Parental education as a confounder in the assessment of low level lead effect on psychological functions in children.
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Biomedical subjects
Publications and source records attributed to D A Otto.
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Nursing regulations exist to protect and benefit the health, safety, and welfare of the individual. Accountability is a multifaceted concept with many interpretations. All nurses are expected to engage in professional role activities appropriate to their education, experience, and position. Ultimately, nurses are accountable to themselves, their patients, and their peers for their professional nursing actions. This article addresses regulatory statutes and other issues of importance in the perioperative setting, including ethical and legal considerations, patient advocacy, delegation of tasks to unlicensed assistive personnel, and selected expanded roles in perioperative nursing practice.
Twenty-five workers, five currently and 20 formerly involved in the manufacture of hybrid microcircuits, underwent clinical evaluations at the request of a management-union committee concerned about chronic solvent exposures in a research and development laboratory. A battery of neurobehavioral tests was administered to compare the solvent-exposed group with 32 age-, gender-, ethnicity-, and education-matched controls. The tests included: MMPI-I, hand grip strength, tactile sensitivity, dexterity, color discrimination, visual acuity and contrast sensitivity, and tests selected from the computerized Neurobehavioral Evaluation System (NES2). Clinical narratives and retrospective exposure assessments in the study group suggested chronic low-level exposure to solvents, with intermittent acute excursions. Work-related diagnoses included upper respiratory mucosal irritation and sinusitis (44%), lower respiratory reactive airway disease (12%), and dermatitis (5%). Three workers (12%) had findings consistent with a solvent-induced encephalopathy. Significant differences (after Bonferroni correction) were found between the two groups on 5 of 11 NES subtests: symptom scale, mood scale, finger tapping, simple reaction time, and symbol-digit substitution. Differences also reached significance for overall vibration sensitivity thresholds, visual contrast sensitivity, and grip strength. The MMPI average clinical scale elevation was significantly higher in the exposed group than controls. These results support an association between chronic low-dose solvent exposure and measurable neurobehavioral changes.
Streptozotocin diabetic rats, with and without insulin replacement, and sham-injected controls were fed a high-fat (30% of energy) menhaden oil (MO) or corn oil (CO) diet for 2 weeks. After an overnight fast, plasma and livers were collected for analysis of insulin, glucose, triacylglycerol, cholesterol and glucose-6-phosphate dehydrogenase activity. Streptozotocin treatment resulted in decreased plasma insulin and elevated glucose. MO-feeding to insulin-replaced diabetic rats resulted in higher insulin and lower glucose levels compared to the respective CO-fed rats, suggesting decreased hepatic insulin extraction and greater peripheral utilization of glucose with MO. Plasma triacylglycerol and cholesterol, and hepatic glucose-6-phosphate dehydrogenase activity were reduced in MO-fed vs. CO-fed control rats. These effects of MO were prevented in the diabetic rats but were restored by insulin replacement. We conclude from our data that the presence of insulin is required to observe at least some of the effects of fish oil (FO). To explain our observations we propose that many of the effects of FO on hepatic metabolism are mediated by an inhibition of insulin action in the liver, thus providing a possible central mechanism for the regulation of hepatic lipid metabolism by dietary FO.
The application of visual (VEP) and chemosensory evoked potentials (CSEP) in occupational and environmental health is briefly reviewed. VEPs have been used extensively in experimental neurotoxicity and play an increasingly important role in human neurotoxicity testing. The similarity of VEP waveforms in different species renders them useful for cross-species extrapolation. CSEPs, used in conjunction with traditional psychophysical tests and rating scales, offer a promising new approach to the study of indoor air pollution.
