Development and validation of a stability-indicating RP-HPLC-FLD method for determination of 5-[[4-chlorophenoxy] methyl]-1, 3, 4- oxadiazole-2-thiol; A novel drug candidate

The present study describes the development and validation of a simple high performance liquid chromatographic method for the determination of a novel drug candidate, 5-[[4-chlorophenoxy] methyl]-1, 3, 4- oxadiazole-2-thiol. The stability-indicating capacity of the method was evaluated by subjecting the compound's solution to hydrolytic, oxidative, photolytic, transition metal- and thermal- stress. The chromatographic separation was achieved over a C18 column [Promosil, 5 microm, 4.60 × 250 mm], maintained at 25°C, using an isocratic mobile phase comprising a mixture of acetonitrile and acidified water of pH 2.67 [1:1, v/v], at a flow rate of 1.00 mL/min and detection using a fluorescent light detector [excitation at 250 nm and emission at 410 nm]. The Beer's law was followed over the concentration range 2.50-50.00 microg/mL. The recovery [98.56-100.19%, SD <5%], intraday accuracy and precision [97.31-100.81%, RSD<5%] and intermediate accuracy and precision [98.10-99.91%, RSD<5%] indicated that the method was reliable, repeatable, reproducible and rugged. The resolution and selectivity factors of the compound's peak from the nearest resolving peak, particularly in case of dry heat and copper metal stress, were found to be greater than 2 and 1, respectively, which indicated specificity and selectivity. The compound was extensively decomposed in alkaline-hydrolytic, oxidative, metal- and dry heat- stress. However, the compound in acidic and neutral conditions was resistant to photolysis. The results of the present study indicate that the developed method is specific, selective, sensitive and suitable, hence, may be used for quality control, stability testing and preformulation studies

Analytical, nutritional and biological evaluation of various brands of fortified and non-fortified wheat flour

In Pakistan, a funded flour fortification program was launched for malnourished population, residing mainly in rural low income areas, but the urban population having comparatively better nutritional as well as economic status was focused wherein excessive intake of fortificants might cause complications. Therefore, the present study describes the physicochemical properties, elemental composition, nutritional components and hemoglobin/ferritin increasing potential of fortified and non-fortified flour. Domesticated chicken [Gallus gallus domesticus], either sex, age one month, weight 380 +/- 18.28 g, were randomly segregated into 4 groups [n=6]. The group I, II and III were fed on fortified flour, whereas group IV was fed on non-fortified flour for 30 days. The birds were weighed and blood samples of each of the birds were analyzed for determination of markers of iron status, hemoglobin [Hb] and serum ferritin [SF]. Moisture, ash and iron contents were found to be lower in non-fortified flour than that of the fortified samples. Hb and SF levels in groups fed on fortified flour were significantly higher than the one received non-fortified flour [P < 0.05]. The consumption of iron-fortified flour increases iron stores in the body without any further complication but long-term usage needs to be monitored.

Early psychosis symptoms

To determine the prodromal symptoms of schizophrenia in the pathways to help-seeking. A cross-sectional study. The Department of Psychiatry, the Aga Khan University, Karachi, from 2008 to 2009. A total of 93 patients were interviewed in the pathways to care of schizophrenia. The diagnosis was based on ICD-10 criteria. The pathways to care were assessed through a semi-structured questionnaire. The onset, course and symptoms of psychosis were assessed through Interview for Retrospective Assessment at Age at Onset of Psychosis [IROAS]. Fifty five [59%] participants were male while 41% [n=38%] were female. Using IROAS, 108 symptoms were identified as concerning behaviour. Alternatively, 60 [55%] concerning behaviours were reported in the open-ended inquiry of the reasons for help seeking as assessed by the pathways to care questionnaire with a statistically significant difference between most symptoms category. The difference was most pronounced [p < 0.001] for depressed mood [66%], worries [65%], tension [63%], withdrawal/mistrust [54%] and loss of self-confidence [53%]. Thought withdrawal [22%] and passivity [15%] were elicited only through structured interview [IROAS]. When symptoms were categorized together, about 83% of the subjects presented with affective and non-specific prodromal symptoms. Roughly, 10% of the subjects presented with positive symptoms and 3% presented with the negative symptoms of psychosis. The non-specific, affective symptoms appear to predominate the prodromal phase of the illness. Prodromal symptoms of schizophrenia include non-specific, affective symptoms. Attention needs to be paid on identifying the prodromal symptoms and change in social functioning in order to identify those who are at risk of longterm psychosis

role of zinc on anti-newcastle disease virus specific antibody response and agranulocytes count in rabbits treated with methotrexate and prednisolone

