Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double-blind controlled multicentre study in Singapore

Roxatidine acetate, a new H₂ receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.     

Smoking topography, brand switching, and nicotine delivery: results from an in vivo study.

OBJECTIVE: Exposure to toxins in tobacco smoke is influenced by how a cigarette is smoked. Cigarettes have been designed to allow for a range of puffing behavior and to provide different, nonlinear tar and nicotine yields in response to different puffing profiles. However, puffing behavior and its influence upon risk-exposure has yet to be assessed outside the laboratory, in smokers' natural environment. METHOD: Fifty-nine adult smokers used a portable device to measure smoking topography over the course of three 1-week trials. Participants were asked to smoke their usual "regular yield" brand through the device for trial 1 and again, 6 weeks later, at trial 2. Half the subjects were then randomly assigned to switch to a "low-yield" brand for trial 3. RESULTS: The findings show a high degree of stability in puffing behavior within the same subject over time but considerable variability between smokers. Smokers who were switched to a "low-yield" cigarette increased their total smoke intake per cigarette by 40% (P = 0.007), with no significant change in their salivary cotinine levels. Cigarettes smoked per day and nicotine yield were only weakly associated with salivary cotinine levels; however, salivary cotinine was strongly associated with a composite measure that included cigarettes per day, brand elasticity, and puffing behavior (sr = 0.61, P < 0.001). CONCLUSIONS: These findings provide strong evidence of behavioral compensation to low-yield cigarettes from in vivo measures of smoking behavior. The findings also show the importance of brand elasticity and smoking topography in predicting nicotine uptake and smoke exposure.     

SEPT9_v4 expression induces morphological change, increased motility and disturbed polarity

Several lines of evidence indicate that altered expression of SEPT9 is seen in human neoplasia. In particular there is evidence of altered expression of the SEPT9_v4 isoform. The functional consequences of this remain unclear. We have studied the expression of wild-type- and GTP-binding mutants (G144V and S148N) of the SEPT9_v4 isoform in the MCF7 cell line as a model for its deregulation in neoplasia. We find that SEPT9_v4 expression induces dramatic actin cytoskeletal reorganization with the formation of processes around the cell periphery. Expression of the SEPT9_v4 isoform and a G144V mutant cause delocalization of endogenous SEPT9 from filamentous structures but the S148N mutant does not have this effect. In addition SEPT9_v4 isoform expression enhances cell motility and is associated with perturbation of directional movement. Expression of SEPT9_v4 GTP binding mutants also has potent effects on morphology and motility and causes loss of normal polarity, as judged by Golgi reorientation assays. The phenotypes induced by expression of the SEPT9_v4 isoform and the GTP mutants provide an insight into possible mechanisms of SEPT9_v4 function and suggest that the GTPase functions have both ras- and rab-like features. We propose a model in which overexpression of the SEPT9_v4 isoform in neoplasia is associated with perturbation of SEPT9 complexes, leading to phenotypes associated with neoplasia.     

Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease

The tremor rat is a spontaneous epilepsy model with a seizure phenotype caused by a deletion in the aspartoacylase (ASPA) gene. The absence of ASPA expression in these animals results in undetectable levels of enzyme activity and the accumulation of the substrate N-acetyl-aspartate (NAA) in brain, leading to generalized myelin vacuolation and severe motor and cognitive impairment. In support of human gene therapy for CD, recombinant adeno-associated viral vector (AAV-2) expressing ASPA was stereotactically delivered to the tremor rat brain and effects on the mutant phenotype were measured. AAV-ASPA gene transfer resulted in elevated aspartoacylase bioactivity compared to untreated mutant animals and elicited a significant decrease in the pathologically elevated whole-brain NAA levels. Assessment of motor function via quantitative rotorod testing demonstrated that rats injected with AAV-ASPA significantly improved on tests of balance and coordinated locomotion compared to animals receiving control vectors. This study provides evidence that AAV-2-mediated aspartoacylase gene transfer to the brain improves biochemical and behavioral deficits in tremor rat mutants (tm/tm) and supports the rationale of human gene transfer for Canavan disease.     

Pulmonary arteriovenous malformations in children: outcomes of transcatheter embolotherapy

OBJECTIVE: To describe outcomes of transcatheter embolotherapy (TCE) in children with pulmonary arteriovenous malformations (PAVMs). STUDY DESIGN: Chart and imaging review of all children (age 相似文献