Renovascular hypertension: factors affecting the outcome following surgical revascularisation

This study was conducted at the Aga Khan University Hospital, Karachi, Pakistan to evaluate factors that affect outcome following revascularisation in patients with renovascular hypertension. We included all the patients diagnosed to have renovascular hypertension, confirmed by renal angiography, between July 1997 and September 2000. Of the total 15 patients, nine were males and six were females. Eleven patients received venous grafts, three received polytetraflouroethyline (PTFE) grafts while one patient underwent angioplasty and stenting. All were followed-up for a period of nine months (median) with the range from 2 to 84 months. A total of 33.3% of the study patients were completely cured, as they became normotensive without anti-hypertensive therapy after operation, while 27% showed marked improvement in blood pressure control post-operatively. Thus, extended cure or improvement of renovascular hypertension was achieved in 60% of patients. Normal pre-operative serum creatinine level, high pre-operative unstimulated peripheral renin levels and renal vein renin ratio of at least 1.75:1 were the most significant predictive factors for favorable outcome (p \u3c 0.012). The pre-operative severity and duration of hypertension as well as degree of disparity in kidney sizes did not predict the post-operative improvement in renal function and blood pressure control

Growth Differentiation Factor 5 Regulates Cardiac Repair After Myocardial Infarction

ObjectivesThe aim of this study was to examine the function of the bone morphogenic protein growth differentiation factor 5 (Gdf5) in a mouse model of myocardial infarction (MI).BackgroundThe Gdf5 has been implicated in skeletal development, but a potential role in the heart had not been studied.MethodsThe Gdf5-knockout (KO) and wild-type (WT) mice were subjected to permanent left anterior descending coronary artery (LAD) ligation. Cardiac pathology, function, gene expression levels, and signaling pathways downstream of Gdf5 were examined. Effects of recombinant Gdf5 (rGdf5) were tested in primary cardiac cell cultures.ResultsThe WT mice showed increased cardiac Gdf5 levels after MI, with increased expression in peri-infarct cardiomyocytes and myofibroblasts. At 1 and 7 days after MI, no differences were observed in ischemic or infarct areas between WT and Gdf5-KO mice. However, by 28 days after MI, Gdf5-KO mice exhibited increased infarct scar expansion and thinning with decreased arteriolar density compared with WT. The Gdf5-KO hearts also displayed increased left ventricular dilation, with decreased contractility after MI. At 4 days after MI, Gdf5-KO mice exhibited increased cardiomyocyte apoptosis and decreased expression of anti-apoptotic genes Bcl2 and Bcl-xL compared with WT. Unexpectedly, Gdf5-KO hearts displayed increased Smad 1/5/8 phosphorylation but decreased p38-mitogen-activated protein kinase (MAPK) phosphorylation versus WT. The latter was associated with increased collagen gene (Col1a1, Col3a1) expression and fibrosis. In cultures, rGdf5 induced p38-MAPK phosphorylation in cardiac fibroblasts and Smad-dependent increases in Bcl2 and Bcl-xL in cardiomyocytes.ConclusionsIncreased expression of Gdf5 after MI limits infarct scar expansion in vivo. These effects might be mediated by Gdf5-induced p38-MAPK signaling in fibroblasts and Gdf5-driven Smad-dependent pro-survival signaling in cardiomyocytes

Ischemic monomelic neuropathy: a complication of vascular access procedure

Ischemic monomelic neuropathy (IMN) is an infrequently recognized type of ischemic neuropathy produced by shunting blood or acute occlusion of a major proximal artery in the extremities. IMN predominantly occurs in diabetic patients with evidence of peripheral atherosclerotic vascular disease and neuropathy. We report a case of ischemic monomelic neuropathy occurring in a diabetic patient with end-stage renal disease following the placement of polytetrafluoroethylene (PTFE) graft as a vascular access in the proximal upper arm for chronic hemodialysis

TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice

Hyperoxia-induced injury to the developing lung, impaired alveolarization, and dysregulated vascularization are critical factors in the pathogenesis of bronchopulmonary dysplasia (BPD); however, mechanisms for hyperoxia-induced development of BPD are not fully known. In this study, we show that TREM-1 (triggering receptor expressed on myeloid cells 1) is upregulated in hyperoxia-exposed neonatal murine lungs as well as in tracheal aspirates and lungs of human neonates with respiratory distress syndrome and BPD as an adaptive response to survival in hyperoxia. Inhibition of TREM-1 function using an siRNA approach or deletion of the Trem 1 gene in mice showed enhanced lung inflammation, alveolar damage, and mortality of hyperoxia-exposed neonatal mice. The treatment of hyperoxia-exposed neonatal mice with agonistic TREM-1 antibody decreased lung inflammation, improved alveolarization, and was associated with diminished necroptosis-regulating protein RIPK3 (receptor-interacting protein kinase 3). Mechanistically, we show that TREM-1 activation alleviates lung inflammation and improves alveolarization through downregulating RIPK3-mediated necroptosis and NLRP3 (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3) inflammasome activation in hyperoxia-exposed neonatal mice. These data show that activating TREM-1, enhancing angiopoietin 1 signaling, or blocking the RIPK3-mediated necroptosis pathway may be used in new therapeutic interventions to control adverse effects of hyperoxia in the development of BPD.Peer reviewe

Pre-operative renal function and selective renal vein rennin levels as markers of favourable outcome in renovascular hypertension

Objective: To evaluate factors that affect outcome following revascularization in patients with renovascular hypertension. Methods: This study was conducted at the Aga Khan University Hospital. It included all the patients diagnosed to have Renovascular hypertension confirmed by renal angiography between July 1996 to September 2000. Using ANOVA (Analysis of variance) and paired-sample t-test, several preoperative factors were evaluated for their ability to predict postoperative improvement of blood pressure and renalfunction. For descriptive purpose patients were divided into cured, improved and failure groups. Results: Of the total 15 patients, 9 were males and 6 were females. Before the surgical procedure, 13 patients were on 3 or more antihypertensive drugs. Eleven patients received vein grafts, three patients had PTFE (polytetraflouroethyline) grafts while one patient underwent angioplasty and stenting. The patients had a median follow-up period of nine months with a range of 2 to 84 months. Five were completely cured, as they became normotensive without antihypertensive therapy after operation, whereas four showed marked improvement in BP control postoperatively, requiring two antihypertensive drugs. Six patients showed no improvement requiring 3 or more drugs. Extended cure or improvement of renovascular hypertension was achieved in nine patients. Normal preoperative serum creatinine level, high preoperative unstimulated peripheral renin levels and renal vein renin ratio of at least 1.75:1 were the most significant predictive factors for favorable outcome. Conclusion: This study confirms the long term effectiveness and safety of renovascular reconstruction in the relief of severe hypertension. The results further suggest that normal preoperative renal function, high renal vein renin ratio and high preoperative unstimulated peripheral renin levels are associated with the most favourable postoperative outcome (p \u3c0.01). Preoperative severity and duration of hypertension and degree of disparity in kidney sizes do not affect the overall results in terms of postoperative improvement in renal function and blood pressure control (p=0.734)

Variation of Peak Expiratory Flow Rate with Body Mass Index in Medical Students of Karachi, Pakistan

OBJECTIVE: The primary aim of our study was to assess the variation of PEFR with BMI in normal medical students of Karachi, PakistanDESIGN: Cross-sectional studySetting: Medical students of Karachi Medical and Dental CollegeParticipants: 138 non-smoker healthy medical students composed of 111 females and 27 males. VARIABLE PARAMETERS: They include mean age, body height and body weight and PEFR. They were marked separately for each genderRESULTS: The mean BMI in females was found out to be 18.54±2.10 corresponding with that of mean PEFR value 431.62±56.62 whereas in males the mean BMI was 25.07±2.96 corresponding with that of mean PEFR value 533.70±23.22. Also there is a statistically significant variation in PEFR with an increase in BMI.CONCLUSION: The study concludes that PEFR is affected positively by variation in BMI. Also young males have more BMI and PEFR values than their young female counterparts. A large sample size with accurate peak flow meter is required along with ethnic consideration of the study population for better and accurate result

