Novel mutations in the calreticulin gene core promoter and coding sequence in schizoaffective disorder.

We have recently reported the first case of mutation in the core promoter sequence of the human calreticulin gene in a family case of schizoaffective disorder. Remarkably, this gene coincides with a region of suggested linkage at 19p13.2, identified in a whole genome scan [Hamshere et al. (2005); Arch Gen Psychiatry 62;1081-1088]. The identified mutation was located at the conserved position -48 from the transcription start site, and was shown to be of functional effect, resulting in the aberrant expression of the gene. Following screening of the gene in 60 independent cases of schizoaffective disorder, we report novel germ-line mutations at positions -205 C > T and the conserved exon 5 (c: 682 C > T, pro228ser) in two unrelated cases of schizoaffective disorder. These mutations were disease-specific, and as for the -48 G > C mutation, neither was detected in a control population of 370 individuals, indicating a contribution of 3.17% in this sample series. To our knowledge, this is the first instance of disease-specific mutations in schizoaffective disorder, which warrants systematic screening of the regulatory and coding regions of the calreticulin gene in this disorder.

The diagnosis of autism and Asperger syndrome: findings from a survey of 770 families.

As part of a wider survey of parents of children with autistic spectrum disorders in the UK, the diagnostic experiences of 614 parents of children with autism and 156 with Asperger syndrome were compared. Although the ages of the children in the two groups were very similar at the time of the survey, parents of children given a diagnosis of Asperger syndrome had experienced significantly longer delays and greater frustration in obtaining a diagnosis than those with a child with autism. In the 'autism group' the average age when diagnosis was confirmed was around 5.5 years; in the 'Asperger group' it was 11 years. Parents of children with a diagnosis of autism were generally aware of problems in their child's development by 18 months of age; in the Asperger group concerns emerged later, at around 30 months of age. Initial worries in both groups centred around abnormal social development but parents of children with Asperger syndrome were less likely to have noted communication problems. Stereotyped or repetitive behaviours were not prominent in the early years in either group. Despite the problems inherent in data collected by postal survey, many of the findings of this study are supported by other research. The practical implications of delayed diagnosis, especially in the case of more able children with Asperger syndrome are discussed.

Intravenous ondansetron for postsurgical opioid-induced nausea and vomiting. S3A-255 Study Group.

The use of opioids for postoperative analgesia may be limited by side effects such as nausea and vomiting. Because ondansetron, a selective serotonin type 3 (5-hydroxytryptamine [5-HT3]) antagonist, is effective for chemotherapy and general anesthesia-induced nausea and vomiting, we hypothesized that it may also be effective for opioid-induced nausea and vomiting. ASA physical status I-III patients undergoing regional anesthesia were eligible for the study. Those who requested an antiemetic after postsurgical opioid administration were randomized to receive a single dose of ondansetron (0.1 mg, 4 mg, or 16 mg intravenously [I.V.]) or placebo in a double-blind fashion. Emetic episodes, nausea and pain ratings, and adverse events were recorded for 24 h after study drug administration. Patient satisfaction scores were obtained 24 h after study drug infusion. A significantly (P < 0.05) larger proportion of patients treated with ondansetron 4 mg and 16 mg experienced no emetic episodes, received no rescue antiemetic, and completed the study compared with placebo. Nausea scores and patient satisfaction scores in the ondansetron 16-mg group were significantly (P < 0.05) more favorable than in the placebo group. Postsurgical pain scores did not differ among groups. The incidence of adverse events was similarly low across groups. The results of this study support our hypothesis that I.V. ondansetron is effective for postsurgical opioid-induced nausea and vomiting.