Identification of sulfamoylbenzamide derivatives as selective cathepsin D inhibitors

Aspartic proteases play very important role in post translational processing of proteins and several of them are essential for organism's viability. Here we present the enzyme inhibition activities of different Sulfamoylbenzamide derivatives against two aspartic proteases cathepsin D and plasmepsin II. Cathepsin D is an aspartic protease that degrades proteins at acidic pH in the lysosomes, or extracellular matrix. It is overexpressed by epithelial breast cancer cells and hence hyper-secreted. On the other hand plasmepsin II is an essential enzyme of Plasmodium falciperum. Cathepsin D and Plasmepsin II are pivotal drug targets for treatment of breast cancer and malaria respectively. Virtual screening of Sulfamoylbenzamide compounds followed by enzyme inhibition assays revealed these compounds as selective Cathepsin D inhibitors while inactive against Plasmepsin-II. IC[50] values of five Sulfamoylbenzamide compounds tested are in range of 1.25-2.0 microM. N-[3-chlorophenyl]-2-sulfamoylbenzamide is identified as the most potent of all tested Sulfamoylbenzamide compounds with IC[50] 1.25 microM. It was also noted that the docking score of theses compounds was better in case of Cathepsin D as compared to Plasmepsin-II. Docking score ranges from -29.9 +/- 1.16 to -35.1 +/- 0.13 in case of Cathepsin D, while from -24.0 +/- 0.10 to -29.5 +/- 0.10 in case of Plasmepsin-II

Prevalence of HBsAg and anti-HCV antibodies in poly-transfused- beta-thalassaemia major children in Lahore

To determine the prevalence of HBsAg and Anti-HCV antibodies in polytransfused thalassaemic children at two different Thalassaemia Centres i.e. The Institute of Haematology and Blood Transfusion Service [IHBTS] Punjab, Lahore and The Thalassaemia Centre at Sir Gangaram Hospital, Lahore. To compare the prevalence of these markers between two centres. To determine association of sero-positivity with number of transfusions. It is a cross sectional study. All information was gathered by questionnaire. Blood samples of 150 thalassaemic patients were collected from two different thalassaemia centres and sera were screened for HBsAg and Anti-HCV antibodies by ELISA technique. SPSS version 16 was used to analyze the data. Chi-square was applied to determine the association between number of transfusions and sero-positivity. The prevalence of HBsAg and Anti-HCV antibodies was 0% and 68% respectively among the patients of IHBTS. 1% and 43% patients were positive for HBsAg and Anti-HCV antibodies respectively at Thalassaemia Centre at Sir Gangaram Hospital. The overall prevalence of HBsAg and Anti-HCV antibodies was 0.66% and 51.3% respectively. Prevalence of anti-HCV was more at IHBTS. An association was observed in increasing number of transfusions and increasing positivity of patients for Anti-HCV [p-value = 0.018]. There is a need to focus on our health safety managements. A higher prevalence of Anti-HCV was observed due to weak infrastructure of health care centres or blood banks

Bacterial pathogens responsible for blood stream infection [BSI] and pattern of drug resistance in a tertiary care hospital of Lahore

The present retrospective analysis was carried out to determine the pattern of bacterial agents responsible for blood stream infection [BSI] in a tertiary care hospital of Lahore and to get an updated knowledge about their antibiotic resistance pattern. It is a cross sectional descriptive study, carried out in the Microbiology Section, Department of Pathology, Services Institute of Medical Sciences [SIMS], Lahore during the period April, 2006 to December, 2006. Among the 1814 blood cultures 1382 [76%] were received from pediatrics/ neonatology wards and 432 [24%] from adult patients. In a total of 508 [27.9%] blood cultures, 465 yielded monomicrobial growth and 43 polymicrobial growth. A total of 454 [97.6%] of the monomicrobial growths were bacterial isolates and 11 [2.4%] were Candida Spp. Gram negative bacteria [Enterobacteriaceae + nonfermenter bacteria] comprised the majority of bacterial isolates. Amongst the gram-negative bacteria the most common organism was Klebsiella Spp. while amongst the gram-positive organisms Staph. aureus was the most common isolate. It was seen that 31.25% Staph. aureus isolates were resistant to Oxacillin, 93.7% of Klebsiella Spp. and E. coli isolates were resistant to 3rd generation Cephalosporins and 6.49% of Pseudomonas Spp. and Acinetobacter Spp. whereas resistant to Carbapenems in the present study. As BSI is an emergency, for appropriate management of these cases an updated knowledge about the causative agents and their susceptibility pattern to antibiotics is required to start appropriate empirical antibiotic therapy till the results of the microbiology report are available. The alarming finding is the high resistance seen amongst Enterobacteriaceae against 3rd generation cephalosporins [93.7%], oxacillin resistance among Staph aureus [31.25%] and increasing resistance against Carbepenems among Pseudomonas and Acinetobacter isolates [6.49%]. In conclusion there are grave implications of these findings for our already strained health care system as the presence of these multidrug resistant organisms leads to longer hospital stay, more expensive/ toxic drugs and higher mortality

