Neuro-endoscopic surgery--experience and outcome analysis of 102 consecutive procedures in a busy neurosurgical centre of India

BACKGROUND: Neuro-endoscopic surgery is finding increasing application for various clinical conditions. We present our experience of 100 cases of diverse intracranial lesions, including infections, managed by neuro-endoscopy in a busy neurosurgical department in the developing world. MATERIAL AND METHODS: One hundred patients treated from March 1996 to February 2002 formed the study group. Management of hydrocephalous by Endoscopic third ventriculostomy (ETV) was the aim in 75 patients with or without diagnostic biopsy. Excision or resection was attempted in 25 patients with juxtaventricular or intraventricular lesions. Endoscopic procedures included total tumour resection, partial resection, biopsy, stent placement, Monroplasty, septostomy and third ventriculostomy. Outcomes of endoscopic surgery were evaluated with respect to clinical and/or radiological improvement, complications and need for additional therapy. FINDINGS: Endoscopy was the only surgical treatment in 59 patients. Intermittent lumbar drainage for cerebrospinal fluid leak, shunt, microsurgery and/or repeat endoscopic surgery were additional treatments needed in 39 patients, who subsequently had increased hospital stay, postoperative morbidity and a higher cost of treatment. Peroperative bleeding due to distorted anatomy and obscured vision in 2 patients with post-infective loculated hydrocephalus (LH) resulted in two fatalities (2%) in the early post-operative period. INTERPRETATION: Neuro-endoscopic surgery cuts down operative time and hospital stay, reduces cost and results in a faster turnover of the patients. It is a versatile and useful tool for a busy neurosurgical department.     

A comparative study of injection placentrex and conventional therapy in treatment of pelvic inflammatory disease

To compare the effect of placentrex injection given along with conventional therapy, with conventional treatment alone on the symptoms and signs of pelvic inflammatory disease (PID) ie, abdominal pain, dysmenorrhoea and adnexal tenderness, 50 out of 100 women with PID were randomly assigned to receive intramuscular placentrex injection along with two-week conventional therapy and 50 received conventional treatment only. Abdominal pain, dysmenorrhoea and adnexal tenderness were evaluated at the end of 2 months. There was marked reduction in the sign of adnexal tenderness in the placentrex group as compared to conventional treatment group (p < 0.001). Subjective symptoms of lower abdominal pain and dysmenorrhoea were also relieved better in placentrex group (p < 0.01 and 0.05 respectively). This study showed significant and persistent improvement of signs and symptoms of PID in women who received injection placentrex.     

A quantitative model to predict pathogenicity of missense variants in the TP53 gene

Germline pathogenic variants in the TP53 gene cause Li‐Fraumeni syndrome, a condition that predisposes individuals to a wide range of cancer types. Identification of individuals carrying a TP53 pathogenic variant is linked to clinical management decisions, such as the avoidance of radiotherapy and use of high‐intensity screening programs. The aim of this study was to develop an evidence‐based quantitative model that integrates independent in silico data (Align‐GVGD and BayesDel) and somatic to germline ratio (SGR), to assign pathogenicity to every possible missense variant in the TP53 gene. To do this, a likelihood ratio for pathogenicity (LR) was derived from each component calibrated using reference sets of assumed pathogenic and benign missense variants. A posterior probability of pathogenicity was generated by combining LRs, and algorithm outputs were validated using different approaches. A total of 730 TP53 missense variants could be assigned to a clinically interpretable class. The outputs of the model correlated well with existing clinical information, functional data, and ClinVar classifications. In conclusion, these quantitative outputs provide the basis for individualized assessment of cancer risk useful for clinical interpretation. In addition, we propose the value of the novel SGR approach for use within the ACMG/AMP guidelines for variant classification.     

Induction of Cyclooxygenase-2 in Alveolar Macrophages after Acid Aspiration: Selective Cyclooxygenase-2 Blockade Reduces Interleukin-6 Production

Background: Gastric acid aspiration can result in acute lung injury. In this study, the authors determined whether alveolar macrophages express cyclooxygenase-2 as a source of inflammatory mediators after acid aspiration.

Methods: Seventy-five microliters of hydrochloric acid solution, pH 1.15, was instilled into one lung in mice. After exposure, alveolar macrophages were harvested, and competitive polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure expression of cyclooxygenase-1 and -2, interleukin-1beta and -6, tumor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The authors used immunocytochemistry to demonstrate expression of cyclooxygenase-2 in alveolar macrophages. Selective cyclooxygenase-2 blockade using N-2(-cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize prostaglandin-cytokine interaction.

Results: Acid aspiration induced upregulation of cyclooxygenase-2 and interleukin-6. Tumor necrosis factor-alpha and iNOS were not upregulated. Interleukin-1beta was upregulated even with saline instillation but could not be detected in the supernatant of the cell culture. Alveolar macrophages harvested from mice instilled with acid showed a trend toward more production of prostaglandin E2 and produced higher concentrations of interleukin-6 compared with alveolar macrophages from mice instilled with saline. Selective cyclooxygenase-2 blockade significantly decreased release of interleukin-6 from alveolar macrophages harvested from mice instilled with acid.     

Atlas of Wnt and R-spondin gene expression in the developing male mouse lower urogenital tract

Prostate development is influenced by β-catenin signaling, but it is unclear which β-catenin activators are involved, where they are synthesized, and whether their mRNA abundance is influenced by androgens. We identified WNT/β-catenin-responsive β-galactosidase activity in the lower urogenital tract (LUT) of transgenic reporter mice, but β-galactosidase activity differed among the four mouse strains we examined. We used in situ hybridization to compare patterns of Wnts, r-spondins (Rspos, co-activators of β-catenin signaling), β-catenin-responsive mRNAs, and an androgen receptor-responsive mRNA in wild type fetal male, fetal female, and neonatal male LUT. Most Wnt and Rspo mRNAs were present in LUT during prostate development. Sexually dimorphic expression patterns were observed for WNT/β-catenin-responsive genes, and for Wnt2b, Wnt4, Wnt7a, Wnt9b, Wnt10b, Wnt11, Wnt16, and Rspo3 mRNAs. These results reveal sexual differences in WNT/β-catenin signaling in fetal LUT, supporting the idea that this pathway may be directly or indirectly responsive to androgens during prostate ductal development.