
an ED1 mutation, DHPLC and direct sequencing were performed in genomic DNA of
hypohidrotic ectodermal dysplasia patients. To investigate p.G381R could alter EDA
overall structure, electrostatic surface and molecular structure were analyzed. The
adenine number in SMN intron 3 in spinal muscular atrophy patients were
determined by GeneScan.
Result
Hirschsprung disease (HSCR): RET rs2435357 showed strongest association with HSCR
both by case-control analysis (p=2.5x10-8) and transmission disequillibrium test
(p=4.2x10-6). NRG1 rs7835688 was modestly associated with HSCR only by casecontrol analysis (p=4.3x10-3), whereas rs16879552 demonstrated no association
(p>0.097).
Hypohidrotic ectodermal dysplasia (HED): We identified two novel mutations,
p.L40fsX100 and p.G381R, in ED1 of HED patients. Simulation analysis suggested that
the p.G381R mutation hampers binding of EDA to its receptor via alteration of overall
EDA structure.
Spinal muscular atrophy (SMA): Almost all individuals, including healthy individuals,
SMA patients and SMA-like patients, carried only alleles with a normal polyadenine
tract. Hypomutability of the polyadenine tract in SMN intron 3 suggests the existence
of transcriptional mechanisms preventing alterations to open reading frame of
axonal SMN and not allowing variability in the protein structure of a-SMN.
Conclusion
Molecular genetic analysis may have a beneficial effect on early diagnosis of
inheritable disease, then, decrease its morbidity and mortality.
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Health Research Expo I, FK UGM
Multiple Markers for Early Identification of Nasopharyngeal Carcinoma
Susanna Hilda Hutajulu,1 Luh Putu Lusy Indrawati,2 Camelia Herdini,2 Jajah Fachiroh,3
Sagung Rai Indrasari,2 Bambang Hariwiyanto,2 Harijadi,4 Hesti Gunarti,5 Retno Dwi
Danarti,5 Sofia Mubarika Haryana,3 Astrid E. Greijer,6 I. Bing Tan,2,7 Jaap M.
Middeldorp6
1
Department of Internal Medicine, 2Department of Ear, Nose and Throat,
3
Department of Histology and Cell Biology, 4Department of Pathology, and
5
Department of Radiodiagnostic and Radiotherapy, Faculty of Medicine/Dr Sardjito
Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, 6Department of Pathology,
VU University Medical Center, Amsterdam, The Netherlands, 7Department of Ear,
Nose and Throat, The Netherlands Cancer Institute/Antoni van Leeuwenhoek
Hospital, Amsterdam, The Netherlands
Background
Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck cancer in
Indonesia and closely linked to active Epstein-Barr virus (EBV) infection. EBV-based
markers are proposed for identifying early stage of NPC allowing aberrant antibodies
against EBV and viral DNA load as screening tools. We performed a clinical,
serological and viral load study in subjects presenting with chronic symptoms in head
and neck to define the serologic response to EBV antigens and EBV DNA load and find
early onset NPC. Besides those markers, methylation analysis in the promoter of
tumor suppressor genes (TSGs) may serve as a complementary marker for identifying
early cases. This study also determined methylation status of multiple TSGs and
evaluated whether it may improve early detection.
Methods
A total of 217 individuals were recruited and underwent clinical examination. Blood
samples were taken from all subjects and nasopharyngeal brushing was collected
from the majority of individuals. Initial serology analysis was done by peptide-based
EBV IgA ELISA and confirmed with IgG immunoblot. Furthermore, nasopharyngeal
brushings from 53 NPC patients, 22 high risk subjects and 25 healthy EBV
carrierswere tested for analysis of methylation-specific PCR (MSP) using primers
targeting ten TSGs.
Results
As many as 75 (34.6%) subjects demonstrated positive EBV IgA ELISA with 23 (10.6%)
showing high response. Sixteen individuals (7.4%) had high IgG immunoblot score.
