Unravelling a novel, promising and convenient tool for differential diagnosis of delayed puberty: GnRHa-stimulated inhibin B (GnRH-iB).

BACKGROUND: Etiological diagnosis of delayed puberty is difficult. Despite availability of various basal and stimulation tests differentiation between constitutional delay in puberty and hypogonadotropic hypogonadism is still challenging. OBJECTIVE: To elucidate the role of GnRH agonist-stimulated inhibin B (GnRH-iB) for the differential diagnosis of delayed puberty. STUDY DESIGN: Participants were recruited into "exploratory cohort" (n = 39) and "validation cohort" (n = 16). "Exploratory cohort" included children with spontaneous puberty and patients with hypogonadotropic hypogonadism. "Validation cohort" constituted children who presented with delayed puberty. INTERVENTION AND OUTCOME: GnRHa (Triptorelin) stimulation test along with measurement of inhibin B level at 24 h after GnRHa injection was performed in all the study participants. Cut-offs for GnRH-iB were derived from the "exploratory cohort". These cut-offs were applied to the "validation cohort". Basal LH, basal inhibin B(INH-B), GnRHa-stimulated LH at 4 h (GnRH-LH) and GnRH-iB were evaluated for the prediction of onset of puberty on prospective follow-up. RESULTS: GnRH-iB at a cut-off value of 113.5 pg/ml in boys and 72.6 pg/ml in girls had 100% sensitivity and specificity for the documentation of puberty. In the "validation cohort" basal LH, basal INH-B, GnRH-LH, and GnRH-iB had a diagnostic accuracy of 68.75%, 81.25%, 68.75% and 93.75% respectively, for the prediction of onset of puberty. Basal LH, basal INH-B and GnRH-LH used alone or in combination were inferior to GnRH-iB used alone. CONCLUSION: GnRHa-stimulated inhibin B (GnRH-iB) is a convenient and easily employable test for the differentiation of constitutional delay in puberty from hypogonadotropic hypogonadism. CTRI REGISTRATION NO: CTRI/2019/10/021570.

MEALTIME BOLUS INSULIN DOSE TIMING IN CHILDREN WITH TYPE 1 DIABETES: REAL-LIFE DATA FROM A TERTIARY CARE CENTRE IN NORTHERN INDIA.

Context: Mealtime insulin bolus is traditionally administered before meals in children with type 1 diabetes (T1D). Controlled studies on the use of pre-and postprandial insulin bolus have shown variable results. There are no real-world studies on postprandial bolusing of insulin in young children with T1D. Methods: Children with T1D aged <7 years were grouped into preprandial (Group 1) or postprandial (Group 2) groups according to the practice of prandial insulin use. Their retrospective data on mean glycosylated hemoglobin (HbA1c), hypoglycemic events, and diabetic ketoacidosis (DKA) episodes were compared. Results: Forty-four children (mean age 4.1±1.3 years, range 2-7 years) with mean diabetes duration of 2.0±0.7 years (range, 1-4 years) were identified; 23 (52.3%) belonged to Group 1 and 21 (47.7%) to Group 2. There were no differences in the mean HbA1c levels, mean hypoglycemic events, and DKA episodes between the two groups during a mean follow-up duration of two years. Conclusion: Young children with T1D administered insulin bolus during or immediately after meals showed similar long-term glycemic control and diabetes-related adverse event profile compared to the premeal timing of insulin bolus. Larger real-world studies are needed on flexible insulin bolus timing in young children with T1D.

Hypoferremic State in Overweight and Obese Children.

Children with high body mass index (BMI) are at risk of iron deficiency. In present study, 71 children with overweight or obesity were screened for iron deficiency. Mean BMI, ferritin and plasma soluble transferrin receptor (sTrfR) levels were 26.1 kg/m2, 41.9 µg/L and 0.375 mg/L, respectively. Twenty (28%) children had anemia, and 44 (62%) had an underlying hypoferraemic state.

