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Biomedical subjects

D Dunbar

Publications and source records attributed to D Dunbar.

At least 37 records · Page 2Linked to original sources
PubMed1994

Tuberculin reactions among attendees at a methadone clinic: relation to infection with the human immunodeficiency virus.

We tested 403 clients at an inner-city methadone clinic to determine the rate of positive tuberculin test reactions and to determine how this rate was influenced by race, gender, and infection with the human immunodeficiency virus (HIV). In addition to skin testing, an experimental urine test for antibody to HIV was offered; 73% of the clients provided urine specimens. Positive urine test results were confirmed by serum antibody testing. Of the subjects who returned for follow-up, 33.9% had indurations > or = 10 mm; 49.7% of these subjects were Black, 30% were Hispanic, and 18% were White. Antibodies to HIV were present in 12.5% of urine specimens. Tuberculin reactions of > or = 5 mm were observed for 32.7% of HIV-positive subjects and 48.4% of HIV-negative subjects. Screening of urine for antibodies to HIV proved to be simple, specific, and well accepted by the subjects. Providing prophylaxis for tuberculosis should be a high priority in populations with rates of tuberculin reactions and HIV infection that are comparable to those for clients of our methadone clinic.

AIDS-Related Opportunistic Infections↗
PubMed1993

Nurse practitioner managed care for persons with HIV infection.

This exploratory study examined whether outcomes of care for HIV-infected patients are related to whether the patient's primary provider is a physician (MD) or a nurse practitioner (NP). Functional status, symptom occurrence, self management, health service use and patients' assessment of their care were evaluated for 87 HIV-infected patients in a teaching hospital outpatient setting. NP patients were three times as likely to report their health status as only fair or poor (odds-ratio = 3.06, p = .028), and reported significantly more unpleasant symptoms over a four-week period. Despite being in poorer health than patients cared for by physicians, NP patients functioned at comparable levels and used no more health care services than MD patients. NP patients reported 45 percent fewer problems with their care (p = 0.003). Findings suggest that more extensive use of nurse practitioners could safely enhance access to care for persons with HIV-related illnesses.

Adult↗
PubMed1992

Rat liver metabolism and toxicity of 2,2,2-trifluoroethanol.

2,2,2-Trifluoroethanol (TFE) is a metabolite of anesthetic agents and chlorofluorocarbon alternatives. Its toxicity in rats is a consequence of its metabolism to 2,2,2-trifluoroacetaldehyde (TFAld) and then to trifluoroacetic acid (TFAA). The enzymes involved in the toxic metabolic pathway have been investigated in this study. For the reaction of TFE to TFAld, the major hepatic metabolism associated with toxicity (as assessed by pyrazole-inhibitability) was NADPH dependent and occurred in the microsomes, whereas for TFAld conversion to TFAA, NADPH-dependent microsomal metabolism was significant, but mitochondrial and cytosolic metabolism in the presence of NADPH were also major contributors. NADPH-dependent hepatic microsomal metabolism of TFE to TFAld and TFAld to TFAA was inhibited by carbon monoxide, 2-allyl-2-isopropylacetamide, SKF-525A, metyrapone, imidazole, and pyrazole, and both reactions were oxygen dependent. The metabolism of TFE to TFAld was inhibited by diethyldithiocarbamate, a specific inhibitor of cytochrome P450E1, and by a monoclonal antibody to P4502E1, whereas the metabolism of TFAld was inhibited by neither. Ethanol pretreatment of rats enhanced the Vmax for hepatic microsomal metabolism of TFE to TFAld from 5.3 to 9.7 nmol/mg protein/min, while for TFAld to TFAA the Vmax was increased from 4.3 to 6.5 and the Km was unaffected for both reactions. Phenobarbital pretreatment of the rats did not affect any of these kinetic parameters. Coadministration of ethanol and a lethal dose of TFE very markedly decreased the lethality. Both the lethality (LD50 0.21 to 0.44 g/kg) and the metabolic kinetic parameters [(Vmax/Km)H(Vmax/Km)D = 4.2] were affected markedly when deuterated TFE replaced TFE. In contrast, deuteration of TFAld did not affect its lethality or rates of metabolism, but did affect its Km. Taken together these results indicate that P4502E1 catalyzed toxicity-associated hepatic metabolism of TFE to TFAld, while TFAld metabolism was catalyzed by a P450 which was not P4502E1. The hepatic metabolism of TFAld was not associated with its toxicity, which has been determined previously to be associated with its intestinal metabolism.

