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Biomedical subjects

P Sweetnam

Publications and source records attributed to P Sweetnam.

At least 19 recordsLinked to original sources

Leg length, insulin resistance, and coronary heart disease risk: the Caerphilly Study.

BACKGROUND: Adult height has been inversely associated with coronary heart disease risk in several studies. The mechanism for this association is not well understood, however, and this was investigated by examining components of stature, cardiovascular disease risk factors and subsequent coronary heart disease in a prospective study. METHODS: All men aged 45-59 years living in the town of Caerphilly, South Wales were approached, and 2512 (89%) responded and underwent a detailed examination, which included measurement of height and sitting height (from which an estimate of leg length was derived). Participants were followed up through repeat examinations and the cumulative incidence of coronary heart disease-both fatal and non-fatal-over a 15 year follow up period is the end point in this report. RESULTS: Cross sectional associations between cardiovascular risk factors and components of stature (total height, leg length and trunk length) demonstrated that factors related to the insulin resistance syndrome-the homeostasis model assessment of insulin resistance, fasting triglyceride levels and total to HDL cholesterol ratio-were less favourable in men with shorter legs, while showing reverse or no associations with trunk length. Fibrinogen levels were inversely associated with leg length and showed a weaker association with trunk length. Forced expiratory volume in one second was unrelated to leg length but strongly positively associated to trunk length. Other risk factors showed little association with components of stature. The risk of coronary heart disease was inversely related to leg length but showed little association with trunk length. CONCLUSION: Leg length is the component of stature related to insulin resistance and coronary heart disease risk. As leg length is unrelated to lung function measures it is unlikely that these can explain the association in this cohort. Factors that influence leg length in adulthood-including nutrition, other influences on growth in early life, genetic and epigenetic influences-merit further investigation in this regard. The reported associations suggest that pre-adult influences are important in the aetiology of coronary heart disease and insulin resistance.

Anthropometry↗

Birthweight, body-mass index in middle age, and incident coronary heart disease.

BACKGROUND: Several studies have shown a relation between fetal development, as shown by birthweight, and later coronary heart disease. This study investigated whether this relation is predominantly the consequence of early life exposures, or can best be explained in terms of an interaction between influences in early life and in adulthood. METHODS: This prospective study in Caerphilly, South Wales, included 1258 men, aged 45-59 at initial screening, who were able to provide birthweight data. These men are from an initial cohort of 2512 men, from whom information has been obtained in a series of examinations since 1979 on health-related behaviours, incidence of coronary heart disease, and risk factors. The main outcome measure was fatal and non-fatal coronary heart disease during 10 years of follow-up. FINDINGS: Higher birthweight was related to lower risk of coronary heart disease during the follow-up period: coronary heart disease occurred in 46 (11.6%) men in the lowest birthweight tertile, 44 (12.0%) of those in the middle tertile, and 38 (9.1%) of those in the highest tertile (p = 0.03). Stratification of the cohort by body-mass index (BMI) revealed a significant interaction such that the inverse association between birthweight and risk of coronary heart disease was restricted to men in the top tertile of BMI (interaction test p = 0.048 adjusted for age, and p = 0.012 fully adjusted). Within the top BMI tertile, coronary heart disease occurred in 19 (16.4%) of men in the lowest birthweight tertile, 13 (12.6%) of those in the middle tertile, and 13 (7.5%) of those in the highest tertile (p = 0.0005). These associations were not changed substantially by adjustment for age, father's social class, own social class, marital status, fibrinogen and cholesterol concentrations, systolic blood pressure, and smoking history. INTERPRETATION: The association between birthweight and risk of coronary heart disease cannot be explained by associations with childhood or adulthood socioeconomic status. Nor do conventional risk factors for coronary heart disease in adulthood account for the association. However, there is an important interaction between birthweight and BMI such that the increased risk of coronary heart disease associated with low birthweight is restricted to people who have high BMI in adulthood. Risk of coronary heart disease seems to be defined by the combined effect of early-life and later-life exposures.

Birth Weight↗

Birthweight, adult risk factors and incident coronary heart disease: the Caerphilly Study.

OBJECTIVE: To determine the relationships between birthweight, the incidence of coronary heart disease, and a range of coronary heart disease risk factors that operate during adult life. DESIGN: Cohort study with a 10-year follow-up period. SETTING: The town of Caerphilly, South Wales, and five adjacent villages. SUBJECTS: 1,258 men aged 45-59 at time of recruitment between 1979 and 1983. MAIN OUTCOME MEASURES: All deaths, coronary heart disease deaths, non-fatal CHD events. RESULTS: The validity of the birthweight data was supported by the strong graded associations between birthweight and anthropometric measures in adulthood, particularly height, body mass index, triceps, skinfold thickness and percentage body fat. An inverse relationship was found between birthweight and incident fatal and non-fatal CHD, (P = 0.01), though no relationship was found between birthweight and all-cause mortality. Amongst the major CHD risk factors, only fibrinogen shows a statistically significant relationship with birthweight (P = 0.008), fibrinogen levels being lower among the men with lower birthweights. When social and biological variables are included in models relating incident CHD and birthweight, the relationship between birthweight and incident fatal and non-fatal CHD remains essentially unchanged. CONCLUSION: A graded association between low birthweight and later CHD has been demonstrated in this cohort. This inverse association cannot be explained by the measured social or behavioural variables, or by other risk factors operating in adult life.

