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Biomedical subjects

D McGee

Publications and source records attributed to D McGee.

At least 19 recordsLinked to original sources

Advanced glycation end-products and methionine sulphoxide in skin collagen of patients with type 1 diabetes.

AIMS/HYPOTHESIS: We determined whether oxidative damage in collagen is increased in (1) patients with diabetes; (2) patients with diabetic complications; and (3) subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, with comparison of subjects from the former standard vs intensive treatment groups 4 years after DCCT completion. SUBJECTS, MATERIALS AND METHODS: We quantified the early glycation product fructose-lysine, the two AGEs N (epsilon)-(carboxymethyl)lysine (CML) and pentosidine, and the oxidised amino acid methionine sulphoxide (MetSO) in skin collagen from 96 patients with type 1 diabetes (taken from three groups: DCCT/EDIC patients and clinic patients from South Carolina and Scotland) and from 78 healthy subjects. RESULTS: Fructose-lysine was increased in diabetic patients (p<0.0001), both with or without complications (p<0.0001). Controlling for HbA(1c), rates of accumulation of AGEs were higher in diabetic patients than control subjects, regardless of whether the former had complications (CML and pentosidine given as log(e)[pentosidine]) or not (CML only) (all p<0.0001). MetSO (log(e)[MetSO]) also accumulated more rapidly in diabetic patients with complications than in controls (p<0.0001), but rates were similar in patients without complications and controls. For all three products, rates of accumulation with age were significantly higher in diabetic patients with complications than in those without (all p<0.0001). At 4 years after the end of the DCCT, no differences were found between the previous DCCT management groups for fructose-lysine, AGEs or MetSO. CONCLUSIONS/INTERPRETATION: The findings suggest that in type 1 diabetic patients enhanced oxidative damage to collagen is associated with the presence of vascular complications.

Adult↗

Psychiatric nurses' perspectives of spirituality and spiritual needs during an amalgamation.

The purpose of this study was to explore the meaning of spirituality and how the spiritual needs of psychiatric nurses could be supported at work during a hospital amalgamation. Forty-six nurses completed the General Information Questionnaire and described the meaning of spirituality and how their spiritual needs could be supported. Data were analysed by the double-coding qualitative method. The themes identified for the meaning of spirituality included: being hopeful, having belief/belief systems, maintaining relatedness/connectedness and the expression of spirituality. The major themes identified to support nursing staffs' spiritual needs at work included communication, offering hope, being valued and support from spiritual sources. Nurses expressed the importance of spirituality in their lives and the need for spiritual support at work. Data for addressing staff spiritual needs are reported; however, further studies are needed to understand the spiritual needs of nursing staff at work during hospital amalgamations.

Adult↗

Nuclear magnetic resonance-determined lipoprotein subclass profile in the DCCT/EDIC cohort: associations with carotid intima-media thickness.

AIMS: To relate nuclear magnetic resonance lipoprotein subclass profiles (NMR-LSP) and other lipoprotein-related factors with carotid intima-media thickness (IMT) in Type 1 diabetes. METHODS: Lipoprotein-related factors were determined in sera (obtained in 1997-1999) from 428 female [age 39 +/- 7 years (mean +/- SD)] and 540 male (age 40 +/- 7 years) Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) participants. NMR quantifies chylomicrons, three very low-density lipoprotein (VLDL) subclasses, intermediate density lipoprotein (IDL), three low-density lipoprotein (LDL) subclasses, two high-density lipoprotein (HDL) subclasses, mean VLDL, LDL and HDL size, and LDL particle concentration. Conventional lipids, ApoA1, ApoB and Lp(a) and in vitro LDL oxidizibility were also measured. IMT was determined (in 1994-1995) using high-resolution B-mode ultrasound. Relationships between IMT and lipoproteins were analysed by multiple linear regression, controlling for age, diabetes-related factors, and cardiovascular disease (CVD) risk factors. RESULTS: IMT associations with lipoproteins were stronger for the internal than the common carotid artery, predominantly involving LDL. Internal carotid IMT was positively (P < 0.05) associated with NMR-based LDL subclasses and particle concentration, and with conventional LDL-cholesterol and ApoB in both genders. Common carotid IMT was associated, in men only, with large VLDL, IDL, conventional LDL cholesterol and ApoB. CONCLUSIONS: NMR-LSP reveals significant associations with carotid IMT in Type 1 diabetic patients, even 4 years after IMT measurement. NMR-LSP may aid early identification of high-risk diabetic patients and facilitate monitoring of interventions. Longer DCCT/EDIC cohort follow-up will yield CVD events and IMT progression, permitting more accurate assessment of pre-morbid lipoprotein profiles as determinants of cardiovascular risk in Type 1 diabetes.

