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Biomedical subjects

D S Sharp

Publications and source records attributed to D S Sharp.

At least 91 records · Page 5Linked to original sources

The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study.

This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.

Adenosine Diphosphate↗

Pharmacoepidemiology of the effect of caffeine on blood pressure.

In experimental studies, caffeine increases blood pressure in caffeine-naive or nontolerant individuals, but not in regular caffeine consumers. Using an epidemiologic approach, we examined the hypothesis that serum-caffeine concentration would be positively associated with blood pressure in infrequent (but not habitual) caffeine users in a group of bus drivers. Infrequent and habitual users of caffeine showed no differences in systolic or diastolic blood pressures when there is no measurable caffeine in the serum. However, at serum concentrations of caffeine typical of those achieved after one to two cups of coffee, infrequent users demonstrated greater systolic and diastolic pressures, averaging +5.3 mm Hg and +3.6 mm Hg, respectively, compared with habitual users. The magnitude of difference remained after adjustment for age, body mass index, race, sex, and tobacco and alcohol use. These elevations are large enough to exaggerate the prevalence of hypertension, if such assessments are based on cross-sectional surveys that fail to assess both proximate caffeine consumption and usual caffeine consumption habits.

Adult↗

Influence of race, tobacco use, and caffeine use on the relation between blood pressure and blood lead concentration.

A number of studies have suggested a small to moderate positive relation between blood pressure and blood lead concentration in males (2-4 mmHg/In(microgram/dl]. However, this 1986 study of San Francisco bus drivers suggests larger relations in black males (n = 132) for both systolic pressure (7.5 mmHg/In(microgram/dl] and diastolic pressure (4.7 mmHg/In(microgram/dl] at very low blood lead concentrations (2-21 micrograms/dl). This increase appears to result from negative confounding, particularly after taking into account tobacco use. Relations are even larger in blacks who infrequently use caffeine (16.7 and 10.4 mmHg/In(microgram/dl) for systolic and diastolic pressure, respectively). In contrast, a negative relation between systolic pressure and blood lead concentration (-5.7 mmHg/In(microgram/dl] is suggested in nonblack males (n = 117). These findings indicate that race, lead accumulation, and physiologic effects related to caffeine use (e.g., catecholamine effects) may interact to produce marked differences in effect on blood pressure.

Black or African American↗

Environmental and biological monitoring for lead exposure in California workplaces.

Patterns of environmental and biological monitoring for lead exposure were surveyed in lead-using industries in California. Employer self-reporting indicates a large proportion of potentially lead-exposed workers have never participated in a monitoring program. Only 2.6 percent of facilities have done environmental monitoring for lead, and only 1.4 percent have routine biological monitoring programs. Monitoring practices vary by size of facility, with higher proportions in industries in which larger facilities predominate. Almost 80 percent of battery manufacturing employees work in job classifications which have been monitored, versus only 1 percent of radiator-repair workers. These findings suggest that laboratory-based surveillance for occupational lead poisoning may seriously underestimate the true number of lead poisoned workers and raise serious questions regarding compliance with key elements of the OSHA Lead Standard.

California↗

Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers.

Blood pressure is, on average, lower in cigarette smokers than in nonsmokers. In a cross-sectional study of 288 normotensive bus drivers, we found a significant inverse correlation between serum cotinine (the major metabolite of nicotine) and systolic and diastolic blood pressure that could not be accounted for by age, body weight, or alcohol consumption. Over the observed range of cotinine values, the average decrease in blood pressure was 10.7 and 7.0 mm Hg for systolic and diastolic blood pressures, respectively. We suggest that cotinine be measured to assess the influence of cigarette smoking in epidemiologic studies of blood pressure.

Adult↗

Blood pressure and blood lead concentration in bus drivers.