Birth Weight↗

Peripheral vascular disease: consequence for survival and association with risk factors in the Speedwell prospective heart disease study.

OBJECTIVE: To measure the prevalence and incidence of intermittent claudication, to describe the mortality associated wtih the condition, and to assess the relevance of risk factors for vascular disease. DESIGN: A standard questionnaire on calf pain when walking was given in the prospective Speedwell study, and a range of risk factors were measured. The men were re-examined at intervals of three years, and deaths over 11 years were identified. SETTING: The general population. PARTICIPANTS: All men aged 45 to 59 registered with 16 general practitioners. RESULTS: The prevalence of intermittent claudication increased from almost nil at ages 45-49 to 2.9% at ages 60-64. The annual incidence increased from 0.3% in the youngest men to 0.5% in those in their early 60s. Intermittent claudication was related to the existence of ischaemic heart disease, particularly angina, at the first examination. The relative odds of men with angina developing intermittent claudication was 6.7 (95% confidence interval (95% CI) 3.6 to 12.4). The risk of death in men with intermittent claudication was substantially raised. After standardisation for age and smoking the relative odds of death was 3.8 (95% CI 2.2 to 6.5). The excess was entirely from circulatory causes. Systolic blood pressure, fasting plasma glucose, triglycerides, and white cell count were all independently associated with the development of intermittent claudication, but the most striking association was with smoking. CONCLUSIONS: Intermittent claudication is an indicator for a very high risk of death. This is only partly explained by its strong association with ischaemic heart disease.

Age Factors↗

Sequence and expression of a neuropeptide Y receptor cDNA.

The polymerase chain reaction was used to isolate novel GTP-binding protein (G protein)-coupled receptors from bovine locus coeruleus (LC), a brain region enriched in the neuropeptide Y (NPY) system, using degenerate primers derived from the third and sixth transmembrane domains of known G protein-coupled receptors. Partial sequence analysis revealed that the polymerase chain reaction cDNA fragments were homologous to other G protein-coupled receptors. One of these cDNA fragments was used to isolate a full length cDNA clone, referred to as LCR1, from an LC cDNA library. LCR1 is 1.7 kilobases in length and encodes a predicted protein of 353 amino acids, with a membrane topology similar to that of other G protein-coupled receptors. Expression of LCR1 in mammalian cells revealed saturable and specific high affinity binding for 125I-NPY but not for any of the other ligands tested. Northern blot analysis revealed that labeled LCR1 DNA hybridized with a predominate mRNA transcript of approximately 1.7 kilobases, which was found to be most abundant in LC, cerebellum, and pons, intermediate in dorsal raphe, substantia nigra, and thalamus, and lowest in cerebral cortex and neostriatum. Significant levels of LCR1 mRNA were also present in heart, kidney, lung, and liver. This cDNA clone will be useful for studies of the regulation and function of NPY receptors, as well as for the isolation of related NPY receptor subtypes.

Amino Acid Sequence↗

Comparison of the molecular structure of GABA/benzodiazepine receptors purified from rat and human cerebellum.

The use of improved affinity chromatographic techniques has allowed for the substantial copurification of both the benzodiazepine and the GABA receptor from brain. These preparations have been used to begin characterization of the benzodiazepine receptor at a molecular level. We have recently purified benzodiazepine receptor from human and rat cerebellum, and SDS-PAGE has revealed that both preparations consist of a major protein of 50 kDa and a minor protein of 55 kDa. These proteins are recognized by a series of monoclonal antibodies prepared against the rat benzodiazepine receptor suggesting the rat and human receptors share several common antigenic domains. Several other approaches have been employed to further investigate possible homology between the rat and human receptors. Proteolytic degradation studies have shown that the major limiting photolabeled peptide fragment generated in rat and human is similar as determined by HPLC analysis. Isoelectric focusing and SDS (two-dimensional) electrophoresis have revealed that the immunoreactive, photolabeled 50 kDa protein, and the purified receptor have identical PI values. The receptor from both human and rat are glycoproteins as determined by lectin binding studies. However, exposure of these proteins to neuraminidase fails to alter the pharmacology of the receptors indicating possible similarities in their posttranslational glycosylation. Thus, it appears that some degree of structural homology exists between the rat and human benzodiazepine receptors.

Animals↗

Automatic measurement of blood pressure: evaluation of the Copal UA-231 automatic sphygmomanometer.

