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Abstrak :
[ABSTRAK
Gastro Entero Pancreatic Neuro Endocrine Tumor (GEP-NET) merupakan keganasan yang jarang dijumpai di dunia dibandingkan dengan keganasan gastrointestinal lainnya. Menurut data GEP-NET kadang sulit dibedakan dengan Irritabel Bowel Syndrome (IBS) dalam mendiagnosisnya. Keluhan GEP-NET antara lain nyeri perut, diare, flushing, sampai penurunan berat badan. Keluhan IBS antara lain nyeri perut, mual, diare atau dengan tanpa konstipasi. Saat ini telah dikembangkan pemeriksaan Chromogranin A (CgA) untuk membantu dalam pemeriksaan penapisan pasien yang menderita IBS maupun pasien yang dicurigai GEP-NET. Penelitian ini merupakan penelitian deskriptif untuk mengetahui kadar CgA pada kelompok normal, mengetahui kadar CgA pada pasien yang didiagnosis IBS, mengetahui kadar CgA pada pasien yang memiliki risiko GEP-NET dan mengetahui perbedaan kadar CgA pada pasien yang didiagnosis IBS dan pasien yang dicurigai menderita GEP-NET yang keduanya memiliki risiko GEP-NET. Pada penelitian ini didapatkan kadar CgA serum pada kelompok kontrol normal dengan nilai mean 50,70 μg/L, median 48,89 μg/L dengan rentang minimum-maksimum antara 42,66-80,62 μg/L. Pada penelitian ini didapatkan kadar CgA serum pada kelompok IBS dengan nilai mean 76,67 μg/L, median 64,82 μg/L dengan rentang minimum-maksimum antara 45,52-243,18 μg/L. Pada penelitian ini didapatkan kadar CgA serum pada kelompok yang dicurigai GEP- NET denga nilai mean median 66,23 μg/L dengan rentang minimum-maksimum antara 49,89-656,41 μg/L.Pada penelitian ini tidak terdapat perbedaan kadar CgA pada populasi pasien yang didiagnosa IBS maupun pada pasien yang dicurigai menderita GEP-NET yang keduanya memiliki risiko menderita GEP-NET dikemudian hari.

