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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 235 records · Page 13Linked to original sources
PubMed1997

The effects of blood pressure resting level and lability on cardiovascular reactions to laboratory stress.

Evidence that individuals with elevated resting blood pressures display excessive cardiovascular reactions to laboratory stress is regarded as implicating excessive reactivity in the pathogenesis of hypertension. However, it remains possible that this relationship is artifactual, in that resting blood pressure levels and cardiovascular reactions might both reflect intrinsic cardiovascular lability. To examine this possibility, blood pressure and heart rate were measured at rest and in response to an active laboratory stressor in 1259 men. Systolic blood pressure and heart rate reactions to the stressor were predicted by resting blood pressure. Although cardiovascular lability showed some association with both reactivity and resting blood pressure level, the resting blood pressure level-reactivity relationship survived statistical adjustment for such associations. Accordingly, the excessive cardiovascular reactions characteristic of individuals with elevated resting blood pressure would not appear to be explainable, to any substantial extent, by lability effects.

Adult↗
PubMed1997

People, places and coronary heart disease risk factors: a multilevel analysis of the Scottish Heart Health Study archive.

The Scottish Heart Health Study (SHHS), which recruited 5123 men and 5236 women between 1984 and 1986, was set up in part to investigate geographical variation in coronary heart disease in Scotland. Multilevel models are particularly appropriate for such hierarchical data, in which the individuals in the study can be represented by the lower level and the districts in which they live by the higher level. Multilevel models are presented for four coronary heart disease risk factors-diastolic blood pressure, cholesterol, alcohol consumption (defined both as units of alcohol consumed per week and as being a non-drinker) and smoking, for men and women separately. Significant district level variance was found for three out of the four variables studied, after controlling for socioeconomic and other variables considered at the level of the individual. These were for diastolic blood pressure, cholesterol and alcohol. Although the large majority of the variance was present at the individual level, the existence of significant variance at the district level is evidence that places may have a role in the distribution of coronary heart disease risk. Health policy aimed at reducing coronary heart disease should therefore consider the characteristics of places as well as individuals.

Alcohol Drinking↗
PubMed1997

The effects of recent food, alcohol, and tobacco intake and the temporal scheduling of testing on cardiovascular activity at rest and during psychological stress.

Participants in cardiovascular psychophysiological studies receive various instructions regarding restraints on alcohol, food, and tobacco intake prior to testing. Further, although the hour of testing is frequently a concern, little attention is paid to month of the year. In the present study, we examined cardiovascular activity at rest and in response to a laboratory stress task in 1,272 men in terms of these variables. Alcohol consumption among alcohol users and food intake within 4 hr of testing were associated with higher baseline diastolic blood pressure (BP) but lower baseline heart rate (HR). Tobacco use in smokers within 1 hr of testing was associated with elevated baseline BP and HR. Hour of testing was related to baseline HR, whereas month of the year was associated with baseline BP. In contrast to these baseline effects, cardiovascular reactions to the laboratory stress task were largely immune to these contextual influences.

Adult↗
PubMed1997

Influence of cholecystectomy on sphincter of Oddi motility.

BACKGROUND: Gall bladder and sphincter of Oddi (SO) function are coordinated by hormonal and neuronal mechanisms. Nerve fibres pass between the gall bladder and the SO via the cystic duct. It is therefore possible that cholecystectomy may alter SO motility. AIM: To investigate the effect of cholecystectomy on SO function. METHODS: SO manometry was performed in five women (median age 52 years), a few days before and six months after laparoscopic cholecystectomy which was undertaken for uncomplicated cholelithiasis. Basal and post-cholecystokinin (CCK) SO motility were measured. RESULTS: All patients were symptom free after laparoscopic cholecystectomy. Prior to surgery common bile duct pressure, and tonic and phasic SO motility were normal and phasic contractions were inhibited by intravenous CCK (1 Ivy Dog Unit/kg). Six months later, common bile duct pressure and baseline tonic and phasic activity were unchanged but CCK failed to suppress phasic activity. CONCLUSION: Cholecystectomy, at least in the short term, suppresses the normal inhibitory effect of pharmacological doses of CCK on the SO. The mechanism of this effect is unknown but it could be due to SO denervation.

