Efficacy and acceptability of dexfenfluramine in women consulting in gynecology. 336 overweight patients treated for 3 months]

The efficacy on bodyweight and the acceptability of a three month treatment with dexfenfluramine (Isoméride), combined with a prescribed diet, were evaluated in 336 women followed by a gynecologist for overweight. These women were divided into three groups, those in the sexually active age group (80%) and perimenopausal and post-menopausal women (20%) and had the following characteristics: mean bodyweight 80.2 +/- 0.6 kg; excess bodyweight 35.0 +/- 0.5% of theoretical ideal weight, mean bodyweight index = 30.6 +/- 0.2 kg/m2. Simultaneously with the weight loss, a study of the change in gynecological symptoms was carried out at each consultation and for each group. Investigation of the bodyweight showed that 80% of the patient who followed the treatment for three months lost weight, the mean loss being 7.2 kg or 41.9% of the initial excess weight. Simultaneously with this loss of weight, there was an improvement in the gynecological symptoms in all three groups. These symptoms included those seen in the premenstrual phase (sexually active age group) and menopause-related symptoms in the perimenopausal and post menopausal groups. The acceptability and safety of Isomeride were also confirmed in this study.     

Loss of heterozygosity for distal markers on 22q in human gliomas.

Loss of constitutional heterozygosity as determined through the analysis of restriction-fragment-length polymorphism (RFLP) on tumoral and constitutional DNA has proven to be helpful to delimit the location of tumor-suppressor genes in the human genome. In malignant gliomas this approach indicates that chromosomes 9p, 10, 17p, and 22 may contain genes of this category involved in its origin and/or progression. Regarding chromosome 22, the data so far provided by molecular studies confirmed those previously reported by cytogenetic studies, suggesting the existence of a sub-group of malignant gliomas characterized by monosomy of this chromosome. However, the precise location of the putative glioma suppressor gene on chromosome 22 remains ambiguous. We have performed a combined cytogenetic and RFLP study on a series of 31 gliomas, looking for structural abnormalities of this chromosome. In 3 instances, terminal deletions of the long arm of chromosome 22 were observed by both methodologies, suggesting that the band q13 region distal to the D22S80 marker might be the critical domain non-randomly involved in tumor suppression of gliomas.     

Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity.

We compared and contrasted the mechanism of action for the cysteine knot protein subfamily, Wise and Sost (Sclerostin). Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway. INTRODUCTION: The human disease sclerosteosis exhibits an increase in bone mass thought to be caused by hyperactive osteoblasts. Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist. However, recent evidence indicates that SOST is highly related to Wise, which can also modulate the Wnt pathway by binding to LRP5 and LRP6. MATERIALS AND METHODS: For this study, we used cell culture to test the BMP and Wnt activity function of both Wise and Sost. In addition, we used Xenopus in vivo Wnt assays along with Xenopus in vitro Wnt assays to support our cell culture results. Epitope tagged cell supernatants containing either Sost or soluble mutant or wildtype LRP5/LRP6 were used for immunoprecipitation. Sost immunoprecipitation results were confirmed in vivo using cell culture. Finally, to support our in vitro data, we co-localized Sost, Wise, LRP5, and LRP6 in mouse long bone sections. Results: In this study, we report in vitro and in vivo evidence to show that Sost physically interacts with Lrp5 and Lrp6 and inhibits the canonical Wnt signaling pathway. Furthermore, using in vitro and in vivo assays, we showed that a variant of LRP5 (LRP5(G171V)) known to cause the human high bone mass (HBM) trait and a homologous change in LRP6 (LRP6(G158V)) abolished protein interactions with Sost. We used variants of Sost amino acids to further identify the contact points between Sost and LRP6. In Xenopus and mammalian cell culture assays, we showed that SOST is able to attenuate Wnt signaling and that this attenuation can be rescued by the addition of alpha-Sost antibodies or by the introduction of single amino acid substitution that alter its binding to LRP6. Sost differs from Wise in that it is unable to stimulate Wnt signaling. Using immunohistochemistry, we found that Sost and Wise are co-localized to osteoblasts, along with LRP5 and LRP6. CONCLUSIONS: Our data suggest that functional interactions between Sost or Wise and LRPs have the potential to regulate bone deposition by modulating Wnt signaling.     

Syringomyelia and Arnold Chiari in scoliosis initially classified as idiopathic: Experience with 25 patients

The authors analysed the clinical and radiological findings and the surgical management of 25 patients admitted for scoliosis classified as idiopathic at first presentation, but in fact associated with spinal cord and/or brain stem anomalies. Twenty patients had syringomyelia, 19 had Chiari malformation. Scoliosis was the only presenting symptom when all these patients were referred to the orthopaedic surgeon. On examination, five patients had normal neurological findings, while the others showed very mild neurological deficits. The diagnosis of syringomyelia and Chiari malformation was established by MRI, which is the best form of neuroradiological examination for discovering spinal abnormalities. Neurosurgical treatment is strongly recommended as the first step in the management of “pseudo” idiopathic scoliosis.     

Case Report: Giant choledochal cyst

We report an adult female with a rare giant choledochal cyst. The patient presented following a normal pregnancy with the classical triad of an abdominal mass associated with jaundice and right upper quadrant abdominal pain. The cyst was excised using an intramural technique and biliary reconstruction achieved with a Roux-en-Y hepaticojejunostomy. Our patient has remained well with no evidence of malignancy over a 12 year review period. The aetiology and current management of this condition are discussed.