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Biomedical subjects

C L Hart

Publications and source records attributed to C L Hart.

At least 37 records · Page 2Linked to original sources

Effects of acute smoked marijuana on complex cognitive performance.

Although the ability to perform complex cognitive operations is assumed to be impaired following acute marijuana smoking, complex cognitive performance after acute marijuana use has not been adequately assessed under experimental conditions. In the present study, we used a within-participant double-blind design to evaluate the effects acute marijuana smoking on complex cognitive performance in experienced marijuana smokers. Eighteen healthy research volunteers (8 females, 10 males), averaging 24 marijuana cigarettes per week, completed this three-session outpatient study; sessions were separated by at least 72-hrs. During sessions, participants completed baseline computerized cognitive tasks, smoked a single marijuana cigarette (0%, 1.8%, or 3.9% Delta(9)-THC w/w), and completed additional cognitive tasks. Blood pressure, heart rate, and subjective effects were also assessed throughout sessions. Marijuana cigarettes were administered in a double-blind fashion and the sequence of Delta(9)-THC concentration order was balanced across participants. Although marijuana significantly increased the number of premature responses and the time participants required to complete several tasks, it had no effect on accuracy on measures of cognitive flexibility, mental calculation, and reasoning. Additionally, heart rate and several subjective-effect ratings (e.g., "Good Drug Effect," "High," "Mellow") were significantly increased in a Delta(9)-THC concentration-dependent manner. These data demonstrate that acute marijuana smoking produced minimal effects on complex cognitive task performance in experienced marijuana users.

Adult↗

Social class differences in lung cancer mortality: risk factor explanations using two Scottish cohort studies.

BACKGROUND: The study investigated differences in lung cancer mortality risk between social classes. METHODS: Twenty years of mortality follow-up were analysed in 7052 men and 8354 women from the Renfrew/Paisley general population study and 4021 working men from the Collaborative study. RESULTS: More manual than non-manual men and women smoked, reported morning phlegm, had worse lung function and lived in more deprived areas. Lung cancer mortality rates were higher in manual than non-manual men and women. Significantly higher lung cancer mortality risks were seen for manual compared to non-manual workers when adjusting for age only and adjustment for smoking reduced these risks to 1.41 (95% CI : 1.12-1.77) for men in the Renfrew/Paisley study, 1.28 (95% CI : 0.94-1.75) for women in the Renfrew/Paisley study and 1.43 (95% CI : 1.02-2.01) for men in the Collaborative study. Adjustment for lung function, phlegm and deprivation category attenuated the risks which were of borderline significance for men in the Renfrew/Paisley study and non significant for women in the Renfrew/Paisley study and men in the Collaborative study. Adding extra socioeconomic variables, available in the Collaborative study only, reduced the difference between the manual and non-manual social classes completely. CONCLUSIONS: There is a difference in lung cancer risk between social classes, in addition to the effect of smoking. This can be explained by poor lung health, deprivation and poor socioeconomic conditions throughout life. As well as anti-smoking measures, reducing socioeconomic inequalities and targeting individuals with poor lung function for help with smoking cessation could help reduce future lung cancer incidence and mortality.

Chi-Square Distribution↗

Are women more sensitive to smoking than men? Findings from the Renfrew and Paisley study.

BACKGROUND: Prescott et al. found that the relative risks associated with smoking for respiratory and vascular deaths were higher for women who inhale than for inhaling men, and found no gender differences in relative risks of smoking-related cancers. The purpose of the present study was to assess whether these findings are reproducible, using data from the Renfrew and Paisley study. METHODS: Age-standardized mortality rate differences and age-adjusted mortality rate ratios (using Cox's proportional hazard model) were calculated for male and female smokers by amount smoked compared with never smokers. These analyses were repeated after excluding non-inhalers. RESULTS: The all-cause mortality rate ratio was higher for men than for women in all categories of amount smoked, although this difference was only statistically significant in the light smokers (1.83 [95% CI : 1.61-2.07] for men and 1.41 [95% CI : 1.28-1.56] for women, P = 0.001). The cause-specific mortality rate ratios tended to be higher for men than for women, and this difference was most substantial for neoplasms (2.57 [95% CI : 2.01-3.29] for male light smokers and 1.35 [95% CI : 1.14-1.61] for female light smokers, P < 0.001) and, in particular, for lung cancer (11.10 [95% CI : 5.89-20.92] for male light smokers and 4.73 [95% CI : 2.99-7.50] for female light smokers, P = 0.03). Furthermore, looking at the rate differences the effects of smoking were uniformly greater in men than in women. These results were virtually unchanged after excluding non-inhalers. CONCLUSION: We found similar results to Prescott et al. when all smokers were considered, but could not reproduce their findings when non-inhalers were excluded. Given the fact that we showed greater rate differences in men than in women, we think that it is too early to conclude that women may be more sensitive than men to some of the deleterious effects of smoking.

