MicroRNA-593-5p contributes to cell death following exposure to 1-methyl-4-phenylpyridinium by targeting PTEN-induced putative kinase 1.

Neurodegenerative diseases are characterized by a decline in neuronal function and structure, leading to neuronal death. Understanding the molecular mechanisms of neuronal death is crucial for developing therapeutics. MiRs are small noncoding RNAs that regulate gene expression by degrading target mRNAs or inhibiting translation. MiR dysregulation has been linked to many neurodegenerative diseases, but the underlying mechanisms are not well understood. As mitochondrial dysfunction is one of the common molecular mechanisms leading to neuronal death in many neurodegenerative diseases, here we studied miRs that modulate neuronal death caused by 1-methyl-4-phenylpyridinium (MPP+), an inhibitor of complex I in mitochondria. We identified miR-593-5p, levels of which were increased in SH-SY5Y human neuronal cells, after exposure to MPP+. We found that intracellular Ca2+, but not of reactive oxygen species, mediated this miR-593-5p increase. Furthermore, we found the increase in miR-593-5p was due to enhanced stability, not increased transcription or miR processing. Importantly, we show the increase in miR-593-5p contributed to MPP+-induced cell death. Our data revealed that miR-593-5p inhibits a signaling pathway involving PTEN-induced putative kinase 1 (PINK1) and Parkin, two proteins responsible for the removal of damaged mitochondria from cells, by targeting the coding sequence of PINK1 mRNA. Our findings suggest that miR-593-5p contributes to neuronal death resulting from MPP+ toxicity, in part, by impeding the PINK1/Parkin-mediated pathway that facilitates the clearance of damaged mitochondria. Taken together, our observations highlight the potential significance of inhibiting miR-593-5p as a therapeutic approach for neurodegenerative diseases.

Evaluation of dose conformity and coverage of target volume for intensity-modulated radiotherapy of pelvic cancer treatment.

BACKGROUND: Better conformity may help in delivering minimum dose to organs at risk (OARs) and maximum dose to planning target volume (PTV). As per the requirements of modern radiotherapy, 95% isodose should cover the PTV, so conformity indices (CIs) are used for evaluating quality of conformation of treatment plans. AIM: This study aimed to investigate degree of conformity for pelvic patients using intensity-modulated radiotherapy (IMRT) technique. Three formulas of CIs described in literature were analyzed in this study. SETTINGS AND DESIGN: This study was performed to evaluate degree of conformity of 18 patients treated with radiotherapy treatment plan using cumulative dose volume histogram. Effectiveness of different CIs was explored for IMRT plans using 15 MV photon beam. Doses delivered to OAR were also studied. STATISTICAL ANALYSIS USED: CI suggested by the International Commission on Radiation Units and Measurements, radiation CI and CI prescription isodose to target volume (PITV) had mean ± standard deviation values of 1.02 ± 0.018, 0.98 ± 0.017, and 1.63 ± 0.333, respectively. RESULTS AND CONCLUSION: Dose distribution for all patients was highly conformal and clinically acceptable. Values of CI PITV exceeded acceptable value for 27% patients with minor deviation. No statistically significant differences were observed for three CIs reported. Target volume lies between 95% and 107% of prescribed dose which shows ideal target coverage. This simple parameter is advantageous since it is easy to interpret and helped determine quality of treatment plan. This study clearly demonstrated that favorable dose distribution in PTV and OARs is achieved using IMRT technique, and hence, the risk of damage to normal tissues is reduced.

Analysis of post operative complications following total thyroidectomy.

This prospective study was carried out to find out the incidence and nature of post operative complications following total thyroidectomy in the management of carcinoma thyroid and multinodular goiter and to analyze the factors which are related with the development of complications. Study was done in the Department of ENT & Head-Neck Surgery, Surgery, Bangabandhu Sheikh Mujib Medical University and Department of ENT & Head-Neck Surgery, Dhaka Medical College Hospital, Dhaka, Bangladesh from April 2006 to September 2006. Fifty patients (50) were included prospectively for this work. The patients were between 12-63 years of age with a maximum incidence in 4th decade. Female was the predominant sex with a ratio of 4.55:1. Twenty eight patients were suffering from papillary carcinoma. Nine patients were suffering from follicular carcinoma, four patients from medullary carcinoma and nine patients from multinodular goiter. Out of 50 patients, 14(28%) developed complications. The complications were haematoma (4%), recurrent laryngeal nerve palsy (6%), hypoparathyroidism (16%) and wound infection (2%). All of them suffered from temporary complications except one patient, who suffered from persistent hypoparathyroidism. Recurrent laryngeal nerve paralysis in all three cases was unilateral. Complications were relatively more common in male. In carcinoma patients the rate of complications was more than twice than the multinodular goiter cases. Among the carcinoma cases, 7.31% cases developed recurrent laryngeal nerve paralysis and 19.51% cases developed hypoparathyroidism. From this study it is observed that a good number of patients still suffer from complications following total thyroidectomy.

