Investigation of the negative chronotropic action of SK&F 86466 in the pithed normotensive rat

SK&F 86466, 6-chloro-3-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine, is a potent and selective antagonist of the α₂-adrenoceptor in vitro. This compound produced a small pressor response accompanied by a marked bradycardia when administered i.v. to the pithed normotensive rat. The pressor response was not affected by reserpine treatment, pretreatment with α- or β-adrenoceptor antagonists, atropine, or hexamethonium. The bradycardia was markedly reduced by bilateral vagotomy and pretreatment with atropine and attenuated by hexamethonium. The negative chronotropic action of SK&F 86466 was abolished by a combination of vagotomy and atropine. Mediation of the bradycardia by a baroreceptor reflex was ruled out by the observations that a lack of change in heart rate was associated with the vasopressor response to phenylephrine in the pithed rat pretreated with propranolol. It is concluded that the negative chronotropic action of SK&F 86466 in the pithed rat is mediated indirectly by activation of the cholinergic innervation of the heart.     

Importance of community size in practice location decisions of final year residents

Final year residents in training in Louisiana were surveyed regarding plans for medical practice and their perceptions of the importance of various factors in choosing practice locations. Most specialty groups selected smaller communities at similar rates. Growing up in small towns is associated with wanting to practice in small towns while concerns about opportunities for the family and income of the region are associated with wanting to practice in a larger city.This study was supported by the Louisiana Council for Statewide Planning for Physician Manpower through Contract No. 23058, Louisiana Department of Health and Human Resources.Ms. Samaha is a data analyst for the Louisiana Council for Statewide Planning for Physician Manpower; Robert R. Franklin, M.D. is Executive Secretary of the Council and Assistant Professor, Department of Biostatistics and Epidemiolgy, Tulane University School of Public Health and Tropical Medicine; Janet C. Rice is Assistant Pofessor, Department of Biostatistics and Epidemiology at the Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112.     

Genetic analysis of the affective disorders: summary of GAW5

Participants in the Affective Disorders component of Genetic Analysis Workshop 5 had access to five distributed data sets: 1) 187 families from the Collaborative Depression Study, 2) 202 families ascertained as part of the NIMH Family Studies on Affective Disorders, 3) a compilation of 46 pedigrees informative for X-linked markers, 4) HLA typing on 116 kindreds from the Toronto-Rochester Depression Study, and 5) 81 members of an Old Order Amish pedigree demonstrating linkage to markers on chromosome 11p. These databases are each summarized after a brief account is given of the genetics of the affective disorders and commonly used diagnoses. The emphasis of the Workshop was methodologic, with contributions divided evenly between linkage and nonlinkage applications. Contributions are summarized under four substantive areas: regressive logistic models, segregation and other familial analyses, methodologic considerations in linkage analysis, and the relationship between HLA and affective disorders.     

Attitudes of direct-care workers at a residential facility

A self-administered questionnaire was developed to examine two dimensions of staff attitudes: (a) the perceived importance of skills that direct-care workers who are asked to teach their clients, and (b) staff expectations that clients will show improvement in these areas. The relationship between importance/ expectancy ratings and self-reported teaching activity was studied in a sample of 32 direct-care workers at a residential facility for adults with developmental disabilities. In general, direct-care workers reported that they were most frequently engaged in escorting clients, watching and teaching clients during recreational activities, and dealing with client's emotional/behavioral outbursts. Improtance/expectancy ratings were correlated significantly with the education level of respondents, but not with self-reported teaching activity.     

Reduced blood clearance and increased urinary excretion of N-nitrosodimethylamine in patas monkeys exposed to ethanol or isopropyl alcohol.

Low concentrations of N-nitrosodimethylamine are metabolized in rodent and human liver by cytochrome P450IIE1, an activity competitively inhibitable by ethanol. In rodents coadministration of ethanol with N-nitrosodimethylamine results in increased tumorigenicity in extrahepatic organs, probably as a result of reduced hepatic clearance. To test this concept in a primate, the effects of ethanol cotreatment on the pharmacokinetics of N-nitrosodimethylamine were measured in male patas monkeys. Ethanol, 1.2 g/kg given p.o. before i.v. N-nitrosodimethylamine (1 mg/kg) or concurrently with an intragastric dose resulted in a 10-50-fold increase in the area under the blood concentration versus time curves and a 4-13-fold increase in mean residence times for N-nitrosodimethylamine. Isopropyl alcohol, 3.2 g/kg 24 h before N-nitrosodimethylamine, also increased these parameters 7-10-fold; this effect was associated with persistence of isopropyl alcohol and its metabolic product acetone, both IIE1 inhibitors, in the blood. While no N-nitrosodimethylamine was detected in expired air, trace amounts were found in urine. Ethanol and isopropyl alcohol pretreatment increased the maximum urinary N-nitrosodimethylamine concentration 15-50-fold and the percentage of the dose excreted in the urine by 100-800-fold. Thus ethanol and isopropyl alcohol greatly increase systemic exposure of extrahepatic organs to N-nitrosodimethylamine in a primate.     

Low Serum Retinol Is Associated with Increased Severity of Measles in New York City Children

Children with no known prior vitamin A deficiency exhibited a significant decline in their serum retinol levels during the acute phase of measles. This decline in circulating retinol was associated with increased duration of fever, higher hospitalization rates, and decreased antibody titers.