EBV DNA load was determined by real-time PCR in 65 seropositive patients and 28
(43.1%) of them showed a high level. Seropositive individuals with high viral load
were sent for diagnostic work-up. Seven cases revealed a nasopharyngeal mass by
CT-scan and three of them (1.4%) were histologically confimed as NPC, two of which
were early stage. Another case showed hyperplasia positive for EBV-encoded small
RNA (EBER). For methylation analysis, NPC samples showed high frequency of
methylation for individual TSGs (range from 29.2%-79.2%). A combination of five
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Health Research Expo I, FK UGM
methylation markers (RASSF1A, p16, WIF1, CHFR and RIZ1) gave best result to
discriminate NPC from healthy individuals with detection rate of 98%.
Conclusions
These results indicated that elevated EBV antibody combined with high viral load can
identify early NPC cases. Periodic follow-up is suggested for individuals revealing EBV
seropositivity and high viral DNA load to anticipate another new early case. Multiple
marker MSP was proposed as a complementary test in combination with EBV-based
markers.
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Health Research Expo I, FK UGM
The incremental cost-effectiveness of engaging private practitioners to refer
tuberculosis suspects to DOTS services in Jogjakarta, Indonesia
Yodi Mahendradhata, Ari Probandari, Riris A. Ahmad, Adi Utarini, Laksono
Trisnantoro, Lars Lindholm, Marieke J. van der Werf, Michael Kimerling, Marleen
Boelaert, Benjamin Johns, Patrick Van der Stuyft
Department of Public Health, Faculty of Medicine, Gadjah Mada University,
Jogjakarta, Indonesia; Centre for Health Service Management, Faculty of Medicine,
Gadjah Mada University, Jogjakarta, Indonesia; Epidemiology and Disease Control
Unit, Public Health Department, Institute of Tropical Medicine, Antwerp, Belgium;
Department of Public Health, Faculty of Medicine, Sebelas Maret University,
Surakarta, Indonesia; Epidemiology and Public Health Sciences, Public Health and
Clinical Medicine, Umeå University, Umeå, Sweden; KNCV Tuberculosis Foundation,
The Hague, The Netherlands; Department of Infectious Diseases, Tropical Medicine &
AIDS, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical
Center, University of Amsterdam, The Netherlands; Gorgas TB Initiative, UAB School
of Medicine, Division of Infectious Diseases, Birmingham, Alabama; WHO Country
Office for Indonesia, Jakarta, Indonesia
Background
We aimed to evaluate the incremental cost-effectiveness of engaging private
practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in
Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between
May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which
57.5% failed to reach a health center. The smear-positive rate among patients
reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306
(21.4%) new smear-positive cases were enrolled through the PPs strategy. The
incremental cost-effectiveness ratio per smear-positive case successfully treated for
the PPs strategy was US$351.66 (95% CI 322.84–601.33). On the basis of an
acceptability curve using the National TB control program's willingness-to-pay
threshold (US$448.61), we estimate the probability that the PPs strategy is costeffective at 66.8%. The strategy of engaging PPs was incrementally cost-effective,
although under specific conditions, most importantly a well-functioning public
directly observed treatment, short-course (DOTS) program.
Methods
We launched, in May 2004, an intervention to involve the PPs in Jogjakarta in TB
control. Private practitioners were encouraged to refer TB suspects to HCs for
diagnosis and treatment, but could also opt for treating their TB patients themselves
in accordance with national guidelines, using free drugs supplied by the National TB
control program. We identified the probability that a strategy is cost-effective using
the cost-effectiveness acceptability curve (CEAC). The CEAC was plotted as the
proportion ofthe Incremental Cost Effectiveness Ratio (ICER) estimates judged to be
cost-effective over the range of values of willingness-to-pay for an additional smear-
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Health Research Expo I, FK UGM
positive case successfully treated.We set a hypothetical willingness-to-pay threshold
based on the National TB control program's estimated marginal cost. We further
analyzed the sensitivity of total costs to input values that are likely to be under the
control of program managers. To do this, we assessed possible scenarios to the
CEACs:
Results
Eventually, only 410 PPs referred suspects during the study intake period. The
number of suspects (1,064) notified by the 410 PPs was much lower than the number
of suspects (10,878) notified through the HCs (Figure 1). Most of the suspects (57.5%)
notified and referred by PPs never reached a health center. The PPs strategy allowed
registering an additional 280 new smear-positive cases over 12 months.