Zinc [Zn] plays a pivotal role in highly proliferative tissues including immune system. The long-term therapy of neoplastic and autoimmune disorders is associated with immunosuppression and myleosuppression. In the current study role of Zn on anti-Newcastle disease virus response and agranulocytes count of methotrexate and prednisolone treated rabbits. Thirty six healthy rabbits were randomly segregated into six groups [group I to VI] each containing six rabbits. Oil based Newcastle disease virus [NDV] vaccine was administered subcutaneously to rabbits of all the groups at day 0 and 21 and after one week, all the groups received Zn, [Zn + prednisolone], prednisolone, [Zn + methotrexate] methotrexate orally from day 7 to day 21, except the control. The serum antibody titer, total and differential leukocyte count were measured weekly for 6 weeks. The administration of zinc in combination with methotrexate showed same antibody titer as that of the control suggesting that Zn has ability to counteract the methotrexate-induced immunosuppression. However, Zn did not show any significant impact in combination with prednisolone [p<0.05]. The results of the present study indicate that co-administration of Zn and methotrexate is beneficial in the activity of immune system

Frequency of prostate cancer in patients undergoing trans-urethral resection of prostate [TURP] for clinically benign symptomatic enlarged prostate

To determine the frequency of carcinoma prostate in patients undergoing trans-urethral resection of prostate [TURP] for clinically benign symptomatic enlarged prostate. A descriptive study including all patients who had the clinical symptoms of BPH and operated with TURP in the RMI was designed. The study spanned from June 2009 to June 2010. Patients' data, clinical history, examination and operation notes were saved in a file. All the patients were properly evaluated by the team comprising of the authors pre-operatively. On the basis of these evaluations, a malignancy was not anticipated. All the patients were operated using TURP by the same team under spinal anesthesia. Prostate chippings collected at TURP from each patient were sent as routine, for histopathological evaluation and reporting. Majority of patients [n=44, 66.7%] were older than 60 years. Patients' ages ranged from 48 to 100 years with a mean of 69.5 years. Out of all the patients in this study, 9 patients [13.6%] presented with acute urinary retention and 57 patients [86.4%] presented with Lower Urinary Tract Symptoms [LUTS] and chronic urinary retention. In 9 patients [13.6%] malignancy of the prostate on histopathological examination was confirmed with 8/9 having definitive adeno-carcinoma. Two patients had Gleason score 6/10 and 6 patients had Gleason score 8/10] of the prostate while 1/9 had carcinoma in situ. Out of the 9 patients with malignancy 8 patients [88.9%] were more than 60 years of age ``while 1 patient [11.11%] was aged 56 years. The substantial proportion of patients with confirmed PCA in patients undergoing TURP for clinically symptomatic benign enlarged prostate emphasizes the need for early diagnosis through histopathological examination

Ureteroscopic pneumatic versus extracorporeal shock wave lithotripsy for lower ureteral stones

