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Idrus Alwi
"Diabetes mellitus (DM) is one of the public health problems worldwide, including in Indonesia. Cardiovascular disease was the main cause of death (75-80%) in DM, three-fourths of this death was caused by coronary heart disease (CHD). Approximately 34.2% of patients with acute coronary syndrome (ACS) receiving care at ICCU of Dr. Cipto Mangunkusumo General Hospital (RSCM) suffered from DM. Mortality rates of ACS in DM patients were still high and ACS prognosis in DM patients were still unfavorable. There are many factors playing a part in atherosclerosis and ACS incidence in DM patients, such as metabolic disorders due to hyperglycemia and the fomration of advanced glycation end product (AGE), oxidative stress, atherogenic dyslipidemia in DM in the form of high triglyceride level and low HDL cholesterol as well as an increase in small dense LDL, and insulin resistance. In addition, other risk factors of CHD frequently encountered with DM were hypertension, obesity, thrombocytc hyperaggregation and hypercoagulation. The management ofthis disease which was based on the control of risk factors was not yet satisfactory.
Inflammatory response played an important role in pathogenesis of atherosclerosis, beginning with early lesion up to acute coronary syndrome. Increase in inflammatory responses (hsCRP) could predict cardiovascular event and predict post-ACS prognosis. Studies in DM population showed an increase in inflammation. ln-depth studies on inflammatory responses in ACS DM patients have not yet been reported. In normal condition, there was a balance of proinflammatory and antiinflammatory cytokines. The ratio of proinflammatory and antiinflammatory cytokines in ACS, particularly DM patients has not been studied. The relationship between metabolic factor (blood glucose, glyco Hb and lipid) and inflammatory response in ACS DM patients has not yet also been studied.
Currently, the effort to decrease inflammatory response is made, among others, by aspirin, statin hypolipidemic medication and insulin sensitizer. Although aspirin and statin were used routinely in ACS patients and have proved to reduce inflammation, morbidity and mortality rates of ACS patients were still high. Thus, we would like to observe whether an addition of other medications in standard therapy could reduce inflammation better. Curcumin in experimental animals-and humans) showed -hypolipidemic effect (decrease 'in absorption and increase in catabolism) and hypoglycemia (effect on PPAR-7). Curcumin also demonstrated antiinflammatory effect. In this study we would like to observe the effects of curcumin on both metabolic factors and inflammatory responses in ACS patients.
PROBLEM IDENTIFICATION
The above elaboration showed a discrepancy associated with inflammatory response in DM ACS patients. Up to now, the relationship of metabolic factor and inflammatory response in DM ACS has not been clear yet. Likewise, the effects of curcumin on metabolic factor and inflammatory response in ACS have not yet been identified.
OBJECTIVES
To evaluate inflammatory responses in DM ACS and its relationship with metabolic factors (glucose, blood; glyco Hb, total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride); to evaluate the ratio of proinflammatory and antiinflammatory cytokines (IL-6/IL-10) in ACS DM patients, and to identify the effects of curcumin on metabolic factors and inflammatory responses in ACS patients.
SETTING
The study was conducted at ICCU of RSCM, ICCU of Persahabatan, ICCU of RS MMC and ICCU of Medistra Hospital, Cardiology Polyclinic, Department of Internal Medicine, Faculty of Medicine University of Indonesia! RSCM and Integrated Cardiac Service Poiyclinic of RSCM.
STUDY SUBJECTS
ACS patients (DM and non-DM) and CHD (DM and non-DM).
DESIGN
There were two studies: l. Observational design to observe inflammatory responses (hscRP, IL-6, IL-IO, VCAM and ICAM) in DM ACS, non-DM ACS, DM CI-ID, and non-DM CHD; to evaluate the relationship between metabolic factors (fasting blood glucose, blood glucose 2 hours PP, glyco Hb, total cholesterol, LDL cholesterol, HDI.. cholesterol and triglyceride) and inflammatory responses (hsCRP, IL-6, IL-10, VCAM and ICAM) in ACS DM. 2. Interventional study which was a double-blind randomized trial to evaluate the effects of curcumin at escalating doses (low dose 3:-:IS mglday, moderate dose 3x30 mg/day and high dose 3x60 mg/day on metabolic factors (fasting blood glucose. blood glucose 2 hours PP and glyco Hb) and the effects of curcumin at escalating doses on inflammatory responses (hsCRP, ll.-6, VCAM and ICAM) in ACS patients.
RESULTS
In observational study, |46 subjects were analyzed, consisting of 84 ACS patients, (30 DM ACS patients and 54 non-DM ACS), and 62 CHD (25 DM CHD patients and 37 non-DM CHD patients). The results of the study in the four groups of patients showed: 1. Inflammatory response in DM ACS was higher than in DM CHD (hsCRP, p=0.00; II..-6, p=0.00; IL-10, p=0.00) and non-DM ACS (ICAM, P=0.03). 2. The ratio of proinflammatory and antiinflammatory cytokines (IL-6/II..-10) in DM ACS did not differ from that of DM CHD (p=0.2l) and non-DM ACS (p=0.5 l). 3. There was a relationship between metabolic factors and inflammatory responses in DM ACS: triglyceride and ll.-6 (r=O.39, p=0.03) and II..-I0 (r=0.37, p=o.o4).
