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Biomedical subjects

C Hart

Publications and source records attributed to C Hart.

At least 19 recordsLinked to original sources
PubMed1997

Lifetime socioeconomic position and mortality: prospective observational study.

OBJECTIVES: To assess the influence of socioeconomic position over a lifetime on risk factors for cardiovascular disease, on morbidity, and on mortality from various causes. DESIGN: Prospective observational study with 21 years of follow up. Social class was determined as manual or non-manual at three stages of participants' lives: from the social class of their father's job, the social class of their first job, and the social class of their job at the time of screening. A cumulative social class indicator was constructed, ranging from non-manual social class at all three stages of life to manual social class at all three stages. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 at the time of examination. MAIN OUTCOME MEASURES: Prevalence and level of risk factors for cardiovascular disease; morbidity; and mortality from broad causes of death. RESULTS: From non-manual social class locations at all three life stages to manual at all stages there were strong positive trends for blood pressure, body mass index, current cigarette smoking, angina, and bronchitis. Inverse trends were seen for height, cholesterol concentration, lung function, and being an ex-smoker. 1580 men died during follow up. Age adjusted relative death rates in comparison with the men of non-manual social class locations at all three stages of life were 1.29 (95% confidence interval 1.08 to 1.56) in men of two non-manual and one manual social class; 1.45 (1.21 to 1.73) in men of two manual and one non-manual social class; and 1.71 (1.46 to 2.01) in men of manual social class at all three stages. Mortality from cardiovascular disease showed a similar graded association with cumulative social class. Mortality from cancer was mainly raised among men of manual social class at all three stages. Adjustment for a wide range of risk factors caused little attenuation in the association of cumulative social class with mortality from all causes and from cardiovascular disease; greater attenuation was seen in the association with mortality from non-cardiovascular, non-cancer disease. Fathers having a manual [corrected] occupation was strongly associated with mortality from cardiovascular disease: relative rate 1.41 (1.15 to 1.72). Participants' social class at the time of screening was more strongly associated than the other social class indicators with mortality from cancer and from non-cardiovascular, non-cancer causes. CONCLUSIONS: Socioeconomic factors acting over the lifetime affect health and risk of premature death. The relative importance of influences at different stages varies for the cause of death. Studies with data on socioeconomic circumstances at only one stage of life are inadequate for fully elucidating the contribution of socioeconomic factors to health and mortality risk.

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

Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers.

OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY DESIGN: This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except for a higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product.

Antibodies, Bacterial↗
PubMed1996

Effects of the calcium channel blocker nimodipine on nicotine-induced locomotion in rats.

The effects of nimodipine, an L-type calcium channel antagonist, on nicotine-induced locomotor activity were investigated in drug-naive rats. Nicotine (0.4 mg/kg i.p.) produced significant increases in locomotion following acute administration. However, when rats were given injections of nimodipine (5, 10, or 20 mg/kg i.p.) 1 h prior to the test drug, nicotine-induced locomotor activity was altered. Nimodipine 5 mg did not significantly block locomotor activity produced by nicotine. In contrast, pretreatment with 10 and 20 mg nimodipine significantly blocked nicotine-induced locomotor activity. These findings clearly indicate that nicotine-induced locomotion is altered by nimodipine in a dose-dependent fashion. Results further suggest that the effect of nicotine on locomotion is calcium-dependent.

Animals↗
PubMed1996

Nicotine effects on dopamine clearance in rat nucleus accumbens.

In vivo voltammetry was used to measure the clearance to exogenously applied dopamine (DA) in the nucleus accumbens following acute systemic nicotine administration in urethane-anesthetized rats. The IVEC-5 system was used for continuous in vivo electrochemical measurements. A finite amount of DA was pressure-ejected (25-100 nl, 200 microM barrel concentration) at 5-min intervals from micropipettes (tip diameter, 10-15 microns) positioned 250 +/- 50 microns from the recording electrode. The peak DA concentration after each DA ejection was significantly decreased in rats following nicotine, but not in rats given saline. In addition, when mecamylamine was administered 20 min before nicotine it clearly antagonized nicotine effects. These results suggest that nicotine may actually facilitate DA transporter systems within the nucleus accumbens.

