PubMed Health⌕ Search

Biomedical subjects

A Donald

Publications and source records attributed to A Donald.

At least 19 recordsLinked to original sources
PubMed1999

Effects of streptozotocin-induced diabetes on neuronal sigma receptors in the rat brain.

To study the effect of diabetes mellitus on the density of sigma receptors, in vitro binding experiments were conducted in whole brain homogenate membranes of 5-week and 10-week control rats and streptozotocin (STZ)-induced diabetic rats. sigma-1 Receptors were labelled with [3H](+)-pentazocine while sigma-2 receptors were labelled with [3H] 1,3-di-o-tolylguanidine (DTG) in the presence of 0.5 microM (+)-pentazocine to mask sigma-1 sites. Non-specific binding was determined in the presence of 20 microM haloperidol. Scatchard analysis revealed a 27% (p<0.01) decreased in sigma-1 receptor density and a 33% (p<0.01) decreased in sigma-2 receptor density in whole brain of 10-week STZ-diabetic rats. No statistically significant difference was found in the sigma receptor content of 5-week STZ-diabetic rats. These results provide evidence that neuronal sigma receptors are reduced in 10-week STZ-diabetic rats and suggest that changes in sigma receptors may play a role in diabetes related abnormalities. Further evaluation is required to determine whether changes observed in the brain are homogeneous for either or both sigma receptor subtypes as well as potential links between other CNS receptor changes previously observed in STZ-induced diabetic rats.

Analgesics, Opioid↗
PubMed1999

Evidence-based practice. Data day.

A project assessing the feasibility of using research data in routine clinical practice showed that most clinicians found it too time-consuming. Obtaining relevant research articles took an average of three days with an on-site library, and a week without one. The most serious barrier was the poor state of the information itself. Investment should focus on developing the information, followed by effective and easy-to-use search methods.

Attitude of Health Personnel↗
PubMed1999

Blood lipids and endothelial function in glycogen storage disease type III.

We have assessed early indicators of arterial disease in patients with glycogen storage disease type III (GSD III; McKusick 232400), investigating the plasma lipid and lipoprotein profile and endothelial function. Eleven patients, aged 10-39 years, were recruited together with age-, sex- and smoking status-matched controls. Brachial artery responses were assessed by high-resolution ultrasonographic measurement of the diameter of the brachial artery at baseline, after reactive hyperaemia and in response to sublingual glyceryl trinitrate (GTN). The means of plasma cholesterol (total and HDL and LDL subfractions), triglycerides, apo-A1, apo-B, Lp(a) and the atherogenic index were similar in both groups. Cardiac troponin I was below the lower limits of detection (< 0.03 g/L) in all subjects. The GSD III patients had similar body mass index (BMI) and brachial artery diameter to the control group (BMI 22.6 +/- 5.6 vs 22.3 +/- 5 kg/m2; brachial artery diameter 3.4 +/- 0.5 vs 3 +/- 0.7 mm). When compared to the baseline diameter, the maximal flow-mediated dilatation of the brachial artery after reactive hyperaemia was 9.3% +/- 2.1% (mean +/- SD) in the GSD III patients and 6.5% +/- 3.5% in the control group, a difference of 1.8% (95% CI 0.07% to 5.5%). The maximal dilatation of the brachial artery after GTN administration was 18.3% +/- 6.4% in the GSD III patients and 17.9% +/- 6.5% in the control group, a difference of 0.4% (95% CI-6.9% to 7.7%). In conclusion, we found no evidence of abnormal plasma lipid and lipoprotein profile or endothelial dysfunction in patients with GSD III. They are unlikely to be at increased risk of premature atherosclerosis.

Adolescent↗
PubMed1999

Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

AIMS: The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. METHODS: Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. RESULTS: There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. CONCLUSIONS: These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.

Adult↗
PubMed1999

Determinants of the response of human blood vessels to nitric oxide donors in vivo.

