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Biomedical subjects

D Bedford

Publications and source records attributed to D Bedford.

At least 37 records · Page 2Linked to original sources
PubMed1997

Metabolic basis of hypotriglyceridemic effects of insulin in normal men.

The mechanism by which acute insulin administration alters VLDL apolipoprotein (apo) B subclass metabolism and thus plasma triglyceride concentration was evaluated in 7 normolipidemic healthy men on two occasions, during a saline infusion and during an 8.5-hour euglycemic hyperinsulinemic clamp (serum insulin, 490 +/- 30 pmol/L). During the insulin infusion, plasma triglycerides decreased by 22% (P < .05), and serum free fatty acid decreased by 85% (P < .05). The plasma concentration of VLDL1 apo B fell 32% during the insulin infusion, while that of VLDL2 apo B remained constant. A bolus injection of [3-(2)H]leucine was given on both occasions to trace apo B kinetics in the VLDL1 and VLDL2 subclasses (Svedberg flotation rate, 60-400 and 20-60, respectively), and the kinetic basis for the change in VLDL levels caused by insulin was examined using a non-steady-state multicompartmental model. The mean rate of VLDL1 apo B synthesis decreased significantly by 35% (P < .05) after 0.5 hour of the insulin infusion (523 +/- 87 mg/d) compared with the saline infusion (808 +/- 91 mg/d). This parameter was allowed to vary with time to explain the fall in VLDL1 concentration. After 8.5 hours of hyperinsulinemia, the rate of VLDL1 apo B synthesis was 51% lower (321 +/- 105 mg/d) than during the saline infusion (651 +/- 81 mg/d, P < .05). VLDL2 apo B production was similar during the saline (269 +/- 35 mg/d) and insulin (265 +/- 37 mg/d) infusions. No significant changes were observed in the fractional catabolic rates of either VLDL1 or VLDL2 apo B. We conclude that acute hyperinsulinemia lowers plasma triglyceride and VLDL levels principally by suppressing VLDL1 apo B production but has no effect on VLDL2 apo B production. These findings indicate that the rates of VLDL1 and VLDL2 apo B production in the liver are independently regulated.

Adult↗
PubMed1997

Lessons to be learned: a case study approach. Hyperactivity and confusion in the presentation of hyoscine overdose.

The case report is presented of a ten-and-a-half year old boy with acute onset of confusion and visual hallucinations, subsequently confirmed to be due to hyoscine toxicity following ingestion of over-the-counter (OTC) travel sickness tablets. It is suggested that packs of such pills should carry a prominent cautionary label. A clear clinical history is very important--not only in aiding the differentiation of acute viral infections involving the central nervous system (such as acute encephalitis) from drug toxicity, but also in rationalizing any further diagnostic investigations. The possible underlying reasons for drug ingestion in this case are discussed.

Antiemetics↗
PubMed1997

The provision of influenza vaccine to patients over 65 years by general practitioners.

Influenza vaccination for all elderly persons is cost effective. Guidelines in Ireland recommend the vaccine for those with chronic illness and to the elderly in care. The aims of this study are to identify how influenza vaccine is provided to elderly patients and to get GPs opinions on what barriers there are to providing the vaccine to persons 65+ years. Of the 143 GPs contacted 117 (81.8%) replied, of whom 116 (99.1%) provide the vaccine to their patients. Ninety nine (85.3%) believe it to be effective in preventing influenza, and only 8 (6.9%) have reservations about the vaccine. Eighteen (15.5%) GPs had a difficulty in identifying those to be vaccinated and only 11 (9.5%) had a computerised system to assist them. Twenty two (19.0%) GPs had difficulty in getting sufficient vaccine for their patients. Ninety six (82.8%) GPs make the vaccine available to those for whom it is recommended and of these 61 make it available to all patients over 65 years. The main patient barriers to an influenza vaccination programme are the patients fear of getting influenza from the vaccine and that many patients do not consider the vaccine to be of value. Barriers identified for GPs are the low level of reimbursement to GPs for vaccinating eligible patients and the lack of proper systems that help identify and contact those who should be getting the vaccine. All of the barriers identified should be easy to overcome so that those who require influenza vaccine can reap the health and social gains that our health services advocate.

