PRENATAL ALCOHOL EXPOSURE INDUCES ANATOMICAL CHANGES IN THE MOUSE SOMATOSENSORY CORTEX.

Atypical tactile responses are implicated in Fetal Alcohol Spectrum Disorders (FASD). Our lab reported diminished tactile sensitivity in young adolescent mice with a history of prenatal alcohol exposure (PAE). Here, I employed immunohistochemistry to investigate the anatomical correlates of altered tactile sensitivity observed in mice with PAE. Using our 3-day binge paradigm, I examined changes in the distribution pattern of pre- (thalamocortical afferents) and postsynaptic (pyramidal neurons) partners involved in processing tactile information in the SSC of Postnatal day (P) 7 mice. In rodents, tactile information is relayed somatotopically to the SSC via TC afferents expressing vesicular glutamate transporter 2 (vGlut2) and aggregating in \u27barrels\u27 in L4, in addition to innervating other layers. With PAE, there was a significant decrease in vGlut2 immunofluorescence intensity in L4 SSC. Moreover, we found the average barrel width to be significantly larger with PAE, indicating disrupted barrel development, consistent with previous studies employing different PAE paradigms. Moreover, ethanol exposure resulted in a significant increase in two main subpopulations of pyramidal neurons: Special AT-rich sequence-binding protein 2 (Satb2)-expressing callosal (CPN) and COUP TF1-interacting protein 2 (Ctip2)-expressing subcortical projection neurons (SCPN) in the SSC. These immunohistochemistry-based findings suggest PAE-induced anatomical changes in SSC

Isolated Gastric Tuberculosis Mimicking Malignancy

Isolated tuberculosis of upper gastrointestinal tract is a rare pathology, often mimicking malignancy in clinical presentation and radiological features. We present a case of middle aged gentleman with isolated tuberculosis of stomach, proven on histopathology and showing remarkable improvement on follow up

Apache II score as a predictor of length of stay and outcome in our ICUs

The APACHE II (acute physiology and chronic health evaluation) is used widely for predicting probability of hospital mortality and length of stay in the ICU. APACHE II forms were available to all ICU residents within 24 hours of admission, and a score was assigned to them. Based on our results the APACHE II score has reliably predicted an outcome of the least amount of length of stay (LOS) in the ICU as well as a 100% probability of being shifted out of the ICU for a score of \u3c 10 (according to international benchmarks). This reliable scoring system can be used for predicting mortality and length of stay and therefore, resource allocation, antibiotic use and ethical decisions regarding counseling families about end of life decisions--all within 24 hours of admissions

Omental Infarction In A Child

Omental infarction is a rare cause of acute abdomen in children. Typical findings on imaging establish the diagnosis. We present case of a 7 years old boy who presented with acute right iliac fossa pain with diagnosis of omental infarction on imaging and findings confirmed on laparotomy. Sound knowledge regarding this infrequent cause of acute abdomen in children is necessary for timely diagnosis

Autoimmune Disease Presenting As Acute Abdomen

Mesenteric vasculitis and resultant bowel ischemia is rare but serious complication of autoimmune disorders. Early detection and treatment is the key to avoid potentially fatal outcomes of bowel perforation and peritonitis. In this series, we present patients presenting with acute abdominal pain and having CT imaging features of bowel ischemia who responded well to immunosuppressive therapy. The aim of this work is to familiarize health professionals with possibility and imaging features of mesenteric vasculitis

Case report on peri-operative surgical and anaesthetic management of ruptured humongous lung abscess

Introduction: Early thoracic empyema is usually treated through video-assisted thoracoscopic (VATS) decortication. Patient selection is important for decortication if an effective surgical outcome is required. Lung isolation techniques are required to provide anesthesia for these patients to facilitate the surgeon while operating on the affected lung. The ultimate target is to protect the non-diseased contra-lateral lung from contamination.Presentation of case: We are presenting a unique case of 20-year-old female, resident of Karachi, who was brought to the emergency room (ER) with signs of sepsis, hypotension, and multi-organ failure. She was brought to the operating room to undergo video-assisted thoracoscopy (VATS) for lung abscess decortication when her medical therapy had failed. On table decision of right upper lobe resection was made and ventilation strategy had to be modified accordingly.Discussion: The main anaesthetic aim was to protect the healthy parts of the lung from the abscess. Regular suctioning of secretions during surgery via the double lumen tube (DLT) lumen on the diseased side is recommended. While performing VATS, the lung abscess got ruptured and immediate measures to isolate the lung was taken to assist with surgical resection of the affected lobe. Lobectomy can only be done once the lung was completely isolated and maintaining perfusion and ventilation of the relatively healthy lung help in managing hypoxia.Conclusion: Peri-operative management of ruptured lung abscesses required thorough pre-op evaluation, intraoperative lung isolation and ventilation, and postoperative analgesia with combined team effort both surgical and anaesthetic, are vital fundamentals to consider in guaranteeing the best outcome