• Sensitivity analysis on the total patient cost ratio between the two strategies
indicates that our estimate is robust to changes across a number of key variables
(Figure 2). Only when the cost for laboratory and consultation before DOT in
patients referred by PPs is at the lower bound of the 95% CI, costs to patients
notified by PPs are not substantially higher than to those notified by HCs.
• Average Cost-Effectiveness Ratio per smear-positive case successfully treated for
the HCs strategy was US$321.66 (95% CI 190.71–342.99), whereas Incremental
Cost-Effectiveness Ratio per smear-positive case successfully treated for the PPs
strategy was US$351.66 (95% CI 322.84–601.33)
• At a willingness-to-pay threshold for a smear-positive case successfully treated of
US$448.61 (the estimated National TB control program's marginal cost in 2004–
2005), the PPs strategy was incrementally cost-effective in 66.8% of simulation
iterations (Figure 3). Adjusting the DOT consultation cost in HCs to the most
efficient observed value (US$1.04) increased this percentage to 83.1%, whereas
lowering the smear-positive rate to 20% and increasing the proportion of suspects
who reached the HCs to 62% reduced the percentage to 63.1%. Lowering the
willingness-to-pay threshold obviously reduces all the above percentages and at,
for instance, US$400 the PPs strategy is less than 50% likely to be cost-effective in
most scenarios.
Conclusions
We have shown that an intervention to engage PPs to refer TB suspects to DOTS
services can be introduced relatively successfully, that this led to detecting or at least
notifying many additional smear-positive cases, and that it formed a path for a
significant number of such cases into the National TB control program, where they
had excellent treatment outcomes. Most importantly, we have showed that our
intervention was cost-effective, albeit under specific conditions and given high
commitment for intensive dialogue and supervision. Before scaling up or replicating
our intervention, one should consider these enabling factors, but also ways to ensure
better screening by PPs and referral effectiveness, possible alternative strategies
(e.g., community participation, involvement of hospitals), and the need for
strengthening of the public sector.
7
Health Research Expo I, FK UGM
Frequent Deregulation Of Rb1 Expression By Loss Of Imprinting In Human
Hepatocellular Carcinoma
Sumadi Lukman Anwar1,3, Till Krech1, Britta Hasemeier1, Elisa Schipper1, Nora
Schweitzer2, Arndt Vogel2, Hans Kreipe1, Ulrich Lehmann1
1Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany;
2Department of Gastroenterology, Hepatology and Endocrinology, Medizinische
Hochschule Hannover, Hannover, Germany; 3Department of Surgery, Faculty of
Medicine Universitas Gadjah Mada, Yogyakarta, Indonesia,
Contact: sl.anwar@ugm.ac.id
Background
The tumour suppressor gene RB1 is frequently silenced in many different types of
human cancer including hepatocellular carcinoma (HCC). However, mutations of the
RB1 gene are relatively rare in HCC.
Method
A systematic screen for the identification of imprinted genes deregulated in human
HCC revealed that RB1 shows imprint abnormalities in a high proportion of primary
patient samples. Quantitative DNA methylation analysis and allele specific
methylation were performed as well as expression of main RB1 and alternative
transcript were performed in HCC cell lines and primary HCC tissues.
