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Biomedical subjects

C C Tangney

Publications and source records attributed to C C Tangney.

At least 37 records · Page 2Linked to original sources

Effects of tourniquet application on plasma viscosity measurements.

Reliable plasma viscosity measurements are required for cardiovascular risk factor assessment. This study was designed to examine the influence of tourniquet pressure and duration on plasma viscosity measurement with a coaxial cylinder at 37 degrees C. Plasma viscosity was evaluated at low (40 mm Hg) and high (mean arterial blood pressure plus 10 mm Hg) tourniquet pressure and at two time intervals following (0-1 and 4-5 min) of tourniquet application in 38 healthy adults. Longer duration of tourniquet application was accompanied by a significant increase in plasma viscosity at both low (1.356 +/- 0.067 mPa s versus 1.393 +/- 0.067 mPa s (p = 0.0001)) and high (1.321 +/- 0.071 mPa s versus 1.430 +/- 0.086 mPa s (p = 0.0002)) tourniquet pressures. Plasma viscosity values were not influenced by the magnitude of tourniquet pressure. The accuracy of plasma viscosity measurements can be improved by sample acquisition within 1 min following tourniquet application.

Adult↗

Postprandial changes in plasma and serum viscosity and plasma lipids and lipoproteins after an acute test meal.

The influence of a fat-rich test meal on postprandial changes in plasma viscosity and serum viscosity was assessed in 12 normolipidemic adults. After a 12-14-h fast, volunteers (five men and seven women aged 23-50 y) were challenged with a test milk shake containing 50 g fat/m2 body surface area (BSA). Plasma viscosity, serum viscosity, and plasma lipids and lipoproteins were assessed at 0, 2, 3, 4, and 6 h. Viscosity values were determined by using a Mettler Contraves LS-40 rotational microviscometer. Postprandial changes in the study variables were assessed by area under the curve and included triacylglycerols (2.02 mmol/L), plasma viscosity (-0.10 mPa.s), and serum viscosity (-0.01 mPa.s). Peak plasma triacylglycerol concentrations were significantly greater than those observed at baseline (P = 0.0022). There were no significant changes in any other variable when fasting and peak values were compared. Peak plasma viscosity increased in three and decreased in two subjects with no changes in the remaining seven subjects. Changes in peak plasma viscosity ranged from -7% to 7% with similar changes for serum viscosity, from -8% to 10%, and a slightly greater range for plasma fibrinogen, -16% to 10%. In this cohort of normotriacylglycerolemic subjects, there were no significant postprandial changes in plasma viscosity or serum viscosity.

Adult↗

Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients: dose-response study and correlations with plasma levels.

OBJECTIVE: To determine if ventricular cerebrospinal fluid (vCSF) alpha-tocopherol levels in Parkinson's disease (PD) patients can be increased by oral alpha-tocopherol supplementation and whether vCSF levels are linearly related to plasma alpha-tocopherol levels. BACKGROUND: In spite of its putative neuroprotective properties, alpha-tocopherol has failed to alter PD clinical progression. However, the ability of supplemental alpha-tocopherol to affect brain or vCSF levels has never been assessed in humans nor has a dose response curve for alpha-tocopherol in vCSF been established. METHODS: Five PD patients with Ommaya catheters received oral dl-alpha-tocopherol over 5 months. Each patient ingested alpha-tocopherol daily with monthly dosage increases (400, 800, 1,600, 3,200, 4,000 IU/day). Plasma and vCSF samples were obtained at baseline and at the end of each month. Alpha-tocopherol levels were determined in triplicate by high-pressure liquid chromatography with fluorometric and electrochemical detection. RESULTS: At baseline, endogenous alpha-tocopherol was detected in plasma and vCSF, with a greater than one-hundred-fold difference between the fluid compartments (mean plasma level 18.76 microM/l (SD +/- 4.69) versus mean CSF level 0.114 microM/l (SD +/- 0.084). A clear dose-response curve occurred in plasma, with statistically significant increases over baseline developing even with 400 IU/d. With higher doses, a significant increase continued without evidence of saturation. However, there was no significant increase in vCSF alpha-tocopherol levels at any dose, including the supraclinical (4,000 IU/d). There was no correlation between plasma and vCSF alpha-tocopherol levels. CONCLUSION: Oral alpha-tocopherol supplementation, even at supraclinical doses, fails to increase vCSF alpha-tocopherol levels. This lack of change may be due to limited passage across the blood-brain barrier or very rapid alpha-tocopherol metabolism. All prior negative studies on efficacy of alpha-tocopherol in PD may need reevaluation in light of these pharmacologic data.

