Formulation development of intermediate release Nimesulide tablets by CCRD for IVIVC studies

Simple and cost effective study consisting of three steps, comparison of micromeritic properties of different blends i.e. placebo without API and Nimesulide containing, Use of central composite design [CCRD] for intermediate release Nimesulide tablets and stability results of three selected Nimesulide tablet formulations which were calculated by using R Gui. Different concentrations of Avicel, hydroxypropyl methyl cellulose [HPMC] and magnesium stearate were used as variables in central composite design and two types blend i.e., with or without Nimesulide were selected for bulk density, tap density, percentage compressibility; angle of repose and Hausner's ratio. Blending rate constant was performed after applying the different mixing times like 3, 6, 9 and 12 minutes. Twenty intermediate release formulations were designed and three formulations were chosen for compression by direct compression method on the basis of compressibility index. Physicochemical properties and best release pattern in four hours in different dissolution medium were successfully measured. Relative densities, porosity of tablets were compared with tensile strength of tablet and weight variation, hardness, friability and dissolution was performed by simple experiments. Presence of Nimesulide in the bulk increased all micromeratic tests while 9 minutes was best mixing time. The hardness of NM containing tablets increased with the increase of relative density. The release pattern was further analyzed by model dependent i.e. zero order, first order and Higuchi, Korse-meyer and Pappas, Hixson Crowell and model independent kinetic model i.e., f2 value respectively. R Gui explained the F16 formulation shows the best result in stability studies with shelf life 72 months

Spectrophotometric method for the determination of Gemifloxacin mesylate in pure and tablet dosage form

A Spectrophotometric method for the determination of Gemifloxacin mesylate [GFX] is developed and validated according to ICH guidelines. GFX is a fluoroquinolone that is used in the treatment of pneumonia. The analysis of the pure drug was carried out at its 'k[max] 270 nm. The method was linear from 0.5-5microg/mL, r[2] 0.999 and equation is 0.102-0.000. The % RSD for inter-day [0.969%] and intra-day [0.714%] assuring a good precision and accuracy was close to 100%. Limit of detection and Limit of quantification were 0.197 and 0.599|ug/mL, respectively

The validation results and statistical data demonstrate that the method is accurate, sensitive, cost effective and reproducible and has an importance in quality assurance of GFX analysis. The developed method was proved suitable for analysis of GFX in the pure and tablet dosage forms without interference of excepients

Frequency of urethrocutaneous fistula following snodgrass hypospadias repair in children

To determine the frequency of urethrocutaneous fistula over a period of three months following snodgrass hypospadias repair for the treatment of distal penile hypospadias in children. This descriptive study was conducted in the pediatric surgery unit, Lady Reading Hospital, Peshawar over a period of eight months from June 2009 to February 2010. Patients with distal penilehypospadia without chordee between 2 and 14 years were included and patients were excluded who had previous repair for hypospadias. All those patients fulfilling the inclusion and exclusion criteria whose parents gave informed consent after explanation of the whole protocol were admitted through outpatient department for the said procedure and data was analyzed. A total of 52 patients were included in the study. All patients were in the range of 2 to 10 years and underwent Snodgrass Tubularized Incised Plate [TIP] urethroplasty for hypospadias repair. The overall rate of urethrocutaneous fistula was 9.6% [5 out of 52 patients]. Mean operative time noted in minutes was 57.52 minutes. No major morbidity or mortality was noted in this study. TIP urethroplasty is simple, single stage operation in the management of hypospadias and has good functional and low complication rate

Modified posterior sagittal ano-rectoplasty: a new approach for the management of ano-rectal malformations in children