Acetaldehyde↗
PubMed1991

Reflotron cholesterol measurements in 1112 Australian children aged 10-12 years.

OBJECTIVE: To study the distribution of blood cholesterol concentration in a sample of Western Australian schoolchildren. DESIGN: The Reflotron dry-chemistry system (Boehringer Mannheim, Germany) was used to measure cholesterol in finger-prick blood samples obtained from Year 6 children aged 10-12 years attending government schools in metropolitan Perth. Recruitment methods ensured that children from different socioeconomic strata were represented. PARTICIPANTS: For the 1239 children enrolled in Year 6 in 30 government schools, parental consent to participate was obtained for 1144; of these cholesterol concentration was measured in 1112. RESULTS: The measurement method proved practicable and was generally well accepted. Cholesterol levels were somewhat lower than those obtained using a laboratory reference method and a bias, relative to national quality assurance standards, was estimated to be -0.32 mmol/L. Mean cholesterol level in boys (4.28 mmol/L, SD 0.69) was not significantly different from that in girls (4.35 mmol/L, SD 0.72). Allowing for measurement bias, 52% of boys and 57% of girls had cholesterol levels exceeding the National Heart Foundation's designated "desirable" level of 4.5 mmol/L for children. CONCLUSIONS: The distribution of cholesterol levels in Australian children compares unfavourably with distributions in children in countries with low rates of cardiovascular disease and indicates a need for widespread, appropriate diet and lifestyle changes.

Australia↗
PubMed1991

Comparison of diets supplemented with fish oil or olive oil on plasma lipoproteins in insulin-dependent diabetics.

This study was designed to compare changes in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol in normolipidaemic male insulin-dependent diabetics (IDD) following dietary supplementation with either the fish oil concentrate Max EPA or olive oil. The contribution of the small quantity of cholesterol in Max EPA to these changes was also examined. Twenty-seven subjects were matched in groups of three and randomly allocated to one of three treatment groups of nine subjects each. Subjects were given 15 1-g capsules of oil daily for 3 weeks, consisting of either Max EPA, olive oil, or olive oil to which was added the same amount of cholesterol as contained in Max EPA, respectively. There was a significant increase in eicosapentaenoic acid, and a decrease in arachidonic acid, in the platelet membrane phospholipids of subjects taking Max EPA. In this group, there was an approximately 30% increase in serum HDL2-cholesterol (0.59 +/- 0.07 to 0.77 +/- 0.11 mmol/L, mean +/- SEM; P less than .01) and a corresponding decrease in HDL3-cholesterol (0.79 +/- 0.03 to 0.71 +/- 0.03 mmol/L; P less than .05). Although total and LDL-cholesterol concentrations were also higher after Max EPA, the changes were not significant. Triglycerides were significantly decreased by Max EPA. There were no significant changes in lipids in the groups given olive oil. These results show that compared with olive oil, dietary supplementation with Max EPA substantially increases HDL2-cholesterol in insulin-dependent diabetics. This is most likely due to a selective effect of omega 3 fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Timing and magnitude of serum creatine kinase-MB after transcatheter cardiac tissue fulguration in man.

