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OBJECTIVES. This work was undertaken to determine whether there are any chronic neurological sequelae to acute organophosphate pesticide poisoning. METHODS. California surveillance data were used in a study of neurological function among 128 men poisoned by organophosphate pesticides in California from 1982 to 1990 and 90 referents. Tests included a neurological physical examination, 5 nerve conduction tests, 2 vibrotactile sensitivity tests, 10 neurobehavioral tests, and 1 postural sway test. RESULTS. After correcting for confounding, the poisoned group performed significantly worse than the referent group on two neurobehavioral tests (sustained visual attention and mood scales). When the data were restricted to men with documented cholinesterase inhibition (n = 83) or to men who had been hospitalized (n = 36), the poisoned subjects also showed significantly worse vibrotactile sensitivity of finger and toe. Significant trends of increased impairment were found with increased days of disability on a wide spectrum of tests of both central and peripheral nerve function. CONCLUSIONS. While these findings are limited by low response rates and by small sample sizes for specific pesticides, this study was based on a large surveillance database and is the largest study to date of the chronic effects of organophosphate pesticide poisoning. The evidence of some long-term effects of poisoning is consistent with two prior studies.

These results demonstrate that NESP safely and effectively corrects and maintains hemoglobin concentrations at a reduced dosing frequency relative to rHuEPO in patients with CRI, providing a potential benefit to patients and health care providers.

To test the hypothesis that chronic neurologic sequelae are associated with cholinesterase depression short of frank organophosphate poisoning, we compared 45 male subjects who had a history of moderate cholinesterase inhibition with 90 male subjects who had neither past cholinesterase inhibition nor current pesticide exposure. Cholinesterase-inhibited subjects were defined as having had a history of (a) red blood cell cholinesterase at 70% or less of baseline or (b) plasma cholinesterase at 60% or less of baseline absent symptoms of frank poisoning. In the subject comparison evaluation, only 1 of 27 neurologic tests (i.e., serial digit performance) was significant statistically, but it was opposite of the direction hypothesized. In a companion study for which the same battery of neurologic tests and the same subjects were used, neurologic sequelae were related to high exposures among subjects who sought treatment for organophosphate poisoning. The data in the current study, in which the subjects experienced lower exposures short of frank poisoning, provide some evidence that preventing acute organophosphate poisoning also prevents neurologic sequelae.

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When the fall in left ventricular pressure during isovolumic relaxation is treated as a monoexponential the rate of relaxation can be measured by a time constant. Though an empirical measurement, the time constant has been used extensively to study relaxation. It can be accepted, however, as a valid measurement only if isovolumic pressure fall approximates very closely to a monoexponential in a wide range of circumstances.We analysed 60 beats recorded at different heart rates in 20 patients with a variety of left ventricular disease. In the first part of the study a powerful non-linear regression program was used off-line to test three exponential models: (1) a monoexponential, the asymptote of which is zero, (2) a monoexponential with a variable asymptote, and (3) a biexponential. The pressures predicted by models 2 and 3 were in very close agreement with measured pressure, whereas the predictions of model 1 were consistently less accurate. Model 3 had no advantage over model 2. Thus, in all the beats tested isovolumic pressure fall approximated very closely to a monoexponential of which both the time constant and asymptote are variable. A second exponential term does not increase precision, and is an unnecessary complication.In the second part of the study the same 60 beats were analysed by a small program on the catheter laboratory computer. The time constant was estimated by two methods, corresponding to models 1 and 2 described above: (1) from the slope of In (pressure) against time, and (2) by a method of exponential analysis. The first method underestimated the time constant of model 1, particularly in beats where pressure fell to low levels. The second method accurately estimated the time constant of model 2.It is concluded that isovolumic pressure fall approximates closely to a monoexponential in a wide variety of circumstances, and it is legitimate, therefore, to describe the rate of relaxation by a time constant. But the time constant must be estimated by a method based upon an exponential model of which both the time constant and asymptote are variable. We have shown that such a time constant can be estimated reliably by a small program suitable for use on-line. The usual method of estimating the time constant, from the slope of In (pressure) against time, provides an unreliable estimate of the time constant of an unsatisfactory model.During isovolumic relaxation the fall in left ventricu-must decay exponentially during relaxation. Its use lar pressure from the point of its maximum rate of can be justified only if isovolumic pressure fall change until it reaches the level of end-diastolic pres-approximates closely to a monoexponential in a wide sure of the preceding beat approximates to a monoex-range of circumstances. In addition, the estimate of ponential and can be characterised by a time con-the time constant is highly dependent upon its stant. 14 Though it has been used widely to study method of calculation.89 The purpose of this study relaxation of the intact ventricle' -7 the time constant was ...

