Foothold of NPHS2 mutations in primary nephrotic syndrome.

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. We searched Medline and Pubmed using the combination of keywords "NPHS2", "podocin", "steroid-resistant nephrotic syndrome," and "genetics" to identify studies describing an association between NPHS2 gene and renal disease. The highly dynamic foot processes contain an actin-based contractile apparatus comparable to that of smooth muscle cells. Mutations affecting several podocyte proteins lead to rearrangement of the cytoskeleton, disruption of the filtration barrier, and subsequent renal disease. The fact that the dynamic regulation of the podocyte cytoskeleton is vital to kidney function has led to podocytes emerging as an excellent model system for studying actin cytoskeleton dynamics in a physiological context. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. Recent studies have led to a considerable increase in our understanding of podocyte biology including composition and arrangement of the cytoskeleton involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of an acquired glomerular disease. In hereditary nephrotic syndromes identified over the last few years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

Normal oesophageal manometric values in healthy adult volunteers.

AIMS: To study the oesophageal pressures in normal Pakistani subjects using oesophageal manometry and compare the results from the studies done abroad. SETTING: Ziauddin Medical University Hospital, North Nazimabad Karachi. SUBJECTS: Twenty-five healthy subjects were studied. RESULTS: Of 25 subjects 19 were males and 6 females. Their ages ranged from 14 to 67 years with a mean age of 41+16 years. The mean resting pressure of the lower oesophageal sphincter was 13.43+/-7.1 mm Hg and relaxation was 96+/-4.1%, with a residual pressure of 0.74+/-1.2 mm Hg. Peristaltic amplitude of the oesophageal body was highest at the lower end of the oesophagus both for dry and wet swallows, the values being 56.23+/-7.9 mm Hg and 74.28+/-35.8 mm Hg respectively. Distal oesophageal peristaltic amplitude was 54.18+/-18.6 and 70.91+/-24.3 mm Hg for dry and wet swallows respectively. Duration of the peristalsis was lowest at the upper end of the oesophagus both for dry and wet swallows being 3.48+/-0.88 and 3.5+/-1.3 seconds respectively. Highest duration of peristaltic amplitude was noted at the lower end of the oesophagus, i.e. 4.43 seconds both for dry and wet swallows. The speed of progression of the peristaltic waves at the proximal end was 2.64+/-1.3 cms / sec and at the distal end 3.37+/-1.6 cms / sec. Mean resting pressure of the upper oesophageal sphincter was 49.84+/-22.4 mm Hg. Residual pressure was 5.2 +/-9.3 mm Hg. CONCLUSION: The results of this study are in accordance with the results reported from abroad.

Aetiology and prognostic factors of patients admitted for stroke.

OBJECTIVE: To see the etiology and prognostic factors related to mortality of patients with stroke. METHODS: Retrospective analysis of patients admitted with stroke in two hospitals of same locality over 8 years. RESULTS: Of the 12,454 cases admitted in medical units of hospital 796 (6.4%) had stroke. Majority of cases were between 4th and 6th decades of life. Fifty percent (304/606) were hypertensive, 19% (113/606) had cardiac disease and 18% (112/606) diabetes mellitus. Four percent (27/606) had previous history of stroke and 17% (102/606) were smokers. Of the 144 cases who had CT Scan 99 (69%) had infarct and 45 (31%) haemorrhage; overall mortality was 30% (288/971) and it was significantly high in cases over 60 years of age, cases with history of unconciousness at the onset and those with severe hypertension. Mortality rate in the community hospital was significantly higher (33%) as compared to private hospital (13%) (p 0.001). CONCLUSION: Cardiac disease is one of the precipitating factors of stroke with infarct being the major cause. Mortality increased with the advancement of age.

Oesophageal carcinoma in Karachi.

Between January, 1979 to August, 1990, 107 histologically proven cases of oesophageal carcinoma were seen. The ages of the patients ranged from 19-85 years (mean 55 +/- 14 years) with a male to female ratio of 1.2:1. Majority (70%) of the cases belonged to lower socioeconomic group and 56% were migrants from India. History of tobacco chewing or smoking was present in 78% cases. In 54%, the lesion was located in the middle third of the oesophagus, followed by lower third in 44%. Histology showed squamous cell carcinoma in 86% and adenocarcinoma in 10% cases. Of the 19 cases followed, 16 underwent surgery and 3 received chemotherapy. Two cases died within 7 months following surgery and in 6 carcinomas recurred. All cases receiving chemotherapy died within 8 months of treatment.

Misoprostol in the treatment of NSAID-induced gastroduodenal lesions.

The cytoprotective effect of misoprostol co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) was assessed in a double blind, placebo controlled study. Thirty-seven patients with rheumatoid arthritis receiving NSAIDs, having upper gastrointestinal symptoms and endoscopically confirmed gastric and/or duodenal lesions, were randomised to receive either misoprostol 200 micrograms or placebo tablets twice daily for 4 weeks. Of 31 evaluable cases, 13 of 16 (81%) patients receiving misoprostol showed endoscopic improvement as compared to 10 of 15 (67%) receiving placebo (P:NS). A significant decrease in mean (+/- SEM) mucosal lesion score was observed with misoprostol (from 3.38 +/- 0.32 to 1.32 +/- 0.44; P less than 0.001) but no change was seen with placebo (from 2.80 +/- 0.42 to 1.60 +/- 0.53; P:NS). Symptomatic relief was similar in both groups, being 44% and 40% respectively. Two patients complained of diarrhea in each group and one developed menorrhagia with misoprostol. It is concluded that though misoprostol decreased the number of NSAID-induced mucosal lesions, it was unable to relieve gastrointestinal symptoms.