Patients with congenital atrial septal defects: effect of age at repair and defect size on pulmonary artery pressures prior to repair.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major complication of atrial septal defect (ASD) and can be responsible for significant functional limitations and early mortality. Various factors have been shown to predispose ASD patients to the development of PAH. Our study aimed to determine the association between the size of the ASD, the age of the patient and the increase in pulmonary artery pressures. METHODS: Data from 74 ASD patients was retrospectively reviewed, including the patients' presenting symptoms, vital parameters, comorbidities, as well as their preoperative diagnostic workup. Echocardiography findings were used to determine the type and size of the ASD, and pulmonary artery pressures were evaluated using tricuspid regurgitation velocity as assessed by echocardiography or based on cardiac catheterization data. All patients underwent ASD repair either surgically or via percutaneous repair. Univariate and multivariate linear regression was performed to analyze the effect of age and defect size on pulmonary artery pressures. Model adequacy check was also done for the final model. Postoperative morbidity/mortality was additionally evaluated. RESULTS: The study sample comprised 44.6% males and 55.4% females. The most prominent presenting features were shortness of breath (70.3%), chest pain (43.2%), and palpitations (33.8%), and arterial hypertension was the commonest morbidity. Using multiple linear regression analysis, age and size of ASD were found to be independently associated with pulmonary artery pressure. We found that for every 1 mm increase in the size of the ASD, pulmonary artery systolic pressure (PASP) increased by 0.32 mmHg ( P ≤ 0.05). Similarly, with every increase of one year in age, pulmonary artery pressure increased by 0.24 mmHg (P ≤ 0.02). No significant postoperative complications were reported following both types of repair. CONCLUSIONS: Our study concludes that ASD patients are at greater risk of developing PAH with increasing age and increasing ASD size. This can potentially help to determine which ASD patients are at greater risk and require urgent repair of their defects. The study also shows that early repair is best to prevent complications.

Comparison between bipolar diathermy tonsillectomy and cold dissection tonsillectomy.

A prospective study was carried out in the department of otolaryngology-Head & Neck Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU) and Bangladesh Medical college Hospital, Dhaka. From January, 2007 to January, 2009 to compare between Bipolar Diathermy Tonsillectomy and Cold Dissection Tonsillectomy. Two hundred patients were divided equally into two groups- bipolar diathermy tonsillectomy and cold dissection tonsillectomy. The two groups were compared in age and sex distribution but there was no significant difference (p>0.05) between the two groups. Operative time, operative blood loss, postoperative pain, diet intake, activity level and complications were compared in the two groups. Operative time and blood loss was significantly less in the diathermy group which was highly significant (p<0.001). No significant difference (p>0.05) in the postoperative pain was observed. Percentage of normal diet taken was higher in the diathermy group on the 1st day and lower on the 7th day while the difference was not statistically significant (p>0.05). No significant difference (p>0.05) was noted between the two groups in terms of postoperative activity and postoperative blood loss. Operative blood loss & time was significantly less in bipolar diathermy tonsillectomy. So it is a safe technique and can be used safely with less morbidity & complication.

Transcatheter closure of a patent ductus arteriosus in a patient with an anomalous inferior vena cava.

A patient with a patent ductus arteriosus (PDA) was catheterized for device closure. Anomalous systemic venous drainage was found with interrupted inferior vena cava and persistence of hepatic vessel plexus. Using the superior vena cava route, the PDA was closed successfully.

Intestinal schistosomiasis following orthotopic liver transplantation: a case report.

Recent World Health Organization (WHO) reports estimate that 500-600 million people worldwide are at risk of schistosomiasis. In areas of high prevalence of hepatitis C (HCV) and schistosomiasis there is an increased risk for end-stage liver disease. Liver transplant is a viable option for those with HCV or other liver pathology and schistosomiasis. Posttransplant recurrence of schistosomiasis has rarely been described. We report a case of posttransplant recurrence of schistosomiasis.

Cardiac disease in beta-thalassaemia major: Is it reversible?

