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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 199 records · Page 11Linked to original sources
PubMed1998

Saltatory propagation of Ca2+ waves by Ca2+ sparks.

Punctate releases of Ca2+, called Ca2+ sparks, originate at the regular array of t-tubules in cardiac myocytes and skeletal muscle. During Ca2+ overload sparks serve as sites for the initiation and propagation of Ca2+ waves in myocytes. Computer simulations of spark-mediated waves are performed with model release sites that reproduce the adaptive Ca2+ release observed for the ryanodine receptor. The speed of these waves is proportional to the diffusion constant of Ca2+, D, rather than D, as is true for reaction-diffusion equations in a continuous excitable medium. A simplified "fire-diffuse-fire" model that mimics the properties of Ca2+-induced Ca2+ release (CICR) from isolated sites is used to explain this saltatory mode of wave propagation. Saltatory and continuous wave propagation can be differentiated by the temperature and Ca2+ buffer dependence of wave speed.

Animals↗
PubMed1998

Mortality in men of Irish heritage in West Scotland.

Britons of Irish parentage have been found to exhibit poorer health and to die at a younger age than the general population. This paper expands the investigation of Irish mortality patterns in Britain, to include men with patrilineal Irish descent from the immigration of the 19th and 20th centuries. Five thousand, seven hundred and sixty-six male employees aged between 35 and 64 y were examined in 27 workplace settings in Glasgow, Grangemouth and Clydebank between 1970 and 1973. Twenty-one years' mortality follow-up was analysed from a survey involving a health questionnaire and medical examination, using name analysis to identify those of patrilineal Irish descent. Fitting Cox's proportional hazards model to date of death, using date of birth and Irish names as covariates, resulted in the patrilineal Irish showing elevated mortality from all cases (relative risk 1.22; 95% CI [1.08, 1.38]) and coronary heart disease (relative risk 1.53; 95% CI [1.27, 1.83]). Mortality risk for men with an Irish surname was also elevated for cerebrovascular disease (relative risk 1.30; 95% CI [0.86, 1.95]), respiratory disease (relative risk 1.17; 95% CI [0.73, 1.86]) and injury or poisoning (relative risk 1.42; 95% CI [0.78, 2.61]), although the low numbers of men dying from these causes, meant that differences did not reach statistical significance at the 5% level. No differences were observed for cancer or other causes. Previous work has shown high mortality for second generation Irish, whereas this study indicates high all-cause mortality and an excess of deaths for coronary heart disease in the much larger group of men with patrilineal Irish descent from the immigration of the 19th and 20th centuries.

Adult↗
PubMed1998

Social mobility and 21 year mortality in a cohort of Scottish men.

The objective of this prospective cohort study was to determine the contribution of changes in social class within and between generations to mortality risk and to socioeconomic differentials in mortality. In 27 workplaces in the west of Scotland. 5567 men aged 35-64 years when screened, provided information on their father's occupation, their own first occupation and their occupation at screening. Mortality risk, from broad causes of death by intergenerational and intragenerational social mobility groups, was measured after 21 years. For all or some of the 3 routes of mobility (childhood to screening, labour market entry to screening and childhood to labour market entry), increasing values were seen across the 4 groups (stable non manual, upwardly mobile, downwardly mobile and stable manual) for diastolic blood pressure, body mass index, current smoking, early school leaving, angina, bronchitis, severe chest pain, and proportion living in deprived areas. Decreasing values were seen for serum cholesterol, height, FEV1, exercise, never and ex-smokers, wine drinkers and car users. For mobility between childhood and screening and between childhood and labour market entry, mortality risk was highest for the stable manual group and lowest for the stable non manual group for all cause, cardiovascular disease and other causes of death. The upwardly and downwardly mobile groups had intermediate risks. For cancer mortality, the stable manual group had the highest risk with the other groups having lower and similar risks. For mobility between labour market entry and screening, the highest risk was for the downwardly mobile group for all cause and cardiovascular mortality. For cancer mortality, the risk was higher for men in manual social classes at all occasions. Adjustment for risk factors attenuated but could not completely explain the differentials in mortality risk. Overall, major differences in mortality risk were seen between the stable non manual and the stable manual groups, to which social mobility does not contribute. With the exception of the small intragenerationally downwardly mobile group there was little evidence that social mobility itself was associated with mortality outcomes different from those expected on the basis of lifetime socioeconomic experience. This is consistent with the suggestion that the main influence of socioeconomic position on mortality risk is an accumulative one, acting across the lifecourse.