Dose-Response Relationship, Drug↗

Dyslipidemias and the secondary prevention of coronary heart disease.

Dyslipidemias in patients with coronary heart disease confer a greater risk of ischemic cardiac events than comparable dyslipidemias in people free of disease. A major dyslipidemia can be diagnosed in more than 80% of patients with established premature coronary heart disease. These dyslipidemias constitute not only elevations of low-density lipoprotein cholesterol (hypercholesterolemia) but also indicate abnormalities in the metabolism of triglyceride-rich lipoproteins, high-density lipoproteins, and lipoprotein(a). Clinical trials have demonstrated that therapy to lower low-density lipoprotein levels can delay angiographic progression of coronary stenoses and reduce recurrent cardiac event rates. These clinical benefits from low-density lipoprotein cholesterol lowering may occur as early as 6 to 12 months after initiation of therapy. Intervention strategies for dyslipidemias are directed toward lowering the low-density lipoprotein cholesterol fraction to 90 to 100 mg/dl. This approach begins with dietary modification, weight loss, smoking cessation, and aerobic exercise. Patients with hypercholesterolemia refractory to nonpharmacologic intervention require lipid-lowering agents. The choice of lipid-lowering medications is influenced by concomitant abnormalities of lipoprotein metabolism, such as hypertriglyceridemia or hypoalphalipoproteinemia. Treatment of primary dyslipidemias other than hypercholesterolemia may be warranted in the presence of other cardiac risk factors; however, a broader spectrum of clinical trial data is needed to support or refute this contention.

Animals↗

Intraindividual variability of fibrinogen levels and cardiovascular risk profile.

Prospective population studies have established that fibrinogen is an independent predictor for ischemic heart disease and stroke. These study conclusions have prompted recommendations that fibrinogen determinations be included in the cardiovascular risk profile. The routine availability of fibrinogen measurements may result in widespread screening prior to establishing the validity of a single fibrinogen level as an accurate descriptor for individual subjects. The objectives of this study were to describe the methodological and intraindividual components of variability in fibrinogen measurements determined by using the Clauss method; to establish the usefulness of a single fibrinogen measurement on risk stratification and retest reproducibility; and to determine the influence of intraindividual fibrinogen variability on sample size estimates. Fibrinogen levels were measured by a modification of the Clauss method. Three cohorts of apparently healthy, nonsmoking volunteers were recruited. The single-day intra-individual component of fibrinogen variability was determined in 39 subjects. For the 5-day intraindividual component of fibrinogen variability, 32 subjects were recruited, and in the 6-week intraindividual study, 28 subjects were included. The coefficient of variation for the methodological component of fibrinogen variability was 5.8% as determined from batch analyses, but the intraindividual coefficient of variation for replicate measures on a single day was 10.7%. The 5-day intraindividual coefficient of variation was 14.2%, and for the 6-week period it was 17.8%. Based on the 6-week data, an average of four fibrinogen measures is required to reduce misclassification error to less than 10%. Sample size estimates were made based on predetermined levels of statistical power and the 6-week intraindividual and interindividual variability estimates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship of plasma alpha tocopherol to index of clinical severity in individuals with sickle cell anemia.