Cause of Death↗

Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study.

OBJECTIVES: Though atrial fibrillation (AF) is an important cause of cardiovascular morbidity, there are few large epidemiological studies of its prevalence, incidence, and risk factors. The epidemiological features of AF are described in one of the largest population cohorts ever studied. METHODS: The prevalence and incidence of AF were studied in the Renfrew/Paisley population cohort of 15 406 men and women aged 45-64 years living in the west of Scotland. This cohort was initially screened between 1972 and 1976 and again between 1977 and 1979. Incident hospitalisations with AF in the 20 year period following initial screening were also studied. RESULTS: The population prevalence of AF in this cohort was 6.5 cases/1000 examinations. Prevalence was higher in men and older subjects. In those who were rescreened, the four year incidence of AF was 0.54 cases/1000 person years. Radiological cardiomegaly was the most powerful predictor of new AF (adjusted odds ratio 14.0). During 20 year follow up, 3.5% of this cohort was discharged from hospital with a diagnosis of AF; the rate of incident hospitalisation for AF was 1.9 cases/1000 person years. Radiological cardiomegaly (adjusted odds ratio 1.46) and systolic blood pressure (adjusted odds ratio 2.1 for >/= 169 mm Hg) were independent predictors of this outcome. CONCLUSIONS: Data from one of the largest epidemiological studies ever undertaken confirm that AF has a large population prevalence and incidence, even in middle aged people. More important, it was shown that the long term incidence of hospitalisation related to AF is high and that two simple clinical measurements are highly predictive of incident AF. These findings have important implications for the prevention of AF.

Age Distribution↗

The relation between questions indicating transient ischaemic attack and stroke in 20 years of follow up in men and women in the Renfrew/Paisley Study.

STUDY OBJECTIVE: Transient ischaemic attack (TIA) is often a precursor to stroke, so identification of people experiencing TIA could assist in stroke prevention by indicating those at high risk of stroke who would benefit most from intervention for other stroke risk factors. The objective of this study was to investigate whether answers to a simple questionnaire for TIA could predict the occurrence of stroke in the following 20 years. DESIGN: Prospective cohort study, conducted between 1972 and 1976, with 20 years of follow up. SETTING: Renfrew and Paisley, Scotland. PARTICIPANTS: 7052 men and 8354 women aged 45-64 years at the time of screening completed a questionnaire and attended a physical examination. The questionnaire asked participants if they had ever, without warning, suddenly lost the power of an arm, suddenly lost the power of a leg, suddenly been unable to speak properly or suddenly lost consciousness. These four questions were taken as indicators of TIA and were related to subsequent stroke mortality or hospital admission. MAIN RESULTS: For women, each question was significantly related to stroke risk, whereas for men only the question on loss of power of arm was significantly related to stroke risk. Men and women answering two or more questions positively had double the relative rate of stroke compared with men and women answering none of the questions positively, even after adjusting for other risk factors for stroke. CONCLUSIONS: A simple questionnaire for TIA could help predict stroke over 20 years of follow up. Targeting men and women who report TIA with early treatment could help to prevent strokes from occurring.

Adult↗

Are two really better than one? Empirical examination of repeat blood pressure measurements and stroke risk in the Renfrew/Paisley and collaborative studies.

