Journal of the Medical Sciences (Berkala ilmu Kedokteran)
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Implementation of Medical Genetics in Medical Education Curriculum
No full textPrimary care physicians should be aware that genomics has arrived at the doorstep of their practice. Genetic knowledge, skills, and attitudes are important to primary care physicians providing support and management to patients and families with (higher risks of) genetic conditions. At least one in ten patients seen in primary care has a disorder with a genetic component, including hereditary cancer.Primary care physicians must be able to advise patients on genetic and genomic manifestations of the associated diseases and disorders, to outline a primary pedigree to deliver the necessary information: the disease which the patients are at risk of, and to decide whether to refer the patients to genetic services.There is more and more evidence to the importance of clinical emphasis in the genetics classes, probably proceeding to a third-year refresher program in the longitudinal curriculum. An enhanced educational experience to improve genetics and genomics knowledge should be better structured in the imminent future.Keywords: primary care physicians, hereditary cancer, genetic curriculum, genetic service
High Resolution Melting (HRM) Analysis for Genetic Changes in BRCA1/2 gene
No full textConventional mutation analysis requires a separation step and include single-strand conformational polymorphism (SSCP) analysis, denaturing gradient gel electrophoresis, heteroduplex analysis, denaturing HPLC, and temperature gradient capillary electrophoresis These methods require separation of PCR products on a gel or other matrix, often take hours to perform, and increase the risk of contamination in future reactions because PCR products are exposed to the environment. High Resolution Melting (HRM) can simplify the mutation scanning analysis in BRCA 1/2 gene. DNA from affected patients and family members were amplified with Real-Time PCR reaction and followed by Sanger Sequencing to reconfirm the mutation status if mutation obtained by HRM Method. HRM Method was able to show distinction in differential curves of mutated BRCA 2 gene c.4600T>C, with codon modification of CAT>TAT, when compared to wildtype. To determine point mutation in a sample, this method requires two groups of experimental standards and standard curves. The first standard produced by using samples without mutation (wildtype/negative control) and the second standard produced by using samples with mutation (positive control), that have been confirmed with Sanger Sequencing. The sequencing analysis of the affected patient and the family members showed that a mutation occurred (BRCA2 c.4600T>C) and was segregated in the family history. This mutation caused amino acid alteration in BRCA2 protein (p.H1458Y). HRM Method is an excellent tool to analyze genetic modification of BRCA1/2 genes, especially to investigate co-segregation of mutated genes among family members of affected patient. This method can provide more sensitive results to determine mutation in patient, before using Sanger Sequencing analysis.Keyword: BRCA, HRM, Gene Mutatio
THE EXPRESSION OF Hsa-miR-21-5p AS MINIMAL INVASIVE MARKER TO ADJUVANT CHEMOTHERAPY IN BREAST CANCER PATIENTS
No full textAbstractBreast cancer remains the leading cause of death among women, and there is a need to develop minimally invasive marker. In our previous study based on clinicopathologic in pre-chemotherapy patients showed miR-21 was upregulated 1.32 times higher at advanced stage compared with early stage. Therefore the matched patients for post-chemotherapy samples were used. The aim of this research is to examine the expression of miR-21 as potential marker to adjuvant chemotherapy in breast cancer patients. The samples were taken by using cross sectional method with total 39 blood plasma samples from breast cancer patients in adjuvant chemotherapy and 12 healthy control samples. Plasma was obtained from blood samples and then RNA isolated were performed. Total RNA was reverse transcribed using cDNA synthesis. The expression of miR-21 was then analyzed using specific primer for miR-21 and miR-16 as the reference gene. Livak Method was used to calculate the expression level in each group. The result showed that there is significant downregulated expression of miR-21 in postchemotherapy 2.61 fold compared with pre-chemotherapy (p<0.05). The expression of miR-21 upregulated 2.2 folds (p<0.05) in pre-chemotherapy compared with healthy control, while in post-chemotherapy compared with healthy control, the expression of miR-21 was 0.8 fold (p<0.05). In conclusion, Hsa-miR-21-5p can be used as marker for adjuvant chemotherapy response in breast cancer because there is significant different expression between prechemotherapy, post-chemotherapy and healthy control. The continuation research in the near future for detecting the expression of tumor suppressor protein regulated by miR-21 is needed.Keywords: breast cancer, adjuvant chemotherapy, miR-21, minimal invasive marke
DNA methylation and expression of Homeobox gene family as diagnostic and prognostic markers in human hepatocellular carcinoma