In interventional study we performed randomization in 75 ACS patients divided into four groups, consisting of low-dose curcumin group of 15 patients, moderate-dose curcumin group of 15 patients, high-dose curcumin group of IS patients, and placebo group of 30 patients. The results of the study in these four groups showed: l. Low-dose curcumin showed a decrease in hsCRP in one week ofthe first month after intervention, there was a significant difference liom that of placebo (p=0.04). Low-dose, moderate-dose, high-dose curcumin groups showed a decrease in IL-6, but was not significantly different from placebo. Low-dose, moderate-dose, high-dose curcumin did not show a decrease in VCAM and ICAM after intervention of 2 months. 2. Low-dose curcumin group tended to experience a decrease in glyco Hb level after intervention of 2 months (p=0.06); however, it was not significantly different from that of placebo. 3. There was a tendency that low-dose curcumin reduced total cholesterol and LDI. cholesterol; however, it was not significantly different from that of placebo. There was a tendency that low-dose curcumin increased HDL cholesterol; however, it was not significantly different from that of placebo. 4. There was a tendency that the pattern of escalating doses had some effects in inflammatory responses and metabolic factors, in which low-dose curcumin showed the best effects, followed by moderate-dose and finally high- dose curcumin.
CONCLUSIONS
In this study, inflammatory responses in DM ACS patients were higher than those in DM CHD and non-DM ACS patients. There was no difference in the ratio of proinflammatory and antiinflammatory cytokines (IL-6fIL-IO) in DM ACS compared with DM CHD and non-DM ACS. ln addition, the present study identified some of the relationships between metabolic factors and inflammatory responses. Low-dose curcumin reduced hsCRP in one week of the first month after the intervention in ACS patients. There was a tendency that low-dose curcumin reduced glyco Hb level in ACS."
Depok: Universitas Indonesia, 2006
D786
UI - Disertasi Membership  Universitas Indonesia Library
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Sarwono Waspadji
"ABSTRAK
Diabetes Melitus (DM) merupakan suatu penyakit menahun yang merupakan problem kesehatan masyarakat di Indonesia, terutama di kota-kota besar, yang meningkat menyertai adanya perubahan pola hidup masyarakat. Di Jakarta, penelitian epidemiologis pada penduduk yang dilakukan pada tahun 1982 mendapatkan prevalensi DM penduduk usia > 15 tahun sebesar 1,7 %, dan pada penelitian tahun 1993 meningkat menjadi 5,7 %. Jika tidak dikelola dengan baik, DM dapat mengakibatkan komplikasi kronik, baik komplikasi mikrovaskular yang dapat mengenai mata dan ginjal, maupun komplikasi makrovaskular yang terutama mengenai pembuluh darah jantung, otak, dan pembuluh darah tungkai bawah. Keadaan hiperglikemia kronik disangka merupakan dasar terjadinya komplikasi kronik, antara lain melalui proses glikasi berbagai macam protein. Terbentuknya produk akhir glikosilasi lanjut (advanced glycation end product) yang ireversibel akan berpengaruh terhadap fungsi protein terkait.
Komplikasi kronik DM terjadi balk pada pasien DM yang tidak tergantung insulin (DMTTI non insulin dependent DM = NIDDM = DM tipe 2) maupun DM yang tergantung insulin (DMTI = insulin dependent DM = IDDM = DM tipe 1), walaupun ada perbedaan dalam kekerapan jenis komplikasi yang terjadi. Komplikasi makrovaskular lebih sering ditemukan pada DM tipe 2, sebaliknya pada DM tipe 1, komplikasi mikrovaskular yang terjadi pada ginjal dan mata tampak lebih menonjol.
Di antara komplikasi menahun makrovaskular DM, "kaki diabetes" merupakan komplikasi yang paling mengesalkan, baik bagi pasien maupun bagi dokter yang mengelolanya. Kasus ulkus/gangren diabetes merupakan kasus DM yang terbanyak dirawat. Diperkirakan sebanyak sepertiga dari seluruh pasien DM akan mengalami masalah pada kakinya. Hari perawatan yang lama dan biaya pengobatan yang mahal merupakan salah satu persoalan yang harus mendapat perhatian sebaik-baiknya. Belum lagi dihitung tenaga yang hilang akibat kecacatan, dan ketidakhadiran di tempat kerja, serta biaya yang diperlukan untuk pengelolaan kecacatan tersebut. Apalagi kalau dilihat nasib pasien pasca amputasi, 30 - 50 % pasien yang telah diamputasi akan memerlukan tindakan amputasi untuk kaki sisi lainnya dalam kurun waktu 1 - 3 tahun setelah amputasi. Suatu nasib yang sungguh sangat suram."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2000
D431
UI - Disertasi Membership  Universitas Indonesia Library
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Christianie Setiadi
