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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 361 records · Page 20Linked to original sources
PubMed1993

Childhood anemia in Africa: to transfuse or not transfuse?

Blood transfusions are an important route for HIV transmission in Africa. To explore whether transfusions are necessary in the case management of childhood anemia, a randomized trial was performed in Ifakara, Tanzania, a holoendemic malaria region. 116 children were randomized to receive either treatment for malaria and hookworm alone or, in addition, a transfusion of whole blood which had been tested negative for antibodies against the human immunodeficiency virus. Mean packed cell volume (PCV) at admission was 14.0% in the transfusion and 14.4% in the no transfusion group. Children were followed up for 8 weeks with measurements of PCV at 2 days, 4 weeks and 8 weeks after study entry. PCV was similar in both groups after 4 and 8 weeks (22.9% in the transfusion and 23.6% in the no transfusion group). There was a trend towards more hospital admissions and deaths in the no transfusion group; however, 95% confidence intervals included both a beneficial and an adverse effect of blood transfusions. The costs and benefits of transfusion for childhood anemia in countries with a high HIV prevalence need to be considered carefully before a rational treatment policy can be adopted. For that purpose, a larger randomized trial is urgently needed.

Anemia↗
PubMed1993

Gender and employment grade differences in blood cholesterol, apolipoproteins and haemostatic factors in the Whitehall II study.

In the first Whitehall study, plasma cholesterol was a strong predictor of coronary heart disease (CHD) but it showed a positive association with grade of employment: the higher the grade the higher the level. Because it could not explain the higher rate of CHD in lower employment grades, further investigation of biochemical CHD risk factors has been conducted with data from the baseline examination of the Whitehall II cohort in 1985-88. These data also allow investigation of gender differences and the effect of menopause. Serum cholesterol (6860 men and 3374 women) and apolipoproteins A-I and B (apo AI and apo B) were measured in those aged 35-55 working in the London offices of twenty Civil Service departments. Plasma fibrinogen and factor VII were determined in 45-55 year olds. The apo B/apo AI ratio (95% confidence interval) after age adjustment is lowest in premenopausal women: 0.557 (0.549-0.565), intermediate in postmenopausal women: 0.601 (0.589-0.613) and highest in men: 0.703 (0.698-0.709). After age adjustment fibrinogen is higher in postmenopausal (2.90 (2.85-2.95) g/l) than in premenopausal women (2.78 (2.71-2.84) g/l), who have higher levels than men (2.64 (2.62-2.67) g/l). A positive association with employment grade is seen for apo AI and a negative association is seen for fibrinogen, apo B (women only) and the apo B/apo AI ratio, after age adjustment. These patterns are consistent with the higher rates of CHD in lower grades. Cholesterol and factor VII show no gradient with our sensitive measure of social position. After adjusting for the effects of smoking rates, alcohol consumption, exercise and dietary pattern, as well as age, ethnicity, body mass index and report of symptoms, the regression coefficient for apo AI on employment grade is reduced by 43% in men and 70% in women. Corresponding reductions for fibrinogen are 53% and 65%. These attenuations suggest that a considerable part of the social gradients in apo AI and fibrinogen are explained by variations in health related behaviours. The remaining gradients may represent effects independent of these behaviours.

Adult↗
PubMed1993

Association between physical and psychological morbidity in the Whitehall II Study.

Mechanisms for the association between psychiatric disorder measured by the General Health Questionnaire and subjective and objective indices of physical illness are examined among 6900 male and 3414 female civil servants aged between 35 and 55 yr from the cross-sectional results of the Whitehall II Study. It was hypothesized that the association between physical illness and psychiatric disorder might be because psychiatric disorder was either secondary to the pain and disability of physical illness, or related to the somatic presentation of psychiatric disorder, or to common causes of both physical and psychiatric illness. Overall health status, and self-reported physical symptoms were strongly associated with psychiatric disorder. Angina in men and severe chest pain in men and women were significantly associated with psychiatric disorder, but electrocardiographic abnormalities were not. Established risk factors for physical illness: alcohol intake in women and men and smoking habit in men were related to psychiatric disorder. Fibrinogen was related to self reported physical symptoms but not psychiatric disorder. The association between psychiatric disorder and self-reported physical symptoms is most likely explained by somatisation and plaintive set. However, psychiatric disorder is likely to be secondary to the pain and disability of conditions such as angina.

Adult↗
PubMed1993

Effects of chloroquine on the dyslipidemia of non-insulin-dependent diabetes mellitus.