No full textABSTRACTHomeobox genes consist of a family of evolutionarily conserved genes that play important roles in morphogenesis, embryogenesis, and cell fate determination. Re-expression of embryogenic genes has been associated with carcinogenesis of human cancers. Aberrant expression of homeobox genes has been increasingly found to modulate diverse processes such as cell proliferation, cell death, metastasis, angiogenesis and DNA repair. We studied DNA methylation and expression of homeobox gene family in human hepatocellular carcinoma (HCC), the fifth most common cancer and the third leading cause of cancer mortality worldwide. We performed microarray for comprehensive DNA methylation and gene expression using primary HCC samples and healthy liver tissues. Confirmation using pyrosequencing and RT-PCR was then performed. Clustering both unsupervised and supervised methods using Qlucore software was then performed. Enrichment of homeobox genes both for DNA methylation and gene expression could differentiate HCC and the healthy liver tissues. Profile of homeobox gene methylation could further predict clinical outcome. Inverse correlation between DNA methylation and gene expression was shown (HOXA9, Spearman r=-0.49, p=0.002). Gain of DNA methylation in HOXA9, HOXA13, and MEOX1 correlated with shorter HCC survival (log-rank Mantel-Cox test p=0.02, with median survival 50 and 490 weeks, respectively). We demonstrated potential roles of DNA methylation and gene expression profiles of Homeobox gene family as diagnostic and prognostic marker in patients with HCC
Increasing Serum Transaminase and The Relation with The Serum Concentration of Isoniazid and Rifampicin of Tuberculosis Patients which Given Antituberculosis Fixed Dose Combination in Yogyakarta
No full textABSTRACT Tuberculosis is still a major health problem in Indonesia. Isoniazid and rifampicin are major antituberculosis drugs. These two drugs have been known to cause hepatotoxicity which is characterized by an increase of serum transaminase concentration. Previous study proved the increase of hepatotoxicity due to isoniazid and rifampicin but did not explain about the correlation with the drugs concentration. The aim of this study is to know the relation between increasing serum transaminase and the serum concentration of isoniazid and rifampicin of tuberculosis patients which given antituberculosis fixed dose combination in Yogyakarta. We carried out a cross sectional study involving 31 TB patients who received antituberculosis fixed dose combination containing isoniazid and rifampicin. Serum transaminase was measured with an automatic chemical analyzer. Isoniazid and rifampicin concentration was measured by using HPLC. We used t- test, Mann Whitney, Fisher and Spearman to analyze the data. There is no correlation between mean isoniazid concentration with high (7,07±6,24mg/ml) and normal ALT (2,42±0,26mg/ml) (p>0,05). There is no correlation between mean isoniazid concentration with high (5,03+4,14 mg/ml) and normal AST (p>0,05). There is no correlation between mean rifampicin concentration with high (10,67+3,76 mg/ml) and normal ALT (3,66+0,30 mg/ml) (p>0,05). There is no correlation between mean rifampicin concentration with high (8,52+3,06 mg/ml) and normal AST (3,64+0,32 mg/ml) (p>0,05). Mean of rifampicin concentration in this study are low (4, 12+0,46 mg/ml). So the conclusion that there are no correlation between isoniazid serum concentration with an increase of serum transaminase and no correlation between rifampicin serum concentration with an increase of serum transaminase
Prevalence of metabolic syndrome and its components based on International Diabetes Federation (IDF) definition in Yogyakarta Special Region, Indonesia
No full textABSTRACTMetabolic syndrome (MetS) is a group of risk factors which increase morbidity and mortality for cardiovascular disease and diabetes. The prevalence of MetS has been on the rise. No previous study has described the prevalence of MetS in Yogyakarta Special Region and its components. The study aim was to determine the prevalence of MetS and it’s components in Yogyakarta Special Region, Indonesia. A total of 766 male and female subjects aged ≥40 were analyzed in this retrospective study based on secondary data from the Indonesian Family Life Survey batch 4 (IFLS 4). MetS was defined by International Diabetes Federation (IDF) criteria with ethnicity-specific values for waist circumference. Prevalence of MetS and characteristic of each component of MetS were expressed as mean or %. The difference of the MetS components was evaluated by t-test and chi-square. Prevalence of MetS in Yogyakarta Special Region was 13.19%. The most common of MetS component was hypertension (60.44%), followed by dyslipidemia (56.27%), central obesity (32.38%), pro-inflammatory state (15.71%) and insulin resistance (0.78%). There was a higher prevalence of MetS in females compared to males (15.88 vs 10.19%), pre-elderly compared to the elderly (13.90 vs 12.19%), Javanese compared to other ethnicities (13.23 vs 10.00%), and urban compared to rural populations (15.06 vs 8.37%). In conclusion,the prevalence of MetS in Yogyakarta Special Region is 13.19% with hypertension and dyslipidemia as the most common component