Adult↗
PubMed1996

A functional chimeric modular polyketide synthase generated via domain replacement.

BACKGROUND: Modular polyketide synthases (PKSs), such as 6-deoxyerythronolide B synthase (DEBS), are large multifunctional enzymes that catalyze the biosynthesis of structurally complex and medically important natural products. Active sites within these assemblies are organized into 'modules', such that each module catalyzes the stereospecific addition of a new monomer onto a growing polyketide chain and also sets the reduction level of the beta-carbon atom of the resulting intermediate. The core of each module is made up of a 'reductive segment', which includes all, some, or none of a set of ketoreductase (KR), dehydratase, and enoylreductase domains, in addition to a large interdomain region which lacks overt function but may contribute to structural stability and inter-domain dynamics within modules. The highly conserved organization of reductive segments within modules suggests that they might be able to function in unnatural contexts to generate novel organic molecules. RESULTS: To investigate domain substitution as a method for altering PKS function, a chimeric enzyme was engineered. Using a bimodular derivative of DEBS (DEBS1+TE), the reductive segment of module 2, which includes a functional KR, was replaced with its homolog from module 3 of DEBS, which contains a (naturally occurring) nonfunctional KR. A recombinant strain expressing the chimeric gene produced the predicted ketolactone with a yield (35 %) comparable to that of a control strain in which the KR2 domain was retained but mutationally inactivated. CONCLUSIONS: These results demonstrate considerable structural tolerance within an important segment found in virtually every PKS module. The domain boundaries defined here could be exploited for the construction of numerous loss-of-function and possibly even gain-of-function mutants within this remarkable family of multifunctional enzymes.

Multienzyme Complexes↗
PubMed1996

A comparison of the effects of strength and aerobic exercise training on exercise capacity and lipids after coronary artery bypass surgery.

BACKGROUND: Coronary artery surgery improves symptoms and prognosis in patients with angina. Aerobic exercise rehabilitation improves exercise capacity and prognosis in cardiac patients. Strength exercise training has not been extensively studied. DESIGN: We studied the effects of 6 months aerobic and strength exercise training after coronary artery surgery in 81 men, mean age 57 years. RESULTS: Treadmill time(s) increased by 130.3 (95% confidence interval 46.4 to 214.2) in the aerobic group; by 83.1 (0.9 to 165.3) in the strength group, and by 34.3 (-1 to 69.6) in the control group (P = 0.04, control versus aerobic) after 3 months; and by 196.4 (112.2 to 280.7) in the aerobic group, by 122.7 (37.7 to 207.6) in the strength group and by 27 (-40.4 to 94.4) in the control group (P = 0.002, control versus aerobic, and P = 0.03 control versus strength) after 6 months. The level of fitness improved more in the strength-trained group, and there was a minor reduction in body weight and degree of fatness. There were no changes in lipoprotein levels. Aerobic exercise training causes early and sustained benefit in treadmill exercise capacity, while the effects of strength exercise training are later in onset. Exercise training alone did not influence lipid levels. CONCLUSION: Cardiac rehabilitation programmes should be comprehensive, including advice on diet and other risk factor modifications in addition to exercise sessions involving aerobic and strength training elements.

Aged↗
PubMed1996

Sensitive methods to study human apolipoprotein B metabolism using stable isotope-labeled amino acids.

The objective of the study was to develop a sensitive method using stable isotope-labeled tracers that would permit the determination of apolipoprotein B (apoB) metabolism in very low-density lipoprotein subfractions (VLDL1, Sf 60-400; VLDL2, Sf 20-60), intermediate-density lipoprotein (IDL, Sf 12-20), and low-density lipoprotein (LDL, Sf 0-12). Six normolipidemic subjects were given trideuterated leucine, and its clearance from plasma and appearance in the four apoB-containing lipoprotein fractions were followed by use of a highly sensitive gas chromatography-mass spectrometry technique in which the m + 3-to-m + 2 ion ratio was selectively monitored. This analytic approach permitted the precise measurement of low enrichments in IDL and LDL and extension of the turnover out to 250-300 h. A compartmental model was developed to derive rate constants from the plasma and apoB enrichment curves. The model was uniquely identifiable once parameter dependencies had been introduced to reduce the number of unknowns. Values were obtained for apoB input into all lipoprotein density intervals, together with rates of interconversion and catabolism; these agreed well with results from radioiodinated tracer experiments. An alternative model structure was also explored in which input occurred only into VLDL1. Altering the protocol of tracer administration (bolus vs. primed constant infusion) and dose (over a 10-fold range) had no influence on the results obtained. The analytic and modeling approach described will permit stable isotopes to be used to elucidate key features of apoB metabolism in normal and pathological states.