"Penyakit kardiovaskular, salah satunya sindrom koroner akut merupakan penyebab utama kematian di dunia akibat penyakit tidak menular, di mana penyakit ini memiliki faktor risiko yang dapat dimodifikasi dengan pengaturan nutrisi. Faktor risiko utama sindrom koroner akut pada pasien serial kasus ini adalah sindrom metabolik yang meningkatkan risiko terjadinya penyakit kardiovaskular dan diabetes melitus tipe 2. Semua pasien memiliki masalah dengan obesitas abdominal, di mana adipositokin yang disekresikan oleh jaringan adiposa abdominal merupakan mediator inflamasi, menyebabkan stres oksidatif, resistensi insulin, dan mengganggu metabolisme lipoprotein. Dua pasien pada serial kasus ini mengalami miokard infark dengan ST elevasi dan dua lainnya dengan non ST elevasi. Faktor risiko penyerta adalah hipertensi, diabetes melitus tipe 2, dislipidemia, gangguan fungsi hati, dan hiperurisemia. Kebutuhan energi sesuai dengan Harris Benedict dengan faktor stres antara 1,3–1,4 sesuai dengan beratnya kasus. Pada saat kondisi akut setelah hemodinamik stabil, nutrisi mulai diberikan sesuai dengan 80% kebutuhan basal. Kebutuhan makronutrien sesuai dengan National Cholesterol Education Program-Adult Treatment Panel III. Kebutuhan cairan dan elektrolit diberikan sesuai dengan kondisi jantung pasien. Pemberian mikronutrien seperti vitamin B dan nutrien spesifik yaitu koenzim Q10 dan omega-3 dapat dilakukan pada beberapa kasus. Monitoring dan evaluasi yang dilakukan meliputi keadaan klinis, antropometri yaitu berat badan, tinggi badan, dan lingkar pinggang, serta toleransi asupan, keseimbangan cairan, dan kapasitas fungsional. Selama pemantauan didapatkan perbaikan klinis dan peningkatan asupan nutrisi pasien. Selanjutnya diperlukan pengendalian faktor risiko pasien dengan modifikasi gaya hidup yaitu pengaturan nutrisi dan peningkatan aktivitas fisik untuk pencegahan sekunder penyakit kardiovaskuler dan mengendalikan komplikasi yang sudah terjadi agar tidak semakin memburuk.

Cardiovascular disease, which one of them is acute coronary syndrome is the most caused of death from non comunicable diseases in the world. It have modified risk factors can be affected by nutrition.In this case series, the risk factor was metabolic syndrome that could elevated risk of cardiovascular diseases and type 2 diabetes mellitus. All of the patients had abdominal obesity, where it secreted adipocytokine, the inflamation mediators that can cause oxidative stress, insulin resistance and interfered lipoprotein metabolism. Two patients in this case series have ST elevation miokard infark dan others were non ST elevation miokard infark. Comorbid risk factors were hypertension, type 2 diabetes mellitus, dyslipidemia, disturbance liver function, and hyperuricaemia. Energy needs were calculated by Harris Benedict with risk factor between 1,3–1,4 depends on severe of the diseases. In acute condition after stable hemodinamic, nutrition was given from 80% basalt. Macronutrients need were appropiate with National Cholesterol Education Program-Adult Treatment Panel III. Fluids need and electrolyte were given appropiate of heart condition. Micronutrients, like vitamin B and specific nutrients like coenzyme Q10 and omega-3 could be given in several cases. Evaluation and monitoring included clinical condition, antropometric : body weight, height, waist circumference, tolerance intake, fluid balance, and functional capacity. During follow up, the clinical improvement and enhancement nutrient intake were developed. After that we concidered to control patients risk factors with lifestyle modification include nutrition arrangement and elevated physical activity for secondary prevention of cardiovascular diseases and to control complications.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
SP-Pdf
UI - Tugas Akhir  Universitas Indonesia Library
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Putriyanny Ratnasari
"Pemantauan Terapi Obat (PTO) merupakan upaya pemastian pengobatan yang diberikan kepada pasien aman, efektif, dan rasional. PTO dilakukan pada pasien dengan kriteria yang sesuai dalam Kepmenkes RI No. 72 Thn 2016. PTO dilakukan pada pasien RSUP Fatmawati, yaitu Rumah Sakit Pusat Rujukan Daerah Jakarta. Pasien terpilih mendapatkan diagnosis utama Sindrom Koroner Akut (SKA) disertai hipokalemia, hipertensi, pneumonia, Diabetes Miletus Tipe 2 dan Cedera Ginjal Akut. PTO dilakukan pada periode 03 Juli 2023–30 Agustus 2023 sebagai bentuk penelitian observasional deskriptif bersifat prospektif yang dituangkan dalam karya tulis. Tahapan penelitian meliputi: penseleksian pasien berdasarkan kriteria; pencatatan identitas, hasil pemeriksaan dan pengobatan pasien terpilih secara berkesinambungan; melakukan interpretasi hasil pemeriksaan penunjang dan tanda vital; evaluasi tata laksana, kesesuaian dosis, efek samping, dan interaksi obat; analisis DRP dengan metode PCNE dan SOAP; merekomendasikan penyelesaian Drug Related Problem; analisis pengobatan antibiotik. Hasil analisis menunjukkan terdapat kode P1.2 efek terapi obat tidak terlalu optimal dalam pemberian Diltiazem, nitrokaf, dan ceftriakson karena pemberian dosis dibawah anjuran literatur, landasan dokter adalah pasien menerima obat lainnya dengan efek terapi serupa sehingga dosis disesuaikan dengan respon pasien. Interaksi obat-obat yang terjadi adalah kategori C dan disarankan melakukan pemantauan timbulnya ADR. Analisis alur gyssens menunjukkan pemilihan antibiotik dalam pengobatan pneumonia belum sesuai dengan PNPK tatalaksana pneumonia 2023 dan pengobatannya diputuskan rawat jalan. Disimpulkan mayoritas pengobatan sudah sesuai dengan indikasi, dosis literatur, dan respon pasien relatif membaik.

