Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats.

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg-1 metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.

Nortriptyline protects testes against germ cell apoptosis and oxidative stress induced by testicular ischaemia/reperfusion.

We designed this experiment to evaluate the effects of nortriptyline on testicular injury after torsion/detorsion (T/D). Ninety-six adult Wistar rats were divided into six groups 16 each in control group (Group 1), sham operated (Group 2), T/D + saline (Group 3), and in groups 4-6; were administered 2, 10 and 20 mg kg-1 , i.p. of nortriptyline 30 and 90 min after torsion respectively. Testicular torsion was created by twisting the right testis 720° in clockwise direction for 1 h. In six rats of each group, tissue MDA level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in compared with control group 4 h after detorsion (P < 0.001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubules diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of rats. Pre- and post-reperfusion nortriptyline could reduce MDA and caspase-3 levels and normalise antioxidant enzymes activities, dose dependently. Germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, were significantly improved. Inhibition of mitochondrial permeability transition pore is probably involved in protective effects of nortriptyline against testicular T/D cell damages.

Efficacy and tolerability of Paroxetine 20 mg daily in the treatment of depression and depression associated anxiety.

OBJECTIVE: To assess the efficacy and tolerability of paroxetine 20mg daily, for the treatment of depression and depression associated with anxiety. METHOD: An open, non-comparative study undertaken at three centers in three cities of Pakistan. A total of 112 in- or out-patients, presenting with a major depressive episode were included in the study. Depression was diagnosed according to DSM IV criteria and a Hamilton Rating Scale for Depression (HAMD-D) score of >18 on the first 17 items of the HAM-D-21. After a placebo washout period of 7 days, patients were given a 20-mg fixed dose of paroxetine daily in the morning for a period of 6 weeks. After baseline, regular assessments were made at 1, 2, 4 and 6 weeks. Efficacy measures included the HAMD-D, the Clinical Anxiety Scale, The Clinical Global Impression Severity of Illness Scale (CGI-S), and the Clinical Global Impression Improvement Scale (CGI-I). Tolerability was assessed by any adverse event. The primary therapeutic outcome measures were patients who achieved a 50% or greater reduction in HAMD-D score at the end of the treatment or achieved a reduction in final HAMD-D score of < or = 10 points. The final scores of 1 or 2 for CGI-S and CGI-I were considered as full clinical response. RESULTS: Of 112 cases evaluated, 57 were males and 55 females whose ages ranged from 18 to 65 years. There was a clear and statistically significant efficacy of paroxetine on all the major outcome variables. A total of 88% patients achieved a reduction in the final HAMD-D score at the end of treatment. The total HAM-D score reduced to 10 or less in 73% patients at 6 weeks and by this week 76% and 92% patients achieved a score of 1 or 2 for CGI-S and CGI-I, respectively. The mean Clinical Anxiety Scale score reduced from 12.6 at the baseline to 4.4 at the end of treatment. Safety data was evaluated in all 112 patients and paroxetine was well tolerated. Adverse events were experienced by 10% of patients of whom 4% were dropped from the study. Nausea was the commonest adverse event reported. CONCLUSION: The study shows that paroxetine is an effective, well-tolerated, and safe drug for the treatment of depression.

Seroepidemiology of varicella-zoster in Pakistan.

The availability of safe and effective vaccines has renewed interest in the epidemiology of varicella worldwide. To date published data on the epidemiology of varicella in Pakistan is very scarce. Therefore, we conducted a study to determine the age-specific seroprevalence rate of varicella-zoster virus (VZV) antibodies in Pakistan. Between December 1997 and March 1998, 1,509 healthy volunteers aged between 1 month and 30 years were recruited from the Islamabad, Karachi, Lahore and Rawalpindi areas. Demographic information, socioeconomic status and past medical history were obtained by questionnaire. Serum samples were assayed for IgG antibodies against VZV by enzyme-linked immunosorbent assay. Overall 41.8% (600/1,435) of those tested were found to be seropositive for VZV antibodies. No difference was found in results obtained from the different cities. A higher seroprevalence was observed among women (45.2%) compared to men (39.6%). Seroprevalence rates increased with age and were 28.4% in those aged 0-5 years, 41.5% in the 6-10 year age group, 42.5% in the 11-15 year age group, 46.7% in the 16-20 year age group and 53.6% in those aged 21-30 years. Socioeconomic status was not a significant risk factor for VZV seropositivity. This is the first report of the seroepidemiology of VZV in Pakistan. The results indicate that seroprevalence of VZV increases with age in the Pakistani population studied. As in other tropical countries, there is greater susceptibility to varicella among the adolescent and young adult population. The results of this study suggest that these at-risk groups should be included in vaccination programs aimed at reducing the public health impact of varicella.

Evaluation of the effect of haemodialysis on cardiac dysfunction in patients of chronic renal failure.

Thirty-eight patients with end stage renal disease who were on haemodialysis and had recurrent congestive cardiac failure were analysed. Echocardiographic findings were evaluated at start of haemodialysis and after 6 dialysis sessions. Seventeen cases (48%) had diastolic dysfunction, 11 (29%) systolic dysfunction 8 (18%) had normal echocardiogram and 2 (5%) had dilated left ventricle with normal ejection fraction. In the systolic dysfunction group the end diastolic diameter decreased after 6 dialysis sessions. In the diastolic dysfunction group the end diastolic diameter and ejection fraction decreased minimally. In the systolic dysfunction group 8 patients (42%) expired within 18 months with a mean survival of 5 months and in the diastolic dysfunction group 5 patients (28%) died within 18 months with a mean survival of 12 months.