Adult↗

Lack of association between androgen receptor polymorphisms and bone mineral density or physical function in older men.

Individuals whose androgen receptors have short polyglutamine tracts (resulting from CAG repeats) may have greater receptor signaling activity of the androgen receptor. We evaluated the association between bone mineral density (BMD) and CAG repeats in 91 older men with normal (control) and low femoral neck (EN) BMD (OP) or a history of femoral fracture (FX). Bioavailable testosterone (BioT) and physical performance, including composite score (EPESE) and physical activity (PASE), were also measured. Comparing FX, OP, and control subjects, we observed BMD Tscores of -2.16 +/- 1.08, -2.26 +/- 0.74, and -0.20 +/- 0.40 (p < 0.001); CAG repeat lengths of 21.9 +/- 2.7, 22.5 +/- 2.4, and 22.3 +/- 2.9 (p = 0.63); BioT levels of 2.29 +/- 1.25, 2.19 +/- 1.11, and 3.99 +/- 1.25 nmol/L (p < 0.001); EPESE scores of 8.0 +/- 3.0, 9.7 +/- 2.0, and 11.3 +/- 0.9 (p < 0.001); and PASE scores of 91 +/- 66, 122 +/- 66, and 200 +/- 55 (p < 0.001), respectively. There were no significant correlations between CAG repeats and BioT or physical performance. Men with osteoporosis or fracture had lower BioT, physical performance, and physical activity than controls. This study found no association between CA G repeats and FN BMD in older men with normal or low BMD or FX.

Aged↗

Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.

BACKGROUND: Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts. RESULTS: Based on the structural differences between the S1 sites of Ser190 and Ala190 protease-arylamidine complexes, we amplified the selectivity of amidine inhibitors toward uPA and against tPA, by factors as high as 220-fold, by incorporating a halo group ortho to the amidine of a lead inhibitor scaffold. Comparison of K(i) values of such halo-substituted and parent inhibitors toward a panel of Ser190 and Ala190 proteases demonstrates pronounced selectivity of the halo analogs for Ser190 proteases over Ala190 counterparts. Crystal structures of Ser190 proteases, uPA and trypsin, and of an Ala190 counterpart, thrombin, bound by a set of ortho (halo, amidino) aryl inhibitors and of non-halo parents reveal the structural basis of the exquisite selectivity and validate the design principle. CONCLUSIONS: Remarkable selectivity enhancements of exceptionally small inhibitors are achieved toward the uPA target over the highly similar tPA anti-target through a single atom substitution on an otherwise relatively non-selective scaffold. Overall selectivities for uPA over tPA as high as 980-fold at physiological pH were realized. The increase in selectivity results from the displacement of a single bound water molecule common to the S1 site of both the uPA target and the tPA anti-target because of the ensuing deficit in hydrogen bonding of the arylamidine inhibitor when bound in the Ala190 protease anti-target.

Animals↗

Reliability and validity of the CANDID--a needs assessment instrument for adults with learning disabilities and mental health problems.