Adult↗
PubMed1998

Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor complex was accomplished using single wavelength anomalous diffraction data and the direct methods program, Snb v2.0, which produced the positions of all 30 crystallographically distinct selenium atoms. The mode of enzyme-cofactor binding is unique, requiring interactions from two protein monomers. An unusual dual role for a catalytic water molecule in the active site is revealed in the complex with the adenosine analog 2'-hydroxy, 3'-ketocyclopent-4'-enyladenine.

Adenosylhomocysteinase↗
PubMed1998

Hypotensive and regional haemodynamic effects of exercise, fasted and after food, in human sympathetic denervation.

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise. 2. When fasted, blood pressure fell during exercise from 162 +/- 7/92 +/- 4 to 129 +/- 9/70 +/- 5 mmHg (mean arterial pressure by 22 +/- 5%), P < 0.0005. After the meal, blood pressure fell from 159 +/- 8/88 +/- 6 to 129 +/- 6/70 +/- 4 mmHg (mean arterial pressure by 22 +/- 3%), P < 0.0001, and further during exercise to 123 +/- 6/61 +/- 3 mmHg (mean arterial pressure by 9 +/- 3%), P < 0.01. The stroke distance-heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance-heart rate product were greater when fasted. 3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 +/- 0.02 compared with 0.32 +/- 0.06, P < 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 +/- 0.12, P < 0.05 (fasted) and by 47%, to 0.29 +/- 0.05, P < 0.05 (fed). 4. On standing, absolute levels of blood pressure were higher when fasted [83 +/- 7/52 +/- 7 compared with 71 +/- 2/41 +/- 3 (fed), each P < 0.05]. Subjects were more symptomatic on standing post-exercise when fed. 5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.

Cardiac Output↗
PubMed1998

Nitric oxide and gall-bladder motor function.

BACKGROUND: The L-arginine: nitric oxide (NO) pathway has been shown to be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission. AIM: To determine the role of the L-arginine: NO pathway in gall-bladder motor function. METHODS: Strips of fresh bovine and human gall-bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb's solution upon CCK-stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L-NG-monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gall-bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall-bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L-NMMA. RESULTS: In the in vitro study, GTN and SNP significantly reduced the tension of CCK-stimulated muscle contraction whilst Kreb's solution had no effect. L-NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall-bladders. In the in vivo study, both GTN and SNP caused significant impairment of gall-bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L-NMMA. CONCLUSION: Pharmacological doses of NO donors impair postprandial gall-bladder emptying in vivo and relax gall-bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.

Adult↗
PubMed1998

Socio-economic and dietary influences on leg length and trunk length in childhood: a reanalysis of the Carnegie (Boyd Orr) survey of diet and health in prewar Britain (1937-39).

Social class differences in height have been recognised for many centuries. However, few studies have examined the extent to which these differences are made up of differences in leg length or trunk length. This paper reanalyses cross-sectional information on children examined in Britain in the 1930s. We assess associations between socio-economic status and diet and the components of childhood stature. The analyses were based on the records of 2990 children aged 2 years to 14 years 9 months who were examined in the Carnegie (Boyd Orr) survey of diet and health (1937-39). z-Scores for the measures of childhood stature were calculated using polynomial regression techniques with the study population as the standard. Univariable and multivariable statistical techniques were used to assess the relationships between childhood height, leg length and trunk length, and dietary and socio-economic factors measured at the level of the household. Leg length was the component of stature most strongly associated with measures of childhood diet and socio-economic status. A greater part of the difference in stature between socio-economic groups was caused by differences in leg length rather than trunk length. In multiple regression analyses, district of residence and family food expenditure were generally the two factors most strongly related to stature. In a subsample of the surveyed children, for whom birthweight information was available, trunk length and leg length were equally strongly related to birthweight. Leg length appears to be a particularly sensitive indicator of childhood socio-economic circumstances. Although contemporary studies highlight the importance of biological factors in determining childhood height, the data analysed in this study suggest that socio-economic circumstances were also important in explaining height differentials in prewar Britain.