APACHE-II Score Correlation With Mortality And Length Of Stay In An Intensive Care Unit

Objective: To correlate the APACHE-II score system with mortality and length of stay in ICU. Study Design: Cohort study. Place and Duration of Study: The Intensive Care Unit (ICU) of the Aga Khan University Hospital, Karachi, from May 2005 to May 2006. Methodology: All adult patients who were admitted in the ICU were included. APACHE-II score was calculated at the second and seventh days of admission in the ICU. Patients who were discharged alive from the ICU or died after first APACHE-II Score (at 2nd day) were noted as the primary outcome measurement. Second APACHE-II score (at 7th day) was used to predict the length of stay in the ICU. Pearson\u27s correlation coefficient (r) was determined with significance at p \u3c 0.05. Results: In the lowest score category 3-10, 27 out of 30 patients (90%) were discharged and only 3 (10%) died. Out of those 39 patients whose APACHE-II score was found in high category 31 - 40, 33 (84.6%) deaths were observed. This revealed that there might be more chances of death in case of high APACHE-II score (p=0.001). Insignificant but an inverse correlation (r = -0.084, p \u3c 0.183) was observed between APACHE-II score and length of ICU stay. Conclusion: The APACHE-II scoring system was found useful for classifying patients according to their disease severity. There was an inverse relationship between the high score and the length of stay as well higher chances of mortality

Pattern of neurological diseases in adult outpatient neurology clinics in tertiary care hospital

Objectives: The burden of neurological diseases in developing countries is rising although little is known about the epidemiology and clinical pattern of neurological disorders. The objective of this study was to understand the burden of disease faced by neurologists a in tertiary care setting. Results: A prospective observational study was conducted of all presentations to neurology clinics at Aga Khan University Hospital Karachi over a period of 2 years. A total of 16,371 out-patients with neurological diseases were seen during the study period. The mean age of the study participants were 46.2 ± 18.3 years and 8508 (52%) were male. Headache disorders were present in 3058 (18.6%) of patients followed by vascular diseases 2842 (17.4%), nerve and root lesions 2311 (14.1%) and epilepsies 2055 (12.5%). Parkinson\u27s disease was more prevalent in male participants 564 (70.8%) as compared to female 257 (62.1%) (p = 0.002). Migraines and vertigo disease were more diagnosed in females as compared to males. Epilepsies were seen more in younger age groups. Parkinson\u27s disease was seen in 50.9% of participants between the ages of 45 and 65 years, and the frequency increased with age

Role of 5\u27TG3\u27-Interacting Factors (TGIFs) in Vorinostat (HDAC Inhibitor)-Mediated Corneal Fibrosis Inhibition

Purpose: We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5′TG3′-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat. Methods: Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were exposed to vorinostat (2.5 μM) to test its effect on TGIF mRNA and protein levels using qPCR and immunoblotting. Myofibroblast formation was induced with TGFβ1 (5 ng/ml) treatment under serum-free conditions. The changes in fibrosis parameters were quantified by measuring fibrosis marker α-smooth muscle actin (αSMA) mRNA and protein levels with qPCR, immunostaining, and immunoblotting. Smad2/3/4 and TGIF knockdowns were performed using pre-validated RNAi/siRNAs and a commercially available transfection reagent. Results: Human corneal fibroblasts showed the expression of TGIF1 and TGIF2. Vorinostat (2.5 μM) caused a 2.8–3.3-fold increase in TGIF1 and TGIF2 mRNA levels and a 1.4–1.8-fold increase in TGIF1 and TGIF2 protein levels. Vorinostat treatment also caused a significant increase in acetylhistone H3 and acetylhistone H4. Vorinostat-induced increases in TGIF1 and TGIF2 were accompanied by a concurrent decrease in corneal fibrosis, as indicated by a decrease in αSMA mRNA by 83±7.7% and protein levels by 97±5%. The RNAi-mediated knockdown of Smad2, Smad3, and Smad4 markedly attenuated TGFβ1-evoked transdifferentiation of fibroblasts to myofibroblasts. The siRNA-mediated knockdown of TGIF1 and TGIF2 neutralized vorinostat-evoked decreases in αSMA mRNA by 31%–45% and protein levels by 12%–23%. Conclusions: Human corneal fibroblasts demonstrate the expression of TGIF1 and TGIF2 transcription factors. These transcriptional repressors are critical, at least partially, in mediating the antifibrotic effect of vorinostat in the cornea