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Two candidate genes (NAIP and SMN) have recently been reported for childhood onset spinal muscular atrophy (SMA). Although affected subjects show deletions of these genes, these deletions can lead to either a very mild or a severe phenotype. We have analysed a large number of clinically well defined patients, carriers, and normal controls to assess the frequency and extent of deletions encompassing both of these genes. A genotype analysis indicates that more extensive deletions are seen in the severe form of SMA than in the milder forms. In addition, 1 center dot 9% of phenotypically normal carriers are deleted for the NAIP gene; no carriers were deleted for the SMN gene. Our data suggest that deletions in both of these genes, using the currently available assays, are associated with both a severe and very mild phenotype.

Autosomal recessive childhood onset spinal muscular atrophy has been mapped to chromosome 5q13. We report the analysis of a polymorphic microsatellite which shows linkage disequilibrium with the disease. The linkage disequilibrium is observed with a null allele which is seen as the non-inheritance of alleles from one or both parents. The inheritance of a null allele was observed in 26 out of 36 (72%) informative childhood onset spinal muscular atrophy (SMA) families tested, of all types of severity and from a variety of ethnic backgrounds. In seven families segregating for the severe Werdnig-Hoffmann or SMA type I, no alleles were inherited from either parent using this microsatellite. This null allele may represent a deletion which is either closely associated with, or causes, the disease.

To assess the efficacy of absolute alcohol as a sclerosant, endoscopic sclerotherapy was carried out using a conventional endoscope and an indigenously designed injector. Forty three patients with portal hypertension who had presented with history of variceal bleeding were included in the study. Portal hypertension was caused by cirrhosis in 30 (69.8%), non-cirrhotic portal fibrosis in eight (18.6%) and extra-hepatic obstruction in five (11.8%). Acute bleeding was successfully controlled in all 11 patients, seven with a fresh bleed and four who rebled while on endoscopic sclerotherapy regimen. All patients with fresh, recent, or old bleeding were treated with a weekly endoscopic sclerotherapy schedule. Reduction in variceal size of two or more grades was achieved in all 20 patients who had completed at least four endoscopic sclerotherapy courses with total eradication of varices in 16 (80%). The mean (+/- SD) number of endoscopic sclerotherapy courses and time required for variceal eradication was 6.06 (+/- 1.87) and 9.1 (+/- 4.69) weeks respectively. None of these patients has shown appearance of fresh varices in a follow up of 18.47 +/- 8.50 weeks (range six to 38 weeks). Six patients died; all deaths were caused by progressive hepatic encephalopathy. Complications usually seen were dysphagia, retrosternal pain and fever; these were mild and easily tolerated by the patients. Rebleeding occurred in four patients who had received less than four endoscopic sclerotherapy courses. Absolute alcohol appears to be an effective, safe, economical, and freely available sclerosant. advocate endoscopic sclerotherapy as the first line of treatment for acute variceal bleeding and recommend a weekly schedule for the early eradication of varices.

Fifty four consecutive patients with oesophageal variceal bleeding were randomised to undergo intravariceal (28 patients) or paravariceal (26 patients) sclerotherapy, every three weeks. Intravariceal technique was found significantly (p less than 0.01) more effective in controlling active variceal bleeding than the paravariceal technique (91% v 18.7% respectively). The mean (+/- SD) time taken for variceal eradication by intravariceal sclerotherapy (15.4 +/- 5.3 weeks) was significantly (p less than 0.001) less than paravariceal (26.8 +/- 6.6 weeks) technique. The number of sclerotherapy sessions needed with intravariceal technique were also significantly less. Rebleeding was seen in 38.5% patients after para and 14.3% after intravariceal injections (NS). Except for retrosternal pain, which occurred more often (p less than 0.01) with paravariceal technique, there was no difference in the incidence of other complications or mortality between the two groups. Variceal recurrence was seen in seven patients (25%) in the intra and one (3.9%) patient in the paravariceal group (p less than 0.01) after a mean follow up of 29.4 +/- 9.1 weeks. Intravariceal sclerotherapy was superior to paravariceal in the control of active variceal bleeding and for total variceal obliteration, but was associated with a higher variceal recurrence.