The effects of 3-day oral chloroquine phosphate treatment administered at a dosage of 250 mg four times daily on fasting serum levels of lipids, lipoproteins, and apolipoproteins were studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Chloroquine reduced the fasting serum concentrations of total cholesterol (6.16 +/- 0.31 to 5.67 +/- 0.31 mmol/L, P < .05), low-density lipoprotein (LDL) cholesterol (4.38 +/- 0.35 to 3.93 +/- 0.32 mmol/L, P < .05), and apolipoprotein (apo) B (1.46 +/- 0.08 to 1.24 +/- 0.06 g/L, P < .01), and the ratio of apo B to apo A-I (0.81 +/- 0.05 to 0.71 +/- 0.03, P < .05). Chloroquine also caused a decrease in fasting plasma glucose levels (11.1 +/- 0.5 to 9.2 +/- 0.4 mmol/L, P < .01) and an increase in fasting plasma insulin levels (0.12 +/- 0.01 to 0.14 +/- 0.01 nmol/L, P < .01). The decrease in total cholesterol and apo B levels correlated with the increase in fasting plasma insulin levels (r = .35, P = .04 and r = .33, P = .03, respectively), but not with changes in plasma levels of glucose or nonesterified fatty acids (NEFA). This study demonstrates that 3 days of oral chloroquine treatment improves abnormalities of lipoprotein metabolism in patients with NIDDM. This may be due to an increase in insulin levels, but there also appears to be a more direct effect of the drug on apo B metabolism.

Adult↗
PubMed1993

The cultural construction of childhood diarrhoea in rural Nicaragua: relevance for epidemiology and health promotion.

As a component of a series of studies of childhood diarrhoea in rural Nicaragua, lay knowledge regarding the condition and its appropriate management has been investigated through semistructured interviews with 70 mothers. These data have been combined with information from focus group discussions and observations from investigators who have been resident in the study area for many years. For any episode of childhood diarrhoea, the lay nosology influences the treatment path followed. Thus for some types of diarrhoea, treatment at a health centre or health post and the use of rehydration fluids is seen to be appropriate, while for other types the use of traditional healers or home-based treatment, often explicitly without the use of rehydration fluids, is applicable. The implications of lay nosological systems for the interpretation of epidemiological studies and for the implementation of health promotion programmes are discussed.

Adolescent↗
PubMed1993

How many people actually use condoms? An investigation of motel clients in Managua.

Motels in Nicaragua are popular venues for both commercial and non-commercial sexual encounters and thus provide a potential location for the spread of sexually transmitted agents, including the human immunodeficiency virus. Condoms are known to be effective barriers against these infections, but are infrequently used by Nicaraguans. We interviewed all motel owners in one district of Managua and in five randomly selected motels ascertained, by retrieval and inspection, actual rates of condom use by clients. Six out of 26 establishments initially supplied condoms: when provided on entry to the motel condoms were used in 37% of observed encounters. Condom use can be assessed objectively in certain circumstances and this method can provide a reliable outcome measure for condom promotion programmes.

Condoms↗
PubMed1993

The design of prospective epidemiological studies: more subjects or better measurements?

Prospective epidemiological studies which seek to relate potential risk factors to the risk of disease are subject to appreciable biases which are often unrecognized. The inability to precisely measure subjects' true values of the risk factors under consideration tends to result in bias towards unity in the univariate relative risks associated with them--the more imprecisely a risk factor is measured, the greater the bias. When correlated risk factors are measured with different degrees of imprecision the adjusted relative risk associated with them can be biased towards or away from unity. When designing a new prospective study cost considerations usually limit the total number of subject-evaluations that are available. The usual design approach is to maximize the study size and evaluate each subject on one occasion only. An alternative approach involves recruitment of a smaller number of subjects so that each can be evaluated on more than one occasion, thus resulting in a more precise measure of subjects' risk factor values and hence less bias in the relative risk estimates. In this paper we use a simulation approach to show that under conditions that prevail for most major prospective epidemiological studies the latter approach is actually more likely to produce accurate relative risk estimates. This emphasizes the importance of bias due to exposure measurement imprecision and suggests that attempts to anticipate and control it be given at least as high a priority as that given to sample size assessment in the design of epidemiological studies.

Causality↗
PubMed1993

The complete sequence and gene organization of the short unique region of herpesvirus of turkeys.

