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Biomedical subjects

D R Jones

Publications and source records attributed to D R Jones.

At least 145 records · Page 8Linked to original sources
PubMed1996

Prevention in practice: results of a 2-year follow-up of routine health promotion interventions in general practice.

BACKGROUND: The effectiveness of health promotion activity in general practice on risk factor reduction for coronary heart disease remains the subject of active debate. OBJECTIVE: The study aimed to assess the impact of practice-based health check-ups on health behaviours over a 2-year period. METHOD: A general practice cohort of 7123 patients from 18 practices was surveyed. Eight hundred and forty (12%) patients had been offered a health check within a 12-month period from September 1992 and 621 (9%) received one. Two hundred and fifty patients (40%) were asked back for follow-up after their health check. RESULTS: Over a 2-year period there was no difference in smoking cessation, alcohol consumption, weight loss nor the amount of exercise taken between those who attended for a health check and those who did not. The food score chosen to assess dietary change (Oxcheck) showed a statistically significant 1.16-point rise for the whole sample over the survey period. There was a significant difference in mean food score change between health check attenders and non-attenders (Mann-Whitney U test: P < 0.002). Maintenance of dietary improvement over a 2-year period was not affected by health check attendance. CONCLUSIONS: This study confirms the low impact of health checks on the self reported modification of cardiovascular risk factors and shows that maintenance of appropriate health behaviour change is no more likely in those who have received a health check.

Adult↗
PubMed1996

Dilution acidosis: evidence for a role of intracellular pH in the control of ventilation.

Acute hyperosmolality results in an extracellular dilution acidosis and hypercarbia that does not stimulate ventilatory compensation. The osmotic stress is also associated with shifts in water and electrolyte balance and an increase in intracellular pH. The alkaline intracellular pH was hypothesized to have a role in preventing a normal respiratory response to the extracellular acidosis and hypercarbia. Therefore, this study examined the effect of ion-exchange blockade on intra- and extracellular pH and ventilation during acute hyperosmolality in the Pekin duck (Anas platyrhynchos) by using 31P-nuclear magnetic resonance spectroscopy. Both 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and amiloride inhibited the development of the intracellular alkalosis that normally develops in muscle during acute hyperosmolality. Instead, exposure to hyperosmotic stress during ion-exchange blockade resulted in a significant acidosis both intracellularly and extracellularly. Arterial pH decreased 0.10 +/- 0.04 pH unit with a sucrose infusion after either blocker, and intracellular pH decreased 0.11 +/- 0.06 and 0.16 +/- 0.04 pH units with a sucrose infusion after DIDS and amiloride, respectively. Ventilation increased 79 +/- 28 and 122 +/- 100%, respectively, during acute hyperosmolality after ion-exchange blockade with either DIDS or amiloride. The results suggest that intracellular pH may play a role in the ventilatory response to acid-base perturbations. The data also indicate that both Cl-/HCO3- and Na+/H+ exchanges are involved in the development of the intracellular alkalosis during hyperosmotically induced extracellular acidosis.

Acidosis↗
PubMed1996

Autonomic nervous control of heart rate in muskrats during exercise in air and under water.

Neural control of the cardiac responses to exercise in air (running) and under water (diving) was studied in the muskrat (Ondatra zibethicus) by means of acute pharmacological blockade with the muscarinic blocker atropine and the beta-adrenergic blocker nadolol. Saline injection was used as a control. Controls running on a treadmill showed a marked increase in heart rate with exercise. Atropine-treated animals had a higher resting heart rate than controls, but heart rate still increased with running. Nadolol-treated animals had a lower resting heart rate than controls and displayed a less pronounced increase in heart rate with running than controls. Animals treated with a combination of atropine and nadolol had a resting heart rate similar to that of controls but their heart rate was unaffected by running. Thus, exercise tachycardia in muskrats is due to activation of the sympathetic system and also to a reduction in parasympathetic tone. Heart rate decreased markedly during voluntary submergence in controls but rose as muskrats swam submerged against increasing water flows. Nevertheless, diving bradycardia was still present. Free-diving bradycardia and the relative increase in heart rate with underwater exercise were abolished by atropine and unaffected by nadolol. Hence, unlike the cardiac response to exercise in air, the cardiac response to underwater exercise is due only to a reduction in parasympathetic tone. Injection of the beta-adrenergic agonist isoproterenol markedly increased heart rate in air but had little effect during voluntary and forced dives, indicating a marked decrease in the sensitivity of cardiac cells to adrenergic stimulation during submergence. These results strongly suggest that accentuated antagonism between the two branches of the autonomic nervous system occurs during diving so that parasympathetic influences on the heart predominate and inhibit any chronotropic response to adrenergic stimulation.