A double-blind study of misoprostol (SC-29333) in the healing of duodenal ulcer.

In a double-blind randomized placebo controlled trial, 50 patients with endoscopically confirmed duodenal ulcer were treated with either misoprostol 200 micrograms or placebo in q.i.d. doses for 4-8 weeks. Of 25 patients in the placebo group, four defaulted and two were withdrawn due to worsening of symptoms. Of 25 misoprostol-treated cases, 17 cases (68%) and 21 cases (84%) healed at 4 and 8 weeks respectively, compared with three (14%) and five (24%) of the 21 placebo-treated cases (P less than 0.001). Except for diarrhoea in 2 patients in each group and itching in one with misoprostol, no serious side effects were noted.

Site of duodenal ulcer and its influence on the mode of presentation and prognosis.

Two hundred and forty-five endoscopically proven or surgically treated duodenal ulcers were retrospectively evaluated to see if the site of ulcer has any influence on the clinical presentation, and healing and relapse rates. Anterior wall ulcer was present in 42%, posterior wall in 33%, lesser curve side of the cap in 12% and greater curve side in 13% cases. Ulcer site showed no correlation to age, sex, duration of illness, analgesic intake or smoking habits. Bleeding (116 cases) and perforation (15 cases) were the major complications encountered; of these perforation was invariably found on the anterior wall, while bleeding was more frequent in ulcers present on the lesser curve side of the cap. Better healing and high relapse rates were seen in ulcers situated on the greater curve, and low healing and relapse rates in lesser curve duodenal ulcers.

Presence of vibrios in surface water and their relation with cholera in a community.

During an epidemic of cholera we simultaneously cultured water from 30 important ponds, tanks and rivers of Dhaka city, to determine the role of surface water as a reservoir of Vibrio cholerae and nonagglutinating (NAG) vibrios and whether their presence or absence can be used as an indicator of a cholera epidemic in the community. Out of 4.016 samples 1216 (30.3%) were positive for NAG vibrios and one (0.025%) for Vibrio cholerae. Ponds showed a higher rate of NAG isolation (31.6%) than did rivers (21.9%). NAG group II constituted 87% and group V 10% of all positives. There were mild-to-moderate seasonal variations in isolation rates. The NAG isolation rate from water was related to the incidence of hospitalized NAG diarrhoea cases, but not to simultaneous cholera cases. Surface water does not appear to be an efficient natural reservoir of Vibrio cholerae, as it is for NAG vibrios. The absence of V. cholerae or presence of NAG vibrios in public surface water sources has no relationship with the extent of cholera cases present in a community.

Changes in the trend of shigellosis in Dhaka: family study on secondary infection, clinical manifestation and sensitivity pattern: 1980.

The incidence of shigellosis and the death rate have increased and the resistance of shigellae to antibiotics has changed in Dhaka during our experiences. In 1980, we investigated the secondary infection and case rates, infection to case ratio, duration of illness, excretion of shigellae and antibiotic sensitivity pattern in 100 families with cases of shigellosis, culturing rectal swabs obtained by home visits for a 10-day period. Standard methods were used for culture and sensitivity tests. The over-all secondary infection rate in contacts was 27.3% and the case rate 10.7%. The rates were higher for Shigella flexneri than for Sh. dysenteriae. When the index cases were nought to four years old the secondary infection and case rates were higher than when index cases were older. Contacts aged nought to four years had highest attack rates. The average duration of excretion of Sh. flexneri was 4.5 and Sh. dysenteriae 2.6 days. Illness was one day longer for Sh. dysenteriae than for Sh. flexneri. Cases of shigellosis in hospital had higher rates of fever and blood in stool than those who were not in-patients. 40% of Sh. dysenteriae and 14% of Sh. flexneri were sensitive to tetracycline, 0 to 5% to streptomycin and 100% to sulphamethoxazole, trimethoprim and gentamicin. Incidence of Sh. flexneri had increased in 1980 but that of Sh. dysenteriae remained the same as in 1973 although Sh. dysenteriae type 1 appeared to be less infective in 1980 than in 1973.

The eltor cholera epidemic in Dhaka in 1974 and 1975.

Surveillance of hospitalized cholera cases from 1970 to 1977 in Dhaka, a matched control study in 1974, and a neighbourhood control study in 1975 were carried out and show a change from classical cholera to the eltor biotype during this period. Of all the hospitalized cholera cases, 9.1% in 1972 and 99.9% in 1973 were due to the eltor biotype. In 1974 and 1975 the distribution of eltor cholera cases in the city was uniform, except for areas with modern sanitation whose residents were spared. The incidence rates of cholera per 1000 infants (under the age of 1 year) were 1.16 and 0.93 for 1974 and 1975, respectively. On the whole, children below 10 years and females between 15 and 44 years of age were the ones most affected with eltor cholera. Higher rates of diarrhoea and hospitalization were noted among the contacts with cholera cases, compared with non-cholera controls. Contracting cholera was significantly associated with eating in places away from home, especially at charitable feeding centres.