Drug Therapy Monitoring (PTO) is an effort to ensure that the treatment given to patients is safe, effective and rational. PTO is carried out on patients who meet the criteria in the Republic of Indonesia Minister of Health Decree No. 72 of 2016. PTO is carried out on patients at Fatmawati Hospital, namely the Jakarta Regional Referral Center Hospital. Selected patients received a primary diagnosis of Acute Coronary Syndrome (ACS) accompanied by hypokalemia, hypertension, pneumonia, Diabetes Miletus Type 2 and Acute Kidney Injury. PTO was carried out in the period 03 July 2023–30 August 2023 as a form of prospective descriptive observational research outlined in written work. Research stages include: patient examination based on criteria; Recording identity, examination results and continuous treatment on selected patients; interpret examination results and vital signs; evaluation of management, dose suitability, side effects, and drug interactions; Drug-Related Problems (DRP) analysis using the PCNE and SOAP methods; providing solutions to DRP; analysis of antibiotic treatment. The results of the analysis show that there is code P1.2, the therapeutic effect of the drug is not very optimal in administering Diltiazem, Nitrocaf, and ceftriaxone because the given dose is under literature recommendations. The drug-drug interactions that occur are category C and recommended to monitor the emergence of ADRs. Gyssens Flow Analysis shows that the choice of antibiotics in the treatment of pneumonia is not in accordance with the 2023 PNPK for pneumonia management and the treatment is decided as an outpatient basis. It was concluded that most of the treatments were in accordance with the indications, dosages in the literature, and the patient's response was relatively improved"
Depok: Fakultas Farmasi Universitas ndonesia, 2023
PR-pdf
UI - Tugas Akhir  Universitas Indonesia Library
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Silalahi, Todung Donald Aposan
"Intervensi koroner perkutan (IKP) terbukti mengurangi morbiditas dan mortalitas penyakit jantung koroner (PJK). Cedera pembuluh darah akibat IKP dapat menyebabkan timbulnya inflamasi dan stress oksidatif. Studi ini menunjukkan bahwa kurkumin memiliki efek menekan inflamasi dan antioksidan pada penderita PJK stabil pasca-IKP. Penelitian ini bertujuan untuk mengetahui efektivitas suplementasi kurkumin per oral dalam menurunkan kadar inflamasi dan stres oksidatif pasca-IKP pasien PJK stabil.
Pasien dewasa PJK stabil dilakukan IKP, dirandomisasi secara acak tersamar ganda ke dalam kelompok kurkumin atau plasebo. Kurkumin (45 mg/hari) atau plasebo diberikan selama 7 hari sebelum IKP hingga 2 hari setelah IKP. Kadar marker inflamasi (hsCRP dan sCD40L) dan marker oksidatif (MDA dan GSH) dalam serum dinilai dalam 3 fase, 7 hari pra-IKP, 24 jam pasca-IKP, dan 48 jam pasca-IKP.
Selama periode April–Juni 2015, terdapat 50 pasien yang direkrut (25 kurkumin dan 25 plasebo) di RSUP Cipto Mangunkusumo dan RS Jantung Jakarta. Konsentrasi hsCRP dan sCD40L pada kelompok kurkumin dalam 3 fase cendrung menurun (p < 0,05) dibanding kelompok plasebo, tetapi konsentrasi hsCRP dan sCD40L pada tiap fase tidak berbedaan bermakna, sedang kadar MDA dan GSH tidak berbeda bermakna setiap fase, namun menunjukkan kecenderungan penurunan kadar MDA (p = 0,6) dan GSH (p = 0,3).
Pemberian kurkumin mempunyai kecenderungan menurunkan respons inflamasi pasca-IKP dan cenderung menghambat pembentukan stress oksidatif yaitu MDA serum melalui mekanisme peningkatan penggunaan antioksidan internal yaitu GSH serum.

Background: Percutaneous coronary intervention (PCI) has been proven to improve morbidities and mortalities in stable coronary heart disease (CHD). However, ischemia-reperfusion injury resulted from PCI might induce inflammation and oxidative stress. Several studies suggested that curcumin exerts anti-inflammatory and antioxidant properties that may be beneficial in post-PCI stable CHD patients.
Objectives: To determine the efficacy of orally administered curcumin in reducing inflammatory response and oxidative stress in post-PCI of stable CHD patients.
Methods: A double-blind randomized controlled trial consisting of 50 adult patients of both sexes with stable CHD who underwent PCI were treated with curcumin or placebo. Either curcumin (45 mg/day) or placebo was given 7 days prior to PCI until 2 days after PCI. Inflammatory markers (hsCRP and sCD40L) and oxidative stress assessment (MDA and GSH) were measured in 3 phases (7 days pre-PCI, 24 hours post-PCI, and 48 hours post-PCI).