Adrenergic beta-Agonists↗
PubMed1996

Do plasma anti phospholipid antibodies in patients with autoimmune haemolytic anaemia correlate with reduced levels of erythrocyte complement receptor 1?

Anti phospholipid antibody (APA), of both IgG and IgM class, was assayed in plasma obtained from patients with autoimmune haemolytic anaemia (AHA) and active haemolysis. Although plasma APA was elevated in some AHA patients, when compared to a normal control population, there was no apparent correlation with levels of erythrocyte complement receptor 1 (RBC-membrane CR1) in this patient group. However, there appeared to be a correlation between RBC-membrane CR1 and plasma IgG APA in a subset of the AHA patients with low RBC-membrane CR1. The potential significance of this observation was complicated by the majority of these patients having a plasma APA within the normal range. These results suggest that the reported inverse correlation between APA and RBC-membrane CR1 may not be definitive.

Adult↗
PubMed1996

In utero haematopoietic stem cell transplantation: current perspectives and future potential.

In utero transplantation (IUT) of haematopoietic cells is a new therapeutic option for families with increased risk of having a child with an inherited disorder. Immunological naiveté and the rapidly expanding haematopoietic system in the first trimester human fetus, make therapeutic intervention by IUT a real possibility for those disorders which can be diagnosed early in gestation. Fewer cells are required than in postnatal BMT and therapy can be offered before the pathological sequelae of a disorder become manifested. However, only a few cases of IUT have been performed in humans and it is imperative that consensus is reached quickly on issues such as cell numbers/cell types so that the benefits of this approach to treatment can be realised. This review presents the current status of IUT, the cases thus far recorded and offers a prospective view of developments in this rapidly expanding area.

Female↗
PubMed1995

A structural assignment for a stable acetaldehyde-lysine adduct.

Acetaldehyde is the first oxidation product of ethanol in vivo. Lysine residues in proteins such as hemoglobin have been implicated as target structures for acetaldehyde adducts resulting from ethanol consumption. Although the presence of both stable and unstable acetaldehyde-hemoglobin adducts has been established, the structural characterization of the adducts has received relatively little attention. As a model for such adduct formation, we studied the peptide pentalysine in vitro. Pentalysine has several potential sites for adduct formation. The amino-terminal amine group as well as the epsilon-amine groups of each lysine side chain can serve as potential sites for modification by acetaldehyde. Mass spectrometry, nuclear magnetic resonance, and Raman spectroscopy were employed to demonstrate that acetaldehyde forms a stable linkage to lysine amine groups via a Schiff base.

Acetaldehyde↗
PubMed1995

Meta-analysis: weighing the evidence.

Use of meta-analytical (quantitative overview) techniques is now commonplace in a wide range of medical research contexts, with a rapid rise in its frequency of use being particularly apparent in the last decade. The history of meta-analyses in other fields, particularly psychology and educational research, is longer. Many methods have been proposed and used, from crude 'vote counting' of studies showing significant or non-significant results, through methods for combination of effect size estimates based on fixed or random effects models, to general linear mixed models and Bayesian methods. The history of meta-analysis and the advantages and disadvantages of various approaches to it are briefly reviewed in this paper, with reference to pharmaceutical product licence applications, other reviews of clinical trials and epidemiological studies, and health services research.

Bayes Theorem↗
PubMed1995

Design and synthesis of nonpeptide peptidomimetic inhibitors of renin.

The desire to replace the amide backbone of renin inhibitors with a new scaffold led us to explore vinylogous amides (enaminones). An initial attempt proved unsuccessful, a result explained after the fact via docking experiments. Based on this lesson, we designed a different vinylogous amide scaffold which incorporated one or more pyrrolinone rings into the backbone. Three of the four compounds gave IC50S in the 0.6 to 18 microM range. These compounds did not inhibit HIV-1 protease. Taken together, the results reported herein provide insights into the role of hydrogen bonding and steric interactions for binding to renin.

Drug Design↗
PubMed1995

Biatrial approach to cardiac myxomas: a 30-year clinical experience.