Urological complications of intrauterine contraceptive device

To elucidate the urological complications of Intrauterine contraceptive device [IUCD]. This study was conducted in Fauji Foundation Hospital Rawalpindi to elucidate. The urological complications of IUCD presenting to Urology department from January 2002 to December 2006. During this period 12 ladies having IUCDs presented with lower urinary tract symptoms [LUTS]. After thorough work up, 6 patients were managed surgically and the remaining 6 were managed conservatively. In all cases the IUCDs were inserted by paramedics. Out of six cases managed surgically, 3 patients had developed complete intravesical migration of device with stone formation. While in two other patients there was partial migration of the IUCD and stone formation over the migrated component of the device. One patient had simultaneously two IUCDs, one in uterus and another in bladder. We successfully performed cystolitholapaxy and retrieved four IUCDs in these patients endoscopically. A large vesical stone and the entombed IUCD in one of our patients were also removed endoscopically. The patient who presented with two IUCDs also got the vesical IUCD removed endoscopically. In remaining six cases, the IUCDs were in proper location and the cause of LUTS in these patients was urinary tract infection. These patients were successfully managed conservatively. Insertion of IUCD necessitates regular follow-up to confirm its correct position. Migration of an IUCD warrants prompt removal, even in asymptomatic patients. Cases presenting with UTI with undisplaced IUCD should be managed with appropriate antimicrobial therapy

hysteria; conversion disorders

To find out the sociodemographic characteristics of conversion disorders and to find if there is any difference between the presenting symptoms of rural and urban population. A non-probability, purposive, hospital based sample. Psychiatry department of Victoria Hospital Bahawalpur, from February 2004 to April 2005. A sample of 100-patients was collected. Both sexes were included. DSM-IV criteria for conversion disorder were applied for diagnosis of all these patients. Informed consent was taken for inclusion in the study. Patients suffering from concurrent physical disorders were excluded. The first author [NM.] using a semi-structured pro-forma interviewed all these patients. The sociodemographic characteristics and the clinical profile were collected. Statistical analysis was made with the statistical package for windows, SPSS [version -10]. The applied method for group comparison was chi square- test. The mean age of patients from the urban area was 24.26 +/- 7.25 years, as compared to 22.15 +/- 7.49 years for the patients from the rural area. Most of the patients were females and were married. Majority of the patients from the urban as well as from the rural area were uneducated and from the lower socio-economic class. The onset of illness was typically acute and sudden, with precipitating life event. Majority of the patients had family history of the illness and co-morbid psychiatric disorders. The presenting symptoms were either sensory, motor, mixed symptoms and psuedoseizures. The presenting symptoms of patient from both urban [p value of 0.008], and rural area [P value =0.013], were statistically significant. There were no statistically significant association between the presenting symptoms and the area of living. The p values of the entire chi square tests were greater than [0.05]. Prompt elimination of the symptoms of conversion disorder is important to prevent secondary gains from reinforcing it and causing it t o persist or reoccur. Psychiatric services need to be developed and updated for the provision of prompt and efficient treatment, for the patients with these chronic and sometimes disabling conversion disorders

Transcatheter embolization of acute non-variceal gastrointestinal hemorrhage

To determine the efficacy and safety of transcatheter embolization of nonvariceal gastrointestinal hemorrhage. Descriptive analytical study. Radiology Department. The Aga Khan University Hospital, Karachi, Pakistan, from October 1999 to August 2004. The study included 27 patients who underwent angiography for suspected gastrointestinal hemorrhage. The presumptive diagnosis was based on the findings of endoscopy in 08 patients, scintigraphy in 05 patients and on clinical findings only in 14 patients. Nine patients had gastroduodenal hemorrhage, 04 patients had hemobilia and 14 patients had lower gastrointestinal bleeding. Five patients had comorbidities. One patient had uremia, 2 had hepatitis C, 1 had cirrhosis and 1 had coagulopathy. Technical success, clinical success, complications and patient survival were assessed. Nine patients had upper gastrointestinal hemorrhage, 4 patients had hemobilia and 14 patients had lower gastrointestinal bleeding. Etiology of bleeding was known in 15 patients and unknown in 12 patients. Clinical success was achieved in 23 [85.18%] of 27 patients. Two patients had early rebleeding. One of these was managed surgically and recovered. The other had severe coagulopathy and was unfit for surgery. Two patients had bowel infarction, one of these was managed surgically and recovered and the other died of complication of procedure. One patient had small splenic infarcts and was managed conservatively. Overall 85.18% success was achieved for the embolization procedure. Two of 27 patients died. One patient died because of recurrence of bleeding and other died because of infarction of right hemi-colon which occurred as complication of embolization. Transcatheter embolization is effective and safe in patients with nonvariceal gastrointestinal hemorrhage

Residual prostatic symptoms; persisting after transurethral resection of prostate for prostatic hyperplasia

