Treatment of essential tremor with the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid).

The effect of the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid; DMMDPB) on essential tremor, given in twice daily doses of 400 and 300 mg, was assessed in two brief, randomized, placebo-controlled, parallel-group, double-blinded, single-center trials in 12 and 22 patients, respectively. These trials represent the first clinical use of T2000 for a specific indication. The primary endpoint was the change in the mean scores of the treated and control groups based on the Fahn-Tolosa-Marin tremor scale. In the first study of 12 patients treated with 400 mg or placebo twice daily for 14 days, the mean change from baseline at day 14 was 19.3 (P < 0.0001) in the treated group and 9.0 (P = 0.0121) in the control group. Using a two-factor mixed ANOVA model to evaluate within group and between group changes, the effect of T2000 was significantly different from that of the placebo group (P = 0.03). In the second study of 22 patients treated with 300 mg of T2000 or placebo twice daily for 20 days, statistically significant changes were seen in treated patients compared to baseline, but the ANOVA model did not demonstrate a significant treatment effect of T2000 compared to placebo. When the treated groups from each study are compared, the 800-mg daily group is significantly different from the 600-mg daily group (P = 0.02). Some treated patients in each study, but no placebo patients, experienced marked improvement. These results support further evaluation of T2000 in the treatment of essential tremor.     

A cluster analysis for threshold perimetry

Cluster analysis in perimetry is a technique used in the evaluation of localised visual field loss. It has previously been applied to suprathreshold data and, unlike the indices currently available to indicate localised loss, it is influenced by the relative positions of individual defects. This paper describes a cluster analysis for use with data from Program 31 of the Octopus perimeter. To demonstrate the technique, sensitivity values of normal 60-year-old subject were altered to simulate localised loss. Illustrative examples of clinical cases are given, showing differing degrees of localised loss that do not influence the corrected loss variance (CLV) but influence the computed cluster parameters. It is hoped that the value of this form of analysis will be demonstrated in clinical follow-up of glaucoma patients.     

Longitudinal predictors of continued tobacco use among patients diagnosed with cancer

Even though continued smoking by cancer patients adversely affects survival and quality of life, about one third of patients who smoked prior to their diagnosis continue to smoke after their diagnosis. The implementation of smoking cessation treatments for cancer patients has been slowed by the lack of data on correlates of tobacco use in this population. Thus, this longitudinal study assessed demographic, medical, addiction, and psychological predictors of tobacco use among 74 head, neck, and lung cancer patients. Multivariable binary logistic regression analyses, with outcome categorized as smoker or nonsmoker, indicated that the likelihoodthat patients would be a smoker was associated with lower levels of perceived risk and a higher level of quitting cons. Multivariable nominal logistic regression, with outcome classified as continuous smoker, continuous quitter, relapser, or follow-up quitter, indicated that: (a) patients categorized as continuous smokers reported significantly lower quitting self-efficacy than follow-up quitters and continuous quitters, (b) relapsers reported a significantly lower level of quitting self-efficacy than either follow-up quitters or continuous quitters, and (c) continuous smokers exhibited a significantly lower level of risk perceptions than continuous abstainers. These findings can be useful for the development and evaluation of treatments to promote smoking cessation among cancer patients. Support for this study was provided by National Institutes of Health Grants CA57708, CA06927, CA88610, CA95678, and CA76644.     

Heightened vulnerability and increased risk-taking among adolescent chat room users: results from a statewide school survey.

PURPOSE: To profile adolescent Internet chat room users in terms of demographic characteristics, psychological and environmental factors, and behavioral risk factors. METHODS: The study sample was drawn from respondents to an anonymous statewide survey of 50,168 9th-grade public school students and included 40,376 students who reported Internet access at home and 19,511 who accessed chat rooms. Data were collected by the Minnesota Student Survey (MSS), a survey that has been administered triennially by the state's education department to public school students in grades 6, 9, and 12 since 1989. The MSS includes more than 117 questions (300 variables) addressing attitudinal, behavioral, and environmental issues. Data analysis consisted of comparing the odds of a particular characteristic or behavior for chat room users with that of nonusers. Analyses were run separately for boys and girls. The homogeneity of odd ratios was tested with the Breslow-Day statistic using SPSS for Windows. RESULTS: For boys and girls, use of Internet chat rooms was associated with psychological distress, a difficult living environment, and a higher likelihood of risky behaviors. Although most chat room users did not report serious problems, this group included a disproportionate number of troubled individuals. CONCLUSIONS: Because chat room use serves as an indicator of heightened vulnerability and risk-taking, parents and others need to be aware of potential dangers posed by online contact between strangers and youth.     

A recombinant bisphosphoglycerate mutase variant with acid phosphatase homology degrades 2,3-diphosphoglycerate.

To date no definite and undisputed treatment has been found for sickle cell anemia, which is characterized by polymerization of a deoxygenated hemoglobin mutant (HbS) giving rise to deformed erythrocytes and vasoocclusive complications. Since the erythrocyte glycerate 2,3-bisphosphate (2,3-DPG) has been shown to facilitate this polymerization, one therapeutic approach would be to decrease the intraerythrocytic level of 2,3-DPG by increasing the phosphatase activity of the bisphosphoglycerate mutase (BPGM; 3-phospho-D-glycerate 1,2-phosphomutase, EC 5.4.2.4). For this purpose, we have investigated the role of Gly-13, which is located in the active site sequence Arg9-His10-Gly11-Glu12-Gly13 in human BPGM. This sequence is similar to the Arg-His-Gly-Xaa-Arg* sequence of the distantly related acid phosphatases, which catalyze as BPGM similar phosphoryl transfers but to a greater extent. We hypothesized that the conserved Arg* residue in acid phosphatase sequences facilitates the phosphoryl transfer. Consequently, in human BPGM, we replaced by site-directed mutagenesis the corresponding amino acid residue Gly13 with an Arg or a Lys. In another experiment, we replaced Gly13 with Ser, the amino acid present at the corresponding position of the homologous yeast phosphoglycerate mutase (D-phosphoglycerate 2,3-phosphomutase, EC 5.4.2.1). Mutation of Gly13 to Ser did not modify the synthase activity, whereas the mutase and the phosphatase were 2-fold increased or decreased, respectively. However, replacing Gly13 with Arg enhanced phosphatase activity 28.6-fold, whereas synthase and mutase activities were 10-fold decreased. The presence of a Lys in position 13 gave rise to a smaller increase in phosphatase activity (6.5-fold) but an identical decrease in synthase and mutase activities. Taken together these results support the hypothesis that a positively charged amino acid residue in position 13, especially Arg, greatly activates the phosphoryl transfer to water. These results also provide elements for locating the conserved Arg* residue in the active site of acid phosphatases and facilitating the phosphoryl transfer. The implications for genetic therapy of sickle cell disease are discussed.