Curcumin has Curative Effect on Isoniazid-Rifampicin Induced Hepatotoxicity

Background: Anti-tuberculosis drugs-induced hepatotoxicity is associated with oxidative stress. Curcumin is a powerful antioxidant and has been found to protect the liver from the damaging effects of oxidative stress. The study aimed to assess the curative and protective effects of Curcumin against hepatotoxicity induced by anti TB- drugs (Isoniazid-Rifampicin) by using an experimental model of Albino rabbits. Methods: Albino rabbits(n=24) were divided into four groups. Group A was the control group, Group B administered Isoniazid (INH) (50 mg/kg/d) and Rifampicin (RMP) (100 mg/kg) alone, Group C received both INH+RMP and Curcumin (60 mg/kg) before and during induction. Group D received INH (50 mg/kg/d) and RMP (100 mg/kg/d) for 7 days, followed by 7 days of Curcumin (60 mg/kg/d). Biochemical testing and liver morphological histopathology was done for all groups. All values were recorded in mean ± standard deviation. Results: Anti-Tuberculosis drugs increased Alanine Transaminase (ALT), Aspartate Transaminase level (AST), Alkaline Phosphatase level (ALP), Total Bilirubin, and Albumin 62.0±2.5, 172.5±1.0, 128±1.5, 0.80±0.05, 5.00±0.5 respectively and decreased Total protein levels (2.05±1.0). Whereas, Curcumin lowered liver enzymes 37.0±2.8, 126.12±1.5, 90.5±1.0, 0.40±0.01, 3.50±0.5 respectively, and increased levels of total protein (5.00±0.5). Group A exhibited normal liver morphology, whereas, Group B had ballooning degeneration, focal cell necrosis, and liver inflammation. Group C had moderate fatty liver but no centrilobular degeneration or focal cell necrosis and Group D exhibited minor liver inflammation and normal liver morphology. Conclusion: Curcumin was found preventative and therapeutic remedy which can be used for the treatment of hepatotoxicity. Keywords: Curcumin; Hepatotoxicity; Hepatoprotective; Isoniazid; Rifampicin

Do clinical manifestations of Systemic Lupus Erythematosus in Pakistan correlate with rest of Asia?

Objective: Systemic Lupus Erythematosus (SLE) is known to be different among people with different racial, geographical and socio-economic back grounds. Asia has diverse ethnic groups broadly, Orientals in the East and Southeast Asia, Indians in South Asia and Arabs in the Middle East. These regions differ significantly from the Caucasians with reference to SLE. The purpose of this study was, therefore, to delineate the clinical pattern and disease course in Pakistani patients with SLE and compare it with Asian data.Methods: Patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association admitted at the Aga Khan University Hospital between 1986 and 2001 were studied by means of a retrospective review of their records. The results were compared with various studies in different regions of Asia.Results: Demographically, it was seen that SLE is a disease predominantly of females in their third decade, which is generally consistent with Asian data. There was less cutaneous manifestations, arthritis, serositis, haematological and renal involvement compared to various regions in Asia. The neurological manifestations of SLE, however, place Pakistani patients in the middle of a spectrum between South Asians and other Asian races.CONCLUSION: This study has shown that the clinical characteristics of SLE patients in our country may be different to those of other Asian races. Although our population is similar to South Asians, but clinical manifestations of our SLE patients are considerably different, suggesting some unknown etiology. Further studies are required to confirm the above results and to find statistically sounder associations

Factors associated with non-adherence among psychiatric patients at a tertiary care hospital, Karachi, Pakistan: a questionnaire based cross-sectional study

OBJECTIVE: To elucidate predictors of non-adherence among psychiatric patients presenting at a tertiary care hospital of Pakistan, for follow-up with consultant psychiatrist. METHODS: A convenient sampleof psychiatric patients from Aga Khan University Hospital was enrolled between April and May, 2005. An interviewer assisted, standardized questionnaire was used for data collection. Patients with cognitive deficit or psychosis and those presenting for the first time were not included in the study. RESULTS: Out of 128 patients, those with co-morbidity (32.81%) were less adherent than those without comorbidity (p-value:0.002). Adherence among depressed was 61.53%; psychotic was 58.82%; bipolar disorder was 73.91%. Reasons for non-adherence included sedation (30%), medication cost (22%), forgot to take medication (36%); and inability of the physicians to explain timing and dose (92%) or benefit of medication (76%). CONCLUSIONS: Non-adherence is a common and important issue. Treatment cost and co-morbidity should be reviewed in order to keep the medication regime affordable and comprehensible