Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl=1.077 ± 0.15 versus ANT:POS StD=0.477 ± 0.11, P<0.03) and was confirmed with radio-labeled microspheres measurements (ANT:POS Cntl=1.18 ± 0.2 ml/min/g versus ANT:POS StD=0.44 ± 0.1 ml/min/g; P<0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P<0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P=NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl=0.964 ± 0.02 versus StD=0.884 ± 0.03; P<0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.     

Day 4 is better than day 3 for a single patch test reading

Readings were performed on day (D)2, D3 and D4 after application of patch tests in NN patients. 90 patch lest reactions in 49 patients were interpreted as allergic und of past or present relevance. A single D2 reading detected 58 of the allergic reactions, with 32 false-negatives and 23 false-positives. A single D3 reading detected 77 allergic reactions, with 13 false-negatives and 17 False-positives. A single D4 reading detected 85 allergic reactions, with 5 false-negatives und 4 false-positives. Therefore, if only a single reading is feasible, it is better performed on D4 than on D3.     

Human dolasetron pharmacokinetics: II Absorption and disposition following single-dose oral administration to normal male subjects

Dolasetron is a 5-hydroxytryptamine antagonist active at type III receptors; it is presently undergoing clinical evaluation for the reduction/prevention of cancer chemotherapyinduced nausea and vomiting. A previous study demonstrated that following intravenous administration to healthy male subjects, dolasetron disappeared extremely rapidly from plasma, and less than 1 per cent of the dose appeared in the urine. A major plasma metabolite, reduced dolasetron, peaked rapidly in the plasma. In this study, dolasetron was administered orally to healthy male subjects at doses ranging from 50 to 400 mg (mesylate monohydrate). Plasma concentrations of dolasetron were low and sporadic, and there was little excreted in urine; this prevented dolasetron pharmacokinetic analysis. Reduced metabolite concentrations peaked rapidly, with a median value of 1.00 h. The median terminal disposition half-life was 7.80 h. Median values for fraction of dose excreted in urine and renal clearance were 22.2 per cent and 2.56 ml min^?1 kg^?1. Whereas areas under the plasma concentration—time curves were proportional to dose, renal clearance increased with dose (p < 0.05). However, given dose proportionality to AUC, this is probably of little therapeutic consequence. Since reduced dolasetron has significant anti-emetic activity in the ferret model, it appears that this metabolite may play a significant role in pharmacodynamic activity.     

Maintenance chlorambucil after CVP in the management of advanced stage, low-grade histologic type non-Hodgkin's lymphoma. A randomized prospective study with an assessment of prognostic factors

One hundred sixty-two patients with Stages III and IV non-Hodgkin's lymphoma of low-grade histologic type were treated with combination chemotherapy using cyclophosphamide, vincristine, and prednisolone (CVP) followed by radiotherapy to sites of previous bulk disease. The patients were randomized to receive either follow-up alone or "maintenance" chemotherapy with 2 years of intermittent chlorambucil. A complete remission was obtained in 56% of patients and the median survival was 64 months (median follow-up, 74 months). Multivariate analysis revealed stage (P less than 0.0001) and Karnofsky performance status (P = 0.021) to predict complete response (CR) and the achievement of a CR (P less than 0.0001), female sex (P = 0.008), the absence of bulk disease (P = 0.038) and low serum alkaline phosphatase (P = 0.002) to predict prolonged survival. The median relapse-free survival (RFS) of the complete responders was 41 months. A prolonged RFS was predicted by low stage (P = 0.014), low serum lactic dehydrogenase (LDH) (P = 0.045) levels, and by the administration of maintenance chlorambucil (P = 0.045). A prolonged survival of the complete responders was predicted by a low number of nodal sites of involvement with lymphoma at presentation (P = 0.022) and lack of liver involvement (P = 0.011). The administration of oral maintenance therapy with chlorambucil for a full 2 years was only possible in 38% of patients, mainly because of progression of disease and the induction of thrombocytopaenia, but despite this it prolonged the median RFS by 38 months and its use could be considered when future studies are being designed.     

