Congenital thrombophilia among patients with venous thromboembolism.

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.     

Pancreatic pseudocysts: treated with dual drainage.

Four patients with retrogastric pancreatic pseudocysts were successfully treated by the combined placement of a transgastric external drain and a cystogastric stent. We describe the advantages of using external transgastric drainage along with the cystogastric stent.     

Effect of peripheral administration of cinnarizine and verapamil on the abstinence syndrome in diazepam-dependent rats

The effects of two calcium channel blockers (verapamil and cinnarizine) were evaluated on diazepam withdrawal symptoms. Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg IP for 3 weeks. On abrupt termination of the drug, animals showed withdrawal hyperactivity that was assessed by autonomic, behavioural and motor signs. The peak effect was seen 3 days after the withdrawal of diazepam. On IP administration, verapamil and cinnarizine (10, 20 and 40 mg/kg) given on eight occasions at an interval of 12 h reversed the withdrawal-induced increase in spontaneous motor activity. Cinnarizine in higher doses (20 and 40 mg/kg) was found to be effective in suppressing the behavioural signs but verapamil did not show any protective effect against startle response and irritability. These results suggest that modulation of the calcium influx in the CNS might influence withdrawal.This study was presented in XIth International Congress of Pharmacology (IUPHAR) at Amsterdam (July 1–6, 1990)     

Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones.

As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).     

Community survey of primary dystonia in the city of Kolkata, India.

An epidemiological study on dystonia has not been reported from India. As part of a major study to find out the prevalence of major neurological disorders in the large urban city of Kolkata, Eastern India, we planned to determine the prevalence of primary dystonia. The study design was a cross-sectional study of a sample population obtained through stratified random selection and conducted in a two-stage procedure of screening by a nonprofessional team followed by confirmation of screened positive cases by the study neurologist. A total population of 52,377 was screened, and 29 subjects with dystonia were diagnosed. Out of them 23 subjects had primary dystonias [crude prevalence rate (CPR), 43.91/100,000; 95% confidence interval (CI), 28.41-64.81; age-standardized rates to world standard population, 49.06 (95% CI,31.74-72.41)] and all cases were focal type and predominantly of limb dystonia variety. Mean onset of dystonias were earlier in women (43.5 years) as compared to men (46.6 years). Thus our study on primary dystonia shows higher prevalence when compared with that of many studies globally, predominantly of focal type, earlier onset among women, and more cases of limb dystonias when compared with more prominent blepharospasm and cervical dystonias in western reports.     

Adverse perinatal factors in the causation of sensorineural hearing impairment in young children

The study involves aetiological evaluation of various adverse perinatal causes leading to bilateral sensorineural hearing impairment in children born during the 5-year period of 1981-1985 (inclusive) in the Greater Manchester area of England, United Kingdom. This group comprised over 12% of the total number of hearing-impaired children in the area. Individual possible adverse factors are discussed in the light of present understanding of the pathogenesis and previous reports.     

The effects of prior exposure to silicone on capsule formation, histology, and pressure

Investigations into the effects of prior silicone exposure on subsequent capsule formation around silicone implants assume particular relevance in light of the exponential increase in the medical application of polymers such as silicone. The inert nature of silicone has been in question with regard to its effects on the immune system, specifically whether or not it may act as a hapten or antigen. The present study analyzes the effects of prior silicone exposure on subsequent capsule formation, histological consistency, and pressures when an animal is reexposed to a silicone implant. Twelve female Lewis rats (body weight 250 g) were randomly divided into two groups. Group 1 (n = 6) rats were subcutaneously injected with 2.5 ml of Freund's Complete Adjuvant, Group 2 (n = 6) rats were injected with an equal volume of adjuvant sonicated with silicone gel. At 4 weeks a gel-filled silicone implant was placed subcutaneously in each animal. Capsule pressures were obtained at 4 months and the capsules from 3 rats from Group 2 were excised and examined microscopically. Pressures were measured again at 8 months and all remaining capsules were excised and examined. No statistically significant differences were noted when comparing two profiles over time between silicone-exposed and nonexposed animals in regard to capsule thickness or capsule pressure. However, capsule pressures were significantly lower at 8 months than at 4 months in both groups (p less than 0.034). In this model, significant reductions in capsule pressure were noted in both groups over time, but prior exposure to silicone did not appear to alter capsule histology, thickness, or pressure.