To introduce a technical modification in Posterior Sagittal Ano-rectoplasty [PSARP], commonly known as Pena's procedure, and to analyse the outcome of such modified procedure in terms of fecal continence and other relevant complications in children with ano-rectal malformations. It was a prospective and descriptive study, conducted at the department of pediatric surgery, Lady Reading Hospital Peshawar from January 2004 to December 2006. Forty patients were studied. All children of either sex with ano-rectal malformation who presented first to our department were included in our study excluding others treated some where else. Relevant investigations were performed in all patients. Diverting colonic or small bowel stoma was created in all patients at presentation to our department. The technique was performed at or after six months of age, depending upon the clinical condition of the patient. After discharge, all patients were examined and monitored in the out-patient department over a period of two years. Out of 40 patients 25[62.5%] were male and 15 [37.5%] were female age range from 6-12 months. On 35 [87.5%]. Isolated PSARP while on 5 [12.5%] patients modified PSARP with abdominal approach were performed. Anal stenosis was found in 3[7.50%] patients, rectal mucosal prolapse in 4[10%], faecal soiling and faecal incontinence in 17[43.58%] and 7[17.05%] patients were respectively. Faecal continence was good, fair and poor in 15[38.46%], 17[43.58%] and 7[17.94%] patients respectively. Our results of the present series suggest that this procedure is a valuable alternative to PSARP for the treatment of anorectal malformations

Sex hormones and erectile dysfunction in hemodialysis patients

To determine the prevalence of Erectile Dysfunction [ED] in hemodialysis patients [HD] and to study the associated changes in sex hormones in these patients. This is a hospital based cross sectional study conducted at hemodialysis units of Shalamar and Mayo Hospitals, Lahore from January to March 2008. All male patients with ESRD on maintenance [HD], whose spouses were alive and able to perform intercourse, were included in the study. Patients with cognitive and communication deficits were excluded from study. International index of erectile function-5[IIEF-5], adopted in Urdu was used for determination of prevalence of ED. Demographic data was collected and sex hormones [total testosterone, Dihydroepiandrosteronediones [DHEA], Follicle Stimulating Hormone [FSH], Leutinizing Hormone [LH] and serum Prolactin] were measured. A total number of fifty patients were included in the study. The major cause of ESRD was diabetes mellitus 28 [56%]. The prevalence of ED was 86% with a mean IIEF-5 score 10.36 +/- 7.13. The majority of patients, 33 [66%], were suffering from a severe degree of ED. The total testosterone level was low in 30 [60%] patients and DHEA were low normal in most of patients, 46 [92%]. Compared to patients with non-ED, those with ED had a significantly lower DHEA [1.93 +/- 0.73 vs 0.81 +/- 0.11, p value = 0.007]. Total testosterone and DHEA had a negative correlation with age and diabetes mellitus. FSH showed a variable response in these patients, it was low [< 1.55 mIU/ml] in three, normal [1.55 +/- 9.74 mIU/ml] in 39 and high [> 9.74 mIU/ml] in eight patients. LH was low [< 1.2 mIU/ml] in two, normal [1.2 +/- 7.8 mIU/ml] in thirty three and high [> 7.8 mIU/ml] in fifteen patients. FSH and LH showed a positive correlation with duration of dialysis. Prolactin level was low in 21[42%] patients. Total testosterone, FSH, LH and Prolactin had no association with ED. The majority of the patients suffering from ESRD, on maintenance HD had ED. DHEA was significantly lower in patients with ED, compared to those with no-ED. Total testosterone and DHEA had an inverse relationship with diabetes and age of the patients. Total testosterone, FSH, LH and prolactin did not affect erectile function

Which age, sex and season brings more chances of intussusception for children-an analysis

To know as to which age, sex and season has more cases of intussusception, in children up to the age of 12 years. This prospective study spread over a period of 18 months. A total of 71 patients with surgically diagnosed intussusception were studied. The relevant data, both pre-operative and post-operative, of children who were operated for intestinal obstruction and finally turned out to be suffering from intussusception, was entered in a pre-designed proforma and the information so obtained was analyzed according to objectives of the study. Out of 71 children 55 [77.45%] were male and 16 [22.55%] were female patients. Male to female ratio was 3.4:1. 16[22.53%] were 3 to 7 months old, 55 [77.46%] below 1 year, 16 [22.53%] between 1 to 2 years and 13 [18.30%] above 2 years. 9 [12.67%] were recorded in January, 6 [8.45%] in February, 8 [11.26%] in March, 2 [2.81%] in April, 11 [15.49%] in May, 4 [5.63%] in June, 4 [5.63%] in July, 2 [2.81%] in August, 9 [12.67%] in September, 6 [8.45%] in October, 7 [9.85%] in November, 3 [4.22%] in December., Intussusception is more common in male than female children and again is more common below the age of 2 years and occurs mostly in January-March, May and September to November months of the year, the first 3 months and month of May coinciding with the period when gastroenteritis is endemic and September - November when respiratory tract infections predominate in children