Cytotoxic activity of simvastatin in T47D breast cancer cell lines and its effect on cyclin D1 expression and apoptosis
No full textBackground: Statins (HMG-CoA Inhibitors) is a drug used for decreasing plasma cholesterol levels and used in therapy to prevent coronary artery disease. Research in animals and epidemiological studies showed that statin therapy can decrease risk against cancer associated with cholesterol. Based on that result then research of cytotoxic activity against simvastatin knowing cultur T47D breast cancer cells and his influence in decreasing expression of cyclin D1 and induction of apoptosis has been done.Research objectives: The aims of this research is to prove activities of simvastatin against T47D breast cancer cell culture, especially to examine cytotoxic activity, cyclin D1 expression, and simvastatin effect in apoptotic induction.Research method: The type of this research is quasi experiment with using posttest with non-equivalent control group design. Cytotoxicity test performed on T47D breast cancer cell cultures using MTT assay to determine IC50 values after given simvastatine. Expression of cyclin D1 and apoptosis induction test detected using flow cytometry with antibody monoclonal anti-cyclin D1 and Annexin V-Pi, then analyzed by FACS-Calibur program.Results: Simvastatin has cytotoxic effect against T47D breast cancer cells with IC50 values 25.25 µg/mL. Simvastatin with concentrations of 6.31; 12.62; 25.25 and 50.5 µg/mL was able to decrease the cyclin D1 expression. Furthermore, simvastatin can induce apoptosis with EC50 values 26.96 µg/mL in T47D breast cancer cells.Conclusion: Simvastatin has cytotoxic activity of in T47D breast cancer cells and decreasing cyclin D1 expression and inducing apoptosis activity in T47D breast cancer cells.Keywords: simvastatin, cytotoxic, cyclin D1, apoptotic, T47D
The effect of hemofilter, preoperative and intraoperative methylprednisolone on complications after open heart surgery
No full textComplications after open heart surgery may threaten patient’s survival rate. Theintraoperative methylprednisolone administration alone shows controversial resultson open heart surgery complications. Similarly, the intraoperative and preoperativemethylprednisolone administration as well as the use of hemofilter in open heart surgeryis still controversial. This study aimed to evaluate the effect of hemofilter, preoperativeand intraoperative methylprednisolone administration on complications following openheart surgery. This was a Prospective Randomized Open-Blinded Evaluation (PROBE)experimental study. Ninety-five patients who had open heart surgery in Dr. SardjitoGeneral Hospital, Yogyakarta, and Integrated Cardiac Care of Dr. Cipto MangunkusumoGeneral Hospital, Jakarta within the period of December 2011 to May 2012 wereinvolved in this study. The patients were divided into two groups i.e. group A, 48 patientsreceived methylprednisolone 15mg/kg intraoperatively, methylprednisolone 5mg/kgpreoperatively, and hemofilter, while group B, 47 patients received methylprednisolone15mg/kg intraoperatively alone. From the total 95 patients, we found 26 (27.4%)patients experienced complications i.e. 19 in group B (40.4%) and 7 in group A(14.6%). The differences of the complications were statistically significant (p<0.05;OR=3.97; 95%CI=1.476-10.71). Complications risk decreased by 63.9% in the groupA compared to the group B with the hazard ratio of 3.2. In conclusion, the application ofhemofilter, preoperative and intraoperative methylprednisolone might decrease the risk ofcomplications after open heart surgery
The role of Clinical Geneticists in Hereditary Cancer Management and Research
No full textAbstractHereditary cancer refers to cancers caused by germline mutations in cancer predisposing genes. These mutations confer a significantly increased risk of cancer, are rare, and are in the majority of cases autosomal dominantly inherited. Since the eighties of last century more than 115 cancer predisposing genes have been identified. In many Western countries genetic testing of patients and families with clustering of cancers started early, and was often performed by clinical geneticists (MDs performed the counselling and pedigree analyses) and by molecular biologists (in laboratories within departments of clinical genetics). It turned out to be a long path to fully realize the promise of cancer predisposing genes. The clinical utility of many cancer genetic tests and subsequent risk reducing interventions has not yet been validated and pitfalls in e.g. misinterpretation of genetic variants showed up. However, without doubt genetic testing for mutations will eventually turn out as a strong tool to save lives from early cancer death and will become part of standard cancer care throughout the developed world. Apart from primary surgical prevention, major progress is to be expected in earlier diagnoses, tailored therapies, and possibly chemoprevention. Ideally researchers, clinical geneticists, molecular biologists, surgeons, oncologists, gynaecologists and other professionals will work together to reach this goal