The potency of the nitric oxide (NO) donors glyceryltrinitrate (GTN) and 3-morpholinosydnonimine was compared in human dorsal hand veins, the radial artery, and the forearm resistance vessels. NO donors were more potent in veins and the radial artery (vessels with minimal basal NO-mediated dilatation) than in the resistance vascular bed (where basal NO is a major determinant of vascular tone). In contrast, 8-bromoguanosine 3',5'-cyclic monophosphate (a cGMP mimetic) was approximately equipotent in resistance arteries and veins and was less potent in the radial artery. Inhibition of phosphodiesterase V with dipyridamole did not alter the arteriovenous profile of GTN. Increasing the local concentration of NO in veins (by infusing sodium nitroprusside) reduced their sensitivity to GTN but not to 8-bromoguanosine 3',5'-cyclic monophosphate. Conversely, reducing endogenous NO production in the resistance vasculature led to time-dependent increases in the response to GTN. These data suggest that soluble guanylate cyclase rather than cGMP-dependent protein kinase or phosphodiesterase V is the site in the second messenger pathway that determines the arteriovenous profile of NO donors. Moreover, the sensitivity of soluble guanylate cyclase to NO donors might be regulated by the ambient concentration of NO, with increased local NO down-regulating the dilator response to NO donors.

Adult↗
PubMed1998

Applying theory to practice--the use of 'ripple effect' plans in continuing education.

The difficulties students experience in applying theory to practice are well documented and educationalists have employed a variety of techniques in an effort to enhance effective application. This paper describes the utilization of one such teaching/learning strategy in a diploma level course in management for registered nurses and midwives. As problem-solving individual contracts of learning, 'ripple effect' plans enabled course participants to apply general principles of management theory to specific nursing management practice in their everyday world of nursing and midwifery work, making changes in practice and procedure which were visible and real.

Clinical Competence↗
PubMed1998

Using biomedical databases in everyday clinical practice: the Front-Line Evidence-Based Medicine project in North Thames.

The aims of this project were to assess the feasibility of using biomedical databases in everyday clinical settings, and the infrastructure needed to support such practice. Fourteen firms or units whose lead clinician was enthusiastic for the principles of evidence-based medicine were provided with 24-h access to databases in their clinics or offices. All members of the firms were trained in the principles of evidence-based practice and in the use of databases for finding evidence. The firms were volunteers from a variety of specialties in both hospital and community Trusts in North Thames Region. Assessment of changes in practice was carried out by questionnaire and interview. Also, any changes needed to improve the use of primary research data in everyday clinical settings was investigated. Seven firms found that the project had made their journal clubs and their clinical discussion meetings more structured and focused, with research evidence for and against interventions discussed. The use of evidence in a case-related form was limited by the time available. The other seven firms were: dissatisfied with their training, dissatisfied with their computer facilities or lacked time. The changes necessary to improve the utilization of research data included: closer collaboration with librarians, continuing training and fast delivery of documents. The limitations of this study are that initial data were not recorded and the assessments made were subjective. Using biomedical databases in everyday clinical practice could be feasible provided that there is a coordinated implementation strategy, which requires a significant commitment of time and resources from all parties involved (clinicians, other health care professionals, librarians and managers).

Computer User Training↗
PubMed1998

Effects of prenatal maternal TRH stimulation on the postnatal ability of neonatal piglets to cope with a cold challenge.

The effect of administering thyrotropin-releasing hormone (TRH) before farrowing on the ability of their newborn piglets to withstand a cold challenge was studied. Sows received intravenous infusions of TRH (5 microg kg(-1); TRH group) or physiological saline (0.9% NaCl; control group) from day 105 of gestation until farrowing. The plasma concentrations of thyroxine and triiodothyronine increased in sows treated with TRH. There were no differences in thyroxine and triiodothyronine between pigs born to sows in the TRH group and those of the control group. The rectal temperature of piglets born to TRH-treated sows decreased less than that of piglets born to controls as a consequence of a 1-hour cold challenge. Piglets born to sows in the TRH group had higher body weights at birth, and by day 28 they were an average 600 g heavier than those born to sows in the control group. Summarizing, prenatal maternal treatment with TRH appears to increase piglets' resistance to cold as well as to have beneficial effects on birth and weaning weights.

