Does the addition of a prokinetic to proton pump inhibitor therapy help reduce duodenogastro-oesophageal reflux in patients with Barrett's oesophagus?

OBJECTIVE: The metaplastic change of Barrett's oesophagus is linked to both acid and duodenal reflux together with impaired motility. Proton pump inhibitors (PPI) reduce acid reflux, but no treatment is available that reduces duodenogastro-oesophageal reflux (DGOR). The aim of this study was to investigate whether adding a prokinetic to PPI treatment could improve oesophageal motility and subsequently reduce reflux. METHODS: Two groups of patients with Barrett's oesophagus on PPI therapy (prokinetic, n = 12; placebo, n = 11) were investigated. At visit 1, ambulatory oesophageal manometry was performed, and peristaltic and simultaneous wave percentage and characteristics were measured. DGOR and pH measurements were also performed. After treatment with either the prokinetic cisapride or placebo, all investigations were repeated (visit 2). Analysis of covariance and Spearman's correlation coefficients of changes from visit 1 to visit 2 were used to compare data. RESULTS: There was no significant difference between the two groups with respect to DGOR, DGOR characteristics, or the percentage of peristalsis and simultaneous waves and their characteristics. There was no correlation between DGOR and motility changes. Although no significant differences existed between acid reflux in the two groups, five patients with high supine acid reflux showed a significant reduction after treatment with cisapride. CONCLUSIONS: Addition of cisapride to PPI treatment does not appear to improve oesophageal motility or reduce DGOR in patients with Barrett's oesophagus.     

Effects of ethnicity on treatment attendance,stimulant response/dose,and 14-month outcome in ADHD

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder--a randomized clinical trial of 579 children ages 7-9 years receiving 14 months of medication management, behavioral treatment, combination, or community care--the authors matched each African American and Latino participant with randomly selected Caucasian participants of same sex, treatment group, and site. Although Caucasian children were significantly less symptomatic than African American and Latino children on some ratings, response to treatment did not differ significantly by ethnicity after controlling for public assistance. Ethnic minority families cooperated with and benefited significantly from combination (multimodal) treatment (d = 0.36, compared with medication). This incremental gain withstood statistical control for mother's education, single-parent status, and public assistance. Treatment for lower socioeconomic status minority children, especially if comorbid, should combine medication and behavioral treatment.     

Child mental health in Latin America: present and future epidemiologic research

OBJECTIVE: This report reviews population studies of child and adolescent mental health carried out in Latin America over the past 15 years. Also considered is the issue of how to meet the needs of children and adolescents who may present mental health problems in Latin America, given that most of them live in poverty in economies that are underdeveloped, providing limited resources. METHOD: Ten studies from six different countries were identified that employed some form of randomized sampling method and used standardized instruments for assessment. The authors present a summary of the main characteristics of these studies, highlighting methodological features that may account for differences in the rates obtained. RESULTS: Overall, a similar pattern of prevalence and risk factors for mental health problems in children and adolescents in Latin American countries emerged. Moreover, rates of disorders in these children are similar to the 15 to 20% found in other countries. These findings are similar to those observed when adult mental health problems are considered. Prevention and treatment strategies are discussed and the peculiarities of the delivery of mental health services for children and adolescents are explored. CONCLUSIONS: Future research needs to focus on understanding of resilience and formal and informal mental health delivery systems of care available in different Latin American countries. Such research has high potential for ameliorating the prevention and treatment of child and adolescent mental health problems in this region of the world.     

The HOXA1 A218G polymorphism and autism: lack of association in white and black patients from the South Carolina Autism Project

A recent study has suggested that the A218G polymorphism in the homeobox Al (HOXA1) gene may influence susceptibility to autism. We have determined the frequencies of the A and G alleles of the HOXA1 A218G polymorphism in both white and black patients from the South Carolina Autism Project (SCAP) and controls. Marked differences were found in allele frequencies between the races, but no deviations from Hardy-Weinberg equilibrium were seen in either white or black SCAP family members. More direct tests, comparing genotype frequencies between probands and controls and tracking transmission of the A versus G alleles to affected offspring, did not support the contention that allele status for the HOXA1 A218G polymorphism influences one's susceptibility to autism.     