Several parameters of micronutrition related to antioxidant activity are reduced in individuals with sickle cell anemia (SCA). The data presented here suggest that vitamin E, specifically alpha tocopherol, has a significant correlation (r = -0.38, P < 0.04) with a retrospective survey of clinical events and a significant correlation with a prospective survey of clinical events (r = -0.42, P < 0.03). The survey of clinical events score takes into account important vaso-occlusive manifestations in SCA. Differences in plasma vitamin E levels explained about 15% of the variability in the clinical manifestations of SCA in the population studied. Previously reported data from our lab suggests that the differences in alpha tocopherol levels are not related to dietary intake. Vitamin E may play an important role in modulating the ability of sickle hemoglobin containing erythrocytes to produce vaso-occlusion. Alternatively, it may simply be a marker of disease activity. Studies are ongoing at our center to determine if the relationship of alpha tocopherol to clinical events is causal.

Adult↗

Serum cholesterol, beta-carotene, and risk of lung cancer.

This paper hypothesizes that beta-carotene mediates the association between low serum cholesterol and increased risk of lung cancer, predicts that the association should be greater in population strata with low intake of beta-carotene than in those with high intake if the hypothesis is correct, and investigates this prediction with data from a 24-year cohort study of 1,960 middle-aged employed men. In the total cohort, serum cholesterol was not related to risk of lung cancer. The relative risk associated with a difference of -1.0 mmol per liter in serum cholesterol was 1.01 (95% confidence interval of 0.80-1.27) after adjustment for cigarette smoking, age, and intake of beta-carotene. In contrast, however, when the study group was restricted to men with intake of beta-carotene less than 5,000 (N = 929) or less than 3,000 IU per day (N = 272), comparable relative risks were 1.10 and 1.21, respectively. Although the 95% confidence intervals for these relative risks were broad and included unity, the result is consistent with expectation. We conclude that the hypothesis warrants further investigation.

Adult↗

Selected indices of micronutrient status in adult patients with sickle cell anemia (SCA).

In 24 adults with hemoglobin SS followed at the Duke University Comprehensive Sickle Cell Center, we have studied the following nutritional parameters: reduced ascorbic acid; dehydroascorbic acid; alpha and beta carotenes; cryptoxanthin; and alpha and gamma tocopherols in whole blood, washed red blood cells, plasma, or serum. In the same population we also examined reduced glutathione (GSH) and oxidized glutathione (GSSG). Fifteen of these 24 patients also were interviewed for usual dietary intakes using a 28-day dietary history. Data obtained from patients with hemoglobin SS, sickle cell anemia (SCA) were compared to those found for seven healthy normal black adults of similar age. Plasma alpha tocopherol levels were significantly lower in SCA individuals than those of the controls (P less than 0.004). Alpha and gamma tocopherol levels in sickle RBCs were significantly higher than those from RBC suspensions of control subjects (P less than 0.007, and P less than 0.001, respectively). All serum values for carotenoids examined, specifically, beta carotene, alpha carotene, and cryptoxanthin were also markedly depressed when compared to those of healthy controls (P less than 0.001, P less than 0.002, and P less than 0.001, respectively). No other statistically significant differences were found between the two groups for any of the remaining variables, including dietary estimates. Dietary analyses suggest that dietary intakes of SCA individuals exceeded the recommended daily allowances (RDA) of all macro- and micronutrients measured, and intakes of most nutrients exceeded those of black controls interviewed. These results suggest that in individuals with SCA, several micronutrients vital to maintaining reducing capacity are present in diminished quantities in plasma/serum. These anomalies exist in SCA patients even though their intake of these micronutrients are similar to those of healthy black men and women.

Adult↗

Comparison of vitamin E levels in plasma, bronchoalveolar lavage, and lung tissues of adult pulmonary patients.

Plasma, bronchoalveolar lavage fluids (BAL), and lung parenchyma were analyzed for vitamin E and polyunsaturated fatty acid (PUFA) concentrations in three groups of patients routinely receiving oxygen therapy--two with adult respiratory distress syndrome (ARDS and SARDS), a third with pneumonia (PNEU), as well as a fourth group of patients receiving little or no oxygen therapy (OTHER). Only plasma alpha- and gamma-tocopherols were significantly lower in patients receiving oxygen therapy compared to those not requiring oxygen. Among diagnosis groups, PNEU patients exhibited highest levels of alpha-tocopherol in BAL, though all groups on oxygen had greater amounts of alpha-tocopheryl quinone in BAL as compared to those of the OTHER group. No significant differences in BAL measures were observed between oxygen and non-oxygen groups, however. No statistical tests on lung measures could be performed between these groups because of insufficient sampling for the OTHER group. A highly significant relationship was observed (r = +0.73, p less than 0.004) between plasma vitamin E and lung vitamin E when expressed in terms of PUFA, whereas no significant relationship was observed if plasma vitamin E and lung vitamin E levels were compared directly. No relationship was obtained for BAL alpha-tocopherol (expressed per number of cells) and lung alpha-tocopherol. These findings support previous reports that in an appropriate setting plasma vitamin E:PUFA ratios along with smoking status may be used to evaluate lung vitamin E levels when also expressed in terms of PUFA.