BACKGROUND AND PURPOSE: Blood pressure measured on 2 occasions in 2 large prospective cohort studies in Scotland was related to stroke, defined as stroke mortality or hospital admission for stroke. The purpose was to investigate whether 2 blood pressure readings gave a more accurate estimate of stroke risk over a long follow-up period than 1 reading. METHODS: In the 1970s, the Renfrew/Paisley general population study investigated 3060 men and 3502 women and the Collaborative study investigated 2683 employed men on 2 occasions. The mean years between screening were 4 and 5, respectively. Blood pressure measured on the 2 occasions was related to stroke risk in 17-year and 21-year follow-up periods after the second screening, respectively. RESULTS: For both systolic and diastolic blood pressure, the mean of the measures on the 2 occasions, the maximum of the 2 measures and the measure corrected for regression dilution was more strongly related to stroke over the follow-up periods than either single measure. CONCLUSIONS: Two blood pressure measurements seem better than 1 for indicating stroke risk. Underestimation using single measures will lead to both misclassification of the risk of disease for individuals and also the population-attributable risk of disease associated with elevated blood pressure.

Adult↗

Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults: the Midspan family study surveys of parents and offspring.

OBJECTIVE: To estimate trends between 1972-6 and 1996 in the prevalences of asthma and hay fever in adults. DESIGN: Two epidemiological surveys 20 years apart. Identical questions were asked about asthma, hay fever, and respiratory symptoms at each survey. SETTING: Renfrew and Paisley, two towns in the west of Scotland. SUBJECTS: 1,477 married couples aged 45-64 participated in a general population survey in 1972-6; and 2,338 offspring aged 30-59 participated in a 1996 survey. Prevalences were compared in 1,708 parents and 1,124 offspring aged 45-54. MAIN OUTCOME MEASURES: Prevalences of asthma, hay fever, and respiratory symptoms. RESULTS: In never smokers, age and sex standardised prevalences of asthma and hay fever were 3.0% and 5.8% respectively in 1972-6, and 8.2% and 19. 9% in 1996. In ever smokers, the corresponding values were 1.6% and 5.4% in 1972-6 and 5.3% and 15.5% in 1996. In both generations, the prevalence of asthma was higher in those who reported hay fever (atopic asthma). In never smokers, reports of wheeze not labelled as asthma were about 10 times more common in 1972-6 than in 1996. With a broader definition of asthma (asthma and/or wheeze), to minimise diagnostic bias, the overall prevalence of asthma changed little. However, diagnostic bias mainly affected non-atopic asthma. Atopic asthma increased more than twofold (prevalence ratio 2.52 (95% confidence interval 1.01 to 6.28)) whereas the prevalence of non-atopic asthma did not change (1.00 (0.53 to 1.90)). CONCLUSION: The prevalence of asthma in adults has increased more than twofold in 20 years, largely in association with trends in atopy, as measured indirectly by the prevalence of hay fever. No evidence was found for an increase in diagnostic awareness being responsible for the trend in atopic asthma, but increased awareness may account for trends in non-atopic asthma.

Adult↗

Role of the kinesin neck linker and catalytic core in microtubule-based motility.

Kinesin motor proteins execute a variety of intracellular microtubule-based transport functions [1]. Kinesin motor domains contain a catalytic core, which is conserved throughout the kinesin superfamily, followed by a neck region, which is conserved within subfamilies and has been implicated in controlling the direction of motion along a microtubule [2] [3]. Here, we have used mutational analysis to determine the functions of the catalytic core and the approximately 15 amino acid 'neck linker' (a sequence contained within the neck region) of human conventional kinesin. Replacement of the neck linker with a designed random coil resulted in a 200-500-fold decrease in microtubule velocity, although basal and microtubule-stimulated ATPase rates were within threefold of wild-type levels. The catalytic core of kinesin, without any additional kinesin sequence, displayed microtubule-stimulated ATPase activity, nucleotide-dependent microtubule binding, and very slow plus-end-directed motor activity. On the basis of these results, we propose that the catalytic core is sufficient for allosteric regulation of microtubule binding and ATPase activity and that the kinesin neck linker functions as a mechanical amplifier for motion. Given that the neck linker undergoes a nucleotide-dependent conformational change [4], this region might act in an analogous fashion to the myosin converter, which amplifies small conformational changes in the myosin catalytic core [5,6].

Adenosine Triphosphatases↗

Comparison of intravenous cocaethylene and cocaine in humans.