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ABSTRACT
Gastro Entero Pancreatic Neuro Endocrine Tumors (GEP-NET) is a malignancy that is rarely found in the world compared to other gastrointestinal malignancies. According to data registration data The Surveillance, Epidemiology and End Results (SEER) an increase in the incidence of sharp from 1973 (from 0.92 to 1.28 in 100,000 population per year), to 2004 (from 5.09 to 5.42 in 100,000 population per year). GEP-NET is difficult to distinguish from Irritabel Bowel Syndrome (IBS) in diagnose sometimes. GEP-NET complaints include abdominal pain, diarrhea, flushing, until the weight loss. Complaints of IBS include abdominal pain, nausea, diarrhea or with no constipation. We have been developed examination Chromogranin A (CgA) to assist in the screening examination of patients who suffer from IBS and patients who are suspected of suffering from GEP-NET.This study is a descriptive study to determine levels of CgA in the normal group, knowing CgA levels in patients diagnosed IBS, knowing CgA levels in patients who have a risk of GEP-NET and know the difference CgA levels in patients diagnosed with IBS and patients suspected of suffering from GEP- NET who both have risk GEP-NET. In this study, serum levels of CgA in the normal control group with a mean of 50,70 μg/L, median 48,89 μg / L with a minimum-maximum range between 42,66 to 80,62 μg/L. In this study, serum levels of CgA in the IBS group with a mean of 76,67μg /L, median 64,82 μg/L with a minimum-maximum range between 45,52 to 243,18 μg/L. In this study, serum levels of CgA in the group suspected of GEP-NET premises mean median value 66,23 μg/L with a minimum-maximum range between 49.89 to 656.41 g / L. In this study there was no difference in the levels of CgA IBS patients diagnosed population and in patients suspected of suffering from GEP-NET are both at risk of suffering from GEP-NET in the future., Gastro Entero Pancreatic Neuro Endocrine Tumors (GEP-NET) is a malignancy that is rarely found in the world compared to other gastrointestinal malignancies. According to data registration data The Surveillance, Epidemiology and End Results (SEER) an increase in the incidence of sharp from 1973 (from 0.92 to 1.28 in 100,000 population per year), to 2004 (from 5.09 to 5.42 in 100,000 population per year). GEP-NET is difficult to distinguish from Irritabel Bowel Syndrome (IBS) in diagnose sometimes. GEP-NET complaints include abdominal pain, diarrhea, flushing, until the weight loss. Complaints of IBS include abdominal pain, nausea, diarrhea or with no constipation. We have been developed examination Chromogranin A (CgA) to assist in the screening examination of patients who suffer from IBS and patients who are suspected of suffering from GEP-NET.This study is a descriptive study to determine levels of CgA in the normal group, knowing CgA levels in patients diagnosed IBS, knowing CgA levels in patients who have a risk of GEP-NET and know the difference CgA levels in patients diagnosed with IBS and patients suspected of suffering from GEP- NET who both have risk GEP-NET. In this study, serum levels of CgA in the normal control group with a mean of 50,70 μg/L, median 48,89 μg / L with a minimum-maximum range between 42,66 to 80,62 μg/L. In this study, serum levels of CgA in the IBS group with a mean of 76,67μg /L, median 64,82 μg/L with a minimum-maximum range between 45,52 to 243,18 μg/L. In this study, serum levels of CgA in the group suspected of GEP-NET premises mean median value 66,23 μg/L with a minimum-maximum range between 49.89 to 656.41 g / L. In this study there was no difference in the levels of CgA IBS patients diagnosed population and in patients suspected of suffering from GEP-NET are both at risk of suffering from GEP-NET in the future.]

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ABSTRAK
Infeksi oleh virus hepatitis B (VHB) dapat menjadi infeksi akut yang berakhir dengan resolusi infeksi ataupun berlanjut menjadi infeksi kronis. Resolusi infeksi dalam infeksi VHB ditandai dengan hilangnya hepatitis B surface antigen (HBsAg) dan keberadaan antibodi terhadap HBsAg (anti-HBs). Kemampuan sel B dalam mensintesis anti-HBs dipengaruhi oleh sel T helper 1 (Th1) ataupun T helper 2 (Th2). Sekresi sitokin yang terkoordinasi dari Th1 ataupun Th2 sangat dibutuhkan mengingat sitokin yang dihasilkan oleh kedua sel T helper (Th) tersebut memiliki peranan yang berbeda dan dapat bekerja secara antagonis. Penelitian ini bertujuan untuk mengetahui kemampuan pasien hepatitis B kronis dalam mensintesis anti-HBs dan membandingkan pola sintesis sitokin IL-10, IFN-gamma dan IL-2 dari pasien hepatitis B kronis dengan pasien yang mengalami resolusi infeksi. Pada penelitian ini sel mononuklear darah tepi manusia (SMDT) diambil dari 10 subjek pasien hepatitis B kronis, 10 subjek pasien yang mengalami resolusi infeksi dari hepatitis B dan 10 subjek individu sehat yang berhasil divaksinasi. SMDT dikultur dengan stimulan HBsAg rekombinan (rHBsAg) atau fitohemaglutinin (PHA) untuk sintesis sitokin dan pokeweed mitogen (PWM) untuk sintesis anti-HBs secara in vitro. Hasil dari penelitian ini ditemukan produksi anti-HBs secara in vitro dari 70% individu sehat yang berhasil divaksinasi dan 40% pasien hepatitis B yang mengalami resolusi infeksi, sementara pada pasien hepatitis B kronis tidak ditemukan hal tersebut. Pola sitokin IL-10, IFN-gamma dan IL-2 antara pasien hepatitis B yang mengalami resolusi infeksi dan pasien hepatitis B kronis tidak memiliki perbedaan yang bermakna. Akan tetapi, respons IFN-gamma terhadap rHBsAg pada pasien hepatitis B yang mengalami resolusi infeksi cenderung lebih kuat. Korelasi antara sitokin IL-10, IFN-gamma dan IL-2 dengan produksi anti-HBs secara in vitro tidak ditemukan pada kedua kelompok tersebut, sementara korelasi IL-2 dengan sintesis anti-HBs in vitro ditemukan pada individu yang divaksinasi. Penelitian ini menunjukkan SMDT dari pasien hepatitis B kronis tidak dapat mensintesis anti-HBs secara in vitro dan pada pasien tersebut tidak memiliki perbedaan pola sintesis sitokin IL-10, IFN-gamma dan IL-2 jika dibandingkan dengan pasien hepatitis B yang mengalami resolusi infeksi.

