Short-term Changes in Urine Beta 2 Microglobulin Following Recovery of Acute Kidney Injury Resulting From Snake Envenomation.

INTRODUCTION: Urine ß2 microglobulin (ß2m) is a validated marker to diagnose sepsis and toxin-related acute kidney injury (AKI). In the current study, we used urine ß2m as a potential marker to identify persistent tubular dysfunction following a clinical recovery from snake venom-related AKI. METHODS: A total of 42 patients who developed AKI following hemotoxic envenomation were followed up for a period of 6 months. Urine albumin excretion, estimated glomerular filtration rate (eGFR), and urine ß2m levels were measured at 2 weeks, 3 months, and 6 months following discharge. RESULTS: At the end of 6 months of follow-up, 6 patients (14.3 %) progressed to chronic kidney disease (CKD) (eGFR < 60 ml and/or urine albumin excretion > 30 mg/d). The urine ß2m levels were 1590 µg/l (interquartile range [IQR] 425-5260), 610 µg/l (IQR 210-1850), 850 µg/l (IQR 270-2780) at 2 weeks, 3 months, and 6 months, respectively (P = 0.020). The levels of urine ß2m in the study population at the end of 6 months remained significantly higher compared with the levels in healthy control population (850 µg/l [IQR 270-2780] vs. 210 µg/l [IQR 150-480]; P = 0.001). The proportion of patients with urine ß2m levels exceeding the 95th percentile of control population (>644 µg/l) during the 3 follow-up visits were 70.7% (n = 29), 48.8 % (n = 20), and 51.2% (n = 21). Similar trends were noticed in a sensitivity analysis, after excluding patients with CKD. CONCLUSIONS: Urine ß2m levels remain persistently elevated in approximately half of the individuals who recover from AKI due to snake envenomation.

Vitamin D deficiency in patients with tuberculous meningitis and its relationship with treatment outcome.

SETTING: Data on vitamin D deficiency in tuberculous meningitis (TBM) and its relationship with treatment outcomes are limited. Some of the beneficial effects of vitamin D might be mediated through interleukin-1ß (IL-1ß). OBJECTIVE: To assess the frequency of vitamin D deficiency among TBM patients, its association with treatment outcomes and correlation between vitamin D and IL-1ß levels in cerebrospinal fluid (CSF). DESIGN: We prospectively studied a consecutive sample of human immunodeficiency virus-negative patients with TBM treated at a hospital in southern India. We defined good outcome as survival without severe neurological disability. Serum total 25-hydroxy vitamin D (25[OH]D) and IL-1ß levels in CSF were estimated on pretreatment samples. RESULTS: We studied 40 patients with TBM; 22 (55%) patients had stage 3 disease. Treatment outcome was poor in 21 (53%) patients: 15 (38%) patients died and 6 (15%) had severe neurological disability. The overall mean serum 25(OH)D level was 32.30 ± 16.38 ng/ml. Ten (25%) patients had vitamin D deficiency (<20 ng/ml), and 12 (30%) patients had vitamin D insufficiency (20-30 ng/ml). However, pretreatment serum 25(OH)D levels did not differ significantly by outcome (good vs. poor outcome: 28.30 ± 14.96 vs. 35.92 ± 17.11 ng/ml, P = 0.141). Moreover, IL-1ß levels in CSF did not correlate with serum 25(OH)D levels (Spearman's ρ 0.083, P = 0.609). CONCLUSION: Vitamin D deficiency/insufficiency is common among patients with TBM. However, serum 25(OH)D levels are not associated with IL-1ß levels in CSF or treatment outcome.

Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience.

There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04-0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022).

Occupational exposure and tuberculosis among medical residents in a high-burden setting: an open-cohort study.

SETTING: Postgraduate (PG) residency programme of a tertiary care teaching hospital in southern India. OBJECTIVE: To estimate the incidence of tuberculosis (TB) among PG residents, determine the frequency of exposure to infectious TB patients and assess whether particular specialties were associated with higher risk of exposure and incident TB. DESIGN: We assembled an open cohort of PG residents who were on the academic rolls for more than 3 months at any time between December 2011 and January 2013. We collected data both retrospectively and prospectively using two surveys-an entry survey at study initiation or entry into the cohort, and an exit survey at residency completion or study closure. RESULTS: Among 398 PG residents enrolled in the study, we identified five cases of incident TB during a cumulative follow-up period of 10 962 person-months. The incidence rate was 547 per 100 000 person-years, which was 3.1 times the incidence in the general population. Nearly two thirds (n = 257, 65%) of the residents were exposed to at least one infectious patient. Across the three specialty-based risk strata, there was an ordered increase in the median number of exposures (P < 0.001) and evaluation for presumptive TB (P = 0.024), as well as a trend towards higher incident TB. CONCLUSION: TB incidence is significantly higher among PG residents than in the general population.