BACKGROUND: People with learning disabilities and mental health problems have complex needs. Care should be provided according to need. AIM: To develop a standardised needs-assessment instrument for adults with learning disabilities and mental health problems. METHOD: The Camberwell Assessment of Need for Adults with Developmental and Intellectual Disabilities (CANDID) was developed by modifying the Camberwell Assessment of Need (CAN). Concurrent validity was tested using the Global Assessment of Functioning (GAF) and the Disability Assessment Schedule (DAS). Test-retest and interrater reliability were investigated using 40 adults with learning disabilities and mental health problems. RESULTS: CANDID scores were significantly correlated with both DAS (P < 0.05) and GAF scores (P < 0.01). Correlation coefficients for interrater reliability were 0.93 (user), 0.90 (career), and 0.97 (staff ratings); for test-retest reliability they were 0.71, 0.69 and 0.86 respectively. Mean interview duration was less than 30 minutes. CONCLUSIONS: The CANDID is a brief, valid and reliable needs assessment instrument for adults with learning disabilities and mental health problems.

Adult↗

Relation between body mass index and body fat in black population samples from Nigeria, Jamaica, and the United States.

Body mass index (BMI) is the most commonly used measure of obesity. Recently, some investigators have advocated direct measurement of adiposity rather than use of the BMI. This study was undertaken to determine the ability of BMI to predict body fat levels in three populations of West African heritage living in different environments. A total of 1,054 black men and women were examined in Nigeria, Jamaica, and the United States during 1994 and 1995. A standardized protocol was used to measure height, weight, waist and hip circumferences, and blood pressure at all sites; percentage of body fat was estimated using bioelectrical impedance analysis. Percentage of body fat and BMI were highly correlated within site- and sex-specific groups, and the resulting r2 ranged from 0.61 to 0.85. The relation was quadratic in all groups except Nigerian men, in whom it was linear. The regression coefficients were similar across sites, yet the mean body fat levels differed significantly (p < 0.001) as estimated by the intercept, making intersite comparison difficult. Compared with BMI, percentage of body fat was not a better predictor of blood pressure or waist or hip circumference.

Adult↗

Serum distribution of lipoprotein(a) in African Americans and Nigerians: potential evidence for a genotype-environmental effect.

Differences in lipoprotein(a) [Lp(a)] levels across populations have been described and blacks are known to have higher Lp(a) values compared to whites. However, environmental factors which influence Lp(a) levels have been difficult to identify. We took advantage of the large environmental contrast which exists against a common genetic background between U.S. and Nigerian blacks to examine the relationship between Lp(a) and apolipoprotein(a) magnitude of apo(a) isoforms. Although the distribution of Lp(a) and apo(a) isoforms was nearly Gaussian in both populations, mean serum Lp(a) values were significantly higher in the United States than in Nigeria (20.5 vs. 12.7 mg/dl; P = 0.0001) and U.S. blacks had a higher frequency of the large molecular weight isoforms compared to Nigerians. Similar trends in the relationship between apo(a) isoform and Lp(a) concentration were seen in both populations; however, the magnitude of the effect was different. Compared to the Nigerians, U.S. blacks had significantly higher mean Lp(a) values for the same apo(a) isoform. The association of Lp(a) with low density lipoprotein-cholesterol (LDL-C) level was not significant after correcting for the contribution of Lp(a) cholesterol to LDL-C in both populations. Surprisingly, the association between Lp(a) and total-C remained significant (r = 0.20, P = 0.04) after similar correction for the contribution of Lp(a) cholesterol in the U.S. sample. Understanding the relationship between other factors including lifestyle characteristics capable of influencing total-C may help explain the unusually high Lp(a) level observed in this U.S. population.

Adult↗

A pilot study of cervical screening in an inner city area--lessons for a national programme.

The objectives of this study were to examine aspects of organization of a proposed national screening programme based in general practice. The target population of women aged 25-59 years and their general practitioners (GPs), in a defined inner city area, was identified from a population register of persons eligible for free medical services; a computerized system was developed for invitations and record linkage of cytology results. Smears were examined in one laboratory and follow up of women with abnormal smears was undertaken by one gynaecologist. A random sample of non-responders was surveyed by questionnaire. Response following two invitations was only 20%. Practices with male doctors only had significantly lower response rates (P < 0.001) than those with a female doctor/nurse. A survey of non-responders showed that over 20% of addresses were incorrect and 16% of those interviewed were ineligible for smear tests. A preference for a female to undertake smears was expressed by 67%, and 77% believed that the purpose of the cervical smear was to detect cancer. An accurate population register, health promotion, support for GP practices, provision of alternative venues for smear tests, development of computer systems, accurate data entry and fail-safe follow up are aspects of a cervical screening service which must be addressed prior to setting up a national service.