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ABSTRACT
Hepatitis B virus (HBV) infection can lead to acute self-limited infection or lead to chronic hepatitis B infection. Resolution of infection is marked by seroconversion of hepatitis B surface antigen (HBsAg) to antibody to HBsAg (anti-HBs) which also give protection to HBV reinfection. Anti-HBs is produced by B cells as response to HBsAg. B cells response to HBsAg is affected by cytokines from T helper 1 (Th1) and T helper 2 (Th2) cells. Coordinated cytokines secreted by Th1 or Th2 cells is necessary due to the fact that they could work antagonistically. Th1 cytokines, such as IFN-gamma, are known to induce cellular immune responses, while Th2 cytokines, such as IL-4, -5 and -10, are known to induce humoral immune responses. This study aimed to investigate the capability of chronic hepatitis B patients (CHB) to synthesize anti-HBs in vitro and to compare IL-10, IFN-gamma and IL-2 levels between CHB patientis with resolved hepatitis B (RHB) patients. In this study, peripheral blood mononuclear cells (PBMCs) were taken from 10 CHB patients, 10 RHB patients and 10 healthy hepatitis B vaccinated individuals. PBMCs were cultured in presence of recombinant HBsAg (rHBsAg) and PHA to cytokines synthesis and pokeweed mitogen (PWM) to anti-HBs synthesis in vitro. As results, synthesis of anti-HBs in vitro were found in PBMCs from 70% of healthy hepatitis B vaccinated individuals and 40% of RHB patients, while PBMCs from CHB patients could not. No significant differences were found in IL-10, IFN-gamma and IL-2 cytokine levels between CHB patients and RHB patients, although IFN-gamma responses to rHBsAg had a tendency to be stronger in RHB patients. Correlation between IL-10, IFN-gamma and IL-2 cytokine levels and anti-HBs synthesis in vitro was not found in CHB patients and RHB patients. Meanwhile, IL-2 and anti-HBs synthesis in vitro were correlated in healthy hepatitis B vaccinated individuals. In conclusion, this study showed that PBMCs from CHB patients were not capable in synthesizing anti-HBs in vitro and had no differences in IL-10, IFN-gamma and IL-2 cytokine levels with RHB patients.

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Background: This study aims to determine the association between neuroinflammation and oxidative stress with prognosis of brain injury patients and the association between neurosurgical procedure with neuroinflammation and oxidative stress condititons. Methods: The study design is a prospective observation of 40 brain injury patients who underwent surgery. IL-6, uric acid, MDA, NR2A antibodies and GSH serum level of pre- and 1 day post-operation on brain injury patients were measured, and their association with GCS, GOS and neurosurgical procedures were analyzed. Results: The post-operative IL-6 serum level showed a downward trend compared to pre-operative value (mean decrease: -190.61 pg/mL). The post-operative IL-6 level was significantly associated with GCS 7 days post-operation (p = 0.006), with OR 24. The post-operative IL-6 serum level was significantly associated with GOS 3 months post-trauma (p = 0.016) with OR 11.6. The post-operative uric acid serum level showed a downward trend compared to pre-operative value (mean decrease: -0.26 mg/dL). There was a significant difference between the mean value of post-operative uric acid serum level in patients with 7 days post-trauma with GCS ≤ 8 (mean: 4.16 mg/dL) and GCS > 8 (mean: 2.71 mg/dL), (p = 0.042). The post-operative MDA serum level showed a downward trend compared to pre-operative value (mean decrease: -0.08 nmol/mL). There is no significant association between MDA serum level, GCS and GOS and no significant association of NR2A antibody and GSH serum level with GCS, GOS and neurosurgical procedure. From the multivariate analysis, the most important neuroinflammatory variable associated with GCS and GOS is IL-6. Conclusion: Neuroinflammation and oxidative stress may have prognostic values in brain-injured patients, in particular IL-6. Neurosurgical procedures may decrease the neuroinflammation process.