Adult↗
PubMed1997

An evaluation of the cross-linking model for the interaction of insulin with its receptor.

The cross-linking model for insulin receptor interactions, in which a single insulin molecule may form a cross-link between an insulin receptor's alpha-subunits, has been expressed as a formal compartmental model and subjected to a systematic analysis, examining a number of predictions that have been made for this model. The kinetic parameters for the model were obtained by matching data from insulin receptor equilibrium binding studies and rates of formation of the insulin receptor complex. This analytical study has allowed a clear description of the kinetics of the ligand receptor complexes involved in such a mechanism. We conclude that the cross-linking model accounts for the anomaly of the 10-fold concentration difference in high- and low-affinity binding sites found when insulin binding is analyzed by conventional means. However, the phenomenon of acceleration of dissociation of labeled ligand by unlabeled ligand cannot be accounted for as an intrinsic part of the model. We suggest that this phenomenon arises from the destabilization of cross-link formation when a second insulin molecule binds.

Binding Sites↗
PubMed1997

Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes.

Insulin action on adipocytes was studied in the offspring of mothers who had been fed either a control (20% protein) or a low (8%)-protein diet during pregnancy and lactation. Adipocytes isolated from low-protein offspring had significantly higher basal and insulin-stimulated glucose uptakes than controls. This may be related to a threefold increase in insulin receptors in low-protein adipocytes. Consistent with these observed changes in glucose transport, adipocytes from low-protein animals had significantly higher basal and insulin-stimulated insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activities. There was also more p85-associated PI 3-kinase activity in these adipocytes. There was no difference in expression in the p85 regulatory subunit or the p110-alpha catalytic subunit of PI 3-kinase. In contrast, there was a sixfold reduction in the p110-beta catalytic subunit of PI 3-kinase in adipocytes from low-protein animals. These results suggest that poor fetal nutrition during pregnancy and lactation can have long-term effects on glucose transport and on the expression of key components of the insulin signaling pathway in adipocytes.

Adipocytes↗
PubMed1997

Anticonvulsant hypersensitivity: an unfortunate case of triple exposure to phenytoin.

Anticonvulsant hypersensitivity manifests 2 to 12 weeks after patients start taking phenytoin, phenobarbital, or carbemazepine. The syndrome begins with fever followed by a rash that can progress to erythema multiforme, toxic epidermal necrolysis, and multi-organ system involvement. Other common manifestations include lymphadenopathy, facial edema, eosinophilia, and elevated transaminase levels. Anticonvulsant hypersensitivity can be fatal in 5% to 50% of patients if hepatic involvement or toxic epidermal necrolysis occurs. Most evidence regarding the etiology points to a genetically related defect in the detoxification enzyme. Early recognition is important in order to discontinue drug therapy. Continuity of care assists in prevention of re-exposure. Treatment includes supportive measures and steroids. All patients with anticonvulsant hypersensitivity should wear a medical identification bracelet.

Aged↗
PubMed1996

Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in a rat model of mononeuropathy.

We have previously described the changes in spinal cord neuropeptides in the unilateral sciatic chronic constriction injury (CCI) model of Bennett and Xie [Pain, 33 (1988) 87-108] at 28 days, a time of maximum mechanical hyperalgesia. In this study we examine the same model 100-120 days post injury by which time resolution of the hyperalgesia and peripheral nerve injury has occurred according to previous studies. Rats underwent either CCI of the sciatic nerve (n = 12) or else sham operation (n = 8) which involved exposure but no ligation of the nerve. Mechanical hyperalgesia was assessed with a Ugo-Basile analgesymeter and immunohistochemistry performed on the spinal cord sections of the animals and quantified using a confocal microscope. At this late time point CCI rats were no longer significantly mechanically hyperalgesic compared to the sham animals (P > or = 0.09). However, examination of the lumbar spinal cord revealed the following changes. (i) The neuropeptides substance P (SP) (P < 0.0001) and galanin (P < 0.003) both showed decreases of about 30% ipsilaterally in immunoreactivity in laminae 1 and 2 of the dorsal horn compared to the sham operated animals. (ii) Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in laminae 1 and 2 showed no significant changes compared to sham animals. (iii) NPY levels in laminae 3 and 4 of the spinal cord showed a 15% increase in immunoreactivity compared to sham animals (P = 0.008). These results indicate that changes in neuronal markers in the spinal cord can persist after apparent resolution of a peripheral nerve injury. We suggest that these changes may form a substrate for subsequent development of abnormal pain states.

