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Biomedical subjects

A Caggiula

Publications and source records attributed to A Caggiula.

17 recordsLinked to original sources
PubMed1997

Acute reinforcing effects of low-dose nicotine nasal spray in humans.

Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers.

Administration, Inhalation↗
PubMed1997

Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.

Blood Pressure↗
PubMed1997

Indexes of food and nutrient intakes as predictors of serum concentrations of nutrients: the problem of inadequate discriminant validity. The Polyp Prevention Trial Study Group.

Nutrient indexes derived from food-frequency questionnaires have generally been regarded as acceptably valid for epidemiologic purposes. Evaluations of these indexes, however, have considered only their convergent validity. We suggest that discriminant validity, or the ability to distinguish among exposures to different nutrients, is also important. Using baseline data from a large clinical trial, we tested the discriminant validity of indexes of intake of vitamin E, alpha-carotene, and beta-carotene. Our results suggest that the vitamin E index possesses neither convergent not discriminant validity, the alpha-carotene index adequate convergent and discriminant validity, and the beta-carotene index adequate convergent but no discriminant validity.

Biomarkers↗
PubMed1996

Relationship to blood pressure of combinations of dietary macronutrients. Findings of the Multiple Risk Factor Intervention Trial (MRFIT).

BACKGROUND: Elevated blood pressure remains a widespread major impediment to health. Obesity and specific dietary factors such as high salt and alcohol intake and low potassium intake adversely affect blood pressure. It is a reasonable hypothesis that additional dietary constituents, particularly macronutrients, may also influence blood pressure. METHODS AND RESULTS: Participants were 11,342 middle-aged men from the Multiple Risk Factor Intervention Trial (MRFIT). Data from repeat 24-hour dietary recalls (four to five per person) and blood pressure measurements at six annual visits were used to assess relationships, singly and in combination, of dietary macronutrients to blood pressure, adjusted for multiple possible confounders (demographic, dietary, and biomedical). Multiple linear regression was used to assess diet-blood pressure relations in two MRFIT treatment groups (special intervention and usual care), with adjustment for confounders, pooling of coefficients from the two groups (weighted by inverse of variance), and correction of coefficients for regression-dilution bias. In multivariate regression models, dietary cholesterol (milligrams per 1000 kilocalories), saturated fatty acids (percent of kilocalories), and starch (percent of kilocalories) were positively related to blood pressure; protein and the ratio of dietary polyunsaturated to saturated fatty acids were inversely related to blood pressure. These macronutrient-blood pressure findings were obtained in analyses that controlled for body mass, dietary sodium and ratio of sodium to potassium, and alcohol intake, each positively related to blood pressure, and intake of potassium and caffeine, both inversely related to blood pressure. CONCLUSIONS: These data support the concept that multiple dietary factors influence blood pressure; hence, broad improvements in nutrition can be important in preventing and controlling high-normal and high blood pressure.

Adult↗
PubMed1996

Nicotine preference in smokers as a function of smoking abstinence.

Overnight smoking abstinence increases desire to smoke and intensity of smoking behavior in smokers, but it is not completely clear that this reflects an increase in reinforcement from the psychoactive effects of nicotine per se. We examined choice of nicotine vs. placebo via nasal spray (Study 1) and nicotine vs. nonnicotine cigarette puffs (Study 2) in separate groups of smokers during each of two sessions, following overnight abstinence vs. no abstinence. In each study, subjects followed a forced choice procedure in which they were instructed to self-administer six sprays/puffs from between the two nasal sprays/cigarettes every 15 min for 2 h following initial exposure to each. In Study 1, choice of nicotine spray (1.5 micrograms/kg per spray) increased significantly following abstinence vs. no abstinence (47 +/- 6% vs. 34 +/- 5%, respectively, p < 0.05). This shift in choice was more pronounced in the subset of smokers (choosers, n = 9 out of 24) who selected nicotine on more than 50% of choices on the abstinent day. Choosers exhibited greater responses to initial nicotine exposure on positive (e.g., pleasant, vigor) but not aversive (e.g., jittery, uneasy) subjective measures, suggesting that greater positive reinforcement from nicotine per se predicted subsequent choice. In Study 2, abstinence similarly increased choice of nicotine vs. nonnicotine cigarette puffs (82 +/- 6% vs. 64 +/- 8%, p < 0.05), although nearly all subjects (12 of 13) preferred the nicotine cigarette following abstinence. These results indicate that choice of nicotine per se, isolated from tobacco smoke, increases significantly after overnight tobacco abstinence.