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Tujuan Untuk mengidentifikasi faktor-faktor prediksi dan biomarker dalam perkembangan lesi prakanker leher rahim atau neoplasia serviks intraepitel (CIN). Metode Penelitian dilakukan dari bulan Agustus 2007 hingga September 2008. Desain penelitian adalah kasus-kontrol dengan stratifikasi uji respons dosis. Kasus adalah penderita dengan CIN. Kontrol adalah pasien non CIN. Dilakukan analisis bivariat diikuti dengan analisis multivariat. Hasil Ada 130 pasien, yang terdiri dari 124 pasien yaitu CIN 1, CIN 2 dan CIN 3, dengan jumlah masing-masing 30, 41,33, dan 26 pasien non CIN. Analisis bivariat menunjukkan bahwa umur <41 tahun, pendidikan ≥ 13 tahun, mitra seksual ≥ 2, hubungan HPV DNA positif, ekspresi p16INK4a, Ki-67, MCM5 dan Survivin tinggi merupakan variabel independen untuk terjadinya CIN dengan nilai P <0,05. Namun demikian, hasil analisis multivariat, menunjukkan bahwa variabel independen yang ditemukan adalah umur, pendidikan ≥ 13 tahun, ≥ 2 orang mitra seksual, HPV DNA positif, dan ekspresi berlebih p16INK4a, Ki-67 dan Survivin yang menunjukkan nilai P <0,005. Kesimpulan Usia muda, pendidikan usia ≥ 13 tahun, mitra seksual ≥ 2 orang, HPV DNA positif, ekspresi p16INK4a,Ki-67 dan Survivin tinggi merupakan faktor risiko untuk terjadinya peningkatan CIN, dan digunakan dalam persamaan untuk memprediksi peningkatan lesi prakanker serviks.

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Aim To identify the predictive factors and biomarkers in the progression of cervical precancer lesion or Cervical Intraepithelial Neoplasia (CIN). Methods The study was conducted from August 2007 to September 2008. Design of the study was case-control with stratifications of test dose response. The cases were patients with CIN. Control patients were non CIN patients. Bivariate analysis followed by multivariate analysis was conducted. Results There were 130 patients, consisting of 124 CIN patients divided into CIN 1, CIN 2 and CIN 3, with the following numbers of patients: 30, 41, and 33, respectively and 26 patients without CIN (non CIN). Bivariate analysis showed that age < 41 years, education ≥ 13 years, sexual partner ≥ 2, fi rst sexual relationship at age < 22 years, smoking, the presence of sexuallly transmitted infections, positive HPV DNA, high p16INK4a, Ki-67, MCM5 and Survivin expression constituted independent variables for the occurrence of CIN with P value of < 0.05. However, on multivariate analysis, independent variables that emerged were age, education ≥ 13 years, sexual partner ≥ 2 persons, positive HPV DNA, and over expression of p16INK4a, Ki-67 and Survivin that showed a P value of < 0.005. Conclusion Younger ages, education age ≥ 13 years, sexual partner ≥ 2 persons, positive HPV DNA, high p16INK4a,Ki-67 and Survivin expression constituted the risk factors for the occurrence of the progress of CIN, and was used in the equation to predict the progress of cervical precancer lesion.