INTRODUCTION: The aim of this study was to evaluate the spectrum of cardiac involvement and its outcome in beta-thalassaemia major. METHODS: There were 75 patients with a mean age of 13.8 (+/- 5.5) years, of whom 33 were male and 42 were female. Clinical history, examination and laboratory investigations were assessed. Electrocardiograms, chest radiographs and echocardiograms were reviewed. RESULTS: 44 patients had cardiac involvement in the form of left ventricular systolic dysfunction in 17, diastolic dysfunction in 22, pericardial effusion in 12 and pulmonary hypertension in 12 patients. With intense chelation therapy and cardiac medications, the condition of 13 of 17 patients with systolic dysfunction, and four of 22 with diastolic dysfunction, improved. CONCLUSION: Cardiac disease is a common complication of siderotic disease in thalassaemia major and it can be prevented with regular chelation. This study has shown improved systolic function after regular chelation therapy.

Non-endoscopic parameters for the identification of esophageal varices in patients with chronic hepatitis.

OBJECTIVE: To develop non-invasive laboratory variables for the identification of esophageal varices in patients with cirrhosis at Digestive Disease Center, Shifa International Hospital, Islamabad. PATIENTS AND METHODS: All patients with chronic viral hepatitis who presented to the Gastroenterology Division between July 2002 to July 2003 were enrolled in the study. All patients with a diagnosis of Chronic Hepatitis who had platelet counts of 140,000, I.N.R of greater than 1.5 and portal vein (PV) diameter of 13 mm or greater were included in the study. All patients underwent endoscopy to see the presence of varices which were graded following the standard criteria RESULTS: Of 140 patients, 100 (71%) were males and 40 (29%) females. Esophageal varices were present in 70% of the patients while 30% had no varices. CONCLUSION: It was seen that using the standard criteria of a PV diameter 13 mm, I.N.R 1.5 and platelet counts 100,000 for the diagnosis of portal hypertension about 70% patients had endoscopic evidence of esophageal varices. As prophylactic beta blockers are recommended to reduce the chances of a bleed from esophageal varices therefore it is suggested that endoscopy should be done only in patients who fulfill the standard criteria of portal hypertension and those found to have varices should be put on beta blockers.

Quality of life assessment in Pakistani patients with chronic liver disease.

OBJECTIVE: To find out if advanced liver disease causes decrement in health related quality of life in Pakistani patients. METHODS: An observational study was conducted at the Shifa International Hospital Islamabad. Chronic Liver Disease Questionnaire (CLDQ) was administered to patients with liver disease who were either admitted or seen as outpatients. Patients were divided into two groups. Those with no cirrhosis or Child's Class A were placed into group A. Those with advanced liver disease i.e. Child's Class B and C into group B. RESULTS: A total of 56 patients (mean age 50.6 years) were included in this study. Hepatitis C was the cause of chronic liver disease (CLD) in 52 (92.9%) patients. Twenty-one (37.5%) patients were in group A and 35 (62.5%) in group B. Patients with advanced liver disease had significantly lower CLDQ scores as well as decrement in five out of the six categories for assessing quality of life. CONCLUSION: Chronic liver disease causes significant impairment in the Quality of Life Index (QLI) in Pakistani patients.

Patent ductus arteriosus: an uncommon cause of tracheobronchial compression in infants.

Tracheobronchial compression is an important cause of respiratory distress in children, requiring precise diagnosis and early surgical management. Common causes of the compression are either intrinsic or extrinsic, the latter being usually due to vascular rings. We report a 10 weeks old boy in whom a dilated pulmonary artery due a large patent ductus arteriosus was the cause for extrinsic compression.

Congenital heart disease and associated malformations in children with cleft lip and palate in Pakistan.