Adult↗

Simultaneous monitoring of heart rate and motion to assess energy expenditure.

Measurement of energy expenditure in free-living individuals represents a methodologic challenge in epidemiologic research. Heart rate monitors, while closely tied to energy expenditure at high levels of energy output, provide much less predictive power at low levels; however, measurement of motion may improve the predictive ability. This study was undertaken to determine the usefulness of simultaneously monitoring heart rate and motion for the estimation of energy expenditure. Ten subjects were studied during simulated activities of daily living (ADLC) and submaximal treadmill tests. Compared to direct measurement, the motion sensor predicted oxygen consumption poorly (r2 = 0.53) for both tests. Heart rate measured simultaneously yielded an r2 of 0.81 for ADLC and 0.90 for the treadmill. Addition of motion data increased the r2 value for the ADLC for all but one individual and increased the group mean from 0.81 to 0.86. This improvement was not observed for the treadmill, confirming the hypothesis that the principle value of monitoring motion occurs at lower heart rates.

Activities of Daily Living↗

The prevalence of hypertension in seven populations of west African origin.

OBJECTIVES: This study was undertaken to describe the distribution of blood pressures, hypertension prevalence, and associated risk factors among seven populations of West African origin. METHODS: The rates of hypertension in West Africa (Nigeria and Cameroon), the Caribbean (Jamaica, St. Lucia, Barbados), and the United States (metropolitan Chicago, Illinois) were compared on the basis of a highly standardized collaborative protocol. After researchers were given central training in survey methods, population-based samples of 800 to 2500 adults over the age of 25 were examined in seven sites, yielding a total sample of 10014. RESULTS: A consistent gradient of hypertension prevalence was observed, rising from 16% in West Africa to 26% in the Caribbean and 33% in the United States. Mean blood pressures were similar among persons aged 25 to 34, while the increase in hypertension prevalence with age was twice as steep in the United States as in Africa. Environmental factors, most notably obesity and the intake of sodium and potassium, varied consistently with disease prevalence across regions. CONCLUSION: The findings demonstrate the determining role of social conditions in the evolution of hypertension risk in these populations.

Adult↗

Obesity in the Caribbean.

People of African origin who live in the Caribbean share a common genetic heritage but live in socioeconomic environments that diverge widely. A cross-cultural study of males and females from Jamaica, St. Lucia and Barbados investigated the prevalence of hypertension and its environmental determinants. Standardized measurement techniques allowed comparable measurements of weight, height, waist and hip circumferences, and blood pressure. The population values for body mass index (BMI), per cent overweight (males BMI > or = 27.8 kg/m2; females BMI > or = 27.3 kg/m2) and per cent obese (males BMI > or = 31.1 kg/m2; females BMI > or = 32.3 kg/m2) are presented. Prevalence of hypertension is based on the age-adjusted total population. The gradient in per capita gross national product in Jamaica, St. Lucia and Barbados parallels the gradient in the proportions of population in those countries who are obese. BMI explained 26% of the variance in blood pressure in females and 13% in males. Obesity is a significant problem in the Caribbean, as it is in many other developing countries, and it is associated with a high prevalence of hypertension, particularly in women.

Body Composition↗

Obesity in peoples of the African diaspora.

People of African descent in the Caribbean and the USA originated from the Bight of Benin in West Africa. Although these populations share a common genetic heritage, they now live under different socioeconomical conditions. Assuming genetic similarity, a cross-cultural examination of these peoples in West Africa, the Caribbean and the USA may attenuate the effect of genetic factors and allow the assessment of environmental contributions to a biological outcome. We carried out an epidemiological survey to determine the prevalence of hypertension and the contribution of risk factors to the variation in blood pressure. We measured the height, weight, waist and hip circumferences, and blood pressure of adults in Nigeria, Cameroon, Jamaica, St. Lucia, Barbados and the USA. In urban populations there was a trend towards increasing weight, height, body mass index, and proportions of those overweight and obese going from West Africa to the USA, with the Caribbean being intermediate. The prevalence of hypertension lay on a similar gradient. Given a common genetic susceptibility, urbanization and western acculturation are therefore associated with increasing hypertension and obesity.