Animals↗
PubMed1996

Differential expression of alpha 1 type VIII collagen in injured platelet-derived growth factor-BB--stimulated rat carotid arteries.

Migration of smooth muscle cells from media to intima is critical for the development of neointimal thickening after balloon catheter injury of the rat carotid artery. The present experiments were designed to identify molecules expressed by smooth muscle cells migrating in vivo in the injured artery. Cell migration was maximized by infusing recombinant platelet-derived growth factor-BB (PDGF-BB) after a minimal filament denudation of the rat carotid artery, whereas cell proliferation was minimized by injecting an antibody against basic fibroblast growth factor (bFGF). This treatment caused an eightfold increase in smooth muscle cell migration into the intima but only a twofold increase in intimal smooth muscle cell replication rates. Differential display screening was used to isolate cDNAs that were overexpressed in the injured PDGF-BB-treated versus unmanipulated rat carotids. One of the clones isolated hybridized to a 4.2-kb mRNA species and shared 90% sequence homology to mouse alpha 1 type VIII collagen. Northern and Western blots confirmed overexpression of type VIII collagen in the injured PDGF-BB-treated vessels. In a separate series of experiments, we performed filament denudation injury and administered antibodies to inhibit the actions of endogenous bFGF and PDGF-BB, thereby decreasing smooth muscle cell migration, and found that type VIII collagen mRNA expression varied with migration. Using a different arterial injury model (balloon catheter injury), we showed that expression of type VIII collagen was maximal 2 to 4 days after injury, in coincidence with cell migration from the media to the intima. This molecule constitutes an important component of smooth muscle cell response to vessel injury and may play an important functional role in mediating migration.

Animals↗
PubMed1995

Nicotine enhances dopamine clearance in rat nucleus accumbens.

1. Adult male rats were urethane-anesthetized and prepared for acute in-vivo voltammetric recording in the nucleus accumbens. 2. Small amounts of 200 uM dopamine were pressure ejected near the tip of the recording electrode at 5-min intervals, while the peak concentration and time course of dopamine clearance were measured voltammetrically. 3. After stable peak amplitudes were established, nicotine (0.4 mg/kg) was injected systemically. 4. Dopamine peak amplitudes decreased following nicotine injection, presumably due to enhanced dopamine reuptake.

Animals↗
PubMed1995

Catecholaminergic inhibition by hypercortisolemia in the paraventricular nucleus of conscious rats.

Administration of glucocorticoids decreases the release of corticotropin-releasing hormone and in vitro turnover of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, and immobilization (IMMO) markedly increases NE release and stimulates corticotropin-releasing hormone neurons in the PVN. This study assessed whether hypercortisolemia affects in vivo indexes of catecholaminergic activation in the PVN. Microdialysis was used to simultaneously measure PVN microdialysate concentrations of NE, the neuronal NE metabolite dihydroxyphenylglycol, the extraneuronal NE metabolite methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid before, during, and after 2 h of IMMO. Catecholamine synthesis was examined based on elevations of 3,4-dihydroxyphenylalanine levels after local perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. Cortisol (CORT; 25 mg/kg.day) or vehicle (VEH; saline) was infused sc for 7 days via an osmotic minipump. CORT-treated rats had lower basal NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and significantly smaller levels of all these compounds during IMMO than VEH-treated rats. CORT-treated rats also had less NSD-1015-induced accumulation of microdialysate 3,4-dihydroxyphenylalanine at baseline and during IMMO than VEH-treated rats. Basal and IMMO-induced plasma ACTH and corticosterone responses were reduced in CORT-treated rats. The results indicate that chronic hypercortisolemia decreases basal levels and stress-induced increments in indexes of release, metabolism, turnover, and synthesis of catecholamines in the PVN and suggest that glucocorticoids restrain the limit of hypothalamo-pituitary-adrenocortical axis activation during stress by attenuating catecholamine synthesis and release in the PVN.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Epidemiology of spinal cord injuries: a reflection of changes in South African society.