Adolescent↗
PubMed1998

Frequency of somatic and germ-line mosaicism in retinoblastoma: implications for genetic counseling.

Although mosaicism can have important implications for genetic counseling of families with hereditary disorders, information regarding the incidence of mosaicism is available for only a few genetic diseases. Here we describe an evaluation of 156 families with retinoblastoma; the initial oncogenic mutation in the retinoblastoma gene had been identified in these families. In 15 ( approximately 10%) families, we were able to document mosaicism for the initial mutation in the retinoblastoma gene, either in the proband or in one of the proband's parents. The true incidence of mosaicism in this group of 156 families is probably higher than our findings indicate; in some additional families beyond the 15 we identified, mosaicism was likely but could not be proven, because somatic or germ-line DNA from key family members was unavailable. Germ-line DNA from two mosaic fathers was analyzed: in one of these, the mutation was detected in both sperm and leukocyte DNA; in the other, the mutation was detected only in sperm DNA. Our data suggest that mosaicism is more common than is generally appreciated, especially in disorders such as retinoblastoma, in which a high proportion of cases represent new mutations. The possibility of mosaicism should always be considered during the genetic counseling of newly identified families with retinoblastoma. As demonstrated here, genetic tests of germ-line DNA can provide valuable information that is not available through analysis of somatic (leukocyte) DNA.

DNA↗
PubMed1998

Lowering blood pressure: a systematic review of sustained effects of non-pharmacological interventions.

BACKGROUND: Risk factors for raised blood pressure include obesity, physical inactivity, high dietary salt intake, stress, and high alcohol consumption. Much less is known about the effects on blood pressure of modification of these risk factors for the purposes of disease prevention. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to estimate the effects of various non-pharmacological interventions on blood pressure. METHODS: RCTs of single interventions aimed at altering these risk factors among adults aged 45 or older with and without hypertension, and with at least six months follow-up were included. MEDLINE was the primary source and the boundaries of the study were from 1966 to April 1995. RESULTS: The majority of RCTs were of short duration and did not provide guidance on the sustainability of effects and were excluded. Totals of eight RCTs of salt restriction, eight RCTs of weight reduction, eight of stress management, eight of exercise, and one of alcohol reduction of longer than six months duration were found. Net (i.e. intervention - control group) systolic blood pressure changes, mean mm Hg (with 95 per cent confidence intervals in parentheses), in hypertensives were as follows: salt restriction -2.9 (-5.8,0.0), weight loss -5.2 (-8.3,-2.0), stress control -1.0 (-2.3,+0.3), and exercise -0.8 (-5.9,+4.2). Smaller changes were found in normotensive participants: salt restriction -1.3 (-2.7,+0.1), weight loss -2.8 (-3.9,-1.8), exercise -0.2 (-2.8,+2.4), and alcohol reduction -2.1 (-4.1,-0.1). Some interventions (e.g. stress control in normotensives) were not examined in either hypertensives or normotensives. The majority of RCTs were of low methodological quality and bias often tended to increase the changes observed. Few of the trials controlled for the confounding effects of concurrent changes in other blood pressure risk factors. CONCLUSION: These net changes are probably overestimates of the effects that might be achieved by non-pharmacological interventions. There is a need for large-scale, long duration trials of these non-pharmacological interventions in both hypertensive patients and normotensive people to determine effect sizes more accurately.

Adult↗
PubMed1998

Transient exposure of rhesus macaque oocytes to calyculin-A and okadaic acid stimulates germinal vesicle breakdown permitting subsequent development and fertilization.