Adult↗

Standardization of blood pressure measurement in an international comparative study.

In the context of a collaborative study on the epidemiology of hypertension in populations of West African origin procedures for standardization of the measurement of blood pressure were evaluated. Comparisons of mean levels of blood pressure, which in large part determine prevalence rates, are highly sensitive to differences in technique. While rotating a single field team may be the ideal approach to multisite studies, it is not practical in international collaborative research. Appropriate techniques to standardize multiple teams over a long period of time have not been well developed, however. In the present study 8981 individuals were examined in eight sites in six countries with the standard mercury sphygmomanometer. An evaluation of the effectiveness of central training, site visits, monitoring of digit preference, and the use of an electronic device for internal standardization is described. In all but one of the sites reliability was high and comparable to the observers at the Coordinating Center. Digit preference for the entire set of measurements was limited (frequency of terminal zero = 23.5% for systolic and 28.9% for diastolic readings) and could be shown to have virtually no effect on prevalence rates or correlation estimates. Mean differences among observers within a given site and between sites were small (+/- 0-5 mmHg). While logistically complex, these methods can provide the basis for standardization in international comparative blood pressure surveys.

Adult↗

Patterns of comorbidity and mortality risk in blacks and whites.

Comorbidity, the co-existence of multiple chronic conditions in a single individual, has been shown to modify the prognosis of disease states. To estimate disease burdens within and among racial subpopulations of the United States, we examined cross-sectional patterns of comorbidity and their impact on survival using data from the NHANES-1 Epidemiologic Follow-up Study (NHEFS). We considered the occurrence of four cardiovascular conditions: stroke, coronary heart disease, hypertension and diabetes. We summarize the joint occurrence of these four conditions using these different methodologies: the number of conditions occurring in each individual and two summaries that weight the conditions according to their prognostic significance. Using all three methodologies, we found an excess burden of chronic disease in black women as compared with white women. Black men had an excess burden compared to white men for the first two methodologies. However, when we model the relationship of the joint occurrence of the conditions to subsequent mortality, black men and white men are seen to have a similar burden. This similarity of black and white men is due to an interaction between race and prevalent stroke in men that we hypothesize may be due to the small number of black men available for study. Given the apparent conditioning effect of co-existing diseases, it is evident that estimation of disease burdens among groups that differ in terms of health status, in particular among U.S. blacks and whites, requires accounting for the occurrence of multiple chronic diseases. Using either the number of conditions or the prognosis weighted summary, we demonstrated a higher burden of the conditions considered in blacks that in whites in a sample of the U.S. population.

Adult↗

Identifying obstructive sleep apnea in patients presenting for laser-assisted uvulopalatoplasty.

The authors report on a series of 850 patients with snoring who were evaluated for laser-assisted uvulopalatoplasty (LAUP). Stepwise multivariate linear regression was employed to correlate patient symptoms and characteristics to the respiratory disturbance index (RDI). Body mass index, falling asleep while driving, snoring every night, and stopping breathing during sleep were found to correlate strongly with an increasing RDI (variance of 25%). Logistic multivariate linear regression analysis was used to predict the outcome of apnea (RDI>10). This model selected all of the above variables, as well as age, male sex, and the total number of symptoms, as being strong predictors of apnea. A receiver operating characteristic curve was used to describe the ability of this model to predict apnea. The authors conclude that otolaryngologists play an important role in the evaluation of OSAS, especially when a snoring patient may undergo LAUP, and they present an algorithm for the evaluation of such a patient. The authors believe that the clinical assessment, including a thorough history and a complete physical examination, remains extremely important in this evaluation. At present, the authors strongly recommend referral for a PSG if there is any suspicion of OSAS.

Adult↗