Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome is a rare autosomal dominant congenital disorder characterized by postnatal growth retardation, psychomotor developmental delay, skeletal anomalies, peculiar facial morphology, and tumorigenesis. Mutations in the gene encoding the cAMP response element-binding protein (CREB, also known as CREBBP or CBP) on chromosome 16p13.3 have been identified. In addition, some patients with low intelligence quotients and autistic features bear large deletions. Based on these observations, we used multiplex ligation-dependent probe amplification to search for large deletions affecting the CREBBP gene in a Rubinstein-Taybi syndrome patient. We identified a novel heterozygote deletion removing five exons (exons 17-21), encoding the histone acetyltransferase domain. We propose the use of multiplex ligation-dependent probe amplification as a fast, accurate and cheap test for detecting large deletions in the CREBBP gene in the sub-group of Rubinstein-Taybi syndrome patients with low intelligence quotients and autistic features.

Estradiol treatment and its interaction with the cholinergic system: effects on cognitive function in healthy young women.

The steroid hormone estradiol has been shown to modulate cognitive function in both animals and humans, and although the exact mechanisms associated with these effects are unknown, interactions with the cholinergic system have been proposed. We examined the neurocognitive effects of short-term estradiol treatment and its interaction with the cholinergic system using the muscarinic receptor antagonist scopolamine in healthy young women. Thirty-four participants (Mean age+/-SD=22.4+/-4.4) completed baseline cognitive assessment and then received either 100 microg/day transdermal estradiol or transdermal placebo for 31 days. On days 28 and 31 of treatment, further cognitive assessment was performed pre- and 90 min post-scopolamine (0.4 mg) or placebo (saline) injection, under a randomized double-blind placebo-controlled design. Short-term estradiol treatment significantly enhanced spatial working memory with a trend for improvement in long-term verbal learning and memory. Overall, estradiol treatment did not protect against or attenuate the scopolamine-induced impairments in the cognitive domains assessed. Findings suggest that estrogen has minimal effects on cholinergic-mediated cognitive processes following short-term treatment. Effects of estradiol treatment may be dependent on age, dose of estradiol, integrity of cholinergic innervation and baseline endogenous estrogen levels, which may in part explain the inconsistent findings in the literature.

Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders.

The gastrin-releasing peptide receptor (GRPR) was implicated for the first time in the pathogenesis of Autism spectrum disorders (ASD) by Ishikawa-Brush et al. [Ishikawa-Brush et al. (1997): Hum Mol Genet 6: 1241-1250]. Since this original observation, only one association study [Marui et al. (2004): Brain Dev 26: 5-7] has further investigated, though unsuccessfully, the involvement of the GRPR gene in ASD. With the aim of contributing further information to this topic we have sequenced the entire coding region and the intron/exon junctions of the GRPR gene in 149 Italian autistic patients. The results of this study led to the identification of four novel point mutations, two of which, that is, C6S and L181F, involve amino acid changes identified in two patients with ASD and Rett syndrome, respectively. Both the leucine at position 181 and the cysteine at position 6 are strongly conserved in vertebrates. C6S and L181F mutant proteins were expressed in COS-7 and BALB/3T3 cells, but they did not affect either GRP's binding affinity or its potency for stimulating phospholipase C-mediated production of inositol 1,4,5-trisphosphate. In summary, our results do not provide support for a major role of the GRPR gene in ASD in the population of patients we have studied. However, there is a potential role of C6S and L181F mutations on GRPR function, and possibly in the pathogenesis of the autistic disorders in the two patients.

Surgical treatment of morbid obesity with biliopancreatic diversion and gastric banding: report on an 8-year experience involving 235 cases.

STUDY AIM: Developments have recently been made in bariatric surgery outside the USA. The aim of this retrospective non-randomized study was to report on our experience regarding biliopancreatic diversion (BPD) and non-adjustable gastric banding (GB) in a population of 235 obese patients. PATIENTS AND METHODS: From March 1990 to March 1998, 235 obese patients were operated on, 142 by BDP and 93 by GB, via laparotomy after rigourous selection of the patient population. RESULTS: The mean duration of surgery was 2 h 50 minutes for BPD and 1 h for GB. One postoperative death occurred due to massive pulmonary embolism. Early major complications were frequent in the BPD group (n = 21) but rare in the GB group (n = 1). Mean duration of hospitalization was 16 days in the BPD group versus 9 days in the GB group. Mean percentage excess weight loss was 48% for the GB group and 60% for the BPD group after two years. Late mortality was limited to the BPD group (3.5%). Late complications were evenly distributed between the two groups, with a prevalence of malnutrition in the BPD group and outlet stenosis in the GB group. A high incidence of band removal was recorded related to this complication (17.2%). Incisional hernias were present in both groups. CONCLUSIONS: GB and BPD are techniques which can induce weight loss and bring about subsequent health benefits. Nevertheless, in a few patients further intervention or adaptation of the approach due to clinical failure or to a high complication rate is required. Additional research is needed regarding determination of the surgical treatment that is best adapted to the case in question, i.e., taking into consideration both the restrictive and malabsorbative aspects.

[Intestinal cystic pneumatosis and gastric banding. Etiopathogenic considerations on a clinical case]. / Pneumatosi cistica intestinale e "gastric banding". Considerazioni etiopatogenetiche su un caso clinico.

The authors describe a case of intestinal cystic pneumatosis in a patient submitted to gastric banding and then proceed with a critical review of the literature on the subject, examining the state of the art with regard to the pathogenetic hypotheses and the clinical manifestations of the disease and outlining the advantages of the instrumental investigations employed. On the basis of clinical considerations, an integrated pathogenetic hypothesis is advanced which takes account of the various indications expressed in the literature. In particular, recurrent vomiting is believed to bring about epithelial microlesions which, in the presence of severe respiratory impairment, the execution of endoscopic examinations and a mainly carbohydrate-based diet, are thought to cause onset of cystic pneumatosis.