Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.      

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002

This prospective study was undertaken to investigate the possibility of a concurrent outbreak of leptospirosis and dengue and to describe the clinical illnesses. From 20 June to 14 November 2002, children who presented to our hospital with a suspected diagnosis of leptospirosis or dengue were admitted. In every child with suspected leptospirosis, a screening latex agglutination test was carried out to detect anti-Leptospira antibodies. The diagnosis of leptospirosis was confirmed by a positive enzyme-linked immunosorbent assay (ELISA) test or microagglutination test. The diagnosis of dengue was confirmed by a positive IgM antibody capture ELISA test. Clinical features in the leptospirosis and leptospirosis-negative groups, and dengue and dengue-negative groups were analysed. Of 90 children screened, 15 (16.7 per cent) had leptospirosis. Two children with Weil's disease died and the remaining 13 responded well to intravenous penicillin. Five clinical features were significantly associated with leptospirosis, namely conjunctival suffusion (p=0.007), haemorrhage (p=0.020), abdominal pain (p=0.011), hepatosplenomegaly (p=0.044), and oedema (p=0.007). As the number of these five features concomitantly present increased, the chances of the child having leptospirosis also increased significantly (p<0.0001). Of 90 children screened, 16 (17.8 per cent) had dengue. All responded well to the treatment and went home. Two clinical features were significantly associated with dengue, namely arthralgia (p=0.020) and thrombocytopenia (p=0.001). If both these features were present, the chances of the child having dengue increased significantly (p=0.001). Our study shows that a concurrent outbreak of leptospirosis and dengue had occurred in the slums of Mumbai city.     

Chronic beryllium disease: diagnosis, radiographic findings, and correlation with pulmonary function tests

Patients with suspected chronic beryllium disease underwent bronchoscopy and bronchoalveolar lavage. Their bronchoalveolar lymphocytes were incubated with beryllium salts, and quantitative lymphocyte transformation was measured. Seventeen patients with a positive lymphocyte proliferation test were evaluated radiographically with the International Labour Office classification. The most common radiographic abnormalities included diffuse small round and reticular opacities. Hilar adenopathy, linear scars, lung distortion, bullae, and pleural thickening were found less commonly. Specific radiographic findings were compared with pulmonary function abnormalities. The extent of radiographic profusion of small opacities and the presence of linear scars did not correlate with pulmonary function abnormalities. There was, however, a significant correlation between extensive pleural disease and reduced vital capacity in this small group of patients.     

Contribution to the study of the tributaries and the termination of the external jugular vein

Summary The dissection of 100 external jugular veins in 50 cadavers was the object of this anatomic study. A certain number of notions concerning the afferent veins, the mode of termination and the valvular system of this vessel were defined. 1)Afferent veins. Along its pathway toward the deep venous system, the external jugular vein successively received: the transverse cervical vein in 88 cases (88%), usually opposite the intersection of the external jugular vein with the dorsal border of the sterno- cleidomastoid muscle; the suprascapular vein in 47 cases (47%); the anterior jugular vein in 46 cases (46%); the cervical vein or anastomosis with the latter in 13 cases (13%). 2)Mode of termination. Forty-three subjects presented a symmetric mechanism. 100 anastomoses can be classed into three types: in 60 cases (60%), the external jugular vein flowed into the jugulo-subclavian venous confluence; in 36 cases (36%), in to the subclavian vein at a distance from its junction with the internal jugular vein; in 4 cases (4%) in to the trunk of the internal jugular vein. 3)Study of the valves. There were studied in 25 subjects (50 external jugular veins). The valves were found in the ostial and paraostial position in 49 out of 50 veins.

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Contribution à l'étude des afférences et de la terminaison de la veine jugulaire externe

Résumé Cette étude anatomique repose sur la dissection de 100 vv. jugulaires externes chez 50 cadavres. Elle a permis de préciser un certain nombre de notions concernant les veines afférentes, le mode de terminaison et le système valvulaire de ce vaisseau. 1)Veines afférentes. Le long de son trajet vers le sytème veineux profond, la v. jugulaire externe reçoit successivement: la v. cervicale transverse dans 88 cas (88 %), habituellement en regard du croisement de la v. jugulaire externe avec le bord dorsal du m. sterno-cléido-mastoïdien ; la v. supra-scapulaire dans 47 cas (47 %); la v. jugulaire antérieure dans 46 cas (46 %) ; la v. céphalique ou une anastomose avec celle-ci dans 13 cas (13 %). 2)Mode de terminaison. Quarante trois sujets présentent un dispositif symétrique. Les 100 abouchements peuvent être classés en trois types : dans 60 cas (60 %) la v. jugulaire externe se déverse dans le confluent veineux jugulo-subclavier ; dans 36 cas (36 %), dans la v. subclavière à distance de sa réunion avec la v. jugulaire interne ; dans 4 cas (4 %) dans le tronc de la v. jugulaire interne. 3)Etude des valvules. Recherchées chez 25 sujets (50 vv. jugulaires externes), les valvules ont été retrouvées dans 49 cas sur 50 en position ostiale ou paraostiale.

     

The infrapyloric artery and cephalic pancreatoduodenectomy with pylorus preservation: preliminary study

Summary Cephalic pancreatoduodenectomy (CPD) with pylorus preservation has been suggested to improve the functional and nutritional result of surgery. At operation, the first two centimeters of the duodenum are preserved, the vascular arch of the lesser gastric curvature is saved and the right gastroepiploic artery is resected at its origin. The aim of this study on 15 fresh cadavers was to determine the origin of the vascularization of the remaining duodenum and also the possibilities of preserving an optimal vascularization after CPD and pylorus preservation. All of the arteries supplying the remaining duodenum and arising either from the right gastric artery or the right gastroepiploic artery were identified. The distances between the origin of the infrapyloric artery and the termination of the gastroduodenal artery on the cranial and ventral pancreaticoduodenal artery and the left gastroepiploic artery were measured. At CPD with pylorus preservation, the study demonstrated that: 1) the cranial side of the remaining duodenum remains vascularized in 80% of the cases by one or two supraduodenal branches coming from the right gastric artery; 2) ligation of the right gastroepiploic artery eliminates all vascular supply to the caudal side of the remaining duodenum in almost half of the cases; 3) in these cases, the dissection of the bifurcation of the gastroduodenal artery and the vascular section beyond the origin of the infrapyloric artery allowed a direct vascular supply to the remaining duodenum to be preserved.This work was presented at the French Section of the European Association of Clinical Anatomy meeting, Bobigny, France, 1992