Exposure of mammalian oocytes to the protein phosphatase (PP)-1 (PP1) and PP2A inhibitor okadaic acid (OA) stimulates oocyte meiosis. However, treated oocytes do not develop beyond metaphase I (MI), and they display morphological aberrations. Experiments were conducted to define inhibitor treatment conditions for macaque oocytes that would result in germinal vesicle breakdown (GVB) stimulation and completion of meiosis without significant cytoplasmic abnormalities. As described above for OA, continual exposure of macaque oocytes to 50 nM calyculin-a (CL-A) significantly enhanced GVB at 24 h compared to that in controls, and the majority of the treated oocytes displayed cytoplasmic abnormalities. However, transient exposure (10 min) of rhesus macaque oocytes to either 50 nM CL-A or 1.0 microM OA enhanced GVB rates compared to that in controls and did not increase the incidence of cytoplasmic abnormalities. Meiotic maturation from germinal vesicle-intact oocytes to MII was enhanced following transient treatment with CL-A or OA compared to that in controls; however, development from MI to MII occurred at a similar frequency. In vitro-matured oocytes transiently exposed to OA and CL-A were capable of fertilization. In addition, ovarian immunohistochemical analysis revealed that both PP1 and PP2A were present in macaque oocytes. PP1 was localized throughout the cytoplasm with a predominance in the nucleus, whereas PP2A was evenly distributed throughout the cytoplasm with a reduction in the nuclear area. These results taken together-differential developmental responses to inhibitor treatment and intracellular enzyme localizations-may be indicative of multiple regulatory roles of PP1 and/or PP2A during meiosis.

Animals↗
PubMed1998

Individual social class, area-based deprivation, cardiovascular disease risk factors, and mortality: the Renfrew and Paisley Study.

OBJECTIVE: To investigate the associations of individual and area-based socioeconomic indicators with cardiovascular disease risk factors and mortality. DESIGN: Prospective study. SETTING: The towns of Renfrew and Paisley in the west of Scotland. PARTICIPANTS: 6961 men and 7991 women included in a population-based cardiovascular disease screening study between 1972 and 1976. MAIN OUTCOME MEASURES: Cardiovascular disease risk factors and cardiorespiratory morbidity at the time of screening: 15 year mortality from all causes and cardiovascular disease. RESULTS: Both the area-based deprivation indicator and individual social class were associated with generally less favourable profiles of cardiovascular disease risk factors at the time of the baseline screening examinations. The exception was plasma cholesterol concentration, which was lower for men and women in manual social class groups. Independent contributions of area-based deprivation and individual social class were generally seen with respect to risk factors and morbidity. All cause and cardiovascular disease mortality rates were both inversely associated with socioeconomic position whether indexed by area-based deprivation or social class. The area-based and individual socioeconomic indicators made independent contributions to mortality risk. CONCLUSIONS: Individually assigned and area-based socioeconomic indicators make independent contributions to several important health outcomes. The degree of inequalities in health that exist will not be demonstrated in studies using only one category of indicator. Similarly, adjustment for confounding by socioeconomic position in aetiological epidemiological studies will be inadequate if only one level of indicator is used. Policies aimed at reducing socioeconomic differentials in health should pay attention to the characteristics of the areas in which people live as well as the characteristics of the people who live in these areas.

Cardiovascular Diseases↗
PubMed1998

Inequalities in mortality by social class measured at 3 stages of the lifecourse.

OBJECTIVES: This study examined how social class, measured at 3 staged of life, contributes to mortality risk. METHODS: A cohort of employed Scottish men (n = 5567) provided their fathers' occupation and their own first and current occupations, from which social class in childhood, at labor-market entry, and at screening (1970 to 1973) was determined. Relative rates of mortality and relative indices of inequality were calculated from 21 years of follow-up. RESULTS: Mortality risk was similar at each stage of life, with men in the higher social classes having the lowest risk. Social class at screening produced the greatest relative indices of inequality. CONCLUSIONS: The widening of inequalities in mortality in adulthood suggests the importance of the accumulation of poor socioeconomic circumstances throughout life.

Adult↗
PubMed1998

An uncertain future: the health effects of threats to employment security in white-collar men and women.