Adaptation, Physiological↗
PubMed1997

An overview of techniques for dealing with large numbers of independent variables in epidemiologic studies.

Many studies of health and production problems in livestock involve the simultaneous evaluation of large numbers of risk factors. These analyses may be complicated by a number of problems including: multicollinearity (which arises because many of the risk factors may be related (correlated) to each other), confounding, interaction, problems related to sample size (and hence the power of the study), and the fact that many associations are evaluated from a single dataset. This paper focuses primarily on the problem of multicollinearity and discusses a number of techniques for dealing with this problem. However, some of the techniques discussed may also help to deal with the other problems identified above. The first general approach to dealing with multicollinearity involves reducing the number of independent variables prior to investigating associations with the disease. Techniques to accomplish this include: (1) excluding variables after screening for associations among independent variables; (2) creating indices or scores which combine data from multiple factors into a single variable; (3) creating a smaller set of independent variables through the use of multivariable techniques such as principal components analysis or factor analysis. The second general approach is to use appropriate steps and statistical techniques to investigate associations between the independent variables and the dependent variable. A preliminary screening of these associations may be performed using simple statistical tests. Subsequently, multivariable techniques such as linear or logistic regression or correspondence analysis can be used to identify important associations. The strengths and limitations of these techniques are discussed and the techniques are demonstrated using a dataset from a recent study of risk factors for pneumonia in swine. Emphasis is placed on comparing correspondence analysis with other techniques as it has been used less in the epidemiology literature.

Animal Diseases↗
PubMed1997

Examination of four 123I-labeled piperidine-based sigma receptor ligands as potential melanoma imaging agents: initial studies in mouse tumor models.

The development of sigma (sigma) receptor radioligands has become the focus of research over the past few years due to their potential uses in nuclear medicine. It has been shown that a wide variety of human tumor cell lines express sigma receptors, including malignant melanoma and tumors of the colon, lung, brain, breast and testes. To provide potential probes for the in vivo SPECT examination of sigma receptor densities, we have synthesized a series of halogenated 4-(phenoxymethyl)piperidines and related compounds as high affinity sigma receptor ligands. Four of these have been labeled with I-123 and evaluated in vivo in mouse tumor models. All four radioligands were synthesized no-carrier-added using oxidative radioiododestannylation methods and specific activities > 74,000 MBq/mumol were obtained. Radiochemical yields were 55-83% EOS and radiochemical purities were > 98%. All four tracers were initially screened in vivo using distribution studies in nude mice with B16 melanoma tumors (8-12 mm diameter in the flank). In all four studies, high uptake (up to 0.90 +/- 0.42 %ID, 12.99 +/- 4.28 %ID/g at 48 h) and excellent retention of radioactivity in tumor tissues was exhibited for as long as 48 h post-injection (PI). In the B16 melanoma model, the most promising results were obtained with [123I]-1-(2-hydroxyethyl)-4-(iodophenoxymethyl)piperidine (123I-3), for which tumor/tissue ratios were significantly > 1.0 by 4 h PI for most organs and increased thereafter. Tumor/tissue ratios at 48 h were as follows: blood, 68.4; muscle 31.7; brain, 7.4; lung, 6.3; liver, 1.3. In subsequent studies, 123I-3 was evaluated in nude mice with A375 human malignant melanoma. As in the B16 model, high uptake and prolonged retention of radioactivity in tumor tissues was noted. These results indicate that 123I-3 shows promise as a SPECT ligand for the detection of malignant melanoma.

Animals↗
PubMed1997

Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli.

OBJECTIVE: To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults, to determine whether these responses are consistent and can be used to assess endothelial function. DESIGN AND SETTING: High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males and three females mean age 31 years (range 25 to 43) with no known risk factors for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial dependent dilatation was compared to duration of cuff occlusion, peak reactive hyperaemia, and duration of increased flow. Nitrate induced, endothelial independent dilatation was compared to dose of ISDN and change in flow. RESULTS: Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was mean (SD) 96 (6)% of maximal response and did not increase significantly with longer occlusion times. No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject. With increasing doses up to 200 micrograms there was an increase in dilatation. Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS: Measures of arterial function vary with duration of blood flow occlusion and ISDN dose. Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables produce consistent reproducible measures of endothelial function.