Adult↗
PubMed1995

Acute tolerance to nicotine in smokers: lack of dissipation within 2 hours.

Greater understanding of development and dissipation of acute tolerance to nicotine may help explain temporal patterns of nicotine self-administration in smokers. The time course of dissipation of acute tolerance to nicotine was examined in 16 smokers (8M, 8F) participating in four sessions differing on pretreatment exposure or time interval prior to nicotine (20 micrograms/kg) challenge: placebo 30 min before, or nicotine (20 micrograms/kg) 30, 60, or 120 min before challenge. Nicotine and placebo were administered by measured-dose nasal spray. The measurement battery consisted of subjective, cardiovascular, thermal pain detection, and behavioral performance measures. Results demonstrated significant acute tolerance (i.e. smaller responses to nicotine challenge following nicotine versus placebo pretreatment) for most subjective measures and for heart rate. Acute tolerance dissipated with lengthening inter-dose interval for two subjective measures, dose strength and arousal, but there was no tolerance dissipation for other measures. In contrast, nicotine pretreatment resulted in acute sensitization of finger temperature (vasoconstriction) response, which dissipated with lengthening interval. No acute tolerance was observed for thermal pain detection or performance measures. These findings demonstrate that acute tolerance develops quickly to some subjective and cardiovascular effects of nicotine. However, acute tolerance to most effects did not dissipate over 2 h, suggesting that, following acute tolerance development during initial exposure, most smokers generally obtain similar magnitude of effects from each subsequent nicotine exposure (i.e. cigarettes smoked later in the day).

Adult↗
PubMed1993

Chronic and acute tolerance to subjective effects of nicotine.

Tolerance to subjective effects of nicotine may induce novice smokers to increase the magnitude and frequency of their nicotine self-dosing. In this study, smokers (n = 8) and nonsmokers (n = 7) participated in three sessions involving presentation of 0, 7.5, or 15 micrograms/kg nicotine 30 min for 2 h via measured-dose nasal spray, with different doses presented on separate days. Subjective responses were assessed using visual analog scales (VASs) of jittery, light-headed, relaxed, dizzy, and head rush, and the Profile of Mood States (POMS) scales of vigor, confusion, fatigue, tension, and the composite scale of arousal. Smaller responses in smokers vs. nonsmokers were viewed as evidence for chronic tolerance. In addition, on each day subjects received a fifth, challenge dose of 30 micrograms/kg 30 min after the previous dosing. Smaller responses to the challenge dose as a function of increasing prior nicotine dosing during Trials 1-4 were viewed as evidence for acute tolerance. Results showed significant changes in most measures as a function of nicotine dose, and the dose-response curves for most VAS and POMS scales tended to be shifted to the right, or dampened, in smokers relative to nonsmokers, consistent with chronic tolerance. However, smokers and nonsmokers tended to respond to nicotine in opposite directions for POMS scales of vigor and arousal, perhaps reflecting withdrawal relief in smokers. Acute tolerance on a few selected VAS and POMS scales was apparent for both smokers and nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Influences of the normal menstrual cycle on physiologic functioning during behavioral stress.

The purpose of this study was to evaluate the influence of the normal menstrual cycle on lipoprotein, cardiovascular, and neuroendocrine stress responses. Fifteen normally-cycling, healthy women participated in a series of behavioral tasks during the menstrual, follicular, and luteal phases of their menstrual cycle. These women had established menstrual cycle regularity for the three months prior to enrollment in this study, were free from menstrual cycle disturbances, biochemically confirmed that they ovulated, and displayed appropriate patterns of reproductive hormone fluctuations during the study period. Heart rate, blood pressure, low density lipoprotein-cholesterol, and total cholesterol all demonstrated significant elevations from baseline levels during tasks. No differences in the magnitude of stress responses during the three menstrual cycle phases were noted for any physiological variable. We conclude that the hormonal fluctuations that occur in healthy, normally-cycling women during the menstrual cycle do not influence the stress responses that were investigated here. Significant influences of menstrual cycle phase previously reported in the literature, albeit not in a consistent direction, may have been due to the recruitment of women with menstrual cycle irregularities, and to the failure to adequately verify menstrual cycle phase.