Intraindividual variation in recent stress exposure as a moderator of cortisol and testosterone levels

Intraindividual variation in recent stress exposure and its impact upon cortisol and testosterone was investigated. Over 1 year, 72 young male firefighters completed the Daily Stress Inventories, for 2 shift cycles (16 days), every 3 months. At the end of each 16-day period each participant attended a 1-hr morning assessment session. Saliva samples and blood pressure measurements were taken at 10-min intervals, and at 30 min, a blood sample was drawn. Across the year of assessment, there were significant linear relationships in reported stress and in neuroendocrine activity. In contrast to expectations, as daily stress decreased across the year (p < .008), salivary cortisol increased (p < .001) and testosterone levels decreased (p < .001). Within-subjects comparisons of the sessions with the highest and lowest stress confirmed these linear relationships: Lower stress prior to the assessment session was associated with higher cortisol levels (p < .01). These results, though in contrast to the orthodoxy concerning the association between stress and cortisol, are supported by findings in a number of other studies and may constitute down regulation of cortisol activity following an increment in stress exposure. This research was supported by the Medical Research Council, United Kingdom. We are grateful to the London Fire & Civil Defence Authority for their cooperation.     

Construction of modern Australian first trimester ultrasound dating and growth charts

Accurate pregnancy dating is vital to obstetric management. However, first trimester fetal charts commonly used in Australia rely on data reported more than three decades ago. This study reports first trimester dating and growth charts for crown‐rump length between 5 and 14 weeks of gestation and biparietal diameter between 9 and 14 weeks of gestation on an Australia population using modern real‐time ultrasound equipment. All consenting eligible women attending a large Sydney clinic for first trimester ultrasound between March 2005 and December 2006 were recruited. Measurements were carried out to Australasian Society for Ultrasound in Medicine standard protocols. Statistical analyses were undertaken using polynomial regression models and thorough diagnostic checks made. Overall 396 eligible women consented to the study, with 268 between 9 and 14 weeks of gestation. The average participant age was 34 years (range 22–45 years), 371 and all yielded valid biometry measurements. Equations, means and 90% reference intervals for crown‐rump length measurements and biparietal diameter measurements were derived using polynomial regression models. Thorough residual and diagnostic checks were made. Once validated by others, we believe they will warrant consideration for use by Australasian Society for Ultrasound in Medicine.     

Biphenylsulfonamide endothelin receptor antagonists. 4. Discovery of N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]- 2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), a highly potent and orally active ET(A) selective antagonist

We have previously disclosed the selective ET(A) receptor antagonist N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (1, BMS-193884) as a clinical development candidate. Additional SAR studies at the 2'-position of 1 led to the identification of several analogues with improved binding affinity as well as selectivity for the ET(A) receptor. Following the discovery that a 3-amino-isoxazole group displays significantly improved metabolic stability in comparison to its 5-regioisomer, the 3-amino-isoxazole group was combined with the optimal 2'-substituent leading to 16a (BMS-207940). Compound 16a is an extremely potent (ET(A) K(i) = 10 pM) and selective (80,000-fold for ET(A) vs ET(B)) antagonist. It is also 150-fold more potent and >6-fold more selective than 1. The bioavailability of 16a was 100% in rats and the systemic clearance and volume of distribution are higher than that of 1. In rats, intravenous 16a blocks big ET pressor responses with 30-fold greater potency than 1. After oral dosing at 3 micromol/kg, 16a displays enhanced duration relative to 1.     

Inhibition of alveolar bone loss by matrix metalloproteinase inhibitors in experimental periodontal disease

Periodontal disease is characterized by excessive host collagenase resulting in loss of gingival and periodontal ligament collagen and adjacent alveolar bone. Intragingival endotoxin injection induces a model of periodontal disease characterized by rapid bone loss with biochemical features similar to that of naturally occurring adult periodontitis. CH1766, a peptide with a zinc binding moeity which fits into the active site of the enzyme, and CH6631, a hydroxamic acid derivative with aryl-substituted sulphonamide residues, are inhibitors of matrix metalloproteinases (MMPIs) with differing inhibitory profiles as characterized by in vitro assays. In this study, endotoxin was injected into the gingivae of rats which were then treated orally with either 3 mg/kg or 30 mg/kg of one of the two inhibitory compounds. The gingival tissues were assessed for collagenase and gelatinase activity, plus three different pro-inflammatory cytokines. In addition, alveolar bone height in defleshed jaws was studied by computerized morphometric analysis and scanning electron microscopy. Both drugs reduced active and/or total MMP activity, in many cases to normal, and also partially normalized cytokine levels as well. A dose-response effect was seen with regard to amelioration of lipopolysaccharide-induced alveolar bone loss with both drugs. Other than studies with tetracyclines, this is the first report of beneficial effects of MMPIs in a model of periodontal disease, strongly suggesting that this class of agents could bring therapeutic benefit to patients with this disorder, and that periodontal disease can be used as a model to demonstrate in vivo efficacy of this class of drugs.