Results: During April–June 2015, 50 patients were recruited (25 curcumin and 25 placebo) from Cipto Mangunkusumo General Hospital and Jakarta Heart Center. The serum concentrations of hsCRP and sCD40L in curcumin group (p < 0.05) in all observation phases were significantly lower compared with placebo group; however, there were no significant differences between groups. No significant difference was observed among phases in MDA and GSH, but there was a trend of decreasing MDA and GSH levels (p = 0.6 and p = 0.3, respectively) in curcumin group.
Conclusion: Curcumin tends to reduce inflammatory response following PCI by decreasing oxidative stress (MDA) through the increase of internal antioxidant utilization (GSH).
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
D-pdf
UI - Disertasi Membership  Universitas Indonesia Library
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Suhardjono
"Pada pasien hemodialisis (HD), banyak penelitian di negara maju membuktikan hubungan yang erat antara inflamasi, komplikasi kardiovaskular, malnutrisi, dan mortalitas yang tinggi. Inflamasi yang ditandai dengan meningkatnya IL-6 dan CRP, serta berkurangnya sitokin anti-inflamasi IL-10, mempunyai peran utama dalam terjadinya berbagai komplikasi pada pasien HD di Indonesia, terdapat perbedaan pelaksanaan HD, yaitu HD yang lebih jarang (2 kali seminggu), banyak menggunakan dialiser selulosal diasetat, proses ulang, low flux, dan tanpa air yang sangat murni, yang kesemuanya menyebabkan risiko respons inflamasi yang tinggi. Pada kenyataannya, prevalensi inflamasi dan nilai rata-rata CRP di Indonesia lebih rendah. Polimorfisme gen IL-6-174G>C dan gen IL-10-1082G>A telah dibuktikan mempengaruhi tingkat produksi IL-6 dan CRP. Perbedaan proporsi alel G, C pada IL-6-174, dan alel G, A pada IL-1082, berbagai bangsa dan ras, mungkin menjadi penyebab perbedaan di atas. Sindrom inflamasi malnutrisi (SIM) pada pasien HD berbeda dengan malnutrisi pada populasi. Pada SIM, faktor inflamasi, uremia dan katabolisme protein lebih berperan. Hal ini memerlukan cara penilaian status malnutrisi yang berbeda. Penelitian ini dilakukan untuk mendapatkan frekuensi polimorfisme gen IL-6-174 dan IL-10-1082, mengetahui faktor yang berperan dalam SIM, mengetahui perbedaan prevalensi inflamasi pada pasien dengan malnutrisi dan sebagai validitas penilaian SGA.
Telah dilakukan penelitian pada pasien yang menjalani HD 2 kali seminggu, 5 jam per kali HD, tanpa komplikasi penyakit lainnya, dan semua memakai dialiser selulosa diasetat yang diproses ulang. Dari 64 pasien yang diperiksa, didapatkan gen IL-6-74GG 95,31%, CC 3,13% dan GC 1,56%. Gen IL-1082AA 89,06%, GA 10,94%, dan GG tidak didapatkan. Proporsi alel ini hampir sama seperti yang didapatkan di Korea, Jepang dan Cina, berbeda dengan yang didapat di AS, ras Kaukasia, Amerika-Afrika, Hispanik dan Eropa (Kaukasia). Selain perbedaan pada proporsi gen, kami mendapatkan konsenlrasi CRP (6,23±5,57 mg/L), frekuensi malnutrisi (24,7%), dan skor MIS (6,7) yang lebih rendah dibanding dengan data dari AS dan Eropa. Mengingat sedikitnya alel C pada gen IL-6-174 dan alel G pada gen IL-10-1082, analisis statistik yang dilakukan tidak dapat memperlihatkan pengaruh perbedaan alel terhadap manifestasi klinik. Inflarnasi kronik mempengaruhi terjadinya malnutrisi (PR 3,03; 1K 95% 1,53-6,06; P = 0,012). Penilaian dengan skala SGA berkorelasi balk dengan parameter antropometri (IMT, LLA, LOLA, HGS), dan albumin serum. Albumin serum sebagai parameter inflamasi kronik berkorelasi balk dengan parameter nutrisi yang lain, sedangkan CRP tidak. Didapatkan kesan yang kuat bahwa pada pasien HD, gen IL-174GG bersifat protektif, sedangkan gen IL-1082AA tidak begitu berperan. Selain itu dibuktikan adanya pengaruh inflamasi terhadap malnutrisi dan SGA terbukti merupakan penilaian sindrom malnutrisi inflamasi yang cukup baik.

Many studies on HD patients in developed countries have conferred strong evidence of closed correlation between inflammation, cardiovascular complication and high mortality rates. Inflammation, indicated by high levels of CRP and IL-6, has a major role in initiating and sustaining complications. Adapting to high cost, HD in Indonesia is conducted in a little different ways. Patients are dialyzed twice a week, 5 hours each, using reprocessed cellulose/diacetate membrane dialyzer, and without ultrapure water. All of these contribute to a high risk of inflammation, but in fact the prevalence of inflammation in Indonesia is relatively low. IL-6-174G>C and IL-10-1082G>A polymorphic gene have been proven to influence the production of IL-6 and CRP. The difference in the proportion of allele G, C in IL-6-174, allele G, A in IL-1082 in a variety of people's races might cause the difference in the prevalence and the level of inflammation. Malnutrition inflammation syndrome (MIS) on HD patients is different from malnutrition in general population. In MIS, the inflammatory factors, uremia, and protein catabolism of protein are more dominant. These matters probably require a different assessment method of malnutrition status. The purpose of this study was to obtain the frequency of polymorphic gene IL-6-174 and IL-10-1082 to find out the prominent factors in MIS, and to find out the difference in the inflammation prevalence in patients with malnutrition and to serve as validity of SGA assessment.