San Francisco bus drivers have an increased prevalence of hypertension. This study examined relationships between blood lead concentration and blood pressure in 342 drivers. The analysis reported in this study was limited to subjects not on treatment for hypertension (n = 288). Systolic and diastolic pressures varied from 102 to 173 mm Hg and from 61 to 105 mm Hg, respectively. The blood lead concentration varied from 2 to 15 micrograms/dL. The relationship between blood pressure and the logarithm of blood lead concentration was examined using multiple regression analysis. Covariates included age, body mass index, sex, race, and caffeine intake. The largest regression coefficient relating systolic blood pressure and blood lead concentration was 1.8 mm Hg/ln (micrograms/dL) [90% C. I., -1.6, 5.3]. The coefficient for diastolic blood pressure was 2.5 mm Hg/ln (micrograms/dL) [90% C. I., 0.1, 4.9]. These findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.

Adult↗

Regression analysis in biological research: sample size and statistical power.

Regression analysis is often used to demonstrate associations among variables believed to be biologically related. Failure to demonstrate a "significant" relationship may be due to two factors: 1) the variables are truly unrelated, or 2) a relationship exists but goes undetected due to inadequate statistical power. Investigators must consider the second possibility since failure to detect a statistically significant relationship is often taken as evidence for no biological relationship. These issues are addressed in the context of the interrelationship between four features common to all statistical methods: the size of effect or relationship worth detecting, the Type I (alpha) error, the sample size, and the Type II (beta) error. An example derived from published data relating morphological characteristics of muscle fiber type and isokinetic strength performance illustrates the practical significance of this dilemma.

Regression Analysis↗

Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia.

One hundred and six patients were studied whose cervical smears showed only non-specific inflammatory changes. Screening for genital pathogens yielded only a few positive cases. Histological examination of biopsy specimens taken by colposcopically directed tissue sampling showed cervical intraepithelial neoplasia in 13 of the women (12.3%). Deoxyribonucleic acid (DNA) hybridisation techniques were used to detect human papillomavirus, which was found in 24 patients (22.6%). In a second group of 104 patients with normal cervical cytology tissue biopsy samples were obtained and examined histologically but in no case was cervical intraepithelial neoplasia found. On DNA hybridisation, however, 12 patients (11.5%) were found to be positive for human papillomavirus. In this group finding human papillomavirus DNA was usually associated with a columnar ectopy. An association between human papillomavirus type 16 DNA and both cervical intraepithelial neoplasia and cervical cancer is well established. In this study it was type 16 which occurred most frequently in both groups.

Adult↗

The influence of muscle metabolic characteristics on physical performance.

This study describes the influence of muscle fiber type composition, enzyme activities and capillary supply on muscle strength, local muscle endurance or aerobic power and capacity. Muscle biopsies were obtained from m. vastus lateralis in thirteen physically active men. Histochemical staining procedures were applied to assess the percentage of fast twitch (FT) fibers, muscle fiber area, and capillary density. Also, the activity of citrate synthase (CS), creatine kinase (CK), hexokinase (HK), lactate dehydrogenase (LDH), and phosphofructokinase (PFK) were analysed using fluorometrical assays. Peak torque at 'low' and 'high' angular velocities was measured during leg extension. Similarly, muscle fatigue (e.g. peak torque decline) and recovery from a short-term exercise task were measured during maximal, voluntary consecutive leg extensions. Aerobic power (VO2max) and aerobic capacity (e.g. onset of blood lactate concentration; OBLA), as defined by a blood lactate concentration of 4 mol X 1(-1) were measured during cycling. Peak torque at a high angular velocity was positively correlated with % FT area (p less than 0.001). Fatigue and recovery were correlated with LDH X CS-1 (p less than 0.001). WOBLA was best correlated with PFK and PFK X CS-1 (p less than 0.001). Hence, muscle strength was partly determined by fiber type composition whereas local muscle endurance, recovery and aerobic capacity reflect mainly capillary supply and the activity of key enzymes involved in aerobic and anaerobic metabolism.

Adult↗

Does fever or myalgia indicate reduced physical performance capacity in viral infections?