To compare the efficacy of ureteroscopic pneumatic lithotripsy [URS] and extracorporeal shock wave lithotripsy [ESWL] in the treatment of lower ureteric stones in terms of stone-free rates. Randomized trial. Department of Urology, Government Institute of Kidney Diseases and Transplant, Hayatabad, Peshawar, from September 2010 to March 2011. Patients [n=136] presented with lower ureteric stones and fulfilling the inclusion criteria for the study were included. They were divided equally into two groups. Division of patients was done by lottery method. Patients in group A were treated with ureteroscopic pneumatic lithotripsy [URS] as compared to those in group B, who were dealt with extracorporeal shock wave lithotripsy [ESWL]. There were 46 males [67.6%] and 22 females [32.3%] with a ratio of 2.1:1 in group A as compared to 50 males [72%] and 18 females [26.4%] with a ratio of 2.8:1 in group B. Mean age was 35.2 +/- 9.5 years in group A and 35.4 +/- 9.2 years in group B. The mean stone size in group A was 12.8 +/- 3.7 [range 5 - 25 mm] and 12.82 +/- 3.5 [range 5 - 25 mm] in group B. Mean hospital stay in group A was 2.07 +/- 0.6, while patients in group B were all day-cases. The statistical difference was significant in terms of repeat procedure, auxiliary procedure postoperative analgesia and stone free status at 3 months [p=0.043, 0.020, 0.000, 0.001] respectively, while it was not significant in respect of complications of procedure [p=0.753]. URS proved more effective than ESWL for the treatment of ureteric calculi. However, ESWL performed as an outpatient procedure showed fewer complications

Bilateral orchiectomy with or without flutamide for advanced carcinoma prostate

To assess the effects of flutamide in patients suffering from advanced carcinoma of the prostate who underwent bilateral orchiectomy. Institute of Kidney Diseases, Hayatabad Medical Complex, Peshawar, from March 2008 to July 2009. A total of 100 patients having advanced carcinoma prostate who had undergone bilateral orchiectomy were divided into two groups .Group A consisted of 50 patients who were treated with flutamide while group B having 50 patients received placebo. Relief of bone pain was more in group A than B. No significant difference was seen in the occurrence of adverse effects like nausea, vomiting, hot flashes and anemia between the groups. Eight patients in each group were lost to follow up. The benefit of combined androgen blockade was better in relief of bone pain

Efficacy of L-ornithine-L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy

To evaluate the efficacy of L-ornithine-L-aspartate [LOLA] as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy [HE]. Randomized placebo controlled study. The Aga Khan University Hospital, Karachi in the year 2003-2004. Patients with HE were randomized to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A [NCT-A], ammonia level, clinical grade of HE and duration of hospitalization were assessed. Out of 120 patients, there were 62 males with mean age of 57 +/- 11 years. Improvement in HE was higher [n=40, 66.7%] in LOLA group as compared to the placebo group [n=28, 46.7%, p=0.027]. In patients with grade I or less encephalopathy, improvement was seen in 6 [35.3%] and 3 [20%] patients in LOLA and placebo groups respectively [p=0.667]. Patients with HE grade II and above showed improvement in 34 [79.1%] and 25 [55.6%] cases in LOLA and placebo group respectively [p=0.019]. On multivariate analysis patients with HE of grade II and above showed prothrombin time, creatinine level and use of LOLA influencing the outcome. Duration of hospitalization was 93.6 +/- 25.7 hours and 135.2 +/- 103.5 hours in LOLA and placebo groups respectively [p=0.025]. No side effects were observed in either groups. In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay

Emergency evaluation of acute chest pain

To determine the sensitivity and specificity of initial clinical assessment about the diagnosis of acute coronary syndrome [ACS] in patients presenting with acute chest pain by a cardiology resident in the emergency room and assess the 30-day outcome of patients with ACS and non ACS. Cohort study. The study was conducted in the emergency department and cardiac care units of the Aga Khan University in 2006-07. A total of 202 patients, who presented to the emergency room with chest pain, were given an initial ECG and troponin check. Patients were assigned to initial ACS and non-ACS groups by the cardiology resident. After cardiac workup, patients were assigned to final ACS/final non ACS group. They were followed for outcome after 30 days of initial presentation. Sensitivity and specificity, if initial workup was determined, keeping final assessment after cardiac workup as the gold standard. Out of the 202 patients, 61.9% were males. Their mean age was 54.05 +/- 13 years. Sixty eight percent were placed in the initial ACS group and 30.7% were placed in the initial non ACS group. After workup, 36% were placed in the final ACS group and 28.7% in the final non-ACS group and 35% were undecided. The sensitivity of initial assessment of ACS by the cardiology resident was 100%. However, the specificity was 54.2%. In the 30-day outcome, one patient [1.3%] died in the ACS group due to myocardial ischemia while no patient died from the non ACS group. Initial assessment about ACS by cardiology resident based on character of chest pain, ECG and troponin I is highly sensitive. However, the specificity is low

