Making better use of research findings.
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Clinical Competence↗
Biomedical subjects
A Donald
Publications and source records attributed to A Donald.
Meta-analysis of homoeopathy trials.
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Homeopathy↗
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↗
Regarding" Hemodynamic assessment of femoropopliteal venous reflux in patients with primary varicose veins".
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Femoral Vein↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Evidence based medicine: an approach to clinical problem-solving.
Doctors within the NHS are confronting major changes at work. While we endeavour to improve the quality of health care, junior doctors' hours have been reduced and the emphasis on continuing medical education has increased. We are confronted by a growing body of information, much of it invalid or irrelevant to clinical practice. This article discusses evidence based medicine, a process of turning clinical problems into questions and then systematically locating, appraising, and using contemporaneous research findings as the basis for clinical decisions. The computerisation of bibliographies and the development of software that permits the rapid location of relevant evidence have made it easier for busy clinicians to make best use of the published literature. Critical appraisal can be used to determine the validity and applicability of the evidence, which is then used to inform clinical decisions. Evidence based medicine can be taught to, and practised by, clinicians at all levels of seniority and can be used to close the gulf between good clinical research and clinical practice. In addition it can help to promote self directed learning and teamwork and produce faster and better doctors.
Clinical Medicine↗
Pharmacokinetics of parenteral and oral sustained-release morphine sulphate in dogs.
The pharmacokinetics of single-dose morphine sulphate (MS) administered intravenously (i.v.) and intramuscularly (i.m.) and of oral sustained-release morphine sulphate (OSRMS) were studied in dogs. Beagles (n = 6) were randomly assigned to six treatment groups using a Latin square design. Treatments included MS 0.5 and 0.8 mg/kg i.v. and i.m. and OSRMS 15 and 30 mg orally (p.o). Serum samples were drawn at intervals up to 420 min following parenteral MS and 720 min following OSRMS. Serum was analysed for morphine concentration using a radioimmunoassay. Pharmacokinetic analysis of the results revealed that MS was eliminated by a first-order process best described by a two-compartment model. For i.v. and i.m. data there were no statistically significant differences (P < 0.05) between steady-state volume of distribution, half-life of elimination and plasma clearance. As expected, area under the concentration vs. time curve (AUC) was significantly greater for the 0.8 mg/kg dosage for i.v. and i.m. routes, and time to maximum serum concentration was significantly longer following i.m. administration. For OSRMS there were no significant differences between dosage for any parameter (AUC, Cmax, tmax, t1/2, F) and prolonged absorption of the drug occurred over approximately 6 h. Bioavailability (F) for both oral dosages was approximately 20%. The i.m. route is an effective method for rapid and complete delivery of MS to dogs. OSRMS may be useful in the provision of long-term analgesic therapy in dogs, but further work is required to verify the safety and effectiveness of this preparation.
Administration, Oral↗
Heterogeneity of pericyte populations in equine skeletal muscle and dermal microvessels: a quantitative study.
The objective of this ultrastructural investigation was to determine if populations of pericytes in equine dermal and skeletal muscle capillaries increase in a head-to-foot direction, as has been reported in human skeletal muscles. Samples of equine microvessels were obtained from the longissimus dorsi skeletal muscle 150 cm. from the ground, from the dermis above this muscle, from the extensor carpi radiali muscle at 55 cm. from the ground, from the dermis adjacent to that muscle, and from dermis 15 cm. from the ground, just above the hoof wall. Tissues were processed for transmission electron microscopy. Electron micrographs were analyzed with a digitizing tablet and computer, to determine the ratios of endothelial cell outer circumference and pericyte inner lengths. Pericytes were separated into two classes; those closest to the endothelial cells were defined as covering capillaries. Those separated from endothelial cells by another layer of pericytes were termed enveloping pericytes. There was much greater coverage and envelopment of dermal capillaries (85% and 135%) than skeletal muscle capillaries (27% and 31%). Regression analysis of the pericyte coverage and envelopment of dermal capillaries revealed a significant increase in pericytes toward the ground. Similarly, the two skeletal muscle tissues differed significantly in their pericyte coverage and envelopment (25/27% at 150 cm., 31/35 at 55 cm.). The data indicate that, as in humans, capillary pericytes are not homogeneously distributed within the same tissues, but are more numerous closer to the ground. Differences in pericyte populations could affect studies of microvessel function.
Analysis of Variance↗
Synthesis of glucosinolate precursors and investigations into the biosynthesis of phenylalkyl- and methylthioalkylglucosinolates.
The alkenyl and aromatic glucosinolates in oilseed rape (Brassica napus) are biosynthesized from chain-extended homologues of protein amino acids, including methionine and phenylalanine. Homologues of these two amino acids, homophenylalanine (2-amino-4-phenylbutyric acid) and dihomomethionine (2-amino-6-methylthiohexanoic acid) were synthesized both with and without a 1-14C label. Microsomal preparations from oilseed rape leaves were shown to contain enzyme systems which metabolize these compounds, with loss of 14CO2, and produce the aldoxime intermediates possible in the biosynthetic pathway utilizing homophenylalanine. These were characterized by comparison with authenticated synthetic compounds. Potential intermediates on the pathway between homophenylalanine and its corresponding aldoxime, the N-hydroxyamino- and the oximino acids, were synthesized and their possible role in the pathway investigated.
Fatty Acids, Monounsaturated↗
Alteration of primate ovary surface epithelium by exposure to hexachlorobenzene: a quantitative study.
Hexachlorobenzene (HCB) is a fungicide and a pollutant of increasing concern in industrialized regions of the world. Reproductive failure is one of the effects of HCB upon mammals. Alteration of cell shape in the ovary surface epithelium (OSE) of Cynomolgus monkeys following oral administration of HCB was observed in this study. At the lowest dose used, 0.1 mg/kg body weight, a dosage that is associated with follicular degeneration, HCB caused quantifiable changes in length-to-width ratios of OSE. Measurement of cell shape by light microscopy offers a reliable indication of OSE changes induced by HCB.
Animals↗
Ultrastructure of pericytes in early stages of histamine-induced inflammation.
Physiological and ultrastructural assessment of changes in the walls of venules in the rat cremaster muscle after administration of histamine indicates that pericytes have essential roles in the normal functioning of venules during inflammation. Fluorescein-labelled albumin was used to quantitate macromolecular leakage and to select suitable venules for ultrastructural analysis 4 and 7 minutes after addition of histamine. Pericytes were concentrated over endothelial cell junctions and gaps. At 4 minutes, when albumin leakage was becoming detectable, gaps between endothelial cells were observed in the venule wall. In 24 serially sectioned gaps, pericytes formed covers, with contact points to the endothelial cells along the sides of the gaps. At 7 minutes, when albumin leakage was maximal, gaps with pericyte covers were still evident, but more commonly observed were pericyte covers over closed endothelial cell junctions. Spaces between the innermost pericytes and endothelial cells were enlarged by an order of magnitude, from 95 nm in controls to 872 nm at 4 minutes and 958 nm at 7 minutes. Pericytes formed coverings or bridges over inclusions of extravasated cells, fluid, proteins, and the vascular label monastral blue. The data indicate that pericytes protect the endothelial lining of venules during histamine-induced inflammation by forming a cohesive covering across gaps.
Animals↗