The DNA sequence of the whole of the short unique region (U(s)) and that of part of the short terminal repeat (TRs) of herpesvirus of turkeys (HVT) were determined. HVT U(s) is 8.6 kbp long and contains eight potential open reading frames (ORFs). Seven of these have counterparts in the U(s) of herpes simplex virus type 1 (HSV-1). The homologous proteins include US1, US2, US10, protein kinase (US3) and the glycoproteins gD, gI and gE. In addition, HVT contains one ORF which has a counterpart in the U(s) of Marek's disease virus (MDV) but is not homologous to any other known herpesvirus gene. Although HVT and MDV proteins encoded by U(s) genes have evident similarities with proteins encoded by alphaherpesviruses, multiple alignment analysis of predicted amino acid sequences show that HVT proteins are more closely related to MDV proteins than to homologous proteins of mammalian alphaherpesviruses. The percentage amino acid identity between HVT and MDV U(s)-encoded proteins ranges from 35 to 65, the most conserved protein being encoded by the homologues of the HSV-1 US2 gene. Most of the genes are colinear with those of HSV-1 except US10 which is transposed in HVT and MDV. A characteristic feature of HVT is the fact that approximately two-thirds of the gE gene is located in the inverted repeats flanking U(s).

Amino Acid Sequence↗
PubMed1993

Identification and sequence analysis of the homologues of the herpes simplex virus type 1 glycoprotein H in Marek's disease virus and the herpesvirus of turkeys.

The glycoprotein H (gH) genes of two avian herpesviruses, Marek's disease virus and the herpesvirus of turkeys, have been cloned and sequenced and the coding regions found to be of 2439 and 2424 nucleotides respectively. The predicted primary polypeptide products of these open reading frames are 813 and 808 amino acids and correspond to Mrs of 90,800 and 91,100. Both amino acid sequences exhibit characteristic glycoprotein features such as hydrophobic signal and anchor sequences and potential sites for N-linked glycosylation. Polypeptide sequence comparison to the other eight available gH sequences revealed more similarity to the alphaherpesvirus subgroup than to either beta- or gammaherpesviruses.

Amino Acid Sequence↗
PubMed1993

Post-exertion dizziness as the sole presenting symptom of autonomic failure.

An otherwise fit young man, leading an active life, whose only complaint at presentation was dizziness after extreme exertion is described. He was found later to have postural and exercise induced hypotension. Subsequently, he developed typical symptoms of autonomic failure, with postural dizziness, urinary abnormalities, and erectile failure. Progression of autonomic failure was documented on testing. A fall in blood pressure during or after exercise has been reported previously in pure autonomic failure, but a presentation with exercise induced symptoms alone is unusual.

Adult↗
PubMed1993

Magnitude and causes of mortality differences between married and unmarried men.

STUDY OBJECTIVE: To determine the effect of marital status on mortality for men. In particular, to examine whether subgroups of unmarried men (widowed, single, and divorced/separated men) have a similar mortality to married men. DESIGN: Cohort study. SETTING: Whitehall civil service, London, between 1967 and 1969. PARTICIPANTS: A total of 18,403 men aged 40-64 years with 18 years' follow up. MEASUREMENTS AND MAIN RESULTS: Cause-specific mortality rates and risk factors at baseline were determined. Overall mortality was greater for all groups of unmarried men. Patterns of mortality were different in the subgroups of unmarried men. Widowed men had a significantly greater risk of dying from ischaemic heart disease (relative risk (RR) 1.46, 95% confidence interval (CI) 1.08, 1.97) which persisted after exclusion of deaths that occurred in the first two years. Divorced men had greater cancer mortality (RR 1.49; 95% CI 1.06, 2.10) that could not be explained simply by their greater consumption of cigarettes. The initial increased mortality for single men was no longer evident after adjustment for other risk factors, suggesting that single status in itself may not increase the risk. The risk for single men may have been underestimated, however, by over adjustment for possible intermediary factors. CONCLUSIONS: Previous studies, which have examined total mortality only or have grouped all unmarried men, have masked interesting differences in the cause of death between subgroups of unmarried men. The extent to which the findings are explicable by psychosocial factors or the role of other environmental factors, which may also differ in relation to marital status, is unclear. Future work should not assume that all unmarried men have similar mortality risks and must examine the life course of each subgroup to advance our understanding of the possible causal role of marital status in disease aetiology.

Adult↗
PubMed1993

Acute effects of ethanol on hepatic endocytosis and processing of insulin in perfused rat liver.