Adult↗
PubMed1996

Accumulation of large very low density lipoprotein in plasma during intravenous infusion of a chylomicron-like triglyceride emulsion reflects competition for a common lipolytic pathway.

Very low density lipoproteins (VLDL) are produced in the liver and contain apolipoprotein (apo) B-100 and endogenous lipids. By contrast, ingestion of fat leads to formation of chylomicrons containing apoB-48 secreted from the intestine. In this study, a 60-min intravenous infusion of a chylomicron-like triglyceride emulsion was given to healthy young men to examine whether competition between chylomicrons and VLDL for the same lipolytic pathway explains the increase in VLDL seen after meals. The responses of two major VLDL subfractions were determined by measuring the concentrations of apoB-100 in fractions of triglyceride-rich lipoproteins with Svedberg flotation rates of 60-400 (large VLDL) and 20-60 (small VLDL) that were separated from plasma by density gradient ultracentrifugation. A threefold elevation in plasma triglycerides was observed during the infusion together with a consistent linear increase of large VLDL. The rate at which large VLDL accumulated in plasma differed markedly among individuals and was not enhanced by doubling of the infusion rate. The response of small VLDL was more heterogeneous; however, a decrease was seen in most subjects. The combined pattern for the two VLDL species is what would be expected if large VLDL particles are the precursors of smaller VLDL species and if lipolysis of large VLDL is inhibited through competition from the triglyceride emulsion. The extent to which the triglyceride emulsion inhibited the lipolysis of VLDL and/or influenced the synthesis rate of large VLDL was estimated from simultaneous stable isotope studies. The emulsion caused a 75-90% block of the conversion of large VLDL apoB to small VLDL apoB and there was no sign of enhanced synthesis of large VLDL after infusion of the triglyceride emulsion. The corollary of these findings is that chylomicrons and their remnants impede the normal lipolytic degradation of VLDL and could thereby be indirectly implicated in the generation of atherogenic remnant lipoproteins.

Adult↗
PubMed1995

The provision of family planning services by family doctors in a health board region.

A survey was carried out to ascertain the extent of family planning services provided by family doctors. Of the 134 doctors surveyed, 119 (88.8%) replied. Of these 97 (81.5%) were male, 30 (25.2%) were aged less than 40 and 22 (18.5%) were greater than 60. Sixty-four (53.8%) worked in single-handed practices, 52(43.7%) were vocationally trained, 101 (84.9%) had the MICGP or equivalent and 42 (35.3%) had a family planning certificate. Of the 119 respondents, 99 (83.2%) give instruction in natural family planning methods, 114 (95.8%) prescribe oral contraceptives, 102 (85.7%) prescribe the "morning after pill", 40 (33.6%) fit diaphragms and 17 (14.3%) fit intrauterine devices. Only 3 (2.5%) perform male sterilisations. Doctors aged less than 60 years were 1.3 times more likely to prescribe oral contraceptives (p < 0.0001), and were four times more likely to fit diaphragms (p < 0.01). Doctors who hold a family planning certificate were 2.4 times more likely to fit diaphragms (p < 0.001) and were 2.5 times more likely to fit intrauterine devices. As to who should provide these services, the family doctor was the preferred option for 95 (79.8%) with regard to natural family planning, 107 (89.9%) for the contraceptive pill, 76 (63.9%) for the diaphragm, 58 (48.7%) for the intrauterine device, 45 (37.8%) for male sterilisations and 4 (3.4%) for female sterilisations. Younger doctors and those with a family planning certificate were more likely to say that family doctors should provide these services.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women.

VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 (P < .001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had and LDL-III in the range associated with high risk of heart disease ( > 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = 39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa.

Previous studies from our laboratory have shown that retinitis pigmentosa (RP), a family of hereditary retinal degenerations, is often accompanied by abnormal levels of cholesterol or polyunsaturated fatty acids. The requirement of the retina for n-3 fatty acids is well known, and a defect in the supply of these lipids (e.g., by apolipoproteins) could affect the course of the disease. The present study confirms and extends a report on apolipoprotein E (apo E) isoforms in German RP patients [Jahn, Oette, Esser, Bergmann, and Leiss, (1987) Ophthalmic Res. 19, 285-288] which showed a tenfold increased frequency of the E2/E2 phenotype compared to the average German population. In our study, apo E phenotypes were determined in the probands of 100 Scottish RP families. The findings revealed a 4-fold increase in the incidence of E2/E2 and an 8-fold increase in E4/E4 compared to a Scottish control population. These increases were statistically significant at the P < 0.05 and P < 0.01 levels, respectively. To investigate the possibility that some of these apparent E2/E2 or E4/E4 phenotypes might actually be new apo E mutations, we examined the behavior of the apo E on sodium dodecyl sulfate-polyacrylamide gels (E2 migrates anomalously) and on isoelectric focusing gels following cysteamine modification of cysteines. These studies showed that two RP patients possibly had new apo E mutations, though amino-terminal sequence analysis revealed no changes in the sequence of the first 19 residues; further sequence analysis is obviously warranted.

Apolipoproteins E↗
PubMed1991

Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects.

This study examined apolipoprotein (apo) B metabolism in normolipemic subjects homozygous for the apo E2 (n = 4), apo E3 (n = 5), or apo E4 (n = 5) phenotype. Radioiodinated very low density lipoprotein (VLDL1) (ultracentrifuge flotation rate [Sf] 60-400) and VLDL2 (Sf 20-60) were injected into volunteers and the conversion of apo B was followed through intermediate density lipoprotein (IDL) to low density lipoprotein (LDL). Subjects homozygous for E3 converted approximately 50% of LVDL2 to LDL, the remainder being lost by direct catabolism. Those with the E2 phenotype produced less VLDL1, but converted more of it to VLDL2 (compared to E3 subjects). They displayed a characteristic dyslipidemia with the presence of slowly catabolized VLDL1 and VLDL2 remnants. LDL levels were low owing to increased direct catabolism of VLDL2 and IDL and a reduced efficiency of delipidation; only 25% of VLDL2 apo B was directed to LDL production. In contrast, E4 subjects converted more VLDL2 apo B to LDL than E3 subjects. About 70% of VLDL2 apo B was found in LDL; direct catabolism of VLDL and IDL was reduced as was the fractional catabolic rate of LDL (0.2 vs. 0.26 in E3 subjects). These changes in the VLDL----IDL----LDL metabolic cascade can in part be explained by alterations in hepatic LDL receptors with E2 subjects having higher and E4 subjects lower activities than those in E3 homozygotes.

Adult↗
PubMed1985

Effects of 1,2-cyclohexanedione modification on the metabolism of very low density lipoprotein apolipoprotein B: potential role of receptors in intermediate density lipoprotein catabolism.

The conversion of very low density (VLDL) to low density lipoproteins (LDL) is a two-step process. The first step is mediated by lipoprotein lipase, but the mechanism responsible for the second is obscure. In this study we examined the possible involvement of receptors at this stage. Apolipoprotein B (apoB)-containing lipoproteins were separated into three fractions, VLDL (Sf 100-400), an intermediate fraction IDL (Sf 12-100), and LDL (Sf 0-12). Autologous 125I-labeled VLDL and 131I-labeled 1,2-cyclohexanedione-modified VLDL were injected into the plasma of four normal subjects and the rate of transfer of apoB radioactivity was followed through IDL to LDL. Modification did not affect VLDL to IDL conversion. Thereafter, however, the catabolism of modified apoB in IDL was retarded and its appearance in LDL was delayed. Hence, functional arginine residues (and by implication, receptors) are required in this process. Confirmation of this was obtained by injecting 125I-labeled IDL and 131I-labeled cyclohexanedione-treated IDL into two additional subjects. Again, IDL metabolism was delayed by approximately 50% as a result of the modification. These data are consistent with the view that receptors are involved in the metabolism of intermediate density lipoprotein.

