Coercion in the community: issues for mature treatment systems

Coercion in community-based mental health treatment refers to much more than just court-ordered treatment. Mature systems can address these issues and adopt clinical approaches that decreased the need for coercion.     

Mutation of the alpha 2 domain disulfide bridge of the class I molecule HLA-A*0201. Effect on maturation and peptide presentation

This report documents the introduction of standard-setting in the haemato-oncological reverse-isolation unit of the Kanton hospital, Basle. The topic is the prevention or reduction of nausea, choking and vomiting, and the treatment of patients who are receiving prolonged chemotherapy. The objective was quality assurance in nursing care. The definition of the desired outcome was the well-being and safety of patients. In addition the wish of the staff to increase their security in dealing with antiemetics was taken into consideration. The authors describe the basic problems they encountered in their strategies and actions for standard setting. By extensive use of measurement and evaluation it was possible, in cooperation with medical leadership, to develop instructional leaflets and checklists. Approximation to the intended outcome was achieved. The well being of patients and satisfaction of the safety-needs of staff and patients reached a high level. The report shows that the introduction of nursing standards requires great effort and a high level of commitment of the entire team. It also shows that the effort is worthwhile for patients and staff.     

Mutagenesis of cardiac troponin I. Role of the unique NH2-terminal peptide in myofilament activation

Phosphorylation of Ser residues in the NH2-terminal extension unique to cardiac troponin I (cTnI) is known to occur through protein kinase A and to alter myofilament Ca2+ activation (Robertson, S. P., Johnson, J. D., Holroyde, M. J., Kranias, E. G., Potter, J. D., and Solaro, R. J. (1982) J. Biol. Chem. 257, 260-263). Yet, how the NH2-terminal extension may itself affect thin filament Ca2+ signaling is unknown. To approach this question we have used molecular cloning, mutagenesis, and bacterial synthesis of a full-length cTnI and a truncated mutant (cTnI/NH2) missing the 32 amino acids. Using reconstituted preparations we could show no differences between cTnI and cTnI/NH2 either in inhibition of actomyosin ATPase activity, in Ca(2+)-reversible inhibitory activity, or in the relation between pCa and Ca2+ binding to the regulatory site of cTnC at either pH 7.0 or 6.5. There were also no significant differences at either pH in the pCa-MgATPase activity relation of myofibrils into which the various species of TnI has been exchanged. Our results indicate: 1) that phosphorylation most likely induces a new state of TnI activity rather than altering an intrinsic effect of the NH2-terminal peptide on Ca2+ activation; and 2) that domains outside the NH2-terminal extension are important with regard to differences in effects of acidic pH on Ca2+ activation on cardiac and skeletal myofilaments.     

The Pristionchus pacificus mab-5 gene is involved in the regulation of ventral epidermal cell fates

One system that can be used to study the evolution of gene function is the nematode vulva. In Caenorhabditis elegans, the vulva is formed from three of the six multipotent precursors P(3-8).p. Comparison of vulval development between C. elegans and Pristionchus pacificus has revealed that, during evolution, there have been changes in the specification of cell fate for certain vulval cells. For example, the cell P8.p is a vulval precursor cell (VPC) in C. elegans, but is incompetent to adopt vulval fate in P. pacificus We have fate specification and have isolated P. pacificus mutants with a second vulva-like structure in the posterior region resulting from the ectopic differentiation of P8.p Genetic and molecular analysis indicated that point mutations in the Hox-cluster gene mab-5 of P. pacificus cause this multivulval phenotype. Further cell ablation studies revealed that the differentiation of P8.p is independent of gonadal signaling. In C. elegans, mab-5 also acts in P8.p specification, but mab-5 mutant animals do not develop differs between species, indicating that alterations in the intrinsic properties of P8.p and corresponding changes in the functional specificity of mab-5 have occurred during evolution.     

Frequency and timing of coital orgasm in women desirous of becoming pregnant

Thirty-seven Vibrio cholerae and four non-cholera Vibrio isolates from Ukraine, including strains from the epidemic of 1994-5, were analysed by molecular methods. Results from PFGE and ribotyping indicated that all Ukrainian toxigenic V. cholerae were closely related to each other and to an isolate from a patient from Pakistan. A non-toxigenic river water strain obtained during the height of the epidemic was more distantly related to these V. cholerae strains, while the Vibrio parahaemolyticus isolates and Vibrio alginolyticus isolate were not closely related to V. cholerae or each other. ERIC- and REP-PCR allowed the differentiation of strains identical by other methods. The results obtained confirm that the epidemic Ukrainian strains are most closely related to seventh pandemic strains from Asia and support a hypothesis that the Ukrainian epidemic of 1994-5 was caused by toxigenic environmental strains surviving since the time of the 1991 Ukrainian epidemic or before.     

Right ventricular arrhythmia in the absence of arrhythmogenic dysplasia: MR imaging of myocardial abnormalities

PURPOSE: To evaluate right ventricular abnormalities with magnetic resonance (MR) imaging in patients with arrhythmia but without arrhythmogenic dysplasia. MATERIALS AND METHODS: In 53 patients being evaluated for right ventricular arrhythmia and 15 control subjects, MR imaging was performed to evaluate fixed thinning, fatty replacement, or reduced systolic wall thickening or motion. A diagnosis of idiopathic right ventricular outflow tract tachycardia or indeterminate was assigned for each patient, and the severity of arrhythmia was categorized. RESULTS: Right ventricular abnormalities were revealed in 32 (60%) of the 53 patients: fixed thinning in 27 (84%), fatty replacement in eight (25%), and reduced wall thickening or motion in 31 (97%). Right ventricular abnormalities were found in 35 (76%) of 46 patients with idiopathic right ventricular outflow tract tachycardia and in seven (39%) of 18 patients with indeterminate diagnoses (P = .022). CONCLUSION: Mild right ventricular abnormalities are likely sources for arrhythmias, even in the absence of arrhythmogenic right ventricular dysplasia.     

Predominance of slow acetylators of N-acetyltransferase in a Hmong population residing in the United States

Pharmacogenetics can be an important determinant of pharmacologic response. To learn more about interpopulation differences in drug metabolism between ethnically diverse populations of subjects cared for by an International Clinic, a study was conducted to describe the prevalence of fast or slow acetylators of N-acetyltransferase (NAT2) in a population of Hmong residing in Minnesota. Ninety-eight healthy Hmong refugees from Laos volunteered to take caffeine as an oral probe drug to establish acetylator phenotype. Participants were classified as either rapid or slow acetylators based on the urinary molar ratio of select metabolites of caffeine. Assignment of phenotype was based on results from analysis of urine collected subsequent to ingestion of caffeine. The ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) to the combined products of the 7-demethylation pathway of paraxanthine (AFMU, 1-methylxanthine (1X), and 1-methylurate (1U)] formed the basis for this determination. A probit plot of the data collected in our subjects qualified a metabolic ratio of 0.34 as an acceptable cut point for phenotype assignment. Participants with an AFMU/(AFMU + 1X + 1U) ratio of < 0.34 were classified as slow acetylators and all others as rapid acetylators. Analysis of the data suggested a bimodal distribution with an excess (74.5%) of slow acetylators in the population. The predominance of slow acetylators found in the Hmong contrast with the prevalence of slow acetylators seen in other ethnic groups. These findings may have important clinical implications given the large number of Hmong treated each year in our International Clinic and the increasing use of medications metabolized by NAT2 in this population.     

ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo

A series of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have Ki's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.