Adult↗
PubMed1997

Retrograde flow in the deep veins of subjects with normal venous function.

BACKGROUND: Duplex ultrasonography has become the optimal non-invasive method of assessing the deep venous system of the leg. The stimuli used to promote reverse flow, subject positioning, and the veins scanned have varied between studies. Reverse flow of less than 0.5 s is accepted as 'normal', however, all published studies have demonstrated 'normal' subjects with deep vein reverse flow exceeding this time. The aim of this study was to establish the duration of reverse flow in all deep vein segments, and to determine the optimal method of eliciting reverse flow in individuals with proven normal deep vein function. METHODS: Duplex scanning was used to detect the presence and duration of reverse flow in the superficial femoral, popliteal and posterior tibial veins of 61 legs with normal venous function. The veins were scanned with each subject inclined at 10 degrees, 45 degrees and standing erect. The abrupt release of distal tourniquet compression and the Valsalva manoeuvre were used as stimuli for reverse flow. RESULTS: There was significantly less reverse flow in distal veins than in proximal veins when the subject was scanned at 10 degrees and 45 degrees. Median (range) reverse flow in the femoral vein at 10 degrees was 0.21 (0-1.18) s, posterior tibial vein 0.08 (0-0.67) s, (P < 0.0001); in the femoral vein at 45 degrees was 0.14 (0.04-2.14) s, posterior tibial vein 0.07 (0-0.56) s, (P < 0.0001). The duration of reverse flow was significantly less in the superficial femoral and popliteal veins when the subjects were erect than when inclined at 10 degrees and 45 degrees. Median (range) reverse flow in the femoral vein at 10 degrees was 0.21 (0-1.18), and when standing 0.1 (0-1.36) (P < 0.0001); below-knee popliteal vein at 10 degrees was 0.15 (0.04-1.95) s, and when standing 0.10 (0-1.03) (P = 0.0004). Reverse flow of more than 0.5 s was never elicited in the posterior tibial veins if the subject stood, nor did it occur in the popliteal vein during a Valsalva manoeuvre. CONCLUSION: The optimal sites to assess deep vein reverse flow are the posterior tibial vein following removal of distal compression with the patient standing, and the popliteal vein during a Valsalva manoeuvre, as retrograde flow more than 0.5 s does not occur in subjects with normal venous function.

Adult↗
PubMed1996

Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults.

BACKGROUND: Passive smoking has been linked to an increased risk of dying from atherosclerotic heart disease. Since endothelial dysfunction is an early feature of atherogenesis and occurs in young adults who actively smoke cigarettes, we hypothesized that passive smoking might also be associated with endothelial damage in healthy young-adult nonsmokers. METHODS: We studied 78 healthy subjects (39 men and 39 women) 15 to 30 years of age (mean +/- SD, 22 +/- 4): 26 control subjects who had never smoked or had regular exposure to environmental tobacco smoke, 26 who had never smoked but had been exposed to environmental tobacco smoke for at least one hour daily for three or more years, and 26 active smokers. Using ultrasonography, we measured the brachial-artery diameter under base-line conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilatation was observed in all control subjects (8.2 +/- 3.1 percent; range, 2.1 to 16.7) but was significantly impaired in the passive smokers (3.1 +/- 2.7 percent; range, 0 to 9; P < 0.001 for the comparison with the controls) and in the active smokers (4.4 +/- 3.1 percent; range, 0 to 10; P < 0.001 for the comparison with the controls; P = 0.48 for the comparison with the passive smokers). In the passive smokers, there was an inverse relation between the intensity of exposure to tobacco smoke and flow-mediated dilatation (r = -0.67, P < 0.001). In contrast, dilatation induced by nitroglycerin was similar in all groups. CONCLUSIONS: Passive smoking is associated with dose-related impairment of endothelium-dependent dilatation in healthy young adults, suggesting early arterial damage.

Adolescent↗