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Rats were fed (for 2 or 6 wk) purified diets containing lard (LD) or menhaden oil (MO) at two levels of dietary fat, i.e., at 11.5 and 20.8% of energy in the low fat (LF) and the medium fat (MF) diets, respectively. Following the diet period, rats were sacrificed after either an overnight fast or after uninterrupted ad libitum feeding. The studies were designed to investigate the dependence of our previously reported effects of MO, i.e. the reduction of plasma free fatty acid (FFA) levels and accumulation of hepatic triacylglycerols, on the dietary fat concentration and the nutritional state of the animal at the time of sacrifice. Reductions in plasma triacylglycerol and cholesterol levels in MO-fed relative to LD-fed rats were observed under all conditions. FFA levels were consistently reduced by MO-feeding at both dietary fat concentrations, but only when blood was sampled from ad libitum fed rats. Under these conditions there was a significant positive relationship between plasma FFA and triacylglycerol concentrations. Reduction in plasma FFA levels may be an additional mechanism associated with the triacylglycerol-lowering effect of fish oil (FO). The LF and MF MO diets caused a rise in plasma glucose levels with no significant change in insulin concentration, indicating that the reduction of FFA by MO was not related to changes in insulin concentration or insulin sensitivity. The MO diets had no effect on skeletal muscle or epididymal adipose tissue lipoprotein lipase activity, demonstrating that catabolism of triacylglycerol-rich lipoproteins contributes little, if any, to the MO-dependent reductions of plasma triacylglycerol and FFA.(ABSTRACT TRUNCATED AT 250 WORDS)
Rats were fed Chow (C; low-fat control) or a purified high-fat (30% of calories) low cholesterol diet containing menhaden oil (MO), corn oil (CO) or lard (L) for 2, 4 or 6 weeks. Rats were killed after an overnight fast. MO-fed rats had a larger weight/body weight that was accompanied by a lower mg liver DNA/g liver but unchanged liver DNA/body weight, indicating that hepatomegaly in the MO-fed rats was due to cellular hypertrophy. MO-feeding prevented the rise in plasma triacylglycerol and cholesterol observed with the other high-fat diets. There was a marked progressive accumulation of total liver triacylglycerol in the MO- and CO-fed rats. Plasma insulin was reduced in the MO-fed rats relative to all other groups. There were strong positive relationships between plasma insulin and triacylglycerol and between insulin and cholesterol in the high-fat-fed rats. Total liver glucose-6-phosphate dehydrogenase and malic enzyme activities were reduced by MO-feeding and were directly correlated with plasma cholesterol and insulin. These data are consistent with an apparent inhibition of hepatic triacylglycerol secretion by high-fat fish oil-feeding that is independent of the inhibitory effects on triacylglycerol synthesis. These data suggest a role for insulin in regulating the plasma triacylglycerol and cholesterol concentrations in MO-fed rats.
Substrate saturation plots of carnitine palmitoyltransferase I activity from isolated rat liver mitochondria vs. palmitoyl-CoA concentration in the presence of bovine serum albumin have been reported to yield sigmoidal kinetics. Under identical assay conditions we have confirmed these observations as reflected by nonlinear Lineweaver-Burke plots (1/vi vs. 1/[S]) an average Hill coefficient of napp. = 1.98 +/- 0.09 (Mean +/- S.E. from four separate experiments). For these determinations the enzyme activity was plotted against the total [palmitoyl-CoA] in the presence of 0.13% bovine serum albumin. Utilizing the total [palmitoyl-CoA] to determine the kinetic properties of carnitine palmitoyltransferase I would be valid only if the relationship between total and free [palmitoyl-CoA] was linear, which is not the case as we have previously shown. When carnitine palmitoyltransferase I substrate saturation kinetics were reanalyzed using the previously determined free [palmitoyl-CoA]'s, the plots revealed a shift to standard hyperbolic kinetics. This observation was confirmed by an average Hill coefficient of napp. = 1.04 +/- 0.10 (Mean +/- S.E.) and linear Lineweaver-Burke plots. The double-reciprocal plots from these analyses yielded an average S0.5 of 2.55 +/- 0.82 microM (Mean +/- S.E.) palmitoyl-CoA and Vmax of 19.69 +/- 5.48 nmol/min per mg protein. These studies clearly demonstrate the importance of defining the free [palmitoyl-CoA] when analyzing the kinetics of carnitine palmitoyltransferase I in the presence of bovine serum albumin.