This study examined the impact of transcatheter fulguration on creatine kinase-MB release in 21 patients (age range 17-71 years). Arrhythmia diagnoses were ventricular tachycardia 9, atrial fibrillation with a rapid ventricular response 7, atrioventricular nodal reentry 2, and reciprocating tachycardia utilizing a posteroseptal accessory pathway 3. Seven patients had apparently normal hearts while 8 had ischemic heart disease and 6 cardiomyopathy. Timing of initial elevated creatine kinase-MB activity (mean 1.34 +/- 0.69 SD hours) and peak creatine kinase-MB activity (mean 3.73 +/- 0.89 SD hours) was relatively uniform in all patients. Time to peak creatine kinase-MB activity was unrelated to either underlying cardiac disease (normal: 3.9 +/- 1.0 hours; ischemic heart disease: 3.5 +/- 0.9 hours; cardiomyopathy: 3.8 +/- 0.9 hours), or fulguration site (His bundle (n = 9): 4.2 +/- 0.9 hours, proximal coronary sinus (n = 3): 3.3 +/- 0.3 hours, ventricle (n = 9): 3.4 +/- 0.8 hours). The magnitude of peak serum creatine kinase-MB activity was independent of myocardial diagnosis or fulguration site, but was linearly related to total energy delivered (r = 0.5, P less than 0.022). The latter correlation was particularly strong within cardiac diagnosis subgroups (normal: r = 0.92, P less than 0.002; ischemic heart disease: 0.73, P less than 0.04; non-ischemic cardiomyopathy: r = 0.57, P = NS). Thus, serum creatine kinase-MB activity following transcatheter fulguration is linearly related to the magnitude of delivered energy, and is similar to that observed after transient coronary artery occlusion and reperfusion.

Adolescent↗
PubMed1989

Dietary fish oils increase serum lipids in insulin-dependent diabetics compared with healthy controls.

The effect of daily dietary supplementation with fish oil on serum lipids and platelet total phospholipid fatty acids was examined in male normolipidemic insulin-dependent diabetics and normal controls. They were given 15 g/d of fish oil as Max EPA (equivalent to 2.7 g/d of eicosapentaenoic acid) for 3 weeks. The diabetics showed a rise in total cholesterol, attributable to increases in LDL- and HDL-cholesterol. The increase in HDL-cholesterol was largely due to a rise in its HDL2 subclass. There was also a decrease in triglycerides in both groups. Similar changes in lipids were seen in the normal controls, although these were not significant. The more pronounced effect in diabetics suggests an altered metabolic response to omega-3 fatty acids in that disorder. However, the results indicate that the possible detrimental effect of the rise in total and LDL-cholesterol following fish oil may be offset by the increase in the protective HDL2 subclass.

Adult↗
PubMed1988

Intracellular lactate dehydrogenase concentration as an index of cytotoxicity in rat hepatocyte primary culture.

In searching for a reliable index for cytotoxicity testing in rat hepatocyte primary culture, lactate dehydrogenase (LDH) concentrations in lysates of attached hepatocytes and LDH released into the culture medium were compared under conditions of exposure to various dosages of sodium chloride, sodium salicylate, R-warfarin, acetaminophen, phenylbutazone, and furosemide (frusemide). The amount of intracellular LDH was assessed by inducing the cells to release the enzyme with 0.1% Triton X-100. The induced LDH leakage was completed in 1 hr and the LDH activity was stable in storage at 10 degrees for 2 weeks. We found that intracellular LDH is a direct indicator of the number of viable hepatocytes in contrast to the LDH released, because released LDH does not account for the significant number of cells detached from monolayer but which are not leaky, during the 6-hr test period. Based on IC50 values (50% inhibitory concentration), the relative cytotoxicities are R-warfarin greater than phenylbutazone greater than furosemide greater than acetaminophen greater than sodium salicylate greater than sodium chloride.

Animals↗
PubMed1988

Diet and blood pressure in 9-year-old Australian children.

Relationships between blood pressure and dietary factors were investigated in 884 9-y-old Australian children. Data on usual diet were obtained from a food frequency questionnaire completed by parents. The data were used to estimate daily energy intake and intakes of 14 nutrients considered to have some potential for influencing blood pressure. Systolic and diastolic blood pressure were tested for relationships with absolute intakes and calorie-adjusted intakes of each nutrient after adjustment for potential confounders. Diastolic pressure in boys was negatively related to energy intake and to calorie-adjusted fiber intake. Mean adjusted diastolic pressure in boys in the top fiber-intake quartile was 2.5 mm Hg lower than that in the bottom fiber-intake quartile. Systolic pressure in girls was negatively related to calorie-adjusted intakes of protein and cholesterol. There were no detectable relationships between blood pressure and calorie-adjusted intakes of fats, carbohydrates, sodium, potassium, calcium, or magnesium.