RATIONALE: Cocaethylene is a pharmacologically active homolog and metabolite of cocaine, formed by transesterification of cocaine in the presence of ethanol. Here we relate findings from a randomized, placebo-controlled, double-blind study in which we examined the physiological and subjective effects and pharmacokinetics of i.v. administered cocaethylene in human volunteers using cocaine as a comparator. METHODS: Cocaine-dependent participants randomly received one study drug, cocaethylene (0.25 or 0.5 mg/kg), cocaine (0.25 or 0.5 mg/kg), or placebo, during each experimental session which occurred on separate days. RESULTS: Cocaethylene was less potent in elevating heart rate than equivalent doses of cocaine. Similar differences between cocaine and cocaethylene were found for subjective measures ("Cocaine High", "Rush", "Stimulated" and "Good Drug Effects"). All active drug conditions produced significant increases in systolic blood pressure relative to placebo, but no significant effect on diastolic blood pressure was observed. Cocaethylene demonstrated a slower clearance, larger volume of distribution and correspondingly longer elimination half-life than cocaine. CONCLUSION: The findings from this study confirm those of previous studies that show that cocaethylene has pharmacological properties in common with cocaine, but is less potent.

Adult↗

Alternative reinforcers differentially modify cocaine self-administration by humans.

Six experienced cocaine smokers (two men, four women) participated in an inpatient study to compare self-administration of smoked cocaine when either a $5 money or merchandise voucher was available as an alternative reinforcer. A six-trial choice procedure was used, with sessions consisting of (1) one sample trial, where participants received the cocaine dose and the alternative reinforcer available that day, and (2) five choice trials, where participants chose between the available cocaine dose and the alternative reinforcer. There were eight sessions: in separate sessions, each dose of cocaine (0, 12, 25, 50 mg) was paired with a money voucher and with a merchandise voucher. The choice to self-administer cocaine significantly increased with escalating cocaine doses, and significantly less cocaine was self-administered when money vouchers were available as compared to merchandise vouchers. These data demonstrate that money vouchers are a more effective alternative reinforcer than merchandise vouchers in cocaine abusers.

Adult↗

Comparison of risk factors for stroke incidence and stroke mortality in 20 years of follow-up in men and women in the Renfrew/Paisley Study in Scotland.

BACKGROUND AND PURPOSE: The aim of this study was to relate risk factors in middle-aged men and women to stroke incidence (defined by having a hospital discharge with a main diagnosis of stroke) and compare this with the associations between risk factors and stroke mortality. METHODS: In the early to mid-1970s, when they were 45 to 64 years of age, 7052 men and 8354 women from the Renfrew/Paisley prospective cohort study in Scotland were screened. Risk factors measured included blood pressure, blood cholesterol and glucose, respiratory function, cardiothoracic ratio, smoking habit, height, body mass index, preexisting coronary heart disease, and diabetes. These were related to stroke incidence over 20 years of follow-up. RESULTS: Diastolic and systolic blood pressure, smoking, cardiothoracic ratio, preexisting coronary heart disease, and diabetes were positively related to stroke incidence for men and women, whereas adjusted FEV(1) (forced expiratory volume in 1 second) and height were negatively related. Cholesterol was not related to stroke. Glucose for nondiabetic subjects had a U-shaped relationship with stroke. Body mass index was not clearly related to stroke, although participants with the highest body mass index had the highest stroke rate. Former smokers had similar stroke rates to never-smokers. Tests between the associations of risk factors and stroke incidence revealed these were not statistically different from the associations with stroke mortality. CONCLUSIONS: The risk factors had a similar effect on stroke incidence as on stroke mortality. Epidemiological studies with information on stroke mortality are likely to give results applicable to stroke incidence.

Blood Glucose↗

Influence of socioeconomic circumstances in early and later life on stroke risk among men in a Scottish cohort study.