Early surgical intervention for atrial myxomas mitigates morbidity and usually offers cure. The operative approach to resect these tumors is controversial. The purpose of this study was to review our experience with the biatrial approach between 1964 and 1994. The location of the myxoma was left atrium in 17 and right atrium in 3. Mean preoperative New York Heart Association functional classification was 2.7. Surgical approach to the tumor was biatrial in all patients. There were no perioperative strokes, myocardial infarctions, or deaths. Mean follow-up was 7.5 years (range, 2 mo to 27 years) with a postoperative New York Heart Association functional classification of 1.4. One late death occurred, which was unrelated to the myxoma. Advantages of biatrial approach include (1) definition of tumor pedicle by direct visualization, (2) minimal manipulation of the tumor, (3) adequate margins of excision, (4) inspection of all heart chambers, and (5) secure closure of the atrial septal defect. Long-term follow-up demonstrates the efficacy of this operative approach to atrial myxomas.

Adolescent↗
PubMed1995

A comprehensive curriculum for thoracic surgery: survey of opinions from program directors and residents.

BACKGROUND: The Comprehensive Thoracic Surgery Curriculum was developed to provide program directors with a basis for planning instruction and evaluating residents, program practices, and outcomes. A survey design was selected to obtain opinions about the curriculum from a large group of people, ie, all program directors and all active residents. METHODS: Two parallel instruments were developed: one to be completed by program directors and one to be completed by active residents. Responses were collated for directors and residents, entered into a computerized database, and compared using the chi 2 statistic. RESULTS: A response rate of 93% was obtained from the directors and 79% from the residents. The survey demonstrates broad-based support for a comprehensive curriculum by the respondents. Current perceptions of and expectations for the curriculum are diverse and regionalized. Serious concerns are expressed about quality issues and particularly the environment for residency education. CONCLUSIONS: The thoughtful responses of our colleagues will guide leaders who will implement the curriculum for thoracic surgery. Strategies for change will necessarily focus on the prerequisite curriculum.

Administrative Personnel↗
PubMed1995

Role of glycosyl-phosphatidylinositol hydrolysis as a mitogenic signal for epidermal growth factor.

We have investigated the role of the hydrolysis of glycosyl-phosphatidylinositol (GPI) as one of the signalling pathways elicited after interaction of epidermal growth factor (EGF) with its specific plasma membrane receptor (EGFR). Endogenous GPI was characterized in both NIH 3T3 mouse fibroblast cells and in EGFR-transfected NIH 3T3 cells (designated EGFR T17). GPI molecules isolated from both cell lines were identical and they incorporated radioactivity from both sugar and fatty acid substrates. Incubation of EGFR T17 cells with EGF, produced a rapid and transient hydrolysis of GPI. Maximum hydrolysis occurred after a 1-min incubation with 50 nM EGF. No such effects of EGF were observed in the parental cell line. Both inositol phosphoglycan (IPG)- and EGF-induced cell proliferation was inhibited in the presence of an IPG-antibody to different extents. The relationship between GPI hydrolysis and the activity of the EGFR was studied using the tyrosine kinase inhibitors tyrphostin (RG50864) and genistein. These agents were able to significantly inhibit EGF-mediated cell proliferation, EGF-dependent hydrolysis of GPI and EGF-regulated autophosphorylation of the EGFR. It is concluded that GPI hydrolysis is one of the earliest intracellular events generated in response to EGF.

3T3 Cells↗
PubMed1995

Like father like son? Sons of patients of European or Indian origin with coronary artery disease reflect their parents' risk factor patterns.

