Experiments with calculated therapeutic and toxic doses of digitalis: III. Effects on the coronary blood flow

Calculated therapeutic doses of digitalis did not produce a significant change in the coronary blood flow of the dog. This confirms the results of Essex, Herrick, Baldes, and Mann.²⁸Calculated toxic doses of digitalis decreased the coronary blood flow of dogs four to six hours after the drug had been administered. The diminution of flow persisted for several days after a single toxic dose of the drug.No myocardial lesions were observed after a therapeutic dose of digitalis, nor were they observed in one animal which received a toxic dose of digitalis. In the latter animal the coronary blood flow returned to the preinjection level within two days.Myocardial lesions were observed in one animal in which the coronary blood flow was kept well below the control level for twelve days by repeated injections of digitalis (toxic range).The diminution of coronary blood flow after the injection of toxic doses of digitalis could not be correlated consistently with changes in the pulse rate or systemic blood pressure.After the injection of toxic doses of digitalis the coronary blood flow returned to the control level in several experiments, and the animals recovered completely.     

Immunosuppression without liver induction by subchronic exposure to 2,7-dichlorodibenzo-p-dioxin in adult female B6C3F1 mice

The overall objective of this investigation was to begin to characterize the structure-activity relationship associated with dioxin-induced suppression of humoral immunity. Subchronic exposure (14 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototype of the class, produced a suppression of the antibody responses to both sheep erythrocytes, a T-dependent antigen, and dinitrophenyl-Ficoll, a T-independent antigen. Surprisingly, similar results were observed with 2,7-dichlorodibenzo-p-dioxin (DCDD), a dioxin congener lacking affinity for the Ah receptor. In contrast, subchronic exposure to octachlorodibenzo-p-dioxin (OCDD), another dioxin congener without affinity for the Ah receptor, was devoid of activity. Subchronic exposure to 2,3,7,8-TCDD, but not 2,7-DCDD, produced an induction of several liver parameters including: liver weight, amount of microsomal protein, amount of cytochrome P-450, activity of aminopyrine-N-demethylase and activity of aryl hydrocarbon hydroxylase. Subchronic exposure to 2,3,7,8-TCDD or 2,7-DCDD produced no marked changes in thymus weight. Acute exposure to 2,3,7,8-TCDD also produced suppression of the antibody response in the absence of effects on the thymus.     

Two novel loci,COBL and SLC10A2, for Alzheimer's disease in African Americans

Introduction

African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.

Effects of Aerosol-Vapor JP-8 Jet Fuel on the Functional Observational Battery,and Learning and Memory in the Rat

To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.     

An Ethnography of Chronic Pain in Veteran Enlisted Women

Enlisted women are an essential subpopulation within the United States (U.S.) Armed Services, yet little is known about their chronic pain experiences. The purpose of this study was to describe veteran enlisted women's chronic pain experiences, both while on active duty and since active duty ended. A total of 15 enlisted women were interviewed. This ethnographic approach produced stories of their beliefs, attitudes, and behaviors regarding their chronic pain and the care they have received both while serving and after discharge or retirement. The findings show that U.S. military culture and training have a major impact on enlisted women's chronic pain experiences. Enlisted women learn to ignore or deny acute pain because it would hamper their ability to complete their military mission. Even when they admit to themselves that they are in pain, they may mask the pain from others for fear of being called weak or fear of discrimination and ostracism. When the pain can no longer be ignored and they seek health care, they are frustrated when their pain reports are not believed by supervisors and health care providers. Chronic pain eventually leads to discharge or retirement when they can no longer do their job. Health care providers must understand both U.S. military culture and enlisted women's strategies concerning pain if they are to accurately diagnose and sufficiently treat enlisted women in pain.     

Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes

We evaluated the possibility that diacylglycerol may function as a second messenger in insulin action. To this end, we employed 12-O-tetradecanoyl phorbol 13-acetate (TPA) to mimic diacylglycerol in BC3H-1 myocytes. Like insulin, TPA provoked rapid increases in 2-deoxyglucose transport and pyruvate dehydrogenase activity in mature insulin-responsive BC3H-1 cultured myocytes. TPA also stimulated amino acid uptake, as evidenced by uptake of alpha-methylaminoisobutyric acid; the relatively slow time course of this effect paralleled that of insulin. In contrast, the effects of TPA were not apparent in undifferentiated BC3H-1 myoblasts, which were also unresponsive to insulin. The insulin-like effects in the myocytes appeared to be specific for TPA, the biologically active phorbol diester which activates protein kinase C, as other tested phorbol derivatives were without effect. Effects of maximally effective concentrations of TPA and insulin were nonadditive. Two synthetic diacylglycerols, 1,2-diolien and 1-oleoyl-2-acetyl-sn-glycerol, also provoked insulin-like effects on 2-deoxyglucose transport. Since insulin rapidly increases diacylglycerol levels in these cells, and TPA mimics diacylglycerol biochemically, it is possible that insulin may control cellular processes through changes in diacylglycerol.     

Antibiotic therapy for treatment in relapse of intestinal Crohn's disease

We have undertaken a prospective randomized trial of one month's antimicrobial therapy for patients with symptomatic relapse of Crohn's disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18=M, 16=C 21=C plus M, 17=P). After two weeks, improvement was reported as follows: M=67 percent, C=17 percent, C plus M=71 percent, P=35 percent. In the metronidazole group, two patients required surgery and one had trouble-some side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M=44 percent, C=62 percent, C plus M=57 percent, P=41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohn's disease.     

Immunotyping of Chlamydia trachomatis with monoclonal antibodies

Rapid and precise immunotyping of Chlamydia trachomatis was achieved by testing whole organisms (elementary bodies) in the microimmunofluorescence test with monoclonal antibodies. Monoclonal antibodies were produced with standard techniques by using an immunization schedule that encouraged the development of immunotype-specific antibodies. Fifteen monotypic or multitypic (subspecies) monoclonal antibodies were chosen for use in a two-step typing system that required strains of C. trachomatis to be tested against six to eight monoclonal antibodies for classification. Immunotyping with monoclonal antibodies was studied by testing 313 strains, typed with the previous method that utilized immunized mouse antisera, that represented each of the 15 established serovars. The two-step monoclonal antibody method resulted in a classification similar to the current one. Only one strain typed differently with the two methods. With the monoclonal antibody method, available lymphogranuloma venereum (LGV) serovars L1 and L3 could not be differentiated from trachoma serovars E and G, respectively, unless the strains had been identified as LGV. Monoclonal antibody typing was simpler to perform and more precise; it allowed easy differentiation between closely related serovars. Three new types were discovered among the strains previously classified as serovars D, I, and L2. These are tentatively being considered subtypes and are labeled D', I', and L2'.