The role of laparoscopy in children with groin problems

The use of laparoscopic surgery has grown dramatically in recent years in most all types of surgery. Historically, the early use of laparoscopic surgery was for pelvic and groin problems. In this article we review the current technique, indications, benefits and complications of laparoscopy in diagnosis and management of various groin problems in children including undescended testes (non-palpable and palpable) and inguinal hernia.     

Bis(Methylpyridine)‐EDTA Derivative as a Potential Ligand for PET Imaging: Synthesis,Complexation, and Biological Evaluation

A novel transitional metal ligand derivatized from EDTA‐conjugated 2‐amino‐4‐methyl pyridine, an acyclic vehicle (EDTA‐Mepy₂) was designed, synthesized, and characterized for PET imaging with ⁶⁸Ga. The drug likeliness and appropriate lipophilicity were first analyzed by molecular docking studies which shows interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at Lys199, Arg257, and His242 residues, which make it more appropriate in transportation as a specific ligand for PET imaging. As a confirmation, binding constant of the ligand with human serum albumin was calculated at λ_ex = 350 nm which was found to be 4.9 × 10³ m ^?1. The pharmacokinetics of ⁶⁸Ga‐EDTA‐Mepy₂ was analyzed by blood kinetics (t_1/2 slow: 3 h 56 min and t_1/2 fast: 32 min) and biodistribution (maximum%ID/g was found in kidney at 1 h). Further the capability of this ligand was analyzed as optical marker also, by recording λ_ex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λ_em = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15–20 times selectivity over the endogenously present metal ions (K_GaL/K_ZnL = 14.3, K_GaL/K_CuL = 18.1).     

Establishing postprandial bio-equivalency and IVIVC for generic metformin sustained release small sized tablets

The objective of current study was to develop metformin hydrochloride modified release small sized tablets, and to evaluate its bioequivalence when compared with the reference product (Glucophage^® SR). The physicochemical properties of the formulated and reference tablets were determined and compared. The in vitro dissolution profiles of formulated tablets were obtained using bio-relevant media and IVIVC was established. Bioequivalence investigation was carried out in 32 healthy male volunteers who received a single dose 1,000 mg of both test and reference products in a randomized two-way crossover design in postprandial conditions. After dosing, serial blood samples were collected for a period of 48 h. Metformin concentration was assayed by using a validated LC–MS/MS method. The log-transformed C_max and AUC were statistically compared by analysis of variance, and the 90 % confidence intervals (CI) of the ratio of the log-transformed C_max and AUC between the most promising developed formulation and the reference product were determined. It was deduced that the dissolution rate profile of the formulated modified release small sized tablets was similar to the reference product employed in the study. Their similarity and difference factors were found to be well within the established limits. In the bioequivalence study, the difference in C_max, AUC_last and AUC_inf between the test and reference product was not statistically significant, with the 90 % CI of 100.73–116.20, 86.16–97.37 and 87.12–96.99 %, respectively. The results suggested that the metformin small tablets formulated with reduced quantity of controlled release polymer were found to be bioequivalent in the postprandial state. For these small tablets, pH 5.5 acetate buffer as a bio-relevant dissolution media for the development of IVIVC.     

Circulating Vimentin Over-Expression in Patients with Oral Sub Mucosal Fibrosis and Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common (90%) types of oral carcinomas in the world. It is the 2nd most common and 3rd deadliest cancer in India. The lack of early detection marker is one of the major causes of worst prognosis. The vimentin belongs to intermediate filament family proteins which plays significant role in maintaining cellular integrity. Over-expression of vimentin has been widely reported in many epithelial cancers however the information regarding its prevalence in the oral cancers still needs further scientific intervention. The expression level of circulating vimentin protein in serum samples (n = 30) of oral submucous fibrosis (OSMF), OSCC patients and healthy controls were measured by performing ELISA. The serum level of vimentin was significantly higher in OSMF (p < 0.01) and OSCC (p < 0.003) patients as compared to healthy subjects. The circulating vimentin levels showed a gradual increase with increasing disease status (normal < OSMF < OSCC). Circulatory levels of vimentin may ba useful indicator of disease progression and as a suitable target for therapeutic intervention of oral submucous fibrosis and oral carcinoma.     