Anatomical position of appendix in emergency care patients

To identify the anatomical position of the appendix in patients presenting at the emergency surgical ward, Lady Reading Hospital Peshawar. This descriptive study was conducted in surgical 'A' Unit, Lady Reading Hospital, Peshawar from January to June 2008. Patients coming to emergency surgical ward were examined after detailed history and investigation; and then operated. Position of appendix along with other findings was noted. 100 patients were admitted and examined. 68% were male and 32% were female. During surgery retrocaecal position was the most common [78%] followed by pelvic position in 16% of patients. Perforated appendix was observed in 06% [all retrocaecal appendixes]. Retrocaecal appendix was the commonest in patients presenting to emergency with acute appendicitis. Less symptoms/signs lead to delay in diagnosis and complications

Associations between the Plasticity Region Genes of Helicobacter pylori and Gastroduodenal Diseases in a High-Prevalence Area

BACKGROUND/AIMS: Genes associated with the Helicobacter pylori (H. pylori) plasticity region may play a role in the pathogenesis of H. pylori. We compared the genes jhp0940, jhp0947, and jhp0986 in H. pylori isolates from patients with different gastroduodenal diseases and in different age groups. METHODS: The H. pylori hyperplasticity region genes jhp0940, jhp0947, and jhp0986 were studied by PCR. We also evaluated whether these genes were related to the cytotoxin-associated gene (cagA) and histology findings. RESULTS: Of the patient cohort, 71 (62%) were positive for jhp0940, 67 (59%) for jhp0947, 12 (10%) for jhp0986, and 69 (60%) for cagA. jhp0940 (n=18, 67%) and jhp0947 (n=23, 85%) were found more frequently in duodenal ulcer (DU) patients than in gastritis patients (n=14, 39%; p=0.029 and p<0.001, respectively). Gastric ulcer (GU) was more frequently associated with jhp0940 (17 patients, 77%; p=0.003) than with gastritis (14 patients, 39%). Gastric carcinoma (GC) was more strongly associated with both jhp0940 (22 patients, 76%; p=0.003) and jhp0947 (22 patients, 76%; p=0.003) than was gastritis (14 patients, 39%). jhp0947 was more frequently associated with chronic active inflammation (58 patients, 87%; p=0.009) than with chronic inflammation (9 patients, 13%). Multivariate analysis demonstrated that jhp0947 was associated with DU (odds ratio, 6.1; 95% confidence interval, 1.87-20). CONCLUSIONS: The genes jhp0947 and jhp0940 were identified in H. pylori isolates from patients with GC and DU, while jhp0940 was also isolated from patients with GU. jhp0947 was independently associated with DU.

Compliance to antihypertensive therapy

To determine compliance, factors affecting compliance to antihypertensive therapy and to compare compliant and non-compliant groups, in a tertiary care setting. Analytical [cross-sectional] study. The outpatient clinics at the Aga Khan University from May 2004 to February 2005. Two hundred patients presenting to the outpatients clinic were included. All patients 18 years and above, who had stage 1 and 2 hypertension, had one clinic visit to a medicine clinic, 6 months prior to presentation and started on antihypertensive medicines, were included. Sixtysix percent were males and 33.5% were females. Mean age was 58.1[ +/- 12] years and mean duration of hypertension was 7.2 [ +/- 6.7] years. Fifty-seven percent were compliant and 43% were noncompliant. In the noncompliant group, 53.4% had mild noncompliance, 24.4% had severe non-compliance, while 22% had moderate noncompliance. Factors of noncompliance were 56.8% missed doses due to forgetfulness, 12.7% deliberately missed their doses, 11.6% could not take the medicine due to side effects, 10.4% did not take the dose due to increased number of tablets, 4.6% were not properly counseled by the physician and 3.48% did not take medicines due to cost issues. The mean systolic blood pressure was 126 +/- 19.2 mmHg in the compliant group while it was 133 +/- 16.5 mmHg in the noncompliant group [p-value 0.004]. The mean diastolic blood pressure in the compliant group was 76 +/- 11.9 mmHg, while in the noncompliant group it was 81.9 +/- 10.9 mmHg [p-value 0.001]. Compliance to antihypertensive therapy in a tertiary care center is significantly good. Forgetfulness was the major reason for noncompliance. The mean blood pressure control was better in the compliant group