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Aim: to evaluate the role of clinical characteristics, functional markers of vasodilation, inflammatory response, and atherosclerosis in predicting wound healing in diabetic foot ulcer. Methods: a cohort study (February-October 2010) was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia. Each subject underwent at least two variable measurements, i.e. during inflammatory phase and proliferation phase. The studied variables were clinical characteristics, complete peripheral blood count (CBC) and differential count, levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG), marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin-1/ET-1, and flow-mediated dilation/FMD of brachial artery), and marker of vascular calcification (osteoprotegerin/OPG). Results: median of time achieving 50% granulation tissue in our study was 21 days. There were nine factors that contribute in the development of 50% granulation tissue, i.e. family history of diabetes mellitus (DM), previous history of wound, wound area, duration of existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and OPG. There were three out of the nine factors that significantly correlated with wound healing, i.e. wound area, OPG levels, and simvastatin medications. Conclusion: in acute diabetic foot ulcers, wound area and OPG levels had positive correlation with wound healing, whereas simvastatin medications had negative correlation with wound healing.

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Background: graves disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA 4 gene on nucleotide 49 at codon 17 of exon 1, CTLA 4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves disease in Indonesia. Methods: this was a case control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. Results: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA 4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). Conclusion: genetic polymorphisms of CTLA 4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in patients with Graves disease.

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Tujuan: untuk menganalisis penanda biologi CXCR4, IL11-RA, TFF1 dan MLF1P, klinikopatologi dan profil ekspresi genetik mRNA sebagai penanda peningkatan kejadian metastasis tulang pada pasien kanker payudara stadium lanjut. Metode: studi ini merupakan penelitian potong lintang. Analisis dilakukan pada total 92 pasien kanker payudara, terdiri atas 46 pasien metastasis tulang dan 46 pasien dengan metastasis nontulang. Analisis imunohistokimia dan microarray, dilakukan pada 81 sampel formalin fixed paraffin embedded (FFPE) dari 81 pasien yang didapat. Data dikumpulkan melalui rekam medis, pemeriksaan imunohistokimia (IHK), dan microarray dengan nanoString nCounterTM. Hasil: artikel ini merupakan bagian satu dari dua tahap pelaporan hasil penelitian. Pada tahap satu diperoleh hasil analisis IHK, IL11-RA dengan cut-off ≥103,5 menunjukkan peningkatan kejadian metastasis tulang, dengan OR 3,803 (95 % interval kepercayaan [IK], 1,375-10,581), p=0,010, dan MLF1P dengan cut-off ≥83,0 menunjukkan peningkatan kejadian metastasis tulang, dengan OR 2,784 (95% IK, 1,009-7,681), p=0,048. Status ER+ menunjukkan peningkatan kejadian metastasis tulang, dengan OR 7,640 (95 % IK, 2,599-22,459), p<0,000. AUC gabungan IL-11RA, MLF1P dan ER+, mempunyai ketepatan hampir 80% (meningkat dibandingkan AUC masing-masing secara terpisah), untuk membedakan dan menjelaskan kejadian metastasis tulang, pada kanker payudara stadium lanjut. Kesimpulan: IL11-RA, MLF1P dan ER+, merupakan determinan peningkatan kejadian metastasis tulang pasien kanker payudara stadium lanjut.

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Aim: to analyze expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, and clinico pathology in advanced breast cancer patients with bone metastatic. Methods: this is a cross-sectional study. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. Immunohistochemistry and microarray analysis was performed in 81 formalin fixed paraffin embedded (FFPE) samples from 81 patients were used. Data were collected through medical records, immunohistochemistry (IHC), and microarray with nanoString nCounterTM. Results: this article is part one of a two stage reporting research results. In part one we got the results of the IHC analysis, IL11-RA with cut-off ≥103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581), p=0.010, MLF1P with cut-off ≥83.0 OR 2.784 (95% CI, 1.009-7.681), p=0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459), p<0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80% to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients. Conclusion: IL11-RA, MLF1P, and ER+ were the determinants that were associated with increasing bone metastasis incidence.