Profile of Renal Diseases in HIV patients

INTRODUCTION: AIDS was first recognized in United States in 1981 when evaluated for Pneumocystis jiroveci infection and Kaposi sarcoma in homosexuals. In 1983 HIV virus was isolated from a patient with lymphadenopathy, and in 1984 it was demonstrated as cause of AIDS. The evolution of HIV pandemic was matched by explosive information’s in areas of HIV virology, pathogenesis, treatment of HIV, opportunistic infections, prevention of infections, and toxicity of drugs used for HIV and opportunistic infections. As early as in 1984 itself physicians of New York and Miami recognized Kidney disease as a devastating complication of AIDS. AIM OF THE STUDY: 1. To study the Profile of Renal diseases in HIV patients. 2. To do comparative evaluation of renal lesions diagnosed in various centers. MATERIALS AND METHODS: The study protocols were approved by The Institutional Review Board of Government Hospital for Thoracic Medicine, Tambaram at Chennai, and also by the Ethical committee for research studies of Government Kilpauk Medical College Hospital Chennai. Informed consent was obtained from the proposed study group of seven thousand three hundred and sixty three (7363) patients. The study protocols include recruitment of patients diagnosed to have HIV at the HIV clinic as well as inpatients from the above institutions. All the consecutive patients excluding those aged below 15 years were screened for renal lesions and assigned separate serial number. The patients include persons newly diagnosed to have HIV those HIV patients who are not on ART because of CD4 above 200cell/cmm, as well as those on ART drugs. Initially all of them were investigated with urine analysis for protein, sugar, and deposits for Red Blood Cells, Pus cells, Casts and crystals. Urine protein was done by sulphosalisylic acid method and or dipstick. Other screening laboratory investigation was serum creatinine. Serum creatinine was done using Jaffe’s method. Patients with proteinuria of >500mg/day, hematuriua >5RBCs/HPF, pathologic casts in urine, serum creatinine of >1.2mg/dl and GFR of <60ml/mt were evaluated further. This include repeat urine analysis, spot urine protein and creatinine ratio, 24 hours urine protein, urine culture and sensitivity, complete blood count (including total and differential WBC count, hemoglobin, total RBC count, ESR, platelet count , bleeding time, clotting time, fragmented RBCs, and toxic granules in WBCs,), blood sugar, blood urea, serum creatinine, serum electrolytes, serum total protein, serum albumin, CD4 count, HbsAg, AntiHCV, complements C3,and C4, and ultra sonogram of kidneys and abdomen. Ultra sonogram evaluation of kidney size, parenchymal thickness, and echogenicity were done. Patients who were identified as acute renal failure were excluded for renal biopsy. Patients with severe illness associated with respiratory, cardiac, pulmonary, neurological systems and hemodynamic instability were excluded from renal biopsy. Patients with reversible causes of renal failure, which include prerenal, renal and post renal causes were identified, and treated. Six patients required peritoneal dialysis prior to renal biopsy. After consent for renal biopsy patients were admitted in nephrology ward. Ultra sonogram guided renal biopsies were done using biopsy gun of Bard maxcore renal biopsy instrument. The renal biopsy study included light microscopy and immunoflourescence. RESULTS: Total number of HIV population screened was 7363 patients. Of this 864 persons are from Government Kilpauk Medical College Hospital and the remaining major group of patients were from Government Hospital for Thoracic Medicine, Tambaram, Chennai. The analysis of this study involves both the groups together. CONCLUSIONS: This study is one of the largest studies of HIV patients evaluated for Renal lesions. • 7363 HIV patients were screened over a period of two years (2008 to 2010). Of them 4942 were males, 2411 were females and 10 were transgenters and the male female ratio was 2.05 :1. • Significant Proteinuria was present in 2582(35.5%) patients. • Hematuria was found in 336 (4.5%) of patients, of them 18 had macroscopic hematuria. • Renal failure was detected in 574 patients (7.79%). • Acute Kidney Injury was detected in 128 patients (1.75%). • 446 patients had chronic kidney disease in Stages 3 - 5 and of this 314(70.41%) were males and 132 (29.59%) were females. 250 Patients were in Stage 3 CKD, 148 in Stage 4 CKD and 48 in Stage 5 CKD. 14 Patients died of ESRD and one patient is on maintenance hemodialysis. • Type 2 Diabetes was the cause of CKD in 24 patients. • Hypertension was seen in 66 of the 574 patients with renal failure. • 4 Patients had Hepatitis B and 2 had hepatitis C. • Pyuria was seen in 1203 (16.33%) patients of the 7363 screened. • Urinary tract infection (UTI) was documented in 42 of the 574 patients in whom urine culture was done. E.Coli was the commonest organism isolated in 66.66% followed by Pseudomonas and Klebsiella of 16.33% each. • Of the 72 renal biopsies performed DMP was the commonest lesion encountered (35.5%). • Other common lesions were HIVAN (29.1%) and IgA Nephropathy (15.49%). • A rare combination of Lupus nephritis (class 4&5 with crescents) and HIVAN was seen in one patient

Synthesis, Antimicrobial and Antitubercular Activities of Some Novel Trihydroxy Benzamido Azetidin-2-one Derivatives