The records of all patients (492 males and 124 females) admitted into a spinal rehabilitation programme over a period of 6 years were reviewed. Most of the patients were in the age group 20-29 years and trauma accounted for 89% of all spinal cord lesions. Gunshot injuries were the commonest (36%), followed by injuries related to motor vehicle accidents (MVA) (25%), stab wounds (20%) and falls from heights (2.4%). Aetiological patterns changed over the 6 year period covered: gunshot injuries increased markedly and stab wounds decreased in number. The records of a medico-legal laboratory in the same geographic region revealed the same trend. Neurological recovery rates were better in patients with stab wounds and nontraumatic lesions than in those with MVA-related injuries and gunshot wounds. When compared to similar studies from other countries, our results show a disproportionately high incidence of violent injuries, particularly gunshot wounds, in South African plegic patients. We concluded that the recent sociopolitical changes and especially the general escalation of violence in the country, is reflected in the observed changes in the epidemiology of spinal cord injuries.

Accidents, Traffic↗
PubMed1993

Specific neurophysiological effects of systemic nicotine on neurons in the nucleus accumbens.

Extracellular recordings of single neurons within the nucleus accumbens (NAS) of halothane-anesthetized rats have revealed that systemic nicotine injections (0.5 and 1.0 mg/kg, s.c.) inhibit the action potentials of normally inactive NAS neurons, evoked by fimbria stimulation (fimbria-driven responses, n = 18). These nicotine inhibitions of fimbria-driven NAS action potentials appear to be centrally mediated because they were reversed by subsequent systemic injections of the centrally acting nicotinic acetylcholine (nAch) antagonist, mecamylamine (1.0 mg/kg, s.c., n = 6) but not by the peripherally acting nAch antagonist, hexamethonium (2.0 mg/kg, s.c., n = 6). Fimbria-driven NAS neurons were also tested with morphine (2.5 mg/kg, s.c.) in some experiments. Consistent with many past observations (Hakan et al., 1989), morphine did not affect these driven neurons. In other experiments, nicotine-induced inhibition of NAS fimbria-driven units was followed by haloperidol (0.5 mg/kg, s.c.), in attempts to reveal the possible role of dopamine in these effects. Haloperidol was successful at reversing nicotine inhibitions in only some cases (n = 2/6). Thus, the role of dopamine in these NAS responses to nicotine remains unclear. In contrast to the fimbria-driven NAS responses, spontaneously active NAS neurons were not affected by nicotine injections yet were subsequently inhibited with systemic morphine. These results suggest a specific neuropharmacological organization in the region of the nucleus accumbens that may relate to the qualitative and subjective differences in the experimental effects of different psychoactive drugs. Iontophoretic studies designed to localize further the site of these nicotine effects on NAS neurons are in progress.

Action Potentials↗
PubMed1993

Host range selection of vaccinia recombinants containing insertions of foreign genes into non-coding sequences.

A simple yet powerful selection system was developed for the insertion of foreign genes in vaccinia virus. The selection system utilizes the vaccinia virus K1L (29K) host range gene which is located in HindIII M. This gene is necessary for growth in RK-13 cells but not in BSC40 or CV-1 cells. A vaccinia mutant (vAbT33) unable to grow on RK-13 cells was constructed having sequences at the 3' end of the K1L gene and the adjacent M2L gene deleted and replaced with the beta-galactosidase gene regulated by the BamHI F (F7L) promoter. A recombination plasmid containing the hepatitis B surface (HBs) antigen gene regulated by the M2L promoter and the complete sequence of the K1L gene was used to insert the HBs gene into vAbT33. The M2L negative K1L positive recombinant was easily isolated in two rounds of plaque purification by plating the virus on RK-13 cell monolayers. The K1L gene selection system allows the isolation of recombinants arising at frequencies as low as 1/100,000. It was noted that recombinants containing vaccinia sequence duplications (promoters) resulted in intragenomic recombinations that eliminated all sequences between the duplications. A second recombination plasmid was constructed that allowed insertion into the vaccinia genome without the loss of vaccinia coding sequences. This was achieved by insertion of the pseudorabies virus GIII gene regulated by the vaccinia H5R (40K) promoter between the translation and transcription stop signals at the 3' end of the K1L gene. The K1L gene transcription stop signal thus became the stop signal for the inserted GIII gene and an upstream transcription stop signal present in the H5R promoter fragment provided the stop signal for the K1L gene. This manipulation of the vaccinia genome had no effect on the accumulation or 5' end of the M2L gene transcripts. Although the insertion lengthened the 3' end and lowered the accumulation of K1L transcripts it altered neither the virulence nor the immunogenicity of the recombinant.