Comparison of nested-multiplex, Taqman & SYBR Green real-time PCR in diagnosis of amoebic liver abscess in a tertiary health care institute in India.

BACKGROUND & OBJECTIVES: Amoebiasis is a common parasitic infection caused by Entamoeba histolytica and amoebic liver abscess (ALA) is the most common extraintestinal manifestation of amoebiasis. The aim of this study was to standardise real-time PCR assays (Taqman and SYBR Green) to detect E. histolytica from liver abscess pus and stool samples and compare its results with nested-multiplex PCR. METHODS: Liver abscess pus specimens were subjected to DNA extraction. The extracted DNA samples were subjected to amplification by nested-multiplex PCR, Taqman (18S rRNA) and SYBR Green real-time PCR (16S-like rRNA assays to detect E. histolytica/E. dispar/E. moshkovskii). The amplification products were further confirmed by DNA sequence analysis. Receiver operator characteristic (ROC) curve analysis was done for nested-multiplex and SYBR Green real-time PCR and the area under the curve was calculated for evaluating the accuracy of the tests to dignose ALA. RESULTS: In all, 17, 19 and 25 liver abscess samples were positive for E. histolytica by nested-multiplex PCR, SYBR Green and Taqman real-time PCR assays, respectively. Significant differences in detection of E. histolytica were noted in the real-time PCR assays evaluated ( P<0.0001). The nested-multiplex PCR, SYBR Green real-time PCR and Taqman real-time PCR evaluated showed a positivity rate of 34, 38 and 50 per cent, respectively. Based on ROC curve analysis (considering Taqman real-time PCR as the gold standard), it was observed that SYBR Green real-time PCR was better than conventional nested-multiplex PCR for the diagnosis of ALA. INTERPRETATION & CONCLUSIONS: Taqman real-time PCR targeting the 18S rRNA had the highest positivity rate evaluated in this study. Both nested multiplex and SYBR Green real-time PCR assays utilized were evaluated to give accurate results. Real-time PCR assays can be used as the gold standard in rapid and reliable diagnosis, and appropriate management of amoebiasis, replacing the conventional molecular methods.

Spontaneous nontraumatic subarachnoid hemorrhage without cerebrovascular malformations in a maintenance hemodialysis patient.

Nontraumatic subarachnoid hemorrhage (SAH) in a dialysis patient is an uncommon occurrence and is often associated with high mortality. We report for the first time in India, a case of spontaneous nontraumatic, nonaneurysmal SAH without any cerebrovascular malformation in a maintenance hemodialysis patient, following a session of hemodialysis. The dialysis prescription needs to be modified in these patients, in order to prevent worsening of cerebral edema and progression of hemorrhage. Where available, continuous forms of renal replacement therapies, with regional anticoagulation seem to be the best option for such patients, till neurologic stabilization is achieved.

Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients.

It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 weeks. The biochemical parameters were assessed at the time of recruitment for study and after 4 weeks of treatment. Turmeric supplementation in metformin treated type 2 diabetic patient significantly decreased fasting glucose (95 ± 11.4 mg/dl, P < 0.001) and HbA1c levels (7.4 ± 0.9 %, P < 0.05). Turmeric administered group showed reduction in lipid peroxidation, MDA (0.51 ± 0.11 µmol/l, P < 0.05) and enhanced total antioxidant status (511 ± 70 µmol/l, P < 0.05). Turmeric also exhibited beneficial effects on dyslipidemia LDL cholesterol (113.2 ± 15.3 mg/dl, P < 0.01), non HDL cholesterol (138.3 ± 12.1 mg/dl, P < 0.05) and LDL/HDL ratio (3.01 ± 0.61, P < 0.01) and reduced inflammatory marker, hsCRP (3.4 ± 2.0 mg/dl, P < 0.05). Turmeric supplementation as an adjuvant to T2DM on metformin treatment had a beneficial effect on blood glucose, oxidative stress and inflammation.

Successful salvage of thrombosed arterio-venous fistula with thrombolytic therapy using tissue plasminogen activator.

A functioning vascular access is crucial to the wellbeing of patients on hemodialysis. Thrombosis is the most common complication of arteriovenous fistula (AVF) resulting in late fistula failure; Its treatment is difficult, and results are often suboptimal. Interventional treatment of AVF thrombosis may not be available all the time, and timely application of an available noninterventional treatment may salvage the fistula. We report the successful treatment of AVF thrombosis using local thrombolytic therapy using tissue plasminogen activator in a patient, for the first time in India.

Medullary sponge kidney and isolated hemihyperplasia.