Acute renal failure due to traumatic rhabdomyolysis.

Between 1990 and 1993, we studied 14 cases of acute renal failure due to prolonged muscular exercise (e.g., squat jumping, sit-ups) and blunt trauma inflicted by law enforcement personnel using sticks or leather belts. None of the patients had a prior history of myopathy, neuropathy, or renal disease. All were critically ill and required renal support in the form of dialysis. Although the morbidity was high, 13 of the patients recovered normal renal function. One patient expired due to sepsis.

Predictors of outcome in malarial renal failure.

We studied 38 patients with acute renal failure (ARF) due to malaria over a 5-year period between 1990 and 1994 at the Institute of Urology and Transplantation. There were 30 males and 8 females who ranged in age from 13 to 75 years. Most were critically ill on presentation with blood urea levels between 116 and 587 mg% and serum creatinine concentrations between 3 and 30 mg%. Anemia accompanied by hyperbilirubinemia was a result of severe hemolysis. Antimalarial therapy consisted of quinine sulfate, chloroquine, or both. Of the 38 patients, 32 required hemodialysis and eventually recovered normal (n = 29) or near normal (n = 3) function. Six patients died.

Analysis of factors causing acute renal failure.

Factors leading to acute renal failure (ARF) were analysed in 376 consecutive patients between January 1993 and December, 1994 in a Karachi centre. Two hundred and sixteen (57%) had medical conditions, 86 (24%) obstetrical, 28 (7%) obstructive, 18 (5%) surgical and in 28 (7%) the causes were uncertain. Within the medical group, the causes were diarrhoea 30%, drugs 23%, malaria 15% and liver disease 5%. In the obstetrical group majority of the patients had multiple etiologies. Sixty percent of patients had ante-partum haemorrhage, 33% post-partum haemorrhage, intrauterine deaths were seen in 31%, septic abortions in 20% and pre-eclamptic toxemia in 22% cases. In the obstructive group, most of the patients had stone disease, where bilateral ureteric calculi constituted 57% of the cases. In surgical group, 11 (61%) had ARF due to post-operative complications. This data confirms the pattern of ARF from other third world countries where obstetrical and obstructive causes are high as compared to western countries.

A co-relation of the eye and kidney-in diabetes mellitus and hypertension.

The study was undertaken to observe the co-relation between microangiopathic changes in diabetic retinopathy and microvascular changes in diabetic nephropathy. Included in the study were 64 patients with chronic renal failure who were on maintenance dialysis, 40 had hypertension alone, 21 hypertension and diabetes and 3 had diabetes alone. On examination of retina, of 40 hypertensive patients, 14 had positive findings, while in the hypertensive and diabetic group, 20 patients out of 21, had positive findings. Nine patients in the hypertensive group had delayed choroidal filling on fluorescein angiography which was not very accurately reflected on Funduscopy. In the diabetic and hypertensive group, 13 patients having proteinuria of more than 1 gm, also had exudates and haemorrhages in the fundus. It was concluded that a correlation exists between the arterial changes in the fundus of the eye and the glomeruli of the kidney.

Acute renal failure due to traumatic rhabdomyolysis.

Trauma and non-traumatic insults can cause muscle damage to such an extent that serious sequelae to other organs may result. Myoglobinuria and subsequent acute renal failure (ARF) is a well known and widely studied fact of such sequelae. Twelve cases of ARF (between 1990-1993) who have developed renal dysfunction after prolonged muscular exercise e.g., squat jumping, sit-ups and blunt trauma from sticks or leather belts mainly given by law enforcing personnel for certain issues were studied. None of them had previous history of myopathy, neuropathy or renal disease. All were critically ill on presentation and required renal support in the form of dialysis. Although morbidity was high in all, eleven of them recovered and one expired due to sepsis.

Epidemiology of salmonellosis and its sensitivity in Karachi.

Over the past five years 25,000 blood cultures were screened for septicaemia. Of these 6.7% were positive for salmonella species, the commonest being salmonella typhi accounting for 92% of total salmonella isolates. Over the years, S. typhi showed a gradual decline ranging from 96.7 to 87%. While salmonella paratyphi A has shown a gradual increase ranging from 2.5% to 11.4%. Salmonellosis peaked in the year 1990 suggesting an epidemic. The antibiotic sensitivity pattern showed a gradual increase in resistance over the years and even resistance to the new quinolones has emerged. Thus salmonellosis poses a major threat to the community and we must look into the alternative antibiotics to combat the threat.

Significance, isolation, identification and sensitivity of Branhaemella (moraxella) catarrhalis.

In a study lasting over two years the frequency and sensitivity of moraxella catarrhalis causing respiratory tract infections were studied. Sputum samples from patients with lower respiratory tract infections were screened for moraxella catarrhalis. The organisms isolated identified and their sensitivity determined by simple methods which are practicable. The study shows that 22.4% of the infections were due to moraxella catarrhalis and 98% of the isolates were sensitive to amoxicillin-culvanalic acid (augmentin). The paper signifies the importance of reporting moraxella catarrhalis and its treatment.