Acute respiratory failure in Pakistani patients: Risk factors associated with mortality

To assess the outcome and risk factors associated with mortality in patients with acute respiratory failure [ARF]. Observational study. The Aga Khan University Hospital, Karachi, between January 1997 and June 2001. All adult patients admitted with a medical cause of acute respiratory failure were reviewed. The primary outcome measure was mortality and secondary outcome measures were factors associated with mortality in ARF. Multiple logistic regression analysis was used to identify the independent risk factors for mortality. A total of 270 patients were admitted with ARF. Hypercapnic respiratory failure was seen in 186 [69%] and hypoxemic in 84 [31%] cases. Pneumonia and COPD exacerbation were the most common underlying causes of ARF. Ventilator support was required in 93 [34.4%] patients. Hospital mortality was 28%. Chronic renal failure, malignancy, hypokalemia, severe acidosis [pH <7.25], septicemia and ARDS independently correlated with mortality. Mortality rate increased sharply [84%] with the presence of three or more risk factors. Acute respiratory failure has a high mortality rate [28%]. Development of ARDS or septicemia was associated with high mortality. Presence of more than one risk factor significantly increased the mortality rate

Phloroglucinol in irritable bowel syndrome

To determine the efficacy and tolerability of phloroglucinol, an antispasmodic agent in the treatment of Irritable Bowel Syndrome [IBS]. It was an open label [quasi interventional] study. One hundred patients coming to the gastroenterology clinics of Aga Khan University Hospital with IBS as defined by the Rome II criteria were enrolled between February 2004 and September 2004 to participate in the trial and were treated as outpatients. Phloroglucinol [Himont] 50mg orally three times daily was given for two months. Symptoms were assessed before and during treatment using a questionnaire. One hundred patients were enrolled in the study. Of them 61% [61/100] were males and 39% [39/100] were females. Their mean age was 41'14 years. Sixty-eight patients completed the study and 28 dropped out. On Phloroglucinol treatment there was an overall statistically significant improvement in abdominal pain [p<0.001], frequency of stools per day [p<0.001], urgency [p<0.001], passage of mucus per rectum [p<0.001], sense of incomplete defecation [p=0.001] and bloating [p=0.001]. However, no response was seen in the feature of straining in both genders [p=0.676]. The difference in response to treatment according to gender separately showed statistically significant improvement in the sense of incomplete defecation in females alone [p=0.003]

Septic arthritis in a tertiary care hospital

To study the epidemiological features of septic arthritis in the adult population and to identify the risk factors for mortality in septic arthritis. A five year reterospective study was performed on cases with septic arthritis admitted in our hospital between January 1999 and December 2004. Patients were identified according to ICD codes, 711.00. Data was recorded on a standardized data sheet and analyzed by SPSS 11.5 software. A total of 116 patients were identified, 69 were male [59.5%] and 47 female [40.55%]. Mean age of patients was 49.22 years. The most common presenting clinical features were joint swelling [99.1%] and fever [60.3%], Knee joint was the most common joint involved [65.5%] followed by hip [11.2%]. Gram stains of synovial fluid was done in 67.2% of cases out of which 22.4% had positive stains. Staphylococcus aureus was the most common organism isolated from blood as well as synovial fluid [18.8%]. Mean haemoglobin was 10.83gm/dl and 57.8% of patients had total leukocyte count less than 11,000/cumm. Platelet count was greater than 150,000/cumm in 90.5% patients. Hypertension, renal failure, chronic liver disease and elevated ESR were identified as some of the potential risk factors for higher mortality in a cohort with septic arthritis. Septic arthritis is associated with significant morbidity and mortality. These results highlight the importance of obtaining cultures before starting any treatment