Results
Altogether 40% of the HCC specimens (16/40) showed hyper -or hypomethylation at
the CpG island in intron 2 of the RB1 gene. Demethylation at the intron 2 CpG island
by DNMT1 knockdown or aza-deoxycytidine (DAC) treatment stimulated expression
of RB1-E2B transcript accompanied by diminished RB1 main transcript expression. No
aberrant DNA methylation was found at the RB1 locus in hepatocellular adenoma
(HCA, n=10), focal nodular hyperplasia (FNH, n=5) and their corresponding adjacent
liver tissue specimens. Deregulated RB1 expression due to hyper- or
hypomethylation in intron 2 of the RB1 gene is found in tumours without loss of
heterozygosity and is associated with a decrease in overall survival (p = 0.032) if
caused by hypermethylation of CpG85.
Conclusion
This unequivocally demonstrates that loss of imprinting represents an important
additional mechanism for RB1 pathway inactivation in human HCC complementing
well-described molecular defects.
8
Fokus #1
Kebugaran, Penuaan Dan Gaya Hidup Sehat
A.
B.
C.
D.
E.
Genetika dan penyakit
Gaya hidup yang mempengaruhi kesehatan
Lingkungan dan gizi
Rehabilitative and palliative care
Mental health problems
Health Research Expo I, FK UGM
A. Genetika dan penyakit
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Discrepancy of acetylation status prediction using genetic polymorphism
in the NAT-2 Coding region examination with acetylsulphadimidine
measurement.
Mammograohic density thresholding method, estradiol, and estrogen
receptor a gen polymorphism (ESR 1) as breast cancer predictor.
Clinical characteristics and gene mutation of tuberculosis sclerosis
patients in Indonesia.
Neurofibromatosis tipe 1: karakteristik gambaran klinis dan indentifikasi
mutasi gen.
Hubungan polimorfisme gen ACE dengan keparahan dan luaran stroke
iskemik.
Association of ondansetron serum concentration and polimorphisms of
CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of
chemoterapy induced nausea and vomiting.
Hubungan antara interaksi polimorfisme gen UCP2, KCNJ11 dan TCF7L2
dengan asupan tinggi lemak dan karbohidrat sederhana dalam kaitannya
dengan kejadian obesitas.
Polymorphism of the DATI and DRD4 genes are not associated with ADHD
in Indonesia children.
Hubungan polimorfisme alel CYP2A6*4 dan CYP2A6*9 dengan kadar
dihydroartemisinin-piperakuin pada penderita malaria falciparum.
Pengaruh polimorfisme reseptor Fc gamma IIIA (FcJRIIIA) dan jumlah sel
efektor terhadap respon kemoterapi trastuzumab pada pasien kanker
payudara lokal lanjut dan metastasis dengan HER2/NEU positif.
Polimorfisme gen p53Arg72Pro, MDM2SNP309, HER2Ile655Val, ER594
A>G, p21 Ser31Arg dan FGFR2 rs2981582; studi risiko kanker payudara
onset dini di Yogyakarta.
Hubungan antara mutasi gen filaggrin dengan dermatiti atopik. Kajian
mutasi gena filaggrin tipe asia di suku Jawa.
Distribusi dan dinamika genotype serta analisis gen vp4, vp7, nsp2, nsp4
dan nsp5 rotavirus penyebab diare anak balita di indonesia.
Korelasi Polimorfisme Genetik Sitokrom P450 2A6 dan 2B6 dengan
Kuantitas Merokok di Kota Yogyakarta
Cytoarchitecture of the olfactory bulb in the laggard mutant mouse.
