Neera Sharma

Detection of Mycobacterium tuberculosis GlcB or HspX Antigens or devR DNA Impacts the Rapid Diagnosis of Tuberculous Meningitis in Children

Background Tuberculous meningitis (TBM) is the most common form of neurotuberculosis and the fifth most common form of extrapulmonary TB. Early diagnosis and prompt treatment are the cornerstones of effective disease management. The accurate diagnosis of TBM poses a challenge due to an extensive differential diagnosis, low bacterial load and paucity of cerebrospinal fluid (CSF) especially in children. Methodology/Principal Findings We describe the utility of ELISA and qPCR for the detection of Mycobacterium tuberculosis (M. tb) proteins (GlcB, HspX, MPT51, Ag85B and PstS1) and DNA for the rapid diagnosis of TBM. CSF filtrates (n = 532) derived from children were classified as ‘Definite’ TBM (M. tb culture positive, n = 29), ‘Probable and Possible’ TBM (n = 165) and ‘Not-TBM’ including other cases of meningitis or neurological disorders (n = 338). ROC curves were generated from ELISA and qPCR data of ‘Definite’ TBM and Non-Tuberculous infectious meningitis (NTIM) samples and cut-off values were derived to provide ≥95% specificity. devR qPCR, GlcB, HspX and PstS1 ELISAs showed 100% (88;100) sensitivity and 96–97% specificity in ‘Definite’ TBM samples. The application of these cut-offs to ‘Probable and Possible’ TBM groups yielded excellent sensitivity (98%, 94;99) and specificity (98%, 96;99) for qPCR and for GlcB, HspX and MPT51 antigen ELISAs (sensitivity 92–95% and specificity 93–96%). A test combination of qPCR with GlcB and HspX ELISAs accurately detected all TBM samples at a specificity of ∼90%. Logistic regression analysis indicated that these tests significantly added value to the currently used algorithms for TBM diagnosis. Conclusions The detection of M. tb GlcB/HspX antigens/devR DNA in CSF is likely to improve the utility of existing algorithms for TBM diagnosis and also hasten the speed of diagnosis.

Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Objective: To determine the relationship of serum troponin I after first acute myocardial infarction with left ventricular ejection fraction as assessed by echocardiography. Methods: A total of 40 patients of acute myocardial infarction were included in the study. Troponin I concentration was measured by ELISA method and echocardiographic ejection fraction was calculated by modified Simpson’s rule. Echocardiographic ejection fraction was compared with serum troponin I concentration. Patients with previous myocardial infarction were excluded. Result: There was strong negative correlation between troponin I concentration and left ventricular ejection fraction, i.e., with an increasing troponin level, there was a fall in ejection fraction. The Pearson’s correlation coefficient was –0.69, which was statistically significant (p 50%, though small in number were having cTnI levels at 24 hrs ≤ 8 ng/ml. Patients with ejection fraction 50% may be due to peak value of biomarker achieved at 24-36 hrs after myocardial injury as most of troponin I are attached to myofibrils. Conclusion: Serum troponin I concentration has a strong negative correlation with left ventricular ejection fraction after first acute myocardial infarction, and hence can be used to assess the LVEF in patients with first myocardial infarction. An observation was made that a cut off level of cTnI ≤ 8 ng/ml was associated with normal left ventricular systolic function.

Hyperprolactinemia in Children with Subclinical Hypothyroidism

Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children <18 years of age undergoing thyroid function evaluation and diagnosed to have normal thyroid function, ScH, or OPH. Children with pituitary adenomas, secondary hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25th–75th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673–0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.

Polycystic ovarian syndrome in patients with lipodystrophy: Report of 2 cases with review of literature.

Lipodystrophy is a clinical disorder characterized by maldistribution of body fat. Hyperinsulinemia, insulin resistance, and abnormalities of glucose homeostasis are commonly described among these patients. Hyperinsulinemia is also involved in the pathogenesis of polycystic ovarian syndrome, a condition, described rarely in patients with lipodystrophy. Here, we describe 2 females of partial lipodystrophy who presented with features of polycystic ovarian disease. Both had severe hyperinsulinemia and irregular periods, one had hyperandrogenism and hirsuitism while the other was non-hirsuite.

Low skeletal mass is an important predictor of osteoporosis in HIV-infected men in India

INTRODUCTION This study evaluated prevalence and predictors of osteoporosis and sarcopenia in men with HIV. MATERIAL AND METHODS 220 men with HIV were screened, of which 115 men, 30-50 years-age, having at least 1-year follow-up, underwent hormonal and DEXA analysis. 40 controls were also evaluated. RESULTS Males with HIV had significantly lower BMD and Z-scores at all sites. Osteoporosis was diagnosed in 64.35%; commonest site being radius total (49.56%), followed by radius 33% (45.21%), radius ultra distal (36.52%), lumbar spine (19.13%), neck of femur (17.39%), total femur and greater trochanter (7.82% each). HIV patients had significantly lower fat mass (FM), lean mass (LM), total fat percent, bone mineral content, gynoid fat, percent skeletal muscle mass (PSMM). Men with osteoporosis had higher use of anti retroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS), tuberculosis, lower FM, LM and PSMM. Logistic regression revealed PSMM, age and delta (Δ) CD4 count (change in CD4 count after 6-12 months of ART, compared to pre-ART) were best predictors of osteoporosis. Greater PSMM was associated with decreased osteoporosis, without adjusting for any variable (Model-1), adjusting for disease duration, tuberculosis and IRIS (Model-2), and model-2 plus gonadotropins and sex steroids (Model-3). Greater ΔCD4 count and age were associated with increased osteoporosis after adjusting for different models. Sarcopenia was observed in 40% men and none in controls. CONCLUSIONS Men with decreased skeletal mass, age, severe immune dysfunction at diagnosis, having rapid increase in CD4 count following ART and IRIS have higher risk of osteoporosis in the long run.