A study on patients who were on hemodialysis twice a week, 5 hours each session has been conducted. The subjects had no other co-morbidities and all of them used reprocessed diasetat cellulose dialyzers. Out of 64 patients examined, IL-6-174GG was obtained 95.31%, CC 3.13% and GC 1.56%, IL-1082AA 89.06%, GA 10.94%, but absence of GG genotype. The proportion of these alleles was almost similar to that obtained in Korea, Japan and China, but it was different from that obtained in the US for the Caucasian race, African Americans, Hispanic people, and the Caucasian people in Europe_ Besides the difference in gene proportion, it was obtained that CRP (6.23±5.57 mg/L), malnutrition (24.7%), and malnutrition inflammation score (6.7) were lower compared with the data from Europe and the United States. Considering the scanty amount of allele C in IL-6-174 gene and G allele in IL-10-1082 gene, based on the statistic analysis performed it did not revealed the influence of the difference in allele on the clinical manifestation. It was found that chronic inflammation influenced the occurrence of malnutrition (PR 3.03; CI 95% 1.53-6.06; P = 0,012). The scoring by the..."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2004
D779
UI - Disertasi Membership  Universitas Indonesia Library
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Astuti Giantini
"Sindrom koroner akut (SKA) merupakan masalah kesehatan nasional karena tingginya angka morbiditas dan mortalitas serta beban biaya yang dibutuhkan. Intervensi koroner perkutan (IKP) dan terapi antiplatelet seperti klopidogrel merupakan tata laksana yang direkomendasikan oleh organisasi kardiologi internasional. Meskipun demikian, pasien SKA masih dapat mengalami kejadian kardiovaskular mayor (KKM). Kemungkinan, resistensi klopidogrel berperan pada KKM sedangkan resistensi klopidogrel mungkin dipengaruhi oleh faktor genetik dan epigenetik. Penelitian ini bertujuan untuk mengetahui hubungan faktor genetik yaitu polimorfisme gen CYP2C19 dan P2Y12, serta epigenetik yaitu metilasi DNA gen CYP2C19 dan P2Y12 serta ekspresi miRNA-26a dengan resistensi klopidogrel dan pengaruhnya terhadap KKM pada pasien SKA pasca IKP.
Untuk menganalisis hubungan faktor genetik dan epigenetik dengan resistensi klopidogrel, penelitian dilakukan dengan desain potong lintang, sedangkan untuk analisis hubungan faktor genetik dan epigenetik dengan KKM dilakukan dengan desain kohort prospektif. Subjek penelitian meliputi 201 pasien SKA pasca IKP dan mendapat terapi klopidogrel di Rumah Sakit Jantung dan Pembuluh Darah Harapan Kita dari bulan September 2018 sampai dengan Juni 2020. Resistensi klopidogrel ditentukan dengan pemeriksaan light transmission aggregometry (LTA) apabila hasilnya lebih besar dari 59% dengan agonis ADP 20 mM. Deteksi polimorfisme gen CYP2C19 dan P2Y12 serta ekspresi miRNA-26a dilakukan dengan metode qRT-PCR, sedangkan metilasi DNA gen CYP2C19 dan P2Y12 dikerjakan dengan metode konversi bisulfit. Pasien diobservasi selama satu tahun dan jika ada angina pektoris, infark miokard akut (IMA) rekuren, stroke, atau kematian, dicatat sebagai KKM.
Dari 201 subjek, terdapat 45,8% carrier mutant polimorfisme *2 dan *3 gen CYP2C19, 36,8% carrier mutant polimorfisme rs3679479 gen P2Y12, 10% hipometilasi DNA gen P2Y12, 80,1% hipometilasi DNA gen CYP2C19, dan 66,2% ekspresi miRNA-26a up regulated. Proporsi resisten klopidogrel adalah 49,8% dan proporsi KKM adalah 14,9% (kematian 7,5%). Terdapat hubungan antara merokok (p = 0,001; OR 0,37 [IK 95%; 0,20–0,68]), hipometilasi DNA gen CYP2C19 (p = 0,037; OR 2,13 [IK 95%; 1,04–4,37]), dan ekspresi miRNA-26a up regulated (p = 0,020; OR 2,03 [IK 95%; 1,12–3,68]) dengan resistensi klopidogrel. Terdapat hubungan antara jenis kelamin perempuan (p = 0,040; HR 2,73 [IK 95%; 1,05–7,14]), usia ≥ 60 tahun (p = 0,035; HR 2,17 [IK 95%; 1,06–4,48]), eGFR rendah (p = 0,001; HR 3,29 [IK 95%; 1,59–6,84]), dan polimorfisme *2 dan *3 gen CYP2C19 (p = 0,047; HR 2,12 [IK 95%; 1,01–4,46]) dengan KKM dalam satu tahun.