Lower Plasma Soluble Transferrin Receptor Range in Healthy Indian Pediatric Cohort as Compared to Asian and Western Data.

Soluble serum transferrin receptor is derived from erythroid transferrin receptor expressed on surface of developing erythroid cells. It can be detected in blood using sensitive ELISA methodology and blood levels reflect physiological iron dependent erythropoiesis state in bone marrow. Normal adult levels vary from 2 to 5 mg/l. However, pediatric studies are few and describe normal ranges to the tune of 1.0-3.0 mg/l, which are relatively lower than that of adults. In present study 40 healthy children (2-12 years) were evaluated to establish normal soluble transferrin receptor range. The mean transferrin receptor levels were 0.39 mg/l with a range of 0.17-2.1 mg/l. The levels were low as compared to mean levels described in other studies from West and our country (4.39 and 2.0 mg/l respectively). Since, no internationally standard method for reporting and testing for transferrin receptor levels are yet available, hence it is imperative to establish normal control ranges in different population cohorts, especially in pediatric age group, to better interpret their levels in diagnostic context.

Deranged regulatory T-cells and transforming growth factor-ß1 levels in type 1 diabetes patients with associated autoimmune diseases.

AIM: This study was designed to enumerate regulatory T-cells (Tregs) and estimate transforming growth factor-ß1 (TGF-ß1) levels in type 1 diabetic (T1D) patients with respect to disease duration and associated autoimmune diseases. METHODS: One hundred and fifty patients and twenty healthy controls were recruited in the study. The patients were subcategorized into eight categories on the basis of disease duration (new onset [NO] and long standing [LS]) and associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease (AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF-ß1 levels were assessed by ELISA. RESULTS: The frequency of Tregs and levels of TGF-ß1 were significantly increased in the patients compared to the healthy controls. Among the different categories of the patients, no significant differences were seen for TGF- ß1 levels, but for Tregs in patients with T1D and AiTD (P = 0.035). A significant correlation was also found between percentage count of Tregs and TGF-ß1 levels in NO cases in all disease subcategories, but not in LS patients. CONCLUSION: Thus, there was an increased percentage of Tregs and serum levels of TGF-ß1 in T1D patients, irrespective of the disease duration and associated autoimmune diseases. The significant correlation in these two parameters at the onset of the disease, but not in LS disease, indicates that the immunological milieu in LS autoimmune diseases is more complicated with disease-associated conditions such as prolonged hyperglycemia, insulin therapy, and/or continued gluten in diet. Treatment and modulation of these long-term complications for improving immunological parameters require further research.

Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 South Asian patients.

BACKGROUND: Data on cutaneous manifestations of type 1 diabetes mellitus (DM) is scarce. OBJECTIVES: To study the spectrum of dermatoses in patients with type 1 DM and the effects of disease duration and long-term glucose control on these cutaneous manifestations. SUBJECTS AND METHODS: After prior consent, clinical examination and relevant investigations were done in 500 subjects with type 1 DM enrolled between July 2011 and June 2012. Statistical tests were performed using SPSS 16. The presence of various dermatoses was correlated with the duration of diabetes. RESULTS: Of five hundred subjects, 339 (67·8%) had one or more dermatoses. The mean age of the patients was 16·9 ± 6·9 years (range 1-25 years) and mean total duration of diabetes was 4·43 ± 4·4 years. Cutaneous adverse effects related to insulin injections (CAII), comprising lipohypertrophy (41%), post-inflammatory hyperpigmentation (3%), lipoatrophy (0·6%) and acanthosis nigricans (0·4%), were the most common findings, followed by limited joint mobility (LJM) (16·8%), xerosis (15·8%) and scleroderma-like skin changes (10%). Patients having long-duration DM (> 4·4 years) were significantly more likely to have lipohypertrophy (P = 0·000), LJM (P = 0·000), scleroderma-like skin changes (P = 0·000), diabetic dermopathy (P = 0·000), acanthosis nigricans (P = 0·005) and skin tags (P = 0·002). Lipohypertrophy, LJM and scleroderma-like skin changes also showed significant correlation with blood glucose level. CONCLUSIONS: Our study suggests that cutaneous changes are common in young Asian patients with type 1 DM. Information, education and counselling of patients and care givers, and awareness among physicians is essential for the prevention and early management of these dermatoses.