Adult↗
PubMed1989

Obesity, obesity-related behaviors and coronary heart disease risk factors in black and white premenopausal women.

Obesity is more common in black women than in white women in the USA, but there are few studies comparing black and white females on behaviors related to obesity or on the relationship between obesity and cardiovascular risk factors. We studied 490 white and 48 black premenopausal, nondiabetic, nonhypertensive women, aged 42-50 years, who were participating in the Pittsburgh Healthy Women Study. Black women had a higher BMI than white women and had a higher suprailiac:triceps ratio, suggesting a more central distribution of body fat. Weight gain since age 20 was greater in black women than in white women. Blacks and whites did not differ in caloric intake, smoking or alcohol consumption. However, there were marked differences in physical activity, with blacks reporting significantly less activity than whites. Differences in body fat distribution, weight gain since age 20 and activity remained after adjusting for education. Blacks also had higher blood pressure and poorer glucose tolerance than whites. The low activity level of black women should be considered when designing weight loss interventions.

Adipose Tissue↗
PubMed1985

Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Factor Intervention Trial.

Thiazide-like diuretics cause an increased excretion of magnesium in the urine. Low serum and selected tissue magnesium levels have been reported among diuretic users. Low magnesium levels have been associated with cardiac arrhythmias, neuromuscular changes, and increases in lipoprotein levels. The dietary intake of magnesium is borderline compared with the recommended dietary allowances. Water sources may therefore play an important role. Hard water contains more magnesium than soft water. The authors studied serum magnesium levels among special intervention Multiple Risk Factor Intervention Trial participants in two centers: Pittsburgh, Pennsylvania and Davis, California. These participants were men aged 35-57 years at entry to the trial in 1972-1974; the blood samples were obtained primarily in 1980-1981. Diuretic users primarily of chlorthalidone had an average 1 ppm lower serum magnesium level than nondiuretic users. About 15% of diuretic users had persistently lower magnesium levels on two samples approximately four months apart. The serum magnesium level was not correlated with the serum potassium level. This study is the first long-term follow-up of a well-defined group of hypertensives taking thiazide-like diuretics versus suitable controls. The results suggest that within similar populations, low serum magnesium levels are relatively rare even in the absence of supplementation with magnesium. Specific high-risk populations may exist in which a combination of diuretic therapy and low intake may contribute to magnesium deficiency. Further epidemiologic studies should include monitoring both serum and intracellular levels of magnesium among these potential high-risk groups on diuretic therapy. This approach may offer the best method of testing the relationship between water hardness, minerals, and cardiovascular disease.

Adult↗
PubMed1985

Effective dietary intervention in hypertensives: sodium restriction and weight reduction.

A Dietary Intervention Study of Hypertension (DISH) was undertaken to determine whether patients whose high blood pressure had been controlled pharmacologically for a period of more than 5 years could maintain that control with sodium restriction or weight reduction instead of drugs. Four hundred ninety-six patients, classified by degree of overweight, were randomly assigned into one of seven groups. Included were those who would be withdrawn from antihypertensive medication and receive intervention for either sodium restriction or weight reduction. After 8 weeks of intervention, an average reduction of 24-hour urinary sodium output from a baseline of 158 mEq to 106 mEq (p less than .001) and from 130 mEq to 96 mEq (p less than .01) was achieved for the overweight and nonoverweight groups, respectively. That decline was still maintained at 56 weeks. Dietary estimates, obtained by analysis of 3-day food records, underestimated urinary output by an average of 12%, with blacks more likely to underestimate than whites, and the overweight more likely to underestimate than the nonoverweight. An average 10-lb weight loss was achieved, with no difference between men and women. Weight declined for 32 weeks, then leveled off and was maintained up to 56 weeks, indicating that sodium intake modification can be accomplished faster than weight reduction. Modest sodium restriction and weight reduction are feasible and achievable in a free-living population and have a positive effect on control of hypertension.