Hanya faktor epigenetik berupa metilasi DNA gen CYP2C19 dan ekspresi miRNA-26a yang berhubungan dengan resistensi klopidogrel. Walaupun resistensi klopidogrel tidak berhubungan dengan KKM, terdapat hubungan antara faktor genetik polimorfisme *2 dan *3 gen CYP2C19 dengan KKM.

Acute coronary syndrome (ACS) is a national health problem due to high morbidity and mortality, and cost burden as well. Percutaneous coronary intervention (PCI) and antiplatelet therapy such as clopidogrel are recommended. However, ACS patients could still experience major adverse cardiovascular events (MACE). Clopidogrel resistance possibly plays a role in MACE whereas it may be affected by genetic and epigenetic factors. Therefore, the objective of this study was to determine the relationship between genetic factors which are CYP2C19 and P2Y12 polymorphisms, as well as epigenetic factors which are DNA methylation of CYP2C19 and P2Y12, and miRNA-26a expression and their effects on MACE in post-PCI patients.
To analyze the association between genetic and epigenetic factors and clopidogrel resistance, the study design was cross-sectional, while the study design of relationship between genetic and epigenetic factors and MACE was prospective cohort. The subjects were 201 post-PCI ACS patients who received clopidogrel therapy at Harapan Kita Hospital from September 2018 to June 2020. Clopidogrel resistance was determined by light transmission aggregometry (LTA) if the result was greater than 59% with agonist ADP 20 µM. The detection of CYP2C19 and P2Y12 gene polymorphisms and miRNA-26a expression were carried out by qRT-PCR method, while the DNA methylation of the CYP2C19 and P2Y12 genes were carried out by bisulfite conversion method. Patients were observed for one year and angina pectoris, recurrent acute myocardial infarction (AMI), stroke, or death, were recorded as MACE.
From 201 subjects, 45.8% were CYP2C19*2 and CYP2C19*3 polymorphism mutant carrier, 36.8% were rs3679479 P2Y12 polymorphism mutant carrier, 10% were hypomethylated of P2Y12, 80.1% were hypomethylated of CYP2C19, and 66.2% were up regulated in miRNA-26a expression. 49.8% of subjects were clopidogrel resistant and 14.9% of subjects experienced MACE (death was 7.5%). Smoking (p = 0.001; OR 0.37 [CI 95%; 0.20–0.68]), hypomethylated of CYP2C19 (p = 0.037; OR 2.13 [CI 95%; 1.04–4.37]), and up regulated miRNA-26a expression (p = 0.020; OR 2.03 [CI 95%; 1.12–3.68]) were associated with clopidogrel resistance. Female gender (p = 0.040; HR 2.73 [CI 95%; 1.05–7.14]), age over 60 years old (p = 0.035; HR 2.17 [CI 95%; 1.06–4.48]), low eGFR (p = 0.001; HR 3.29 [CI 95%; 1.59–6.84]), and CYP2C19*2 and CYP2C19*3 polymorphisms (p = 0.047; HR 2.12 [CI 95%; 1.01–4.46]) were associated with MACE in one year.
Only DNA methylation of CYP2C19 and miRNA-26a expression were associated with clopidogrel resistance. Although clopidogrel resistance was not associated with MACE, there was association between CYP2C19*2 and CYP2C19*3 polymorphisms and MACE.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2021
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UI - Disertasi Membership  Universitas Indonesia Library
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Erpryta Nurdia Tetrasiwi
"Latar Belakang: Individu dengan diabetes melitus tipe 2 (DMT2) dilaporkan mengalami peningkatan risiko terjadinya sarkopenia dan juga sebaliknya. Penelitian mengenai DMT2 dengan sarkopenia mayoritas berasal dari populasi geriatri. Sampai saat ini belum ada studi yang membandingkan profil metabolik dan parameter inflamasi di kelompok DMT2 dengan dan tanpa sarkopenia pada usia yang lebih muda.
Tujuan: Penelitian ini bertujuan untuk mengetahui adanya perbedaan rerata profil metabolik dan parameter inflamasi pada penyandang DMT2 nongeriatri dengan dan tanpa sarkopenia.
Metode: Penelitian potong lintang ini melibatkan individu dengan DMT2 nongeriatri berusia  18-59 tahun yang berobat di Rumah Sakit Cipto Mangunkusumo (RSCM), Jakarta, Indonesia pada bulan Januari 2021- Januari 2022. Dilakukan pengambilan data sekunder berupa antropometri dan laboratorium yang mencakup Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), HbA1c dan profil lipid. Kadar interleukin (IL)-6 dan IL-10 serum diukur menggunakan teknik ELISA. Kelompok sarkopenia terdiri atas possible dan true sarcopenia berdasarkan kriteria Asian Working Group for Sarcopenia (AWGS) 2019.
Hasil: Dari 100 subjek, 35 subjek dikategorikan ke dalam possible sarkopenia dan 4 subjek true sarkopenia. Subjek DMT2 nongeriatri dengan sarkopenia memiliki median (RIK) nilai HOMA-IR dan kadar HbA1c yang lebih tinggi dibanding subjek tanpa sarkopenia yaitu berturut-turut [6,52 (4,05-17,26) vs. 4,66 (2,61-10,14); p=0,025] dan [9,0% (7,3-10,3)% vs. 7,4% (6,6-8,45)%; p=0,002]. Tidak terdapat perbedaan kadar profil metabolik lain dan IL-6 antara kedua kelompok, sementara kadar IL-10 hanya terdeteksi pada 33 sampel sehingga tidak dapat dianalisis lebih lanjut.