Age Factors↗

Effects of hyperoxia and diet on murine tissue levels of vitamin E and polyunsaturated fatty acids.

One hundred eighty-six adult female mice were studied to examine the effect of manipulating dietary vitamin E and fractional inspired oxygen concentrations (FiO2) on tissue levels of vitamin E, total polyunsaturated fatty acids (TPUFA) and conjugated dienes (CD) as an index of lipid peroxidation. Animals were fed custom diets containing either 0, 50 or 150 ppm DL-alpha-tocopheryl acetate. Once plasma vitamin E levels of mice fell below 0.2 mg/dl (at week 19), all mice were placed in chambers containing either room air (FiO2 approximately 0.21) or FiO2 greater than 0.95 for the next 72 hr. Dietary manipulation had a major impact on the levels of vitamin E in plasma, lung and perirenal adipose tissues (p less than 0.0001, p less than 0.0001 and p less than 0.005, respectively). Dietary vitamin E deprivation was associated with significant reductions in lung glutathione peroxidase (GPX) activities (p less than 0.05) and in plasma TPUFA levels (p less than 0.05). No significant effect attributable to either diet or FiO2 was observed for liver vitamin E, liver TPUFA or lung TPUFA levels, or for those of CD in any tissue examined. Adipose TPUFA levels were depressed in all dietary groups exposed to FiO2 greater than 0.95, when compared with those of groups exposed to room air. The high FiO2 exposures also were associated with marked reductions in lung to body weight ratios (p less than 0.01). These data suggest that dietary vitamin E treatment after long-term feeding can modify vitamin levels in plasma, lung and adipose tissues, and lung GPX activities. Vitamin E levels in liver seemed less responsive to our dietary manipulations in adult female mice, though expressing liver vitamin E levels in terms of TPUFA revealed significant differences between the ratios from 0 and 150 ppm vitamin E groups (p less than 0.05).

Animals↗

Analyses of vitamin C in biological samples with an emphasis on recent chromatographic techniques.

AA analyses are rife with problems - but primarily stability of the sample AA and specificity are the most prevalent shortcomings of the assays reviewed. Should one desire to quantify AA alone with no consideration for DHAA or DKG, chromatographic separations such as those described by Nahrwold (1981) with reductants added to samples and standards using UV detection, or Iwata et al. (1985) with fluorescence or Tsao and Salimi (1982) with EC detection would probably be appropriate depending upon the equipment available. The initial preparation of sample must be tested to ensure that no spontaneous oxidation of AA occurs during the sample preparation. The main advantage of these chromatographic assays is simply that one is measuring AA directly. On the other hand, manual assays such as that proposed by Zannoni et al. (1974) or Samyn (1983) have apparently demonstrated sufficient specificity and sensitivity to be used as well. When other vitamin C compounds need to be quantified, chromatographic assays should be considered but the selection is largely dependant on the sample size (and thus sensitivity required), the possible interfering compounds, and the detector available. Ideally HPLC should ensure the specificity by resolving the compounds of interest from artifacts. However, the optical characteristics of DHAA and DKG which are quite different from that of AA and detection limitations have fostered a number of complicated manipulations to quantify the former.

2,3-Diketogulonic Acid↗

Intra- and interindividual variation in measurements of beta-carotene, retinol, and tocopherols in diet and plasma.