To investigate the role of lipoprotein lipase (LPL) and hepatic lipase in the triacylglycerol lowering effects of fish oil, rats were fed lard (L), corn oil (CO) or menhaden oil (MO) as the primary fat source in otherwise identical diets. After 2 weeks, soleus muscle LPL differed between groups (MO greater than CO greater than L). Hepatic lipase did not differ between CO- and MO-fed rats but was elevated in L-fed rats. Adipose LPL did not differ between diet groups. Total epididymal fat weight was reduced in MO-fed rats. There was a significant positive correlation between adipose tissue weight and plasma free fatty acids. MO-fed rats had lower plasma insulin levels. Insulin was directly correlated with plasma triacylglycerol and glucose, consistent with a hyperinsulinemic, insulin-resistant state in CO- and L-fed rats, and a protective effect with MO feeding. In addition, insulin was directly correlated with adipose LPL. A negative relationship between soleus muscle LPL and insulin approached significance. Soleus muscle LPL was significantly inversely correlated with triacylglycerol. The data indicate that increased skeletal muscle LPL, in response to MO or a MO-induced decrease in insulin, may contribute to the triacylglycerol-lowering effects of fish oil. Decreased fat weight and adipose LPL and increased soleus muscle LPL and decreased plasma triacylglycerol suggest a shift from fat deposition to oxidation with MO feeding. The lack of response of hepatic lipase to MO feeding suggests that this enzyme does not contribute to the fish oil-stimulated lowering of plasma triacylglycerol via hepatic reuptake of very low density lipoproteins or other triacylglycerol-rich lipoproteins.
Pancreatic islet allografts are rejected very rapidly due to their high immunogenicity. Several attempts have been made to reduce the immunogenicity prior to transplantation. We treated islets with MHC Ia (class II) antigen monoclonal antibody and complement in order to lyse Ia antigen bearing cells within the islets. This treatment caused a distinct reduction of Ia antigen positive cells, which was demonstrated by indirect immunofluorescence tests. A total depletion of the Ia antigens, however, could not be achieved. As a second in-vitro test to evaluate the effect of the antibody treatment a mixed lymphocyte islet culture (MLIC) was performed. The partial Ia antigen reduction provoked a significantly reduced but not completely suppressed allogenic T-cell response. Antibody treatment did neither impair the morphological integrity nor the function of the islets as could be demonstrated by syngenic transplantation of islets pretreated by antibodies in the same way. After allotransplantation of antibody-pretreated islets across a major histocompatibility barrier into non immunosuppressed rats, however, there was no significant prolongation of the graft survival. Thus, a partial reduction of the number of the Ia antigen positive cells within the islets is not sufficient for the prevention of allograft rejection.
Using an intraabdominal heterotopic cardiac transplant procedure, we determined that the Fischer 344 rat (donor)/Long Evans rat (recipient) combination provides a suitable model for studying acute rejection of cardiac allografts. Rejection time was 9.7 +/- 0.2 days. With this model we investigated the effect of donor pretreatment with methotrexate on allograft survival. Methotrexate injection at a single optimum dose of 100-200 mg/kg, i.p., resulted in a 55-60% increase in allograft survival with indefinite survival of some allografts. The optimum time for methotrexate administration was found to be 3-24 hr before transplant, indicating the clinical feasibility of this approach. Combining methotrexate with different recipient treatments (cyclosporine, methylprednisolone, or methylprednisolone plus azathioprine) resulted in significantly longer allograft survival than with any treatment alone. We have demonstrated a novel and clinically feasible approach to the treatment or prevention of acute allograft rejection. Such a treatment could allow reduction in the dose of immunosuppressant drugs to the recipient and thus lessen the toxicity of immunosuppressant therapy.