Adult↗
PubMed1982

Serum gamma-glutamyltransferase and alkaline phosphatase in rheumatoid arthritis.

Serum gamma-glutamyltransferase (GGT) and alkaline phosphatase (AP) were assayed in 98 consecutive patients with rheumatoid arthritis. Twenty-three patients had increased GGT activities and 45 an increased AP activity. Twelve patients showed an increase in both enzyme activities and AP isoenzyme studies were performed on seven of this group. In three subjects an increase in the bone isoenzyme was observed and in three others the increase in activity was attributed to the liver isoenzyme. The remaining patient, who probably suffered from coexistent primary biliary cirrhosis, showed an increase in both bone and liver isoenzymes. The liver involvement, suggested by the alkaline phosphatase isoenzyme results, was largely confirmed by the butanol extraction of GGT. The changes in these enzymes in this small series could not be related definitely to drug therapy. It is concluded that though increases in GGT and AP are common in rheumatoid arthritis, this does not necessarily indicate hepatic involvement. Further isoenzyme studies are needed to define the extent to which organs other than the liver bring about increases in these serum enzymes in rheumatoid disease.

Adult↗
PubMedDate not supplied

How to improve the uptake of influenza vaccination in older persons at risk.

A study was carried out to ascertain if those older persons at risk from influenza in Ireland would respond to a personalized invitation to attend for vaccination. Of the 193 patients invited to attend for vaccination, 126 (65.3 per cent) presented for vaccination. This rose to 142 (73.6 per cent) after a reminder letter was went out. In the year previous to the study only 80 (41.5 per cent) of the same cohort of patients were vaccinated. This study has demonstrated how a simple invitation for influenza vaccination can dramatically improve the uptake rates.

Aged↗
PubMedDate not supplied

Outpatient experiences in acute hospitals.

BACKGROUND: Patient satisfaction surveys are useful in gaining an understanding of users' needs and their perceptions of the service received. AIM; To assess the views of outpatient department (OPD) attendees on the quality of service received. METHODS: OPD attendees were randomly selected from four acute hospitals in one health board region and sent a confidential postal questionnaire to assess their views on their visit. RESULTS: Of 3,037 attendees surveyed, there was a response rate of 75.7%. Levels of satisfaction were high at 94%. Doctors and nurses were perceived as friendly by 61% and 72%, professional by 44% and 30%, rushed by 8% and 7%, and rude by 1% and 1% of patients, respectively. Using logistic regression, age (being older), sex (being male), pain level (no pain), decisions about care (wanting more involvement) and being satisfied with their waiting time from arrival to being seen were significantly associated with a greater likelihood of being satisfied overall. CONCLUSION; Whilst there was a high level of satisfaction with the quality of care received, areas for improvement were highlighted from the patient's perspective.

Adolescent↗
PubMedDate not supplied

Factors associated with self-reported depression and self-esteem among school-going adolescents from a geographically defined region in Ireland.

BACKGROUND: Recent reviews indicate that mental health problems in the young are increasing. AIMS: To measure the prevalence of, and risk factors associated with, depression and low self-esteem among Irish post-primary students. METHOD: 1,428 students, randomly selected from a sample of post-primary schools, were given an anonymised questionnaire. Analyses included bivariate and multivariate logistic regression. RESULTS: Questionnaires were completed by 992 (69.9%) respondents. 206 (20.8%) had a high depression score. Being from a single parent family (OR 2.8, 95% CI 1.5-5.4, p<0.001); having low self esteem (OR 13.44 95% CI 8.9-20.3, p<0.001); being female (OR, 3.7, 95% CI 2.5-5.6 p<0.001) and having a low fitness level (OR 1.8, 95% CI 1.2-2.8 p<0.006) were independently associated with a high depression score. CONCLUSIONS: The level of self-reported depression was high among these respondents and risk factors identified include having low self-esteem, being female, being from a single parent family and having a low fitness level.

Adolescent↗