Animals↗
PubMed1996

The characterization of endosomal insulin degradation intermediates and their sequence of production.

Insulin degradation within isolated rat liver endosomes was studied in vitro with the aid of three 125I-insulin isomers specifically labelled at tyrosine (A14, B16 and B26). Chloroquine and 1,10-phenanthroline were used to minimize insulin proteolysis during endosome preparation, whereas the manipulation of endosomal processing of insulin in vitro by Co2+ ions (to activate) and 1,10-phenanthroline (to inhibit) permitted the study of degradation intermediates and their time-dependent production. Structural and kinetic analysis of intermediates isolated from both intra- and extra-endosomal compartments allowed the determination of major cleavage sites and the probable sequence of proteolytic events. It was found that 125I-tyrosine is the ultimate labelled degradation product of all iodo-insulin isomers, suggesting that endosomal proteases are able to degrade insulin to the level of its constituent amino acids. 125I-tyrosine was also the only radiolabelled product able to cross the endosomal membrane. Intra-endosomal insulin degradation proceeds via two inter-related cleavage routes after metalloendoprotease cleavage of the B-chain. One pathway results from an initial cleavage in the centre region of the B-chain (B7-19), probably at B14-15, whereas the major route results from a cleavage at B24-25. B24-25 cleavage removes the B-chain C-terminal hexapeptide (B25-30), which is subsequently cleaved by an aminopeptidase activity to produce first the pentapeptide B26-30 and then 125I-tyrosine. The isolation of intact radiolabelled A-chain from the degradation of 125I-[A14]-insulin suggests that further degradation of proteolytic intermediates containing cleaved B-chain proceeds via interchain disulphide reduction. The A-chain is then processed by several cleavages, one of which occurs at A13-14.

Amino Acid Sequence↗
PubMed1996

Association of cardiovascular disease risk factors with socioeconomic position during childhood and during adulthood.

OBJECTIVE: To investigate strength of associations between risk factors for cardiovascular disease and socioeconomic position during childhood and adulthood. DESIGN: Cross sectional analysis of status of cardiovascular risk factors and past and present social circumstances. SUBJECTS: 5645 male participants in the west of Scotland collaborative study, a workplace screening study. MAIN OUTCOME MEASURES: Strength of association between each risk factor for cardiovascular disease (diastolic blood pressure, serum cholesterol concentration, level of recreational physical exercise, cigarette smoking, body mass index, and FEV1 score (forced expiratory volume in one second as percentage of expected value) and social class during childhood (based on father's main occupation) and adulthood (based on own occupation at time of screening). RESULTS: All the measured risk factors were significantly associated with both father's and own social class (P < 0.05), apart from exercise and smoking (not significantly associated with father's social class) and body mass index (not significantly associated with own social class). For all risk factors except body mass index, the regression coefficient of own social class was larger than the regression coefficient of father's social class. The difference between the coefficients was significant for serum cholesterol concentration, cigarette smoking, body mass index, and FEV1 score (all P < 0.001). CONCLUSIONS: Subjects' status for behavioural risk factors (exercise and smoking) was associated primarily with current socioeconomic circumstances, while status for physiological risk factors (serum cholesterol, blood pressure, body mass index, and FEV1) was associated to varying extents with both past and present socioeconomic circumstances.

Adult↗