Vitamin D and bone metabolism in breast cancer patients in Karachi, Pakistan.

Breast cancer is one of the common types of malignancy worldwide and in Pakistan. The heterogeneous disease itself and its complex treatment leads to various bone-affecting complications that make breast cancer patients more vulnerable to bone fractures. Vitamin D deficiency among these women worsens the condition and promotes breast cancer growth. Thus, the purpose of the study was to assess serum levels of 25-hydroxyvitamin D (25OHD) and bone markers in women suffering from breast cancer. Serum levels of 25OHD, alkaline phosphatase (ALP), bone specific ALP, calcium (Ca), phosphorus (P), magnesium (Mg), albumin (Alb) and beta carboxyl terminal collagen crosslink (ß-CTx) were analyzed in 201 histological diagnosed patient volunteers from breast cancer clinic. Vitamin D insufficiency was present among the total study population and deficiency was particularly observed among women with metastases. These patients had significantly increased serum levels of ß-CTx and bone specific ALP when compared with the non-metastatic group. No significant difference was observed in other biochemical parameters. A weak correlation between serum levels of 25OHD and ß-CTx was observed. Therefore, monitoring of serum levels of 25OHD and bone markers at the time of diagnosis and during the course of treatment will endeavor a better overall health status.

Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion.

Chronic cerebrovascular hypoperfusion results in vascular dementia and increases predisposition to lacunar infarcts. However, there are no suitable animal models. In this study, we developed a novel model for chronic irreversible cerebral hypoperfusion in mice. Briefly, an ameroid constrictor was placed on the right carotid artery to gradually occlude the vessel, while a microcoil was placed on the left carotid artery to prevent compensation of the blood flow. This procedure resulted in a gradual hypoperfusion developing over a period of 34 days with no cerebral blood flow recovery. Histological analysis of the brain revealed neuronal and axonal degeneration as well as necrotic lesions. The most severely affected regions were located in the hippocampus and the corpus callosum. Overall, our paradigm is a viable model to study brain pathology resulting from gradual cerebrovascular hypoperfusion.

Computed Tomography-Guided Biopsy for Potts Disease: An Institutional Experience from an Endemic Developing Country.

STUDY DESIGN: A retrospective chart review. PURPOSE: In endemic resource poor countries like Pakistan, most patients are diagnosed and treated for Potts disease on clinical and radiological grounds without a routine biopsy. The purpose of this study was to evaluate the use and effect of computed tomography (CT)-guided biopsy in the management of Potts disease since the technique is becoming increasingly available. OVERVIEW OF LITERATURE: CT-guided biopsy of spinal lesions is routinely performed. Literature on the utility of the technique in endemic resource poor countries is little. METHODS: This study was conducted at the Neurosurgery section of Aga Khan University Hospital Karachi. All the patients with suspected Potts disease who underwent CT-guided biopsy during the 7 year period from 2007 to 2013 were included in this study. Details of the procedure, histopathology and microbiology were recorded. RESULTS: One hundred and seventy-eight patients were treated for suspected Potts disease during the study period. CT-guided biopsies of the spinal lesions were performed in 91 patients (51.12%). Of the 91 procedures, 22 (24.2%) were inconclusive because of inadequate sample (10), normal tissue (6) or reactive tissue (6). Sixty-nine biopsies were positive (75.8%). Granulomatous inflammation was seen in 58 patients (84.05%), positive acid-fast bacillus (AFB) smear in 4 (5.7%) and positive AFB culture in 12 patients (17.3%). All 91 cases in which CT-guided biopsy was performed responded positively to antituberculosis therapy (ATT). CONCLUSIONS: 75.8% of the specimens yielded positive diagnoses. Granulomatous inflammation on histopathology was the commonest diagnostic feature. In this series, the rates of positive AFB smear and culture were low compared to previous literature.

Investigating the utility of previously developed prediction scores in acute ischemic stroke patients in the stroke belt.

BACKGROUND: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. METHODS: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). RESULTS: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). CONCLUSIONS: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples.

Emergence and diversification of dengue 2 cosmopolitan genotype in Pakistan, 2011.

Major dengue epidemics have been observed in the Indian subcontinent since the 1980s and have occurred with increased hospitalizations and mortality. In 2011, the first major epidemic of dengue occurred in Lahore, the second largest city in Pakistan, and resulted in 21,685 confirmed cases and 350 deaths. To investigate the possible viral causes for the increased epidemic activity, we determined the predominant serotype and characterized the viruses genetically. Of 50 patients carefully selected as probable dengue fever or dengue hemorrhagic fever, 34 were positive by virologic testing (i.e. PCR and/or virus isolation). DENV-2 was detected in 32 patients and DENV-1 in two. A total of 24 partial and three full DENV genomes were sequenced. Phylogenetic analyses of the capsid (C), pre-membrane (prM), and envelope genes comprising 2500 nucleotides in length indicated that all DENV-2 isolates in Pakistan since 2007 form a monophyletic lineage that is endemic in the country. These viruses were all of the cosmopolitan genotype (IV) and most closely related to viruses isolated in India and Sri Lanka in the past two decades. Phylogenetic analyses of data currently available in GenBank suggest that the Cosmopolitan genotype has diverged into two geographically distinct sub-lineages: sub-lineage IV-a has only been observed in Southeast Asia, China and Oceania, while IV-b is prevalent in the Indian subcontinent. These results highlight the increased diversity of dengue viruses as they spread geographically within the region.