Study of Cell Viability and Etiology of Contamination in Decalcified Bone Allograft: A Pilot Study

BackgroundBone allografts can elicit immune responses which is correlated with the presence of Human Leukocyte Antigen (HLA) and cellular DNA. It also has risk of causing occult infection arising out of contamination during its processing and storage. The presence of immunogenic materials like cells, cellular remnants and DNA in a decalcified bone allograft during different phases of processing has never been studied. Present study was conducted to explore- the cell viability using routine Hematoxylin and Eosin, presence of DNA using Feulgen staining and etiology of contamination in decalcified bone allograft during procurement, demineralization and ethanol preservation.MethodsThe harvested bones from patients undergoing hemireplacement/THR/TKR were processed to prepare decalcified bone allografts. The samples during procurement (A), HCL treatment (B) and ethanol preservation (C) were sent for histopathological analysis (number of osteocytes in the maximum density field under 40x and the cells demonstrating presence of DNA on feulgen stain) and microbiological assessment (aerobic/anaerobic/fungal cultures).ResultsHistopathological study demonstrated the presence of osteocytes and other cells like bone marrow, adipocytes, endothelial cells in the decal bone allograft. The average number of osteocytes gradually decreased from 55.47, 9.6, 0.86 in sample A, B, C, respectively. Feulgen staining confirmed the presence of DNA in osteocytes and other cells which decreased both qualitatively and quantitatively in subsequent stages of processing. Rate of contamination demonstrated at the procurement was 6.67% (Staphylococcus aureus). After treatment with HCl (demineralisation), 7.14% of non-contaminated allografts were found contaminated (Staphylococcus epidermidis). None of the remaining 13 non-contaminated allografts showed contamination after storage in ethanol. Overall 13% of the patients had positive cultures on microbiological assessment.ConclusionThe population of osteocytes in the harvested bone reduced significantly after processing with HCl and ethanol preservation. Presence of DNA, demonstrated by using Feulgen staining, was observed in bone marrow cells, adipocytes along with osteocytes which showed quantitative reduction on processing. Hence, antigenicity, conferred by cells and their DNA, reduced significantly after processing of decal bone. Contamination rate of banked decalcified allograft was 13%. Thus, culture and sensitivity tests should be carried out at each step of processing of decal bone allograft.     

Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia

Abstract

Imatinib-induced tyrosine kinase inhibition extends beyond the BCR-ABL mutation, resulting in adverse effects. We evaluated hypogammaglobulinemia as a potential ‘off-target’ action of imatinib in children with CML. A cross-sectional, observational study was performed. Patients with CML in chronic phase, age <18-years at diagnosis, receiving imatinib for a duration exceeding 6-months were enrolled. Serum immunoglobulin G, A, and M were measured by end-point nephelometry. Thirty patients were enrolled. The mean age at diagnosis was 10.4?±?3.1?years (range: 5-18). The mean age at enrollment was 16.4?±?4.1?years (range: 9-23). The median dose of imatinib was 287.5?mg/m² (IQR: 267.3, 345.0). The median duration of imatinib-therapy was 6-years (IQR: 3.0, 10.3). The median (IQR) normalized levels of IgG, IgA, and IgM were 33.0% (IQR: ?12.8, 58.7), 28.1% (IQR: ?17.0, 90.1) and 15.9% (IQR: ?9.3, 40.5), respectively. The IgG, IgA, and IgM levels were reduced in 9 (30%), 8 (27%), and 10 (33%) patients, respectively. Five (17%) patients had pan-hypogammaglobulinemia. We suggest checking immunoglobulin levels in patients with CML receiving imatinib with recurrent/unusual infections.     

SARS-CoV-2 and Influenza Virus Co-Infection Cases Identified through ILI/SARI Sentinel Surveillance: A Pan-India Report

SARS-CoV-2/influenza virus co-infection studies have focused on hospitalized patients who usually had grave sequelae. Here, we report SARS-CoV-2/influenza virus co-infection cases from both community and hospital settings reported through integrated ILI/SARI (Influenza Like Illness/Severe Acute Respiratory Infection) sentinel surveillance established by the Indian Council of Medical Research. We describe the disease progression and outcomes in these cases. Out of 13,467 samples tested from 4 July 2021–31 January 2022, only 5 (0.04%) were of SARS-CoV-2/influenza virus co-infection from 3 different sites in distinct geographic regions. Of these, three patients with extremes of age required hospital admission, but none required ICU admission or mechanical ventilation. No mortality was reported. The other two co-infection cases from community settings were managed at home. This is the first report on SARS-CoV-2/Influenza virus co-infection from community as well as hospital settings in India and shows that influenza viruses are circulating in the community even during COVID-19. The results emphasize the need for continuous surveillance for multiple respiratory pathogens for effective public health management of ILI/SARI cases in line with the WHO (World Health Organization) recommendations.