The suitability of an automatic sphygmomanometer for epidemiological work was evaluated in two studies. In the first, blood pressure measurements were made alternately on the automatic machine and on a Hawksley random zero instrument on 14 volunteers on each of four consecutive days by a single medical observer. No significant difference was found between the mean diastolic pressure obtained by each instrument but the mean systolic pressure was 5 mm higher on average on the automatic machine. In the second study, the effect of cuff position for the automatic instrument was examined. Differences between recommended and errant cuff positions of up to 4.5 mmHg were recorded but these did not reach statistical significance. These studies indicate that if used carefully this automatic instrument is suitable for survey and experimental use.

Adult↗

Epidemiology in anaesthesia: a method for predicting hospital mortality.

Data on 13 043 operations were abstracted from 108 878 anaesthetic records in the Cardiff Anaesthetic Record System. Nine groups of surgical operations with high mortality in hospital were identified. These records were analysed using a logistic regression model to determine the probability of death in hospital. Variables included in the model were age, sex, elective or emergency operation and five intercurrent diseases. The significance of individual variables was assessed: age was the most important single variable in six of the nine operation groups. The model was used to calculate the risk of death in hospital for individuals with specific characteristics. With further development, this technique might be used by clinicians at other centres to predict the outcome for patients under their care.

Age Factors↗

The Cardiff Cervical Cytology Study: prevalence of cytological grades and initial histological findings.

Among 45 266 women in the Cardiff Cervical Cytology Survey the peak prevalence of suspicious or positive smears was 11.2/1000 at age 45-50 years and of dyskaryosis 10.2/1000 at age 25-29. A suspicious or positive cytological picture at prevalence testing was associated with occult or clinical invasion in 24% of cases, and only 4% of patients with suspicious or positive smears were normal histologically. When dyskaryosis was detected in the prevalence test 20% had carcinoma in situ or microinvasion and 3% had occult or clinically invasive carcinoma. One hundred and twenty-nine (51%) women with dyskaryotic smears did not have a biopsy initially (that is, within two years of the prevalence test), but they were followed up at regular intervals. Subsequently 15 of the 129 gave smears consistently dyskaryotic or worse cytologically and were subjected to biopsy. Of these, two showed dysplasia, 12 carcinoma in situ, and one clinically invasive carcinoma. These findings emphasise the need for repeat cytological or histological examination in any woman with evidence of dyskaryosis in a cervical smear.

Adult↗

The Cardiff Cervical Cytology Study. Prevalence and epidemiology of cervical neoplasia.

The Cardiff Cervical Cytology Study showed a prevalence of carcinoma-in-situ that rose to a peak of 6.1/1000 in age group 35-44 and then decreased. Prevalence of microinvasive and occult invasive carcinoma rose to peaks of 1.8/1000 and 1.1/1000 respectively in age group 45-54 and then declined. Epidemiological analysis was based on comparison to three groups-dysplasia, carcinoma-in-situ and microinvasive carcinoma combined, and occult and clinical invasive carcinoma combined. For all groups prevalence increased with lower social class, was higher in widowed, divorced and separated women than in married women, and increased with decreasing age at first marriage and at first pregnancy and with increasing number of pregnancies. The magnitude of these association was remarkably similar for all three histological groups. Screening for cervical neoplasia is based on the belief that the various histological categories are part of a continuum, a spectrum of disease, and the existence of a common epidemiological pattern for the three histological groups is consistent with such a hypothesis.

Adult↗

The outcome of pregnancy after cone biopsy of the cervix: a case-control study.

We investigated the outcome of pregnancy after cone biopsy of the cervix. We found that preterm delivery and low birth weight were commoner and the mean duration of labour longer in women who had a cone biopsy than amongst matched controls. Rapid labour (under two hours) was not significantly more common after cone biopsy.

Abortion, Spontaneous↗

Temperature and deaths from ischaemic heart disease.

Certain features of the relationship between 11 measurements of weekly temperature and the number of deaths from ischaemic heart disease (IHD) within age groups in Greater London between 1970 and 1974 are described. Firstly, the correlation coefficients between age-specific deaths from IHD and each of the temperature variables are of a similar order. Secondly, in contrast, the linear regression coefficients between deaths and temperature are more variable and depend upon the particular measurement of temperature chosen. Thirdly, the proportional changes in the number of deaths with the temperature variables are similar within specific age groups; consequently it is suggested that deaths from IHD and temperature may be directly related.

Adult↗

Cardiovascular surveys in areas with different water supplies.

Cardiovascular surveys were conducted in areas with different water supplies. In two areas with hard water 243 men were seen and in three areas with soft water 357 men were seen. There was no evidence of an important difference between the two areas in blood pressure, serum cholesterol, blood sugar, or packed cell volume. A variety of measurements were made on an E.C.G. The P-R interval was significantly longer in the men in the hard water area, and a 40-complex trace showed ventricular extrasystoles in a significantly higher proportion of these men than in those in the soft water area.

Adult↗