Bovine serum albumin (BSA) is routinely utilized in vitro to prevent the adverse detergent effects of long-chain acyl-CoA esters (i.e., palmitoyl-CoA) in enzyme assays. Determination of substrate saturation kinetics in the presence of albumin would only be valid if the relationship between bound and free substrate concentrations was known. To elucidate the relationship between bound and free palmitoyl-CoA concentrations in the presence of BSA, several different techniques including equilibrium dialysis, equilibrium partitioning, fluorescence polarization and direct fluorescence enhancement were investigated. Direct fluorescence enhancement using a custom synthesized fluorescent probe, 16-(9-anthroyloxy)palmitoyl-CoA (AP-CoA), was the best approach to this question. Measurement of the relationship between mol of palmitoyl-CoA bound per mol of BSA (nu) versus -log[free palmitoyl-CoA] revealed that the binding of palmitoyl-CoA to BSA, like palmitate was nonlinear, suggesting the presence of more than one class of acyl-CoA binding sites. Computer analyses of the binding data gave a best fit to the 2,4 two-class Scatchard model, suggesting the presence of two high-affinity primary binding sites (k1 = (1.55 +/- 0.46) x 10(-6) M-1) and four lower affinity secondary binding sites (k2 = (1.90 +/- 0.09) x 10(-8) M-1). Further analyses using the six parameter stoichiometric (stepwise) ligand binding model supports the existence of six binding sites with the higher affinities associated with the binding of the first mole of palmitoyl-CoA and weaker binding occurring after the first two sites are occupied. The association constants from this model of multiple binding diminish sequentially (i.e., K1 greater than K2 greater than K3 greater than...greater than or equal to K6), suggesting that each mol of long-chain acyl-CoA binds to BSA with decreasing affinities.
A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection.
Rat pancreatic islets were treated with MHC Ia antigen monoclonal antibody and complement in order to lyse Ia antigen bearing cells within the islets. Ia antigen expression was significantly reduced after this treatment as shown by indirect immunofluorescence tests. Glucose stimulated insulin secretion and viability of the islets were not impaired. The partial reduction of the Ia antigen expression, however, did not provoke a prolongation of the graft acceptance after islet allotransplantation across a major histocompatibility barrier.
Using rats previously anesthetized with pentobarbital and with subtle modifications to existing procedures, rat brown adipocytes of good yield, viability, and stability were consistently obtained. The metabolic integrity of the cells, indicated by an 8-11 fold norepinephrine-dependent stimulation of respiration, was reproducible between cell preparations and maintained even after 3-5 hours of cell storage at room temperature. The ATP content of freshly isolated and stored cells per mg DNA (using a modified DNA assay) closely reflected the in vivo content determined from freeze clamped tissue.
When [1-14C], [U-14C], and [16-14C]palmitate were oxidized by isolated rat hepatocytes, there was a differential distribution of label as a percent of total oxidized products, such that 14CO2 from [1-14C] greater than [U-14C] greater than [16-14C]palmitate and acid-soluble radioactivity from [16-14C] greater than [U-14C] greater than [1-14C]palmitate. The oxidation of [2,3-14C]succinate to 14CO2 by isolated hepatocytes was only 9.1% of that from [1,4-14C]succinate, demonstrating that the differences in distribution of labeled products are in part due to less 14CO2 production from label in the even carbon positions entering the citric acid cycle. Apparent total ketone body production from [16-14C]palmitate was markedly higher than [1-14C] and [U-14C]palmitate. In addition, the 14C-acetone:14CO2 ratio derived from decarboxylation of labeled acetoacetate from [1-14C]palmitate was less than 1 and positively correlated to the rate of fatty acid oxidation in hepatocytes. These findings indicate that the known preferential incorporation of the omega-C2 unit of fatty acids into 14C-ketone bodies also contributed to the differential distribution of labeled products and that this contribution was greatest at the lower rates of fatty acid oxidation. In isolated mitochondria, the distribution of label to 14CO2 and acid-soluble radioactivity from [1-14C], [U-14C] and [16-14C]palmitate was qualitatively similar to that seen with hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
This article presents the findings of a study on how health policy is integrated into the nursing curriculum at both the graduate and undergraduate levels, with particular emphasis on type of coursework, faculty preparation, and teaching strategies. The sample for the study included 210 randomly selected schools of nursing: 150 with undergraduate programs only and 60 with both graduate and undergraduate programs. The findings indicate that health policy has not yet received optimal placement in the curriculum at either the undergraduate or graduate level of nursing preparation. Recommendations are made based upon the findings of the study, a review of the literature, and the collective experience of the authors.