Glucose-6-phosphate dehydrogenase [G6PD] deficency in neonates presenting with Jaundice

To determine the frequency of Glucose-6-phosphate dehydrogenase [G6PD] deficiency in infants presenting with jaundice. This retrospective study was conducted in Fazal Rahim Clinical Laboratory Timergara District Dir North West Frontier Province of Pakistan, from 1st January 2004 to 31st December 2004 on 120 neonates. Data regarding sex and age, serum bilirubin total, serum bilirubin direct and G6PD status was extracted using database software designed by the principal author. The inclusion criterion was neonates with high serum bilirubin and G6PD test performed simultaneously. The exclusion criterion was premature babies and incomplete request forms. Microsoft Excel 2000 was used for data analysis Out of 120 patients, 97 [80.8%] were male and 23 [19.2%] were female ranging in age from 3 - 10 days with mean 6.5 days and median 5 days. Thirty two [26.6%] neonates were found G6PD deficient. Among patients with normal G6PD level male to female ratio was 3.63:1. In G6PD deficient patients male to female ratio was 7:1. The serum bilirubin of the G6PD normal patients was 12.8 + 5.0 mg/dl and that of G6PD deficient patients was 13.5 + 6.8 mg/dl. G6PD deficiency is quite high in neonates presenting with jaundice. The diagnosis is simple and if left undetected may cause serious consequences in situations of oxidant stress

Surgical management of hepatic hydatid cyst in children

To know the effectiveness of removal of hydatid cyst of liver along with pericyst [pericystectomy] as operative treatment, in terms of intra-operative and post-operative complications in the pediatric age group. This study was conducted on paediatric patients with liver hydatid cysts at Department of Paediatric Surgery, Lady Reading Hospital, Peshawar from January 2000 to December 2006. All patients with ultrasound findings for hydatid cyst disease of the liver were included in the study. They were evaluated according to age, clinical presentation, ultrasound and CT scan findings for operative management. After Laparatomy through right transverse incision, half of the contents of the cyst were aspirated, refilled with hypertonic saline solution of the aspirated volume and after waiting for five minutes Pericystectomy was carried out, followed by careful examination and stoppage of any leakage of blood or bile from the residual cavity. In infected cases the cavity was drained. Out of 21 paediatric patients operated for liver hydatid cysts during the study period, 11[52.4%] were girls and 10 [47.6%] were boys, with age ranging from 4 to 15 years. Cystectomy with tube drainage was performed in 20 patients while in one patient de-roofing was performed because of rupture. Hypertonic saline was used as a scoliocidal agent. There was no operative mortality. The mean hospital stay was 6.5+3.8 days. Recurrence after operation was seen in one [4.8%] patient. Hepatic hydatid cysts in children can be treated successfully by peri-cystectomy

Hyperhomocysteinaemia and acute myocardial infarction in patients admitted at Isra Uneversity Hospital, Hyderabad

Myocardial infarction is a major consequence of coronary artery disease. Recently many reports have been suggested that hyperhomocysteinemia had an important role in myocardial infarction. Plasma homocysteine level was determined in 60 myocardial infarction patient [Group A] and 35 healthy controls [Group B]. Statistically significant difference was observed in plasma homocystine concentrations between the patients of acute myocardial infarction [Group A] and in normal healthy individuals [Group B]. The level of homocystine in patients of myocardial infraction is significantly increased when compared with controls. This indicates a strong association between hyperhomocysteinemia and acute myocardial infraction in the peoples of Hyderabad, thus showing plasma homocysteine as a risk factor for myocardial infarction

Retrospective analysis of clinical presentation of children with diagnosed intussusception