The term hemihyperplasia refers to an enlargement of body parts beyond the normal asymmetry. Hemihyperplasia can be isolated or associated with various well-described malformation syndromes. Medullary sponge kidney (MSK) has been described with isolated and syndromic hemihyperplasia; the actual prevalence is not known The hemi hypertrophy can be so subtle that it may be easily overlooked. MSK need not be limited to the side of hemihyperplasia - most often it is bilateral. Around 33 cases has been reported from different parts of the world of which 15 cases are isolated hemi hyperplasia (IHH), the remaining occurring in the context of various malformation syndromes So far only one case has been reported from India. We report a case of IHH involving right side of the body, recurrent renal stones, incomplete distal renal tubular acidosis hypercalciuria and imaging showing bilateral MSKs.

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk.

BACKGROUND: Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension. METHODS: In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension. RESULTS: No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group. CONCLUSIONS: We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene-gene-environment interactions may generate more conclusive claims about the molecular genetics of hypertension.

Polymorphic variants of beta1 adrenergic receptor gene (Ser49Gly & Arg389Gly) in healthy Tamilian volunteers.

BACKGROUND & OBJECTIVES: Several studies reported the polymorphisms of beta1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. METHODS: The genetic variants were determined by using Taqman 5' nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. RESULTS: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. INTERPRETATION & CONCLUSIONS: Our study shows that interethnic variation exists in the polymorphisms of beta1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population.

Genetic variants of beta(1)-adrenoceptor gene polymorphisms (Ser49Gly and Arg389Gly) and essential hypertension in a south Indian Tamil population.

1. Essential hypertension is a complex polygenic disorder, the pathogenesis of which is dependent on an interplay between genetic and environmental factors. Various studies suggest an association between beta(1)-adrenoceptor gene polymorphisms (Ser49Gly and Arg389Gly) and cardiovascular disorders, including hypertension, cardiomyopathy and congestive heart failure. 2. The genetic profile of the beta(1)-adrenoceptor gene has not yet been documented for any Indian population. Thus, the aim of the present study was to investigate the association between beta(1)-adrenoceptor gene polymorphisms and essential hypertension in a south Indian Tamil population. 3. The present case-control study included 438 patients with essential hypertensives and 444 healthy volunteers from the Tamil population. Genotyping was performed using real-time polymerase chain reaction. 4. Genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared between hypertensive patients and healthy volunteers. The homozygous variant genotype Gly49Gly of the Ser49Gly polymorphism was higher in hypertensive patients compared with controls (12.3 vs 7.4%, respectively). After adjusting for confounding variables (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2-2.9; P < 0.01) by multilogistic regression analysis, the gene was found to be associated with hypertension. A significant interaction was observed in hypertensive patients carrying the Ser49Gly/Gly49Gly x Arg389Gly/Gly389Gly genotypes (OR 1.9; 95% CI 1.1 2.7). 5. In conclusion, the Ser49Gly polymorphism is associated with essential hypertension in a south Indian Tamil population. The results of the present study deviate from those of previous studies, implying that marked interethnic difference exist in beta(1)-adrenoceptor gene polymorphisms.

Isolated cerebral aspergilloma in a young immunocompetent patient.

Aspergillosis of the central nervous system is uncommon. It is encountered mainly in the immunocompromised. We describe an unusual case of cerebral aspergillosis in a young but immunocompetent patient. Despite delayed diagnosis, specific anti-fungal therapy lead to a good recovery. Unfortunately, non-adherence with the costly drugs for an adequate period of time was followed by a fatal relapse.

Neuroparalysis and ventilatory support in severe tetanus.

In severe form of tetanus, even with maximum dose of muscle relaxants, spasms and apnoeic spells may persist and that may be life-threatening. The aim of this study was to assess the effect of neuroparalysing the patients and then providing ventilatory support in bringing about their recovery. Forty-nine adult patients of severe tetanus (Ablett's grade IIIA--6 patients and Ablett's grade IIIB--43 patients) were studied during the period from April, 1993 to February, 1996. Mean period of onset ie, period from trismus to first spasm, in these patients was 24 hours. Patients were neuroparalysed with a bolus dose of 2-4 mg of pancuronium followed by a continuous infusion of 1-2 mg/hour and simultaneously supported with mechanical ventilation until spasms subsided. Fourteen patients (28.6%) survived and rest died. Mean duration of ventilatory support on survived patients was 14.4 days. The commonest complication encountered during ventilatory support was respiratory tract infection observed in 36 patients (73.5%). Commonest cause of death was autonomic imbalance encountered in 15 patients (30.6%). Treatment of choice in severe tetanus should be neuroparalytic ventilatory support. With use of new generation ventilators and better intensive care facility, death in severe tetanus is likely to be very less.