Severity of dependence and route of administration of heroin, cocaine and amphetamines

This study investigates severity of dependence upon heroin, cocaine and amphetamines in a group of 200 heroin users, 75% of whom were not in contact with any treatment agency. For drug takers who were current users of more than one drug, heroin produced more severe dependence than either cocaine or amphetamine and many users of these stimulant drugs reported having experienced no problems of dependence. Severity of dependence was influenced by route of administration as welt as type of drug. Heroin taken by injection was associated with more severe dependence than smoked heroin. For cocaine, injection and smoking were associated with equivalent dependence ratings, and both of these routes were associated with more severe dependence than cocaine used intranasally. For amphetamine, there were no differences in severity of dependence ratings for injection, intranasal or oral use. Severity of dependence was correlated with dose and duration of drug use; it was also associated with previous attendance at a drug treatment agency, though dependence problems were also common among heroin users who had never received treatment. Implications of these findings are discussed.     

Slowing of the Ventricular Rate During Atrial Fibrillation by Ablation of the Slow Pathway of AV Nodal Reentrant Tachycardia

Influence of Slow Pathway Ablation on Atrial Fibrillation. Introduction : The mechanisms whereby radiofrequency catheter modification of AV nodal conduction slows the ventricular response are not well defined. Whether a successful modification procedure can be achieved by ablating posterior inputs to the AV node or by partial ablation of the compact AV node is unclear. We hypothesized that ablation of the well-defined slow pathway in patients with AV nodal reentrant tachycardia would slow the ventricular response during atrial fibrillation.
Methods and Results : In 34 patients with dual AV physiology and inducible AV nodal reentrant tachycardia, atrial fibrillation was induced at baseline and immediately after successful slow pathway ablation and at 1-week follow-up. The minimal, maximal, and mean RR intervals during atrial fibrillation increased from 353 ± 76,500 ± 121, and 405 ± 91 msec to 429 ± 84 (P < 0.01), 673 ± 161 (P < 0.01), and 535 ± 98 msec (P < 0.01), respectively. These effects remained stable during follow-up at 1 week. The AV block cycle length increased from 343 ± 68 msec to 375 ± 60 msec (P < 0.05) immediately and to 400 ± 56 msec (P < 0.01) at 1-week follow-up. The effective refractory period of the AV node prolonged from 282 ± 83 msec to 312 ± 89 msec and to 318 ± 81 msec after 1 week (P < 0.05), respectively.
Conclusion : This study shows a decrease in ventricular response to pacing-induced atrial fibrillation after ablation of the slow pathway in patients with AV nodal reentrant tachycardia. Since the AV nodal conduction properties could be defined, this study supports the hypothesis that the main mechanism of AV nodal modification in chronic atrial fibrillation is caused by ablation of posterior inputs to the AV node.     

Variable expression of the murine natural resistance gene Lsh in different macrophage populations infected in vitro with Leishmania donovani

Various macrophage populations isolated from mice (including congenic C57BL/10ScSn and B10.LLshr) bearing resistant or susceptible alleles for the natural resistance gene (Lsh) were infected with Leishmania donovani amastigotes in vitro and examined (a) for their ability to support growth of the amastigote population over 7 days of culture in vitro, and (b) for their ability to express Lsh gene controlled resistance and susceptibility in vitro. Resident macrophages from liver (Kupffer cells), spleen and lung, as well as 7-day bone marrow-derived macrophages and bone marrow macrophages obtained after 6 weeks of continuous culture in vitro, all supported growth of the amastigote population. Of these, significant differences in amastigote numbers in macrophages from Lshs and Lshr mice were observed after 48 h of infection in vitro for liver, lung and 7-day bone marrow macrophage populations only. Resident peritoneal macrophages grown in adherent or suspension cultures neither supported growth of the amastigote population nor showed any evidence of Lsh gene expression in vitro. Hence, multiplication of the parasite appeared to be a necessary but not sufficient condition for observation of Lsh gene activity against L. donovani in vitro. Use of tritiated thymidine incorporation and autoradiography to label dividing amastigotes showed equivalent multiplication of the parasite in liver macrophages from Lshs and Lshr mice between 24 h and 48 h after infection in vitro, with a dramatic difference observed thereafter. This was consistent with earlier observations of a 2-3 day delay in expression of Lsh gene controlled resistance in vivo. Comparison with studies using Salmonella typhimurium and Mycobacterium bovis suggests that the gene may be restricted in its action to a particular point in the parasite cell cycle, perhaps at the level of regulating DNA replication.     

THE PROTECTIVE IMMUNE RESPONSE AGAINST VAGINAL CANDIDIASIS: LESSONS LEARNED FROM CLINICAL STUDIES AND ANIMAL MODELS

Recurrent vulvovaginal candidiasis (RVVC) is a significant problem in women of childbearing ages and is caused by Candida albicans, a commensal organism of the intestinal and reproductive tracts. As a result of this commensalism, most healthy individuals have demonstrable Candida -specific adaptive immunity that is considered protective. In women with RVVC, a deficiency/dysfunction of this protective immunity is postulated to affect susceptibility to infection. Although cell-mediated immunity (CMI) is considered important for protection against mucosal candidal infections, little is understood about specific host defenses that are important at the vaginal mucosa. Studies to date suggest that a compartmentalized local, rather than systemic, immunity is important for defense against vaginitis. This review will summarize the current state of knowledge regarding protective host defense mechanisms against vaginal C. albicans infections both from clinical studies and animal models. From these data, hypotheses are presented for what host defense mechanisms appear important for resistance/susceptibility to vaginal infection.     

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971