Base Sequence↗
PubMed1992

Streptokinase resistance: when might streptokinase administration be ineffective?

OBJECTIVE: (a) To develop an assay for streptokinase resistance. (b) To determine the prevalence of streptokinase resistance in patients presenting with acute myocardial infarction for the first time. (c) To determine the prevalence of streptokinase resistance in patients after exposure to streptokinase or streptococcal infection. DESIGN: Open, prospective. PATIENTS: 30 healthy volunteers. 40 patients admitted to the coronary care unit at Addenbrooke's Hospital with suspected acute myocardial infarction, 12 patients 12 months after streptokinase treatment, eight patients 24 months after streptokinase treatment, and sera from 12 patients with raised anti-streptolysin O (ASO) titres. METHODS: Three assays were used; a dilution neutralisation assay, an enzyme linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) anti-streptokinase antibodies, and an in vitro fibrin plate lysis assay. All measurements were performed on venous blood samples. RESULTS: Neutralisation and IgG antibody titres were positively correlated. Mean (SEM) antistreptokinase concentrations in the 30 controls were 87 (10) U/ml (neutralisation assay) and 28 (6.3) U/ml (ELISA). Corresponding concentrations in patients before streptokinase were 68 (6.1) U/ml and 18 (4.5) U/ml with a mean fibrin plate assay 117 (7.1)% that of controls. Resistance to streptokinase was detectable in one patient after 72 hours and in all patients by day 10. By day 10 concentrations were 4388 (919) U/ml, 773 (109) U/ml, and 17 (5.4)%. At both 12 and 24 months resistance was present in 75% of patients. Similarly 66% of high ASO titre sera showed resistance. The fibrin plate lysis assay detected significantly reduced streptokinase dependent fibrinolysis in vitro in the absence of raised total concentrations of antistreptokinase antibodies. CONCLUSIONS: The prevalence of streptokinase resistance in patients presenting with their first myocardial infarction is low. Resistance develops early after treatment and is still present in 75% of patients after 24 months. Retreatment with streptokinase is likely to be suboptimal even after 24 months. The fibrin plate lysis assay detects resistance in patients with normal concentrations of streptokinase antibodies. Streptococcal infection is associated with a high incidence of streptokinase resistance.

Antibodies↗
PubMed1991

Two cases of interstitial deletion 1p.

We report two cases of interstitial deletion of the short arm of chromosome 1. The first was a 10 year old boy whose karyotype was 46,XY,del(1) (p22.1p31.2); the second was a 6 month old boy with a chromosome complement of 46,XY,del(1) (p22.3p31.3). A number of the malformations observed were common to both cases. There has been one previously reported case with the same breakpoints as our case 1 and a phenotype that was strikingly similar.

Abnormalities, Multiple↗
PubMed1991

Ruptured petrous carotid aneurysm presenting with otorrhagia and epistaxis.

Aneurysm formation and rupture within the petrous internal carotid artery (ICA) is an extremely rare occurrence with approximately 10 such cases in the literature. Etiologies of petrous ICA aneurysms include atherosclerosis, closed head trauma, iatrogenic injury during mastoid surgery, chronic middle ear infections, and congenital causes. Therapeutic options include carotid artery ligation, aneurysm resection with or without reconstruction, and radiographically controlled vessel occlusion. The case of a patient who presented with otorrhagia, epistaxis, and transient focal neurologic signs due to a ruptured petrous ICA aneurysm is presented. The incidence, etiology, and anatomy of these aneurysms is reviewed, and the various tests for determining adequacy of collateral cerebral blood flow are described. Factors that affect the selection of surgical versus radiologic control of these lesions are also discussed.

Adult↗