Children with cleft lip and palate often have other associated malformations. The reported incidence and types of associated malformations vary between different studies. There is a great paucity of literature on the subject from the region in general and none from Pakistan at all. The purpose of this study was to assess the frequency of associated malformations, particularly congenital heart disease, in children with cleft lip and palate presenting to the Aga Khan University (AKU) and Murshid Hospital (MH). From 1st October 1999 to 31st March 2002, all children with cleft lip and palate who presented to AKU and MH were prospectively enrolled in the study group. Socio-demographic characteristics and a number of other variables were documented. All children underwent a thorough clinical examination and an echocardiogram as part of the study protocol. 123 children formed the study group. Thirty-five (29%) of these children were found to have associated malformations. The most common of these was congenital heart disease, which accounted for 51% of all associated malformations. Thirty percent of cleft palate children had associated anomalies while 27% of cleft lip, with or without cleft palate, children had associated anomalies. There was a significant association between children born of a consanguineous marriage and the risk of associated malformations (p-value: 0.001). Consanguinity was present in 74% of children with associated anomalies as compared to 40% of children with no associated anomaly. Dysmorphic features and the presence of associated anomalies were also significantly associated (p-value: 0.009). Dysmorphic features were present in 46% of children with anomalies as compared to 21% of children with no associated anomaly. Fifty percent of children with associated anomalies had a low birth weight compared to 34% of children with no anomalies, but the difference was not statistically significant. The presence of consanguinity in a child with dysmorphic features should raise the suspicion of an associated anomaly. The likelihood of this being a cardiac defect is high and should be ruled out with a thorough clinical examination, supplemented with an echocardiogram in certain cases.

Seasonal variation in bacterial pathogens isolated from stool samples in Karachi, Pakistan.

OBJECTIVE: To determine the seasonal variation of the commonly isolated bacterial pathogens in stool samples. MATERIAL AND METHODS: A retrospective descriptive study was undertaken of all the stool samples submitted from within Karachi to the Aga Khan University Hospital Laboratory over a period of five years (January 1997- December 2001) in order to determine the commonly isolated bacterial pathogens and to predict their seasonal variation. RESULTS: A total of 16379 stool samples were included in this review. Bacterial isolates were found in 6670 stool samples (culture detection rate=40.7%). The mean age at the time of culture of each sub-group was < or = 1 year group (6.58 +/- 3.1 months), 1-5 years (2.13 +/- 0.94 years), 5-14 years (8.3 +/- 2.6 yrs) and adults (43.2 +/- 18.5 years). Male: Female ratio was 1.2:1. Vibrio cholera 01 Ogawa (32.8%), Campylobacter jejuni (17.3%), Enteropathogenic Escherichia coli (9.9%), Salmonella paratyphi b (6.6%) and Shigella flexneri (6.2%) were the most common organisms isolated. These organisms show a distinct seasonal variation with summer predilection. CONCLUSION: In contrast to the previous studies from South Asia, which have identified E. coil, followed by Vibrio cholerae as the most common enteric isolates, we found Vibrio cholera 01 Ogawa followed by Campylobacter jejuni as the most common enteric pathogens isolated in an urban setting. It is important to consider seasonal variation when empirically treating diarrheal diseases in our region.

Closure of aortopulmonary window with amplatzer duct occluder device.

Aortopulmonary window is a relatively uncommon congenital heart defect. We report on a patient with a small aortopulmonary window, who presented with an asymptomatic murmur and in whom catheter closure was successfully performed with an Amplatzer Duct Occluder.

Anorexic behaviour and attitudes among female medical and nursing students at a private university hospital.

OBJECTIVE: To study the anorexic behaviour and attitude among female medical and nursing students in a tertiary care hospital. SUBJECTS AND METHODS: A cross-sectional survey to determine the proportion of anorexic behaviour among female medical and nursing students at The Aga Khan University Hospital Karachi was conducted. A multistaged sampling technique was utilized in which our study population was first divided according to field of enrollment (medical or nursing school) and then stratified by class. Within each stratum, we used convenience sampling due to time and availability constraints. We utilized a modified Eating Attitudes Test (EAT-26) to collect data. The Eating Attitude Test is probably the most widely used standardized measure of symptoms characteristic of eating disorders, including anorexia nervosa. RESULTS: A total of 180 female students were interviewed. Ninety-four (52.2%) were medical students and 86 (47.8%) were nursing students. Among the 94 medical students, 26 (27.7%) were from first year, 14 (14.9%) from second year, 15 (16.0%) from third year, 20 (21.3%) from fourth year and 19 (20.2%) from the final year of medical college. Among the 86 nursing students 34 (39.5%) were from first year, 23 (26.7%) from second year, 27 (31.4%) from third year and 2 (2.4%) from fourth year. The proportion of anorexic behaviour among medical students was 8.0%, 7.1% and 20.0% in first, third and fourth years respectively. No individuals with anorexic behaviour were found in second and fifth years. The total proportion of anorexic behaviour among female health care students was 21.7%. CONCLUSION: Results showed a 21.7% prevalence of anorexic behaviour, a figure much higher than that reported in similar studies conducted in Asia. We also found that the proportion was much higher among female nursing students as compared to female medical students. A previous visit to a psychiatrist for reasons other than eating disorders was found to be associated with anorexic behaviour.