This study utilizes the perfused rat liver combined with subcellular fractionation and compartmental analysis to investigate the effects of ethanol on hepatic uptake, endocytosis, and processing of insulin. At 4 min after the start of a 2-min pulse of radiolabeled insulin, increasing ethanol concentrations progressively inhibited insulin uptake by the liver (57% at 50 mM ethanol). Subcellular fractionation of the perfused livers showed a progressive shift in distribution from a predominantly endosomal location (control) to a bimodal distribution between endosomes and plasma membrane. This could be largely accounted for by a specific reduction in the endosome-associated insulin. Binding studies showed no changes in the binding properties of the plasma membrane insulin receptor. Compartmental analysis of the perfusate efflux curves confirmed the lack of effect of ethanol on the binding constants but showed a significant decrease in the endocytic rate constant (50%) together with an increase in the retroendocytic rate constant (33%). Simulation studies with the compartmental model showed that these changes could account for the observed decrease in uptake by the liver. No changes were found in the subsequent endocytic degradation of insulin.

Animals↗
PubMed1993

Five-compartment model of insulin kinetics and its use to investigate action of chloroquine in NIDDM.

We have constructed a five-compartment model of insulin kinetics. The model structure was chosen to reflect insulin distribution in systemic plasma, hepatic plasma, and interstitial fluid and insulin binding to the liver and peripheral receptors, and it included receptor-mediated and non-receptor-mediated insulin degradation. Model parameters were estimated from plasma insulin concentrations measured during hyperinsulinemic euglycemic clamp studies. In the fasting condition, the model-derived mean residence time of endogenously secreted insulin was 71 min, of which 62 min were spent bound to the liver receptor, 6 min bound to the peripheral receptor, 2 min circulating in hepatic or systemic plasma, and 1 min in the interstitial fluid. More than 80% of total insulin was bound to the liver receptor, indicating that the liver is by far the largest insulin reservoir. The model was employed to assess the effect of chloroquine on insulin kinetics in patients with non-insulin-dependent diabetes mellitus (NIDDM). Chloroquine significantly altered parameter vector. However, the mean residence times of insulin in the system and in the periphery were not affected, indicating that the beneficial effect of chloroquine in patients with NIDDM under conditions of euglycemia could not be attributed to changes in insulin kinetics.

Chloroquine↗
PubMed1993

AIDS in Nicaragua: epidemiological, political, and sociocultural perspectives.

The AIDS epidemic in Nicaragua is several years behind that in the United States and neighboring countries of Central and South America. A combination of events, including the isolation caused by the war of the U.S.-backed Contra army against the Sandinista government, the complete economic embargo imposed on Nicaragua by the United States in 1985, self-sufficiency for blood products, and a low rate of recreational injectable-drug use, have contributed to this situation. Since the Sandinistas were defeated in the general election of 1990, people have returned to Nicaragua from areas where HIV is more prevalent, such as Honduras and the United States. It is probable that many HIV-infected persons have now entered the country. Because of the high rates of sexually transmitted diseases and cultural factors such as "machismo," HIV is likely to spread rapidly by heterosexual transmission, unless effective, culturally appropriate education and sexually transmitted disease prevention programs are implemented now.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Risk factors for the development of type II diabetes among men enrolled in the usual care group of the Multiple Risk Factor Intervention Trial.

OBJECTIVE: To study the association between selected risk factors and the subsequent incidence of type II diabetes over a 5-yr period. RESEARCH DESIGN AND METHODS: Between 1973 and 1976, a cohort of men from 22 clinical centers throughout the U.S. enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial. The men (5420 white, 428 black, 56 Asian, 70 Hispanic, and 26 other) were nondiabetic at baseline, were in the upper 15% of risk for coronary heart disease, and had at least two annual follow-up visits for fasting glucose measurements. The average age was 46 yr and average body mass index was 27.6 kg/m2. Incidence of diabetes was defined as use of insulin or hypoglycemic agents, fasting glucose > or = 140 mg/dl on two consecutive annual visits, or fasting glucose > or = 140 mg/dl followed the next year by insulin or hypoglycemic use. Observations were taken annually over a 5-yr period. RESULTS: Cumulative incidence of diabetes over 5 yr was 4.1%, with 247 incident cases. Development of diabetes was directly associated with race (blacks higher than non-blacks), reported parental history of diabetes, and with baseline levels of body mass index, fasting glucose, and glucose 1 h after a 75-g oral glucose load. These associations were statistically significant in both univariate and multivariate models. A significant interaction was observed between race and reported parental history of diabetes in development of diabetes, particularly within black men who reported a parental history. These individuals had higher than expected rates of diabetes development. CONCLUSIONS: The data from men in the Usual Care group enrolled in the Multiple Risk Factor Intervention Trial confirm previous findings regarding the associations between the development of diabetes and baseline glucose levels, obesity, race, and parental history of diabetes. The identification of these risk factors provides very powerful tools to identify individuals at high risk of diabetes mellitus who may be amenable to intervention, thereby reducing their risk of developing the disease and its complications.

Adult↗