Prevalence and associations with hepatitis B and hepatitis C infection among HIV-infected adults in South Africa.

We assessed prevalence and factors associated with hepatitis B in a cross section of HIV-infected primary care and antinatal clinic patients in South Africa and evaluated a rapid hepatitis B surface antigen (HBsAg) assay. We enrolled 998 patients; 88% were women, median age was 29 years and median CD4 count was 354 cells/mm(3). HBsAg enzyme-linked immunosorbent assay (ELISA), anti-hepatitis B core (HBc) antibodies and hepatitis C virus antibody were positive among 4.2%, 37% and 0.1% of subjects, respectively. Univariate and multivariate associations were assessed using logistic regression. Anti-HBc antibodies were associated with alcohol use, traditional medicines and higher CD4 counts; HBsAg positivity was associated with lower CD4. Compared with the HBsAg ELISA, a rapid HBsAg test had a sensitivity of 75.0% and specificity of 99.6%. In conclusion, we identified a moderate prevalence of both HBsAg and anti-HBc. Importantly, we found that subjects with HBsAg positivity had lower CD4 counts.

Chemo-immunotherapy and immunological study in carcinoma of larynx and laryngopharynx.

Eighteen of 25 patients had squamous cell carcinoma in the supraglottic region. Anergy to skin test antigen (DNCB) and T-cell mitogen (PHA) was observed in 17 patients with laryngeal and laryngopharyngeal malignancies. Chemo-immunotherapy did not improve the skin reactivity to either agents. However, a rise in absolute T-cell counts was observed following combined therapy. Moreover, T-lymphopenia was detected in the patient group prior to therapy as compared to mean T-cell counts in normal control subjects.

Nasal myiasis: review of 10 years experience.

Nasal myiasis is a manifestation of the nasal cavities by larvae of the fly of genus Chrysomia. It is prevalent in tropical countries. Atrophic rhinitis is the most commonest predisposing factor for this condition. The maggots can cause extensive erosion of the nose, face and intra-cranial structures occasionally causing meningitis and death. Conservative management by packing the nose with a chloroform and turpentine (1:4) mixture followed by manual removal of the dead maggots is an effective method. Recurrence is known but partial closure of both nostrils to improve the condition of nasal mucosa is the important part of management.

In vitro and in vivo evaluation of change of local pH on bacteria in C.S.O.M.

An in vitro study has shown a high bactericidal activity of 2 per cent acetic acid. An in vitro study in 400 cases of C.S.O.M. has shown that conservative treatment of C.S.O.M. by pH change with 2 per cent acetic acid is better than antibiotic ear drops alone. However, combined therapy (pH change plus antibiotic ear drops) is definitely superior to single treatment by either of the two methods. Two per cent acetic acid is well tolerated by the middle ear mucosa except in 1 per cent cases, where its use had to be discontinued because of irritation. The use of 2 per cent acetic acid is highly recommended, particularly for poor nations, because of its negligible cost as compared to antibiotic ear drops.

Heat stress limits for the sedentary worker.

Performance on four sedentary tasks was monitored during temperatures of 85 degrees f, 95 degrees F, and 105 degrees F WBGT for work periods up to 2 hours. Results were compared with limits recommedned for occupational safety and health regulations. It is suggested that this limit is not a single line, but rather a range of temperture-time combinations. Further, man's compensating nature during short exposures supports a higher temperature limit for brief work bouts.