To know the presenting clinical features of intussusception in children up-to the age of twelve years. The study was conducted at the Department of Paediatric Surgery, Post-Graduate Medical Institute, Lady Reading Hospital, Peshawar, over a period of 18 months. A total of 71 patients with diagnosed intussusception were included. The relevant data, both pre-operative and postoperative, of children who were operated for intestinal obstruction and finally turned out to be suffering from intussusception, was fed into a pre-designed proforma and the information so obtained was analyzed according to objectives of the study. The common presenting features were colicky abdominal pain in 70 [98:59%] cases, vomiting in 67 [94.36%] cases, abdominal distension in 67 [94.36%] cases, constipation in 63 [88.73%] cases, bleeding per rectum in 61 [85.91%] cases, palpable mass per abdomen in 56 [78.87%] cases and fever in 18 [25.35%] cases. In 11 [15.49%] cases there was a mass palpable per digital rectal examination and 05 [07.04%] patients had diarrhoea on presentation. Colicky abdominal pain, vomiting, abdominal distention, constipation, bleeding per rectum, palpable mass per abdomen are the commonest presenting clinical features of intussusception in children

Role of focused appendiceal computed tomography in clinically equivocal acute appendicitis

To determine the accuracy of FACT [focused appendiceal computed tomography] in evaluation of acute appendicitis. The study was conducted in Aga Khan University Hospital, Karachi, over a period of one year. Sixty-three patients with clinically equivocal acute appendicitis underwent thin-section non-enhanced helical CT. Axial scans were obtained in a single breath hold from L2 vertebral level to the pubic symphysis with 5-mm collimation and a pitch of 1.5. All scans were obtained without oral, intravenous, or rectal contrast material. Criteria for diagnosis of acute appendicitis included an enlarged appendix [>6 mm diameter] and periappendiceal inflammation. Final diagnoses were established with the results of surgical or clinical follow-up. There were 21 true-positive diagnoses, 38 true-negative diagnoses, no false-positive diagnoses, and 2 false-negative diagnoses, which yielded a sensitivity of 91% and a specificity of 100%. Non-enhanced FACT is a highly accurate problem solving technique in clinically equivocal cases of acute appendicitis

Non contrast helical CT scan for acute flank pain: non calculus urinary and extra urinary causes

To determine the value of non contrast helical CT in the diagnosis of non calculus renal and extraurinary causes of acute flank pain. A prospective descriptive study. Radiology Department, Aga Khan University Hospital Karachi from January 2005 to June 2005. 130 consecutive patients with acute flank pain underwent Noncontrast enhanced helical CT scan [NHCT]. 100[73%] were male and 30[23%] were female. Scans were observed for noncalculus renal and extraurinary causes of acute flank pain. Out of 130 patients, 30 patients were excluded. In 23[23%] patients non calculus causes of pain were diagnosed. In 5 [5%] patients incidental findings were recorded which were most likely not cause of pain. Three patients had non calculus renal abnormalities which included renal cell carcinoma, horseshoe kidney adult polycystic kidney disease. The accurate and timely diagnosis of an obstructing ureteral calculus, a non calculus urinary abnormality or an extra urinary tract pathology, establishes non contrast helical CT as the diagnostic study of choice for the evaluation of patients with flank pain

Bolton tooth size discrepancies among different malocclusion groups

One of the goals in comprehensive orthodontic treatment is to obtain an optimal final occlusion, overbite and overjet. It is the descriptive, cross sectional study conducted in orthodontic department of KMDC. Sampling methods was non probability convenient. Sample sizes were 55 patients. Age ranges between 12 to 23 years old. In the current study the men of anterior and overall ratio for class I malocclusion were similar to those of Bolton figures when comparing the mean tooth size ratio for these malocclusion group. It was found that class III> class II> class I for the overall anterior ratio. In the orthodontics treatment during diagnostics phase Bolton analysis should be used for the initial diagnostics and for treatment planning. In our study the mean and overall ratio for class I malocclusion similar to Bolton, no statistical difference were found among different malocclusion groups