Australia↗
PubMed1988

Serum lipids in insulin-dependent diabetics are markedly altered by dietary fish oils.

1. The effect of dietary fish oil supplementation on serum lipids was examined in normolipidaemic insulin-dependent male diabetics and healthy controls. Fish oil was given as Max eicosapentaenoic acid (EPA), 15 g daily (equivalent to 2.7 g/day of EPA) for 3 weeks. 2. There was a substantial increase in EPA but a depletion of arachidonic acid content of platelet phospholipids. 3. Diabetics showed a rise in total cholesterol, attributable to increases in low density and high density lipoprotein (LDL and HDL) cholesterol. The rise in HDL cholesterol was largely due to an increase in its HDL2 subclass. Similar changes were found in the healthy men although these were not as marked. A decrease in triglycerides was observed in both diabetics and normal controls. 4. Generally, diabetics showed greater changes in lipid concentrations which may suggest an altered metabolic response to w3 fatty acids. Therefore, the possible detrimental effect of the rise in total cholesterol and LDL cholesterol following fish oil administration may be offset by the increase in the protective HDL2 subclass.

Adult↗
PubMed1987

Detergents as probes of reconstituted rat liver cytochrome P-450 function.

A series of 16 ionic, zwitterionic, and nonionic detergents have been used to perturb the catalytic activities of major cytochrome P-450 (P-450) forms from untreated (UT-A), phenobarbital-treated (PB-B) and beta-naphthoflavone-treated (BNF-B) rats in reconstituted systems with NADPH--P-450 reductase Detergent effects on R warfarin hydroxylase activities were correlated with detergent effects on the quaternary structures of P-450 and reductase, and on their 1:1 complexes as determined by gel exclusion chromatography using sodium cholate as a prototype detergent. The detergent concentrations used did not in most cases affect rates of NADPH-dependent reduction of cytochrome c by the reductase. With P-450 BNF-B, ionic and zwitterionic detergents enhanced warfarin hydroxylase activities at low concentrations and produced marked inhibition at higher concentrations, while nonionic detergents only inhibited. With P-450 UT-A, some nonionic and zwitterionic detergents increased rates at low concentrations and inhibited at higher concentrations. P-450 PB-B was inhibited by detergents of all three classes at low and high concentrations. The concentrations of a detergent required to affect 50% inhibition differed for the three P-450s, suggesting, together with the differential susceptibilities to detergent-mediated rate enhancing effects, that the reductase interacts functionally differently with the three P-450s. Chromatographic studies demonstrated that concentrations of sodium cholate which optimally enhanced metabolic rates with P-450 BNF-B facilitated the uptake of the P-450 into the functional reductase/P-450 complex, and higher concentrations of cholate, which completely inhibited activity, produced profound disruptions of the complex. The data have provided insight into the functional interactions required for monooxygenase activity.

Animals↗
PubMed1987

Hypokalemia after cardioversion from ventricular tachycardia induced in the electrophysiology laboratory.

Serum potassium is often low after resuscitation from out-of-hospital ventricular fibrillation. We hypothesized that hypokalemia develops after ventricular tachycardia induced by programmed electrical stimulation. We measured serum potassium in 10 patients before induction of ventricular tachycardia and 15 minutes, 45 minutes, and 3 hours following cardioversion from ventricular tachycardia. Ventricular tachycardia rate was 243 +/- 71 bpm and duration was 57 +/- 87 seconds. Mean serum potassium (mEq/L) decreased from 4.1 +/- 0.3 at baseline to 3.8 +/- 0.5 at 15 minutes (p less than 0.01 vs baseline) and 3.7 +/- 0.6 at 45 minutes (p less than 0.005 vs baseline), but returned to 4.1 +/- 0.5 at 3 hours. Although no patients were hypokalemic (potassium less than 3.5 mEq/L) at baseline, 33% were hypokalemic at 15 minutes and 40% were hypokalemic at 45 minutes (p = 0.06 vs baseline). A low serum potassium was found in several of these patients immediately after the clinical arrhythmia that led to electrophysiologic study, and rapid resolution of the hypokalemia was observed. Thus, serum potassium decreases rapidly in man after resuscitation from brief but hemodynamically significant ventricular tachycardia. This suggests that patients with hypokalemia after resuscitation from out-of-hospital ventricular fibrillation have hypokalemia secondary to the event. The electrophysiologic effects of post-cardioversion hypokalemia are unknown.