To see the residual prostatic symptoms after TURP for PH. DESIGN: Case study period from Nov 1994 to Dec 1995. SETTING: Department of Urology Mayo Hospital Lahore. PATIENTS AND METHODS: One hundred consecutive patients admitted for BPH underwent TURP and were followed for four months after removal of catheter on first day, one week, one month, two months and four months. They were asked about the symptoms and were examined thoroughly at each visit. Patients with neurological deficits, diabetes, external genital pathology, urethral strictures and malignancy were excluded form the study. Patients were divided into two groups. Group I [below 60 years] and group II [above 60 years] to see the effect of age on symptoms. Out of preoperative symptoms, retention, frequency, urgency, sense of incomplete emptying, poor urinary stream were found in 73.8%, 85.7%, 23.8%, 9.5% and 80.9% respectively for patients of group I [age below 60 years]. These figures for patients of group II [age above 60 years] were 84.5%, 79.3%, 20.7%, 13.8% and 86.2% respectively. At fourth month of follow up for group I, urinary retention [0%], mild degree of straining at micturition [4.8%], poor urinary stream [2.4%], frequently [14.3%], sense of incomplete emptying [7.1%]. For group II these figures are 0%, 3.5%, 3.4%. 24.2% and 6.9% respectively

Carcinoma gall bladder; Local risk factors

Seccia and cavina have divided the risk factors for carcinoma gallbladder into three main groups: local, systemic and genetic. LOCAL RISK FACTORS FOR CA GALLBLADDER ARE AS FOLLOWS: 1. Cholelithiasis. 2. Polypoidal lesions of gallbladder. 3. Congenital anomalies. 4. Porcelain gallbladder. 5. Chronic typhoid infection

Prevalence of different clinical symptoms in patients with prostatic hyperplasia

Present study was carried out at Mayo Hospital Lahore in which 100 consecutive patients admitted to the department of Urology for prostatectomy for BPH were examined to see the prevalence of different presenting clinical features. Age of the patients ranged from 45 to 85 years with average age being 61.7 years and maximum patients were of the age between 60-69 years. Urinary retention was the most common presenting feature present in 73.8% patients of age below 60 years and 84.5% in patients of age above 60 years. Obstructive symptoms were more common in older age group than younger patients where irritative symptoms were more prevalent. Figures recorded in this series for urinary frequency and poor urinary stream in younger patients were 85.7% and 80.9% respectively and these were 79.3% and 86.2% for those above 60 years of age

Nodular goitre. Presentation and prevalence of complications.

OBJECTIVE: To evaluate the presentation and prevalence of different preoperative complications in patients with nodular goitre. DESIGN: Patients of either age and sex with nodular thyroid swelling [goitre] admitted from January 1992 to November 1992. SETTING: Surgical Unit-Il of Services Hospital, Lahore SUBJECTS: Forty patients of either sex and age presenting with nodular goitre were included. MAIN OUTCOME MEASURE: Mode of presentation and prevalence of different preoperative complications in patients with nodular goitre. Peak incidence of nodular goitre was in age group between 20-40 years. 75% patients belonged to this group with male to female ratio being 1:4. Simple non toxic multi-nodular goitre was present in 57.50%, adenoma in 27.50%, toxic adenoma in 2.50%, secondary toxic goitre in 2.50% where as 10% patient had malignant goitre. 70% of patients of present study did not have any symptoms other than a swelling in front of neck. 30% patients had some symptoms like respiratory obstruction in 50%, dysphagia in 8.33%, hoarseness in 16.66%, weight loss and anorexia in 33,33%, toxicity in 16.66"lo, histo-pathological evidence of malignancy was found in 10% of patients and papillary carcinoma was heading the list

Efficacy of extracorporeal shock wave lithotripsy in paediatric urolithiasis

To determine the efficacy of extracorporeal shock wave lithotripsy with reference to stone size and radiodensity in children. Design: Patients of either sex were treated with ESWL from April 1994 to January 1995. Setting: Department of Urology, Mayo Hospital, Lahore. Twenty five patients of age below twelve years presenting with renal, ureteric and bladder stone of size between '5-20 mm along their long axis were included. Main outcome measure: Efficacy. Single treatment session was sufficient in 40%, two in 28% and three in 8% patients. No stone clearance was observed in 20% patients after three sessions and 4% patients had to be operated after one session. There were 60% low density stones, 28% stones were equibone dense and 12% stones had radiodensity more than that of bone. Among low density stones 77.78% renal, 100% ureteric and 100% bladder stones were successfully fragmented with overall success rate of 86.6% [13/15]. Out of equibone density stones 14.28% renal, 14.28% ureteric and 42.86% bladder stones were successfully fragmented. So the success rate for equibone dense stone was 71.4% [5/7]. There were 3 [12%] stones with radiodensity greater than that of bone and had successful fragmentation rate of 33.33% [1/3]. Kidney stones 5-10mm in size were cleared in aII [100%] cases after one treatment session and those 11-15mm in size needed more shock waves on an average 1.8 treatment session. Stones 15-20 mm in size required 2-3 treatment session. Success rate for 5-10mm size ureteric stones was 100% but it was 0% for those of size 11-15mm. Bladder stones which measured 10-15 mm in size required one session while those measuring 15-20 mm were fragmented during1.16 treatment session. ESWL is an effective modality for treatment of urinary stones as monotherapy in selected patients