OBJECTIVES: This study examined changes in the health status of civil servants whose employment security was threatened. METHODS: Data were derived from a longitudinal cohort of 10,308 men and women, office staff in 20 British civil service departments. Physiological measurements, self-reported morbidity, and health-related behaviors for 530 members of the department under threat were compared with those of 19 other departments, during the period of uncertainty and during stable employment 5 years earlier. RESULTS: From a position of advantage or no difference at baseline, self-reported morbidity and physiological risk factors tended to increase among respondents from the threatened department compared with those from other departments. For both sexes, increases were significant for body mass index (P < .001) and sleeping 9 or more hours (odds ratio [OR] = 1.88; 95% confidence interval [CI] = 1.3, 2.8; P < .01); modest but significant increases were seen in ischemia (OR = 1.45; 95% CI = 1.0, 2.1) and cholesterol concentration (0.08 mmol/L; 95% CI = 0.01, 0.14). Among women only, a significant relative increase in blood pressure (P < .01) was recorded. Over the same period health-related behaviors changed little. CONCLUSIONS: Threats to employment security have adverse consequences for health status that are unexplained by health selection or health-related behaviors.

Adult↗
PubMed1998

Observations of sexually transmitted disease consultations in India.

OBJECTIVES: To assess the quality of sexually transmitted disease (STD) case management provided in public and private health facilities in selected areas of Madras, Tamil Nadu, India, in order to make recommendations for improving the quality of care and promote the syndromic approach to STD treatment. METHODS: Structured observations of consultations for STDs in health care facilities. Scoring of the observations according to standards for history taking, examination, treatment and provision of basic health promotion advice allows evaluation of STD case management. RESULTS: With STD treatment adequacy scored against Indian national guidelines (which recommend aetiologic treatment), history taking, examination and treatment were satisfactory in 76 out of 108 (70%) of observed consultations. However, if STD treatment adequacy is scored with respect to the syndrome approach towards selected STD (male urethritis and non herpetic genital ulcer for both sexes), only 8 out of 81 (10%) of the patients were satisfactory managed. During 32 out of 108 (30%) of the consultations, advice on the use of condoms in order to prevent STD or HIV/AIDS was given. Instructions regarding how to use condoms were offered to seven (6%) patients and condoms were only provided to one patient (1%). Patients were urged to refer their partner(s) for treatment during 29 (27%) of consultations. A criterion of adequate use of the STD consultation for health promotion, requiring both promotion of condoms and encouragement to refer partner(s) for treatment, was met during 13 (12%) of consultations. CONCLUSIONS: Monitoring and improving the standards of care at facilities at which STDs are treated have become key roles of STD/HIV/AIDS programmes. The present report suggests that in Madras the activities of medical practitioners who treat STD patients are far from ideal at present. Improvements would involve simplifying existing treatment guidelines by promoting the syndromic approach to STD management, continuing education programmes for health care providers in the public and private sectors and repeat assessments and feedback of the quality of STD care.

Case Management↗
PubMed1998

The excitatory behavioral and antianalgesic pharmacology of normorphine-3-glucuronide after intracerebroventricular administration to rats.

In the adult male Sprague-Dawley rat, a species commonly used to study tolerance to the antinociceptive effects of morphine, approximately 10% of the morphine dose is metabolized to normorphine-3-glucuronide (NM3G). In contrast, NM3G is a relatively minor metabolite of morphine in human urine reportedly accounting for approximately 1% of the morphine dose. To date, the pharmacology of NM3G has been poorly characterized. Therefore, our studies were designed to determine whether the intrinsic pharmacology of NM3G is similar to that of morphine-3-glucuronide (M3G), the major metabolite of morphine, which has been shown to be a potent central nervous system (CNS) excitant and to attenuate the intrinsic antinociceptive effects of morphine in rats. The CNS excitatory potency of NM3G was found to be approximately half that of M3G, inducing convulsions in rats at intracerebroventricular (i.c.v.) doses of >/=16.8 nmol. When administered before morphine (70 nmol i. c.v.), NM3G (8.9 nmol i.c.v.) attenuated antinociception for up to 2 hr, but when administered after morphine, no significant attenuation of morphine antinociception was observed. Thus, after i.c.v. administration, NM3G like M3G, is a potent CNS excitant and antianalgesic in the rat. NM3G may therefore play a role in the development of tolerance to the antinociceptive effects of morphine in the rat as has been proposed previously for M3G.

Analgesics, Opioid↗