Kesimpulan: Median nilai HOMA-IR dan kadar HbA1c kelompok DMT2 nongeriatri dengan sarkopenia lebih tinggi dibanding kelompok tanpa sarkopenia. Tidak ditemukan perbedaan kadar profil metabolik lain dan IL-6 sebagai parameter inflamasi antara kedua kelompok tersebut. Tidak dilakukan analisis beda rerata kadar IL-10 karena sedikitnya sampel yang terdeteksi.

Background: Individuals with type 2 diabetes mellitus (T2DM) are at increased risk for sarcopenia and vice versa. Studies in T2DM with sarcopenia mostly came from the geriatric population. To date, no study has compared the metabolic profile and inflammatory parameters in younger T2DM subjects with and without sarcopenia.
Aim: This study aimed to assess the mean differences in the metabolic profile and inflammatory parameters of nongeriatric T2DM individuals with vs. without sarcopenia.
Method: This cross-sectional study involved nongeriatric T2DM individuals aged 18-59 years old visiting Cipto Mangunkusumo Hospital, Jakarta, Indonesia between January 2021 and January 2022. Secondary data was obtained, namely anthropometric and laboratory data including Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), HbA1c and lipid profile. Serum levels of interleukin (IL)-6 and IL-10 were measured using the ELISA technique. The sarcopenia group consists of individuals with possible and true sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria.
Results: From 100 subjects, 35 was categorized as possible sarcopenia and 4 as true sarcopenia. Nongeriatric T2DM subjects with sarcopenia had significantly higher median (interquartile range) HOMA-IR and HbA1c compared to nonsarcopenic subjects [6.52 (4.05-17.26) vs. 4.66 (2.61-10.14); p=0.025] and [9.0% (7.3-10.3)% vs. 7.4% (6.6-8.45)%; p=0.002]. There were no differences in other levels of metabolic profile and IL-6 between the two groups, while IL-10 levels were only detected in 33 samples and could not be analyzed further.
Conclusion: Median HOMA-IR and HbA1c nongeriatric T2DM subjects with sarcopenia was higher than those without sarcopenia. There was no difference in other metabolic profile and IL-6 level as inflammation parameter between the two groups. IL-10 was not analysed further due to the small sample number that were detected.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2022
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UI - Tugas Akhir  Universitas Indonesia Library
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Mohammad Fadjri AS
"Adesi dan agregasi pletelet serta pembentukan trombin merupakan rangkaian proses pembentukan trombus yang mendasari sindrom koroner akut (SKA). Oleh karena itu terapi utama SKA adalah heparin dan anti agregasi platelet, disamping obat anti iskemia. Heparin berat molekul rendah (low molecular weight heparin LMWH) memiliki profil farmakokinetik yang lebih baik jika dibandingkan dengan heparin tak terfraksinasi (unfractionated heparin / UFH). Dari berbagai jenis LMWH, hanya enoxaparine yang memperlihatkan keuntungan jika dibandingkan dengan UFH dalam mencegah kematian, infark miokard dan angina berulang pada SKA. Manfaat tersebut mungkin bukan hanya disebabkan oleh efeknya terhadap pembentukan trombin tetapi juga oleh pengaruhnya terhadap adesi dan agregasi platelet melalui interaksi dengan faktor von Willebrand (vWF). Penelitian ini dilakukan untuk melihat efek UFH dan enoxaparine terhadap peningkatan nilai vWF pada akhir terapi dan 48 jam setelah penghentian terapi pada penderita APTS atau IMA non-Q. Pada penelitian ini nilai vWF diperiksa dengan menggunakan teknik double antibody sandwich ELISA Penelitian dilakukan terhadap 37 subyek yang terdiri dari 19 subyek yang diterapi UFH dengan target APTT 1,5 - 2 x kontrol dan 18 subyek diterapi enoxaparine 1 mg/kg BB subkutan, 2 x sehari. Dilakukan pemeriksaan nilai vWF pada awal terapi (vWF1), akhir terapi (vWF2) dan 48 jam setelah penghentian terapi (vWF3). Terdapat efek penekanan. terhadap peningkatan nilai vWF hingga saat penghentian terapi secara bermakna oleh enoxaparine (192,1 ± 57,5 % menjadi 172,8 ± 63,0 %, rerata lama terapi 4,8 ± 1,0 hari, p=0,23), tetapi tidak demikian halnya dengan UFH (165,4 ±42,1 % menjadi 216,1 ±66,5 % rerata lama terapi 52,0 hari, p= 0,009). Terdapat perbedaan bermakna peningkatan nilai vWF pada awal hingga saat penghentian terapi (A vWF2-1) antara kedua kelompok tersebut (p =0,01). Dengan menggunakan data yang dapat dilengkapi hingga pemeriksaan nilai vWF 48 jam setelah penghentian terapi (UFH n=9 dan Enoxaparine n-13) masih dijumpai efek penekanan oleh enoxaparine terhadap peningkatan nilai vWF. Efek tersebut tidak dijumpai pada subyek yang diterapi dengan UFH."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 1999
T57290
UI - Tesis Membership  Universitas Indonesia Library
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