Prognostic Impact Of Metastatic Status In Patients With
Nasopharyngeal Carcinoma
Factors Influencing Treatment Adherence Of Nasopharyngeal
Cancer And The Clinical Outcomes: A Hospital-Based Study
Differential expression of microRNA-21 on nasopharyngeal
carcinoma plasma patient
10
Health Research Expo I, FK UGM
19. Case report on pediatric nasopharyngeal carcinoma at Dr. Sardjito
Hospital, Yogyakarta
20. Results of Treatment With Neoadjuvant Cisplatin-5fu In Locally
Advanced Nasopharyngeal Carcinoma: A Local Experience
21. Geriatrics with Nasopharyngeal Cancer
22. The Expression of miR-141 in Patients with Nasopharyngeal Cancer
11
Health Research Expo I, FK UGM
Discrepancy of acetylation status prediction using genetic polymorphisms in the
NAT-2 coding region examination with acetylsulphadimidine measurement
Erna Kristin, Dwi Aris Agung Nugrahaningsih, Mustofa
Department of Pharmacology and Therapy, Faculty of Medicine, UGM
Contact: erna_kristin@yahoo.co.uk
Background
N-acetyltransferase2 (NAT2) gene polymorphism is known to be associated with the
isoniazid hepatotoxicity. NAT2 polymorphism results in slow and fast acetylator
phenotype. Using NAT2 polymorphism to predict acetylator status is a future project
to individualized isoniazid therapy.
Methods
The aim of our study is to investigate the NAT2 genotype in Javanese, one of
dominant ethnics in Indonesia, to predict hepatotoxicity in tuberculosis (TB) patients
receiving isoniazid in combination with other TB drugs. We examined NAT2
polymorphisms on coding region using PCR direct sequencing. We also determined
the acetylation status by measuring acetyl sulphadimidine.
Results
Nineteen subjects were enrolled in this study. Most of them were male. The age
average was 43.58 ± 15.43 years old. Their average body mass index and serum
transaminase were within normal range. In this study, we identified 11 different
NAT2 genotypes. We found that the major NAT2 genotypes were NAT2*4/*4
(31.58%) and NAT2*6A/*6A (21.05%). Based on the genotype prediction, most of the
subjects were slow acetylator (63.16%). Meanwhile based on acetylation status
determination using acetylsulphadimidine measurement in the urine, 52.63% were
fast acetylator and 47.37% were slow acetylator. The serum transaminase increase
also tended to be higher on slow acetylator group compared with those on fast
acetylator group, even though the different was not statistically significant.
Interestingly, we found discrepancy between acetylation status prediction using
NAT2 genotype and acetylsulphadimidine examination.
Conclusions
We find that NAT2 gene polymorphism on coding region do not predict the
acetylator status accurately. We suggest that NAT2 gene polymorphism might have
to be examined on promoter region for better prediction of acetylation status.
12
Health Research Expo I, FK UGM
Mammographic density thresholding method, estradiol level and estrogen
receptorɲ gene polymorphism (ESR1) as breast cancer predictor
Lina Choridah1, Teguh Aryandono2, Arif Faisal1, Ahmad Hamim Sadewa3
Department of Radiology. 2Department of Surgery, Faculty of Medicine, Universitas
Gadjah Mada. 3Department of Biochemistry, Faculty of Medicine, Universitas Gadjah
Mada.
Contact:linachoridah@ugm.ac.id
1
Background
Estrogen is believed to play an important role in the development and progression of
breast cancer. Mammographic densities equivalent to the cell proliferation, estradiol
and ESR 1 Gene Polymorfism allegedly acted as a predictor of breast cancer.
Methods
We performed an observational study, data were collected prospectively using a
cohort study design. Subjects were women who came to oncologic clinic for
mammographic screening, with either high or low breast density. Subjects were then
grouped into two, with and without breast cancer. The data were analyzed using
relative risk and multivariate logistic regression.
Results
Women with PMD 25-34% , 35-49%, 50-64% and >65% had relative risk of 1.67 (95%
CI, 0.47 to 5.89), 3.4 (95% CI, 1.16 to 9.97), 3.43 (95% CI, 31.19 to 9.88) and 3.45 (95%
CI, 1.174 to 10.14%) times, respectively, compared to PMD