Aged↗
PubMed1987

Environmental temperature and blood pressure in 9-year-old Australian children.

Relationships between blood pressure (BP) and environmental temperature were investigated as part of a broader study of constitutional and environmental determinants of BP in a sample of 1037 9-year-old Australian children. A Dinamap semi-automatic device was used to obtain three BP readings for each child. Average systolic blood pressure (SBP) and diastolic blood pressure (DBP) differed according to month of examination, with higher levels in the colder months. Negative relationships were observed between BP and temperature on the measurement day; computed regression equations indicated that a rise in maximum daily temperature of 10 degrees C was associated with falls of 5-7 mmHg in SBP and DBP. The relationships were independent of age, weight, height, socio-economic status and heart rate (HR). The results emphasize the importance of taking environmental temperatures into account in epidemiological studies of BP.

Anthropometry↗
PubMed1985

Isozyme selectivity of the inhibition of rat liver cytochromes P-450 by chloramphenicol in vivo.

The isozyme-selectivity of chloramphenicol as an inhibitor of rat liver cytochromes P-450 has been investigated. Untreated rats and rats treated with the inducers phenobarbital, beta-naphthoflavone, pregnenolone 16 alpha-carbonitrile, and clofibrate have been injected intraperitoneally with chloramphenicol, and inhibition of specific cytochrome P-450 isozymes has been assessed by monitoring the metabolism of warfarin, testosterone, isosafrole, or lauric acid in subsequently prepared hepatic microsomal preparations. Of eight major cytochrome P-450 isozymes which could be monitored in this fashion, three were inhibited by more than 50% by a dose of chloramphenicol of 300 mg/kg, whereas no evidence of inhibition of the remaining isozymes was obtained. P-450PB-C, an isozyme which is present in significant amounts in untreated rats and which is induced approximately 2-fold by phenobarbital, was the most susceptible cytochrome P-450 to inhibition by chloramphenicol both in vivo and in vitro. P-450PB-B, the major phenobarbital-inducible isozyme, and P-450UT-A, a male-specific testosterone 2 alpha- and 16 alpha-hydroxylase, were intermediate in their susceptibility to chloramphenicol. In contrast, the major isozymes induced by beta-naphthoflavone, pregnenolone 16 alpha-carbonitrile, and clofibrate, as well as a constitutive testosterone 7 alpha-hydroxylase, were not inhibited by chloramphenicol.

Animals↗
PubMed1983

Trifluorinated ether anesthetic lethality in rats: the role of bacterial infection.

The lethal effects of the fluorinated ether anesthetics fluroxene (2,2,2-trifluoroethyl vinyl ether) and its ethyl (TFEE) and allyl analogues in male Wistar rats have previously been demonstrated to be potentiated by specific hepatic microsomal cytochromes P-450, and mediated by the common metabolite 2,2,2-trifluoroethanol (TFE). We report here that administration of lethal combinations of anesthetic and cytochrome P-450-inducing agents or of lethal doses of TFE (0.21 g/kg and higher) to rats caused decreased white blood cell counts, necrosis of sternum bone marrow cells and lymphocytes in the thymic cortex, and resulted in Escherichia coli contamination of the blood, lungs, liver, and kidneys of treated rats. Control animals in identical environments were free of bacterial contamination. Pretreatment of rats with the antibiotic tetracycline-HCl in the drinking water (0.6 g/liter) from 24 hr before anesthetic or TFE administration significantly diminished the mortality. With TFEE and beta-naphthoflavone induction, mortality was reduced from 85 to 30% by the antibiotic. However, the antibody plaque assay following immunization with sheep erythrocytes indicated that the primary humoral immune response to a thymus-dependent antigen was not impaired in treated rats. These results considered together indicate that metabolic formation of TFE from the anesthetic agents produced a decreased host resistance with subsequent increased susceptibility to bacterial infection. If not administered the antibiotic, the animals succumbed to the infection.

Anesthetics↗