To study prospectively the effects of a brief febrile viral infection on parameters of muscle and circulatory function, seven volunteers were inoculated with sandfly fever virus and two control subjects with sterile saline. During but not after fever, decreased isometric and dynamic strength and endurance were recorded in various muscles. Impairment could not be explained by altered activities of relevant muscle enzymes in serum or muscle tissue or by altered muscle ultrastructure, but correlated with the severity of perceived symptoms, including myalgia, as rated by each subject. Compared to baseline, cardiac stroke volume was lower during and after fever. During fever, an increased heart rate maintained cardiac output at pre-inoculation values, whereas cardiac output fell in early convalescence. This decrease in cardiac output correlated significantly with the severity of fever. Thus, in brief viral infections a transient impairment of muscle performance capacity is correlated to subjective symptoms such as myalgia, rather than to fever, whereas a decreased cardiac output following such infections seems to be associated with the fever reaction.

Adult↗

A standardized benchmark approach to the use of cancer epidemiology data for risk assessment.

Clarity and scientific validity are two criteria for assessing the quality of communications between scientists and risk managers. Regulating permissible exposures on the basis of very-low-dose risk extrapolation uses scientific information that may not meet either criterion. With regard to clarity, it is difficult for an individual to conceive of the meaning of risks on the order of 1 in 1,000,000 lifetime excess. With regard to scientific validity, the uncertainties of extrapolating risks at very low doses are evident in the wide variation in results produced depending on the statistical and pharmacokinetic assumptions made. An alternative approach is to fix benchmarks from which safety factors are chosen (Gaylor, 1983). For epidemiological data, we propose a benchmark of that exposure which would cause 1% cancer excess with 10 yr of exposure followed by 30 yr of further followup. These values have been chosen at this stage of development since they are close to observable values in many cancer epidemiology studies. In the first stage, excess cancer risk versus duration of exposure is plotted and the excess risk is estimated for a exposure duration of 10 yr. The next step involves a short linear extrapolation from the exposure levels linked with this excess risk to the exposure levels that would cause a 1% excess risk over a duration of 10 yr. We have established preliminary benchmarks from published data for benzene and radon daughter exposure. Permissable exposure levels might then be set by deciding on safety factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogens, Environmental↗

Lactate accumulation in muscle and blood during submaximal exercise.

Muscle and blood lactate concentration was studied in 10 healthy males during cycling exercise. For each subject the exercise intensity corresponding to a blood lactate concentration of 4 mmol.l-1 (OBLAw) was assessed by a step-wise increased exercise intensity protocol. In a second series of experiments the same protocol was performed but exercise was terminated at OBLAw and a muscle biopsy for subsequent analysis of lactate concentration was obtained from m. vastus lateralis. Biopsies were also taken at rest for histochemical determination of fiber type composition and capillary supply. The exercise intensity, which corresponded to OBLAw, averaged 159(117-216) W, equal to 65 (range 55-84)% of VO2max, and was found to be correlated to capillaries per fiber of the exercising muscle (r = 0.83, p less than 0.01). Muscle lactate concentration averaged 6.9 (range 2.1-12.6) mmol.kg-1 w.w. The change in blood lactate concentration (prior to and 1 min post exercise) was correlated to muscle lactate concentration (r = 0.71, p less than 0.05). It is concluded that great individual variations in the muscle/blood lactate gradient do exist during submaximal steady-state exercise, performed at a certain blood lactate level.

Adult↗

The effect of two years' training on aerobic power and muscle strength in male and female cadets.

During their first 2 years of training at the U.S. Military Academy, 11 male and 7 female cadets were studied on five occasions. VO2 max (1/min), lean body mass and body weight increased significantly in both groups. Percent body fat was significantly reduced only after the first summer of training and then returned to initial values. VO2 max (ml/kg.min) did not change in males during the study. However, females increased significantly after the initial 6 weeks of training (44.2 to 48.8 ml/kg.min). They remained at this level through the second summer of training. However, by the end of their second academic year, females' values dropped to 45.9 ml/kg.min. Maximal isometric strength measured 30-40% higher in males than in females. During the last year of training, arm and shoulder strength increased 10.2% in males, but was unchanged in females. Our results suggest that even extended military training did not enable females to significantly narrow the difference with male cadets in muscle strength and aerobic power.

Adult↗