Distribution of cerebral blood flow during deep isoflurane vs. pentobarbital anesthesia in rats with middle cerebral artery occlusion

While previous studies have identified a protective effect for barbiturate anesthesia during focal cerebral ischemia, no such effect has been demonstrated for isoflurane. To better understand the effects of these anesthetics on cerebral blood flow and metabolism that might have relevance to their respective potential for cerebral protection, fasted physiologically stable rats underwent autoradiographic determination of CBF and CMRglu during deep isoflurane or pentobarbital anesthesia (burst suppression of EEG). As expected, cerebral blood flow was significantly greater during isoflurane anesthesia (isoflurane = 157 +/- 18 and pentobarbital = 54 +/- 12 ml/100 g/min) while CMRglu values were nearly identical (isoflurane = 35 +/- 5 and pentobarbital = 33 +/- 4 mumol/100 g/min). Additional identically anesthetized rats underwent middle cerebral artery occlusion with CBF autoradiographically determined 1 h later. While the insult resulted in a significant reduction in the ipsilateral hemispheric and cortical blood flow in both anesthetic groups, flow remained at least twofold greater in isoflurane as opposed to pentobarbital-anesthetized rats. When regional flow was assessed, no difference between groups was observed with respect to the area of tissue with flow values falling between 0-10 ml/100 g/min. In contrast, isoflurane-anesthetized rats had significantly less hemispheric and cortical area with flow values in the ranges of 10-20 and 20-30 ml/100 g/min, respectively. These data, therefore, do not support the contention that isoflurane causes maldistribution of CBF during focal ischemia.     

Dietary and weight control practices among persons with hypertension: findings from the 1986 Behavioral Risk Factor Surveys

The National Heart, Lung, and Blood Institute has concluded that reducing sodium intake, controlling weight, and moderating alcohol consumption can help patients with hypertension control their blood pressure. To determine whether such patients have adopted recommended dietary practices, we analyzed data collected in 1986 from telephone surveys of adults in 26 states (no. = 34,395). The self-reported dietary practices that we evaluated were: use of table salt, alcohol consumption, and weight control practices. In comparison with persons who did not have hypertension (no. = 26,848), those with hypertension who were receiving pharmacological therapy ("treated hypertensives," no. = 5,025) were more likely to report limiting their use of table salt (odds ratio [OR] = 2.5) and were less likely to have their weight controlled (OR = 0.4). Although overweight persons with hypertension were more likely than persons with normal blood pressure to attempt to lose weight, most have not included exercise in their weight loss efforts. There was no difference between persons who do not have hypertension and treated patients with hypertension in their use of alcohol. Untreated persons with hypertension (no. = 2,378) were less likely to limit their use of table salt and less likely to moderate their use of alcohol than treated persons with hypertension but otherwise reported similar dietary practices. Dietetic practitioners may need to emphasize moderation of alcohol use and the use of physical activity to lose weight when counseling patients with hypertension.     

Health promotion data for state health departments: telephone versus in-person survey estimates of smoking and alcohol use

Abstract During 1988, more than 40 state health departments conducted telephone surveys to obtain state-specific population estimates of the prevalence of adult health behaviors and health practices. However, the comparability of estimates obtained from these telephone surveys with more expensive in-person surveys has not been assessed in an applied setting. This study compared the prevalence estimates of smoking and binge drinking obtained from a telephone survey (N = 1,492) with an in-person survey (N = 2,802) which were conducted by the state of Michigan during 1982-1983. Although the standard errors for the differences in the estimates for the two surveys were relatively large, the actual differences were consistently small within most age-, sex-, and education-specific groups. Despite certain limitations, telephone surveys provide a reasonable alternative to in-person surveys for estimating the prevalence of health behaviors. The data obtained from these surveys are being used to set state health objectives, to plan state-wide health promotion programs, and to support public health legislation.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.