BACKGROUND AND PURPOSE: The purpose of the study was to investigate stroke risk by socioeconomic measures. METHODS: The analysis was based on a large cohort study of 5765 working men, from 27 workplaces in Scotland, who were screened between 1970 and 1973. Stroke was defined as having a hospital admission with a main diagnosis of stroke or dying of stroke in the 25-year follow-up period. RESULTS: There were 416 men who had a stroke. Men with manual occupations when screened, on first entering the workforce, men with manual occupations, and men whose fathers had manual occupations had significantly higher rates of stroke than men in the nonmanual categories. Men who left full-time education at age 16 years or under also had significantly higher rates of stroke. Men living in more deprived areas had higher rates of stroke, but the rates were not statistically significant. The most marked difference was in relation to father's social class, and although adjusting for risk factors for stroke attenuated the relative rates, men whose fathers were in manual social classes had higher relative rates of stroke than men whose fathers were in nonmanual classes (adjusted relative rate for father's social class III manual was 1.37 [95% CI 1.03 to 1.81] and for father's social class IV or V was 1.46 [1.09 to 1.96]). Men who were upwardly mobile (father's social class manual, own social class nonmanual) had a rate of stroke similar to that of stable manual men. CONCLUSIONS: Poorer socioeconomic circumstance was associated with greater stroke risk, with adverse early-life circumstances of particular importance.

Cohort Studies↗

The contribution of risk factors to stroke differentials, by socioeconomic position in adulthood: the Renfrew/Paisley Study.

OBJECTIVES: This study investigated stroke differentials by socioeconomic position in adulthood. METHODS: The relation of risk of stroke to deprivation category and social class was assessed among 6955 men and 7992 women who were aged 45 to 64 years and had been screened in 1972 to 1976. RESULTS: A total of 594 men and 677 women had a hospital admission for stroke or died from stroke. There were large differences in stroke by deprivation category or social class. Adjustment for risk factors (smoking, blood pressure, height, respiratory function, body mass index, cholesterol, diabetes, and preexisting heart disease) attenuated these differences. CONCLUSIONS: Risk factors for stroke can explain some of the socioeconomic differences in stroke risk. Women living in the most deprived areas seem particularly at risk of stroke.

Diabetes Complications↗

The influence of gender, social circumstances and smoking on survival: the Renfrew and Paisley study.

The present study aimed to compare survival to age 75 between men and women, by social circumstances and smoking behaviour. A 20 year follow up was carried out of a large representative cohort of Scottish men and women in the Renfrew and Paisley study, and was combined with Scottish mortality statistics. 6831 men and 7993 women aged 45-64 y at time of examination (between 1972 and 1976) were considered. Combining the estimates from the Renfrew and Paisley study with those from Scottish mortality statistics for men and women younger than 45 y of age, it was calculated that 28% of the male smokers and 44% of the male never smokers in disadvantaged social circumstances will have survived to age 75 y, compared with 46% and 56% of the female smokers and never smokers respectively. In more privileged social circumstances, 41% of the male smokers and 62% of the male never smokers will have survived to age 75 y, compared with 56% and 70% of the female smokers and never smokers respectively. The difference between male smokers in low social classes and female never smokers in high social classes is 42% in absolute terms (28% vs 70%), which gives an indication of the combined influence of gender, social circumstances and smoking on survival. These results show that gender, social circumstances and smoking are important determinants of mortality which have led to substantial differences in survival. The influence of additional factors related to mortality could usefully be compared to these to put their effects into perspective.

Adolescent↗

Objectivity and accuracy of mammogram interpretation using the BI-RADS final assessment categories in 40- to 49-year-old women.

To determine if use of the five final assessment categories of the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS) improved objectivity or accuracy of mammographic evaluation in 40- to 49-year-old women, fifty mammograms of 40- to 49-year-old women that were obtained at a tertiary referral teaching hospital were classified according to those five final assessment categories. The mammograms were blinded to six American Osteopathic Board of Radiology-certified radiologists who were asked to classify each mammogram within the five final BI-RADS categories based on the mediolateral oblique and craniocaudal views presented. No history was allowed. Use of the BI-RADS five final assessment categories provided moderate interobserver objectivity, moderately high agreement among the radiologists' interpretation (reliability), and moderate accuracy of interpretation (validity) when compared to criterion. Moderate interobserver reliability and accuracy has been previously identified; however, no scientific review of the BI-RADS five final assessment categories in 40- to 49-year-old females was discovered in the current literature. No overall improvement of objectivity or accuracy was demonstrated using the five final assessment categories of the BI-RADS lexicon in 40- to 49-year-old women.

Adult↗

A structural change in the kinesin motor protein that drives motility.

Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.

Adenosine Triphosphatases↗