Clinical Trials as Topic↗
PubMed1984

Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men.

High-density lipoprotein (HDL) cholesterol is inversely associated with risk of heart attack. Sex hormones have been suggested as possible factors contributing to the gender difference of coronary heart disease risk. Little is known about how endogenous sex hormone concentration might be related to HDL cholesterol. The relation was examined in 225 men participating in the Multiple Risk Factor Intervention Trial. Plasma testosterone concentration was positively correlated with HDL cholesterol and the change in testosterone concentration was also positively correlated with change in HDL cholesterol. The relation between testosterone and HDL cholesterol could not be fully explained by age, relative weight, alcohol consumption and cigarette smoking in the cross-sectional study. However, when this relation was examined longitudinally, the partial correlation between changes in testosterone and HDL cholesterol did not quite achieve statistical significance (0.05 less than p less than 0.10). The biologic process that relates HDL cholesterol to testosterone is not known. The results suggest an inverse relation between plasma estradiol concentration and low-density lipoprotein cholesterol, but no statistical significant correlation with HDL cholesterol. In addition, there was no association noted in the current research between estradiol concentrations and the known determinants of HDL cholesterol.

Adult↗
PubMed1981

Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions.

High density lipoprotein (HDL) cholesterol levels are strongly related to risk of heart attack. Identification of determinants of high density lipoprotein cholesterol may provide important information concerning the cause of heart disease. The relation between one possible determinant, testosterone, and high density lipoprotein cholesterol and other lipoprotein fractions was evaluated in 247 middle-aged men. The results indicate that testosterone levels (both free and total) were positively correlated with high density lipoprotein cholesterol (r = +0.24, p less than 0.01) and negatively correlated with triglycerides and very low density lipoprotein cholesterol. The association between testosterone and high density lipoprotein cholesterol could not be explained by intake of alcohol, obesity, age, smoking or physical activity. Furthermore, the relation of testosterone to HDL cholesterol was independent of the relation of testosterone to very low density lipoprotein (VLDL) cholesterol or triglycerides.

Age Factors↗
PubMed1981

The epidemiology of plasma testosterone levels in middle-aged men.

Several diseases, e.g., coronary heart disease, cancer, etc., have been related to sex hormones. Thus, research on the epidemiology of sex hormones may be productive. The epidemiologic study of testosterone has been limited due to the circadian and circannual variations and the wide interindividual variability. The authors evaluated the reliability and repeatability of a single blood draw to measure individual plasma testosterone levels in three pilot studies. The results indicated that the measurements of the hormone level are highly repeatable and a single morning specimen appeared to be sufficient for characterization of individual testosterone levels. Research then focussed on 243 men in the Multiple Risk Factor Intervention Trial to investigate the determinants of plasma testosterone level. The results indicated that age and obesity were significantly correlated with plasma testosterone level. (The multiple R of these two variables in the multiple regression analysis for plasma total testosterone was 0.32.) Smoking was positively related to testosterone through a relationship with age. Daily physical activity, history of alcohol intake, and behavior factors of A and B behavior types were not found to be related to testosterone concentrations.

Adult↗
PubMedDate not supplied

Putting medical practice guidelines into practice: the cholesterol model.

As more and more medical practice guidelines are developed in the United States, commensurate evaluation efforts should assess their impact on professional practice and patient outcomes. We describe an ongoing research program designed to develop and test practice models for applying the 1988 Adult Treatment Panel Guidelines for the clinical management of high blood cholesterol. Four studies are evaluating different models to assist nonacademic community practices in the detection, evaluation, and treatment of high blood cholesterol. We have designed randomized controlled trials set in solo and small-group primary care practices of family or general practitioners and internists situated in rural, suburban, and urban settings. Patients include adult men and women who represent diverse socioeconomic and ethnic backgrounds. We are measuring rates of cholesterol screening; dietary and drug treatment and follow-up; changes in dietary intake and compliance with drug therapy; changes in quality of life and cost of intervention; and reduction in cholesterol level. Scheduled for completion in 1994, this program will provide insights into practical and effective methods of lipid management. It serves as a model for studying the application of health guidelines in the context of nonacademic primary care practices serving diverse patient populations.

Cholesterol↗