Purpose: To synthesize and characterize novel trihydroxy benzamido azetidin-2-one derivatives and screen them for antimicrobial and antitubercular activities.Methods: A series of novel 4-aryl-3-chloro-N-(3,4,5-trihydroxy benzamido)-2-azetidinones, 3a-o, were synthesized by reacting various Schiff bases of galloyl hydrazide, 2a-o, with chloroacetyl chloride in thepresence of dioxan and triethylamine. Schiff bases of galloyl hydrazide, 2a-o, were synthesized from galloyl hydrazide. The newly synthesized compounds were characterized by infrared spectroscopy (IR),mass spectroscopy (MS) and proton nuclear magnetic spectroscopy (1H NMR) and elemental analysis; they were also screened for in vitro antibacterial, antifungal and antitubercular activities. Ciprofloxacinand ketoconazole were used as reference standards for antibacterial and antifungal activities, respectively, while isoniazid was used as reference standard for antitubercular activity.Results: Compounds 3f, 3g and 3o with chlorophenyl group and compound 3k with 4-dimethyl amino phenyl group exhibited good antimicrobial activity. Also, compounds 3f, 3g, 3k and 3o showed antitubercular activity with minimum inhibitory concentration (MIC) values equivalent to the standard drug (isoniazid). MIC values of 3f, 3g, 3k and 3o were 0.76, 0.57.0.62 and 0.83 ìg/ml, respectively, while the MIC of isoniazid was 0.56.Conclusion: We report the successful synthesis, spectral characterization, as well as in vitro antimicrobial and antitubercular evaluation of a series of novel trihydroxy benzamido azetidin-2-one derivatives. The work shows the emergence of new antimicrobial and antitubercular compounds

An Effective Data Sampling Procedure for Imbalanced Data Learning on Health Insurance Fraud Detection

Fraud detection has received considerable attention from many academic research and industries worldwide due to its increasing popularity. Insurance datasets are enormous, with skewed distributions and high dimensionality. Skewed class distribution and its volume are considered significant problems while analyzing insurance datasets, as these issues increase the misclassification rates. Although sampling approaches, such as random oversampling and SMOTE can help balance the data, they can also increase the computational complexity and lead to a deterioration of model\u27s performance. So, more sophisticated techniques are needed to balance the skewed classes efficiently. This research focuses on optimizing the learner for fraud detection by applying a Fused Resampling and Cleaning Ensemble (FusedRCE) for effective sampling in health insurance fraud detection. We hypothesized that meticulous oversampling followed with a guided data cleaning would improve the prediction performance and learner\u27s understanding of the minority fraudulent classes compared to other sampling techniques. The proposed model works in three steps. As a first step, PCA is applied to extract the necessary features and reduce the dimensions in the data. In the second step, a hybrid combination of k-means clustering and SMOTE oversampling is used to resample the imbalanced data. Oversampling introduces lots of noise in the data. A thorough cleaning is performed on the balanced data to remove the noisy samples generated during oversampling using the Tomek Link algorithm in the third step. Tomek Link algorithm clears the boundary between minority and majority class samples and makes the data more precise and freer from noise. The resultant dataset is used by four different classification algorithms: Logistic Regression, Decision Tree Classifier, k-Nearest Neighbors, and Neural Networks using repeated 5-fold cross-validation. Compared to other classifiers, Neural Networks with FusedRCE had the highest average prediction rate of 98.9%. The results were also measured using parameters such as F1 score, Precision, Recall and AUC values. The results obtained show that the proposed method performed significantly better than any other fraud detection approach in health insurance by predicting more fraudulent data with greater accuracy and a 3x increase in speed during training

Application of a Stability-Indicating HPTLC Method for Simultaneous Quantitative Determination of Olmesartan Medoxomil and Hydrochlorothiazide in Pharmaceutical Dosage Forms

A rapid, precise, sensitive, economical, and validated high performance thin layer chromatographic method is developed for simultaneous quantification of olmesartan medoxomil and hydrochlorothiazide in combined tablet dosage form. The method used amlodipine as internal standard (IS). Chromatographic separations were achieved on silica gel 60 F(254) plates using toluene-methanol-ethyl acetate-acetone (2.5 : 1 : 0.5 : 2, v/v/v/v) as mobile phase. Densitometric analysis was carried out in the reflectance mode at 258 nm. Calibration curves were linear over a range of 80–480 ng/band for olmesartan medoxomil and 25–150 ng/band for hydrochlorothiazide. The detection and quantification limits were found to be 18.12 and 56.35 ng/band for olmesartan medoxomil and 6.31 and 18.56 ng/band for hydrochlorothiazide, respectively. Intra- and interassay precision provided relative standard deviations lower than 2% for both analytes. Recovery from 99.60 to 101.22% for olmesartan medoxomil and 98.30 to 99.32% for hydrochlorothiazide show good accuracy. Both the drugs were also subjected to acid, alkali, oxidation, heat, and photodegradation studies. The degradation products obtained were well resolved from pure drugs with significantly different R (f) values. As the method could effectively separate the drugs from their degradation products, it can be used for stability-indicating analysis. Validation of the method was carried out as per international conference on harmonization (ICH) guidelines