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

Role of magnetic resonance imaging in lumbar spondylosis

To assess the frequency of various MRI findings in patients with lumbar spondylosis and determine their association with symptoms of patients. Cross-sectional analytical study. Radiology Department,The Aga Khan University Hospital, Karachi, from January to December, 2002. The study included 120 patients who presented with low back and leg pain. Segmental classification system was used to classify the pain distribution. All patients underwent lumbar MRI using 1.5 T-scanner. MRI scans was evaluated for magnitude and location of nerve compression, disc extrusion and the nature of nerve and thecal sac deformation in the central canal, lateral recess and intervertebral foramen at each spinal level. Statistical analysis was performed using computer program SPSS [Version; 10]. Chi-square test was also used to determine significance of association between degree of compression, duration of symptoms, site of pain and presence of weakness and numbness. Independent samples test [Levenes test] and Chi-square test were used to determine the significance of associations between age, gender, chronicity of symptoms and MRI findings. A p-value of <0.05 was considered to indicate statistically significant association. The study included 120 patients, the age range was 22 to 88 years [mean 47 years]. Twenty-three patients had acute pain of less than 2 months, 40 patients had recurrence of previous symptoms within past 2 months and 57 patients had chronic pain. Disc herniation was most frequent finding seen in 107 patients [89%]. Eighty-eight patients [73%] had MRI evidence showing some degree of nerve or thecal sac compression. Severe nerve compression was present in 48 patients [40%]. Disc extrusion was present in 22 patients [18%]. There was no significant association between segmental distribution of symptoms and presence of anatomic impairment. However, severe nerve compression and disc extrusion were significantly associated with pain distal to the knees. The presence of disc extrusion or ipsilateral severe nerve compression at one or multiple side is strongly associated with distal leg pain. There should be a correlation between patient symptoms and signs of sciatica and imaging demonstration of nerve root compression before invasive therapy is undertaken

Unenhanced helical CT scan for ureterolithiasis

The study was carried out from November 2002 to January 2004 and included patients who presented with flank pain at the Aga Khan University Hospital. One hundred and twenty patients were excluded from the study that were less than 15 years of age, pregnant or had history of trauma and infection. A total of 80 out of these 200 patients were included in this study that had a CT diagnosis of ureteric calculus after a UEHCT. In all those 80 patients with diagnosis of ureteric calculus on CT scan was confirmed later on either IVU, stone passage in the urine, ESWL [extracorporeal shock wave lithotripsy] or on the ureteroscopic removal of calculus. The images were interpreted for site, size and location of ureteric calculus, hydronephrosis, hydroureter, perinephric stranding, periureteral stranding, nephromegaly and incidental findings. The age range was 15-69 years, with a mean age of 37.5 years. Out of 80 patients, 32 [40%] patients presented with right sided flank pain and 48 [60%] of the patients had left sided flank pain. In 12 [15%] patients, calculi were present in the proximal ureter, in 24 [30%] in the mid ureter and in 44 [55%] in distal ureter. Most of the stones were between 3-5 mm size range [47%]; 20% stones were less than 3 mm in size and 32.5% of stones were more than 5 mm in size. Most common secondary sign was perinephric stranding seen in 48 patients [60%]. The second most common secondary sign was periureteral stranding seen in 44 [55%] patients. In 30 of the patients [37.5%] hydronephrosis was observed. In 18 [22.5%] hydroureter was present. Nephromegaly was observed in 2.3% of the patients. In 2 of 120 patients in which CT was negative, ureteric calculus was present on IVU which was carried out 3 days after UEHCT. In 2 of 120 patients in which CT was negative for ureteric calculus, ureteric calculus was present on IVU which was carried out 3 days after UEHCT. The sensitivity, specificity, positive and negative predictive values of unenhanced helical CT scan for detection of ureteric calculi was 97.5%, 98.3%, 97.5% and 98.3% respectively

outbreak of cutaneous leishmaniasis in a village of district Dir, N.W.F.P.

To study the frequency of cutaneous leishmaniasis at a village inundated by s and fly.A leishmaniasis diagnosis camp was arranged at village Wattangi, district Dir. All patients with suspected cutaneous leishmaniasis having active lesion were recruited in the study. Data of the patients e.g. name, age, sex and site of lesions were entered into a register. Smears were prepared from the sides of the lesions with sterile lancets, fixed with absolute alcohol, stained with Geimsa stain and examined under microscope. Out of 40 examined patients, 37 were positive for Leishmania Tropica [L.T.] bodies. The most common site involved was face and the most common age group affected was less than 10 years. The frequency of cutoneous leishmaniasis is quite high at Watangi village of distt. Dir, due to infestation by s and flies, lack of medical education and low socio economic status in the area