Twenty-four men were studied for 4 wk to estimate intra- and interindividual variation of retinol, beta-carotene, and tocopherols in diet and plasma. Ratios of intra- to interindividual variances ranged from 0.62 for beta-carotene in plasma to 6.02 for vitamin E in diet. Results indicate that 3-9 independent measurements may be required to distinguish reliably even large differences (approximately 1 SD) in these micronutrients; 28-86 independent measurements may be needed for small differences (approximately 0.25 SD). If uncontrolled, large ratios of intra- to interindividual variance can constitute an important source of error in studies of micronutrients.

Adult↗

Effects of vitamin E deficiency on the relative incorporation of 14C-arachidonate into platelet lipids of rabbits.

THe potential influence of vitamin E in vivo on the transformation of 14C-arachidonate (14C-ArA) in washed platelets from vitamin E-depleted, pair-fed control and ad libitum-fed control rabbits was investigated. We considered rabbits vitamin E-depleted when their plasma total tocopherol levels were less than 50% of initial values. By week 7 deficient rabbits exhibited significantly lower (p less than 0.01) plasma and platelet tocopherol levels and significantly higher (p less than 0.01) urinary creatine:creatinine ratios than those of controls. Thrombin treatment of platelet suspensions that were previously incubated with 14C-ArA resulted in significantly greater (P less than 0.05) losses of radiolabel from phospholipids (PL) and significantly greater (P less than 0.05) 14C incorporation into prostaglandin E2 (PGE2) fractions from deficient animals than those of either control group. The significantly greater (P less than 0.05) losses in lipid phosphorus content of phosphatidylcholine (PC) fractions corroborated the significantly diminished (P less than 0.05) radiolabel detected in the PC fraction of deficient animals with thrombin activation. Such findings suggest an enhancement of thrombin-induced phospholipase A2 (PLPA) activity in platelets of vitamin E-deficient rabbits compared to that of controls.

Animals↗

Nutritional status of white college students in Virginia.

The nutritional status of the fifty men, fifty-three women, and forty-seven women taking oral contraceptives--all white--between the ages of seventeen and twenty-two years--as reflected by height-weight measurements, hemoglobin-hematocrit values, and dietary records, was similar or slightly better than reported by other investigators. Low hemoglobin values were observed in 2 to 4 per cent of these students, and low hematocrits, in 8 to 17 per cent. Similar hemoglobin and hematocrit values were observed in all women, regardless of whether they were taking oral contraceptives. Exercise patterns; use of vitamin-mineral supplements, "pot," alcoholic beverages, special diets; whether subjects ate alone; where subjects ate; snacking; number of meals consumed daily; whether subjects had ever been diagnosed as being anemic; and what subjects thought of their food habits did not affect hemoglobin or hematocrit. Iron intakes of many of the women students were below the allowance.

Adolescent↗

Vitamin E status of young women on combined-type oral contraceptives.

Differences in vitamin E status between young Caucasian women using oral contraceptives (OCs) for 1 yr or more and control females were obtained with regard to the following parameters: 1) hemolysis, 2) plasma total tocopherols by spectrophotometric analysis, 3) individual tocopherols by a thin-layer gas-liquid chromatographic (TLC-GLC) technique, and 4) dietary intakes of vitamin E, polyunsaturated and saturated lipids, cholesterol and kilocalories. Ten subjects were on Ortho-Novum- or Norinyl-1/50, 8 on Ortho-Novum- or Norinyl-1/80, and 10 had never taken OCs. Analyses of 24-hr recalls and 7-day dietary records revealed no significant differences among groups for intakes of nutrients listed above. No significant differences among groups were observed from hemolytic values. Plasma total tocopherol concentrations measured by spectrophotometric and TLC-GLC techniques revealed that OC-1/80 subjects had significantly lower values than controls. Marginally inadequate vitamin E status as assessed by the various techniques was observed in approximately one subject in the control and OC-1/50 groups and in 2 of the OC-1/80 women. Large individual variations in vitamin E status were observed for subjects in all groups on similar estimated vitamin E intakes. TLC-GLC measurements of total tocopherols in plasma seemed to be perhaps a more sensitive indicator of vitamin E status of subjects than spectrophotometric analysis of tocopherols.

Adolescent↗