OBJECTIVE: To investigate the extent to which risk factor patterns associated with coronary artery disease (CAD) in patients of Indian origin and in those of North European origin undergoing coronary angiography for suspected angina were reflected in their apparently healthy sons aged 15-30 years. DESIGN: Prospective study in which risk markers were measured in patients of Indian origin and in matched European patients undergoing angiography and in their sons. SETTING: Patients attending a regional cardiac centre and their families. PATIENTS: 102 consecutive male patients of Indian origin undergoing diagnostic coronary angiography for suspected angina and 89 of their sons aged between 15 and 30 years; 102 age matched male European patients and 82 sons. MAIN OUTCOME MEASURES: Father son correlations for risk markers predicting the severity of parental CAD; differences in mean levels of these markers between young males of Indian origin and those of North European origin. RESULTS: Lp(a) lipoprotein, total cholesterol, and serum insulin were independent predictors of the severity of CAD in patients of Indian origin and in those of North European origin. In both groups, there was strong correlation between paternal and filial serum insulin (r = 0.41 Indian origin, r = 0.49 North European, P < 0.001), Lp(a) lipoprotein (r = 0.44 Indian origin, r = 0.48 North European, P < 0.001), and total cholesterol (r = 0.39 Indian origin, r = 0.45 North European, P < 0.001) concentrations, and the risk factor profiles of the sons were predictive of CAD severity in their fathers. Sons of patients of Indian origin had significantly higher serum insulin (Indian origin 14.3 mU/l v North European 8.4 mU/l, P = 0.002) and Lp(a) lipoprotein (Indian origin 19.1 mmol/l v North European 10.5 mmol/l, P = 0.001) concentrations than sons of patients of North European origin. CONCLUSIONS: Apparently healthy young men aged 15-30 years from either ethnic community already reflect risk marker patterns associated with coronary artery disease in their parents, both for genetically determined factors such as Lp(a) lipoprotein and environmentally influenced factors such as insulin and cholesterol. Health promotion measures aimed at reducing the prevalence of CAD should include the adolescent and young adult populations, particularly those with a family history of CAD, or who are from ethnic communities in which this diagnosis is prevalent.

Adolescent↗
PubMed1995

Effect of pharmacological blockade on cardiovascular responses to voluntary and forced diving in muskrats.

Neural control of free and forced diving bradycardia and peripheral resistance was studied in the muskrat (Ondatra zibethicus) by means of acute pharmacological blockade with the muscarinic blocker atropine, the alpha-adrenergic blocker phentolamine and the beta-adrenergic blockers nadolol and propranolol. Saline injection was used as a control. Heart rate in control animals increased before voluntary dives and dropped markedly as soon as the animals submerged. Heart rate started increasing towards the end of voluntary dives and reached pre-dive values within the first 5 s of recovery. Pre-dive and post-dive tachycardia were reduced in beta-blocked animals, emphasizing the role of the sympathetic system during the preparatory and recovery periods of voluntary dives. Diving bradycardia and the acceleration in heart rate before surfacing were abolished by atropine and unaffected by nadolol, demonstrating the importance of vagal efferent activity during diving. The results after blockade with nadolol suggest that there is an accentuated antagonism between the two branches of the autonomic nervous system during diving, so that parasympathetic influences on the heart predominate. Propranolol-treated muskrats had a higher diving heart rate than saline- and nadolol-treated animals, which may be due to a sedative effect caused by propranolol crossing the blood-brain barrier, a blockade of central catecholaminergic pathways or a peripheral neural effect, due to the anaesthetic properties of propranolol. Phentolamine did not affect diving bradycardia, indicating that diving bradycardia occurs independently of peripheral vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1995

Preservation of adenosine 5'-triphosphate and mitochondrial function during hypercalcemic reperfusion using verapamil cardioplegia.

Immediate hypercalcemic reperfusion results in ventricular dysfunction and loss of high-energy stores. The purpose of this study was to evaluate the effect of verapamil cardioplegia on the preservation of myocardial energy stores, mitochondrial ultrastructure, and ventricular dysfunction in the postischemic rat heart during immediate hypercalcemic reperfusion. Rats in the control group were subjected to cardioplegia with potassium, while rats in groups 1 to 3 were subjected to the same with verapamil (0.5 mg/L). The control and group 1 rats underwent normocalcemic reperfusion and groups 2 and 3 rats underwent hypercalcemic reperfusion. Myocardial samples were analyzed for adenosine 5'-triphosphate (ATP) content and mitochondrial ultrastructural damage. Hemodynamic parameters of heart rate, aortic flow (AF), and postischemic rate of aortic pressure change (dP/dT) also were evaluated. Data were analyzed using analysis of variance. The ATP stores were preserved at greater than 100% control levels in hearts subjected to verapamil cardioplegia. There was no evidence of irreversible mitochondrial damage. Heart rate, AF, and dP/dT were significantly (p < 0.05) depressed in hearts subjected to verapamil cardioplegia. This study suggests verapamil cardioplegia preserves ATP and mitochondrial function during immediate hypercalcemic reperfusion but does not improve postischemic hemodynamics.

Adenosine Triphosphate↗