1. Dietary supplementation with vitamin E reduces ischaemic events in patients with established coronary artery disease and improves endothelial function in cholesterol-fed rabbits. We examined whether such dietary supplementation with vitamin E improves endothelial function in patients with mild hypercholesterolaemia and coronary artery disease. 2. Twenty patients (total cholesterol 6.8 +/- 1.1 mmol/l, mean +/- SD) with angiographically documented coronary artery disease were randomly allocated to receive placebo (n = 10) or vitamin E, 400 i.u. daily, (n = 10) for 8 weeks. Endothelium-dependent and independent vasodilatation within forearm vasculature was assessed by brachial artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine) and nitroprusside before and after supplementation. 3. Plasma concentrations of vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mumol/l (means +/- SE) in the vitamin E-supplemented group (P < 0.01) but did not change significantly in the placebo group. Lipid profiles remained similar before and after supplementation in both groups. Forearm blood flow responses to acetylcholine (7.5 and 15 micrograms/min) and nitroprusside (3 and 10 micrograms/min) were similar before and after supplementation in both groups. Acute intra-arterial administration of L-arginine (10 mg/min) augmented the response to acetylcholine (15 micrograms/min) in both groups before and after supplementation to a similar degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L-arginine reverses endothelial dysfunction in forearm vasculature of patients with mild hypercholesterolaemia and coronary artery disease but supplementation with vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive endothelial dysfunction.

Myocardial substrate extraction, coronary sinus flow, cardiac output, and left ventricular pressure were measured at increasing pacing rates before and after propranolol (0.2 mg/kg) in 13 patients with hypertrophic obstructive cardiomyopathy (HOCM) during diagnostic cardiac catheterisation. At the lowest pacing rate myocardial oxygen consumption varied considerably between patients and very high values were found in several individuals (range 10.1 to 57.5 ml/min). These large differences between patients were not explicable by differences in cardiac work; consequently, cardiac efficiency, estimated from the oxygen cost of external work, varied between patients and was lower than normal in all but two. The pattern of substrate extraction at the lowest pacing rate was similar to results reported for the normal heart, and measured oxygen consumption could be accounted for by complete oxidation of the substrates extracted; thus there was no evidence of a gross abnormality of oxidative metabolism, suggesting that low efficiency lay in the utilisation rather than in the production of energy. Each of the four patients with the highest myocardial oxygen consumption and lowest values of efficiency sustained progressive reductions in lactate and pyruvate extraction as heart rate increased, and at the highest pacing rate had low (< 3%) or negative lactate extraction ratios. In three of these four, coronary sinus flow did not increase progressively with each increment in heart rate. One patient with low oxygen consumption and normal efficiency also failed to increase coronary flow with the final increment in heart rate, and produced lactate at the highest pacing rate. Thus the five patients in whom pacing provoked biochemical evidence of ischaemia all had excessive myocardial oxygen demand and/or limited capacity to increase coronary flow. Propranolol did not change lactate extraction significantly at any pacing rate in either the ischaemic or non-ischaemic groups. In only one patient was ischaemia at the highest pacing rate abolished after propranolol, and this was associated with a 30 per cent reduction in oxygen consumption. These results do not demonstrate a direct effect of propranolol upon myocardial metabolism in patients with HOCM, but emphasise the potential value of beta-blockade in protecting these patients from excessive increases in heart rate.