The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia

The synaptosomal-associated protein of 25 kDa (SNAP-25) is an essential component of the core complex that mediates presynaptic vesicle trafficking. Thus, SNAP-25 is directly involved in the release of neurotransmitters. Quantitative alterations of SNAP-25 expression have been reported in brain regions and cerebrospinal fluid (CSF) of schizophrenics and in haloperidol treated rats. This observed altered expression may be influenced by genetic variants of SNAP-25. We hypothesized that polymorphisms of the SNAP-25 gene (sites DdeI, MnlI and TaiI in the 3'UTR) are associated with antipsychotic drug response and induced weight gain. A sample of 59 patients with prior suboptimal response to antipsychotic treatment and diagnosed with DSM-IV schizophrenia or schizoaffective disorder was examined. Patients were administered clozapine, haloperidol, olanzapine or risperidone for up to 14 weeks. Clinical response was defined as the difference between the baseline and the endpoint total scores on the Positive and Negative Syndrome Scale (PANSS). Weight was assessed at baseline and at study endpoint. ANOVA revealed that the MnlI and TaiI polymorphisms were associated with response (F[2,53] = 4.57, p = 0.01 and F[2,52] = 3.53, p = 0.03) and with weight gain (F[2,52] = 4.28, p = 0.01 and F[2,51] = 3.38, p = 0.04). When covariates were included, the MnlI polymorphism remained significantly associated with changes of PANSS scores, but not with weight gain. The DdeI polymorphism was not associated with response or weight gain. These findings suggest that SNAP-25 gene variants affect clinical response in patients with prior poor response to antipsychotics. Weight changes do not seem to be associated with polymorphism of the SNAP-25 gene, however, replication in independent samples is warranted.     

Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function

RATIONALE: Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. OBJECTIVES: Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene and early-life lung function. METHODS: Children were genotyped for 17 SNPs in ADAM33. Lung function at age 3 (n = 285) and 5 years (n = 470) was assessed using plethysmographic measurement of specific airway resistance (sRaw). At age 5, we also measured FEV(1). SNPs were analyzed individually using logistic regression, followed by linkage disequilibrium mapping to identify the causal locus. MAIN RESULTS: Carriers of the rare allele of F+1 SNP had reduced lung function at age 3 years (p = 0.003). When the recessive model was considered, four SNPs (F+1, S1, ST+5, V4) showed association with sRaw at age 5 years (p < 0.04). Using linkage disequilibrium mapping, we found evidence of a significant causal location between BC+1 and F1 SNPs, at the 5' end of the gene. Four SNPs were associated with lower FEV(1) (F+1, M+1, T1, and T2; p < or = 0.04). The risk of transient early wheezing more than doubled among children homozygous for the A allele of F+1 (odds ratio, 2.39; 95% confidence intervals, 1.18-4.86; p = 0.02), but there was no association between any SNP and allergic sensitization or physician-diagnosed asthma. CONCLUSIONS: Polymorphisms in ADAM33 predict impaired early-life lung function. The functionally relevant polymorphism is likely to be at the 5' end of the gene.     

Positron emission tomography in the investigation of pediatric inflammatory bowel disease

BACKGROUND: Endoscopic and radiologic studies are frequently required in inflammatory bowel disease (IBD) to determine disease activity, extent of disease, and delineating disease type. Positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose to identify metabolically active tissues may offer a simple noninvasive alternative to conventional studies in identification and localization of active intestinal inflammation in children with IBD. The aim of this study was to assess the value of PET in identifying active intestinal inflammation compared with conventional endoscopic and radiologic studies, including small bowel follow-through and colonoscopy. METHODS: Sixty-five children were enrolled in the study. This included 55 children (mean age, 13.3 yr; range, 7-18 yr; 20 girls) with newly diagnosed IBD (37) or symptoms suggestive of recurrent disease (18) and 10 children with recurrent abdominal pain (mean age, 12.7 yr; range, 8-15 yr; 7 girls) who were studied with PET, and the results were compared with small bowel follow-through with pneumocolon and/or colonoscopy. Thirty-eight patients had Crohn's disease (17 ileal, 12 ileocolic, 5 pancolonic, 3 left-sided disease, 1 right-sided disease), and 17 had ulcerative colitis (15 pan-colitis, 2 left-sided colitis). Mean time interval between PET and other studies was 30 +/- 17.6 days. RESULTS: PET correctly identified active inflammatory disease in 80% of children with IBD (81.5% with Crohn's disease; 76.4% with ulcerative colitis) and correctly showed no evidence of inflammation in children with recurrent abdominal pain. Gluorine-18-fluoro-deoxyglucose accumulated at sites that corresponded with active disease at colonoscopy in 83.8% of patients and with small bowel follow-through with pneumocolon 75.0% of the time. CONCLUSION: This study suggests that PET offers a noninvasive tool for identifying and localizing active intestinal inflammation in children with IBD. PET may not be able to replace conventional studies; however, it may be useful when conventional studies cannot be performed or fail to be completed.     

Hyperparathyroidism and pregnancy

Six pregnancies occurring in four mothers with hyperparathyroidism have been presented. Four of the pregnancies were completed without therapy; in two, parathyroidectomy was performed. The outcome of each of the pregnancies was satisfactory. The 49 cases previously reported are reviewed. This experience demonstrates that parathyroidectomy is indicated if the mother has symptomatic hypercalcemia, and it can be safely performed during the second trimester. Pregnant women with mild, asymptomatic hypercalcemia may be followed nonoperatively during pregnancy with satisfactory outcome to both the mother and fetus.     

Benign hepatic lesions in women taking oral contraceptives

Four previously unreported cases of benign hepatic cell lesions in young women taking oral contraceptives are described. A brief review of the literature is presented with emphasis on the clinical symptoms, the findings on angiography and radionuclide scan, and the relation of the lesions to oral contraceptives.     

Acute acromioclavicular joint dislocation: results of operative treatment with the Bosworth screw.

The results are reported in 21 patients who had acute acromioclavicular joint dislocation treated by open reduction and Bosworth screw fixation, with an average follow-up period of ten years. Nineteen patients had a good or excellent functional result. Good cosmetic results were obtained. Full recovery of shoulder movement occurred in all patients but one, although coracoclavicular calcification was a frequent finding. Complications following this technique were few.     

Pharmacokinetics of topically applied radiolabeled retinoids in hairless mouse epidermis and dermis after single applications

The retention of tritium-labeled all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester in the epidermis and dermis of hairless mice was measured up to 24 h following a single topical application in an acetone vehicle. The radioactivity in the tissues was extractable with chloroform:methanol, and the identities of the radioactive species extracted were confirmed as retinoids using thin-layer chromatography. All the retinoids were absorbed into the skin rapidly. After an initial period of distribution and penetration (lasting for about 1 h) the amount of the applied retinoid remaining in the epidermis and dermis decreased more slowly, obeying first order (exponential) decay kinetics. Both the arotinoid and the aromatic retinoid persisted for longer in the epidermis than equivalent doses of RA or 13-cis-RA. The half-lives of the retinoids in the dermis tended to be longer than in the epidermis, except for the arotinoid. Aromatic retinoid persisted for longest in the dermis with a half-life of 11 h.