Frequency of NSAID induced peptic ulcer disease

To determine the frequency of peptic ulcer disease in patients on nonsteroidal anti-inflammatory drugs [NSAID]. Record of eight hundred and twenty consecutive patients undergoing upper gastrointestinal [GI] endoscopy; from January 1998 to December 2000 were reviewed. The endoscopic diagnosis varied from gastritis, peptic ulcer to duodenitis. The use of NSAID was documented by reviewing medical records of patients with peptic ulcer. Peptic ulcers were found in 43% [353/820] patients. NSAID associated peptic ulcers were identified in 14.7% [52/353] patients. Diclofenac and aspirin were most common NSAIDs associated with peptic ulcers in 32.7% [17/52] and 30.7% [16/52] patients, respectively. Duodenal ulcer was more common than gastric ulcer 65.3% [34/52] and 42.3% [22/52], respectively. H. pylori infection was present in 46% [24/52] of the cases. NSAIDs treatment and / or H. pylori infection compared to non NSAIDs and non H. pylori infected peptic ulcer disease were significantly associated with gastric ulcer [p = 0.004] and duodenal ulcer [p = 0.009] respectively. NSAID-associated peptic ulcer disease is common in Pakistan and most frequently associated with gastric and duodenal ulcer. H. pylori infection is common in association with NSAID related peptic ulcers

Perception of gastroesophageal reflux disease in urban population in Pakistan

To determine the frequency and health care seeking behavior of patients with gastroesophageal reflux symptoms using American College of Gastroenterology [ACG] questionnaire for gastroesophageal reflux disease [GERD]. Cross-sectional study. Section of Gastroenterology, Department of Medicine, The Aga Khan University Hospital, Karachi, from April 2002 to November 2003. A total of 1267 persons above 15 years of age were interviewed using a modified questionnaire for GERD from the American College of Gastroenterology [ACG], which previously validated in our section as a screening tool in an urban population in Pakistan. Nine hundred and sixty-three individuals responded to the questionnaire. Mean age of the surveyed sample was 24 ' 9.3 years. Using the ACG criteria, the overall frequency of gastroesophageal reflux symptoms was 24% [228/963] with 58% [133/228] males and 42% [95/228] females. Symptoms experienced frequently were reflux from the stomach, 58% [133/228], with a bitter, acid taste in the mouth. Seventy-four percent [169/228] experienced this postprandially. Symptoms were associated with spicy fried food in 71% [161/228]. Sixty-seven percent [152/228] did not seek health care advice, 32% [74/228] practiced self-medications and 33% [76/228] consulted a physician. Gastroesophageal reflux is a common problem in the urban population of Pakistan

Polymerase chain reaction in the detection of helicobacter pylori infection

To determine the presence of Helicobacter pylori [H. pylori] infection, in patients suffering from gastritis and peptic ulcer disease by polymerase chain reaction [PCR] and correlate the results with the histological diagnosis. Design: Analytical, comparative study. Place and Duration of Study: Section of Gastroenterology, Department of Medicine and Pathology, Aga Khan University Hospital and School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore from November, 2001 to December, 2002. Patients and Gastric antral biopsies were obtained from 64 patients attending the Gastroenterology Section of Aga Khan University Hospital. Patients on nonsteroidal-anti-inflammatory drugs [NSAIDS] were excluded. Gastric biopsies were sent for histopathology and used for DNA extraction and PCR amplification of H. pylori 16S ribosomal RNA [rRNA] gene. Results were compared and statistically analyzed. H. pylori were not visible by histology in 57.6% [34/59] and could be seen in 42.4% [25/59]. PCR test was negative for H. pylori DNA in 44.1% [26/59] and positive in 55.9% [33/59] with p<0.001. PCR H. pylori DNA is a sensitive method for the diagnosis of H. pylori infection and its use as a diagnostic tool along with histology increases the detection rate of H. pylori infection. Two different staining methods for the organism should be used to avoid missing diagnosis of H. pylori infection