Search PubMed⌕ Search

Biomedical subjects

M Wood

Publications and source records attributed to M Wood.

At least 109 records · Page 6Linked to original sources

The relationship between cytochrome P4502E1 activity and plasma fluoride levels after sevoflurane anesthesia in humans.

UNLABELLED: We determined whether the perianesthetic plasma fluoride levels after sevoflurane anesthesia in humans were correlated with the metabolic ratio (MR) of 6-hydroxychlorzoxazone to chlorzoxazone, an in vivo probe for cytochrome P4502E1 (CYP2E1) activity. Thirty ASA physical status I or II patients scheduled for extraabdominal surgery were randomized to a chlorzoxazone (n = 20) or a control group (n = 10). Patients in the chlorzoxazone group received 500 mg chlorzoxazone orally on the morning of the day of surgery. Chlorzoxazone and its 6-hydroxymetabolite concentrations were measured in plasma 2 h after drug administration. Anesthesia was induced with propofol, fentanyl, and atracurium intravenously and maintained with sevoflurane (inspired concentration 1-3 vol%). Plasma fluoride concentrations were determined before the induction of anesthesia, at the cessation of sevoflurane, and 2, 4, 6, 10, and 24 h thereafter. The area under the plasma fluoride concentration-time curve (AUC) was calculated up to 24 h after sevoflurane cessation. MR correlated significantly with the plasma fluoride AUC (r2 = 0.28, P < 0.025), the elimination constant calculated for the postanesthetic 10- to 24-h period (r2 = 0.30, P < 0.025), and the plasma fluoride levels 24 h after the cessation of sevoflurane (r2 = 0.48, P < 0.05). A comparison between groups indicated that the administration of chlorzoxazone itself did not alter the postanesthetic fluoride kinetics. Thus, the interindividual variability in perianesthetic plasma fluoride levels after sevoflurane anesthesia is reflected by differences in the MR of chlorzoxazone and hence is related to the interindividual variability in CYP2E1 activity. We conclude that although the predictive value is limited, this study provides a reasonable basis for examining renal function after sevoflurane anesthesia in a subgroup of patients with a high preoperative metabolic ratio of chlorzoxazone. IMPLICATIONS: CYP2E1 metabolizes sevoflurane as measured by the metabolic ratio of chlorzoxazone. Patients with a high ratio may be used to justify examining renal function in patients receiving sevoflurane.

Adult↗

Evolution of the lateral canthoplasty: techniques and indications.

Lateral canthoplasty is a useful method to restore eyelid function and to protect the ocular surfaces. The success of the procedure depends on the proper analysis of periorbital anatomy as it relates to the specific indication for lateral canthoplasty. We report the experience with 1565 lateral canthoplasties with emphasis on the evaluation of newer techniques that better address anatomic and functional requirements. Between 1981 and 1994, 1565 lateral canthoplasties were performed in 684 patients. Of these, 1369 "reconstructive" lateral canthoplasties were performed in 586 patients and 196 "cosmetic" lateral canthoplasties were performed in 98 patients. All operations were performed by a single surgeon (Jelks), and follow-up ranged from 1 to 14 years. The evolution of the operative technique for lateral canthoplasty has been toward an operation that corresponds with the anatomy of the individual. Indications for the procedure include lateral canthal dystopia, horizontal lid laxity, ectropion, entropion, lid margin eversion, lid retraction with or without soft-tissue deficiency, and aesthetic improvement. The types of procedures performed will be reviewed in detail. The evaluation of the newer forms of lateral canthoplasty as unique reconstructive tools and as adjuncts to aesthetic surgery will be discussed.

Adult↗

Managing patient records and documenting service delivery: the results of a 'best practice' remote area nursing program.

This paper describes a 'best practice' demonstration program for monitoring nursing services in remote locations. A four-phase project involving paper- and computer-based patient information systems was implemented at nursing clinics on islands off the coast of Queensland. Patient demographics, diagnoses and details of health service provision were recorded. Results showed a marked improvement in the detail of patient records over the program period. Monitoring of services also provided useful planning and policy information for company management, while a systematic approach to maintaining patient records addressed several medico-legal issues.

Benchmarking↗

Blunted blood pressure response to central sympathoinhibition in normotensive blacks: increased importance of nonsympathetic factors in blood pressure maintenance in blacks.

Enhanced sympathetic reactivity may predispose blacks to the development of hypertension and may occur because of increased sympathetic stimulation and/or attenuated sympathoinhibition. A potential site for such attenuated sympathetic inhibition may be at the level of central alpha2-adrenergic receptors, which play an important role in the feedback inhibition of norepinephrine release. We used cumulative doses (1, 2, and 3 microg/kg I.V.) of the centrally acting alpha2-adrenergic agonist clonidine to measure the sensitivity of alpha2-adrenoceptor-mediated sympathoinhibition and the resultant hypotensive response in 8 normotensive blacks and 10 normotensive whites. Sympathetic activity was determined by radioisotope dilution methodology. Basal norepinephrine spillover was similar in blacks (0.80+/-0.14 microg/min) and whites (0.73+/-0.19 microg/min, P=NS) and after clonidine decreased significantly in both blacks (0.21+/-0.07 microg/min, P<.0001) and whites (0.24+/-0.06 microg/min, P<.0001), with no difference between the groups (P=NS). Despite this similar degree of sympathoinhibition, the hypotensive response to clonidine was markedly blunted in blacks, such that mean arterial pressure decreased by only 10% in blacks but by 21% in whites (P<.0001). The smaller blood pressure decrement after clonidine in normotensive blacks, in the face of an equal degree of sympathoinhibition, suggests that even when sympathetic tone is decreased to the same level in blacks and whites, normotensive blacks have less reduction in blood pressure than whites, implying that nonadrenergic mechanisms contribute more to blood pressure maintenance in blacks than whites. Whether a similar interethnic difference in response to sympathoinhibition occurs in hypertensive patients is as yet unknown.

Adult↗

Sympathoinhibitory response to clonidine is blunted in patients with heart failure.

To determine whether alpha2-adrenergic-mediated sympathoinhibition was altered in chronic heart failure, sympathoinhibitory sensitivity was assessed using the alpha2-adrenergic agonist clonidine in 7 patients with heart failure and in 10 healthy control subjects. Basal norepinephrine spillover was significantly higher in patients with heart failure (1.3+/-0.3 microg/min) than in control subjects (0.7+/-0.1 microg/min, P=.05). Compared with control subjects, the decrement in norepinephrine spillover to cumulative doses of clonidine (1, 2, and 3 microg/kg administered intravenously) was significantly less in patients with heart failure (P<.05). Blood pressure also tended to decrease less in patients with heart failure (P=.06). The doses of clonidine required to produce a 10% decrease in blood pressure and a 25% decrease in norepinephrine spillover were significantly higher in heart failure (P<.01 and P=.05, respectively). Thus, although clonidine lowers norepinephrine spillover significantly in patients with heart failure, such patients are less sensitive to clonidine than healthy control subjects. This difference in sensitivity suggests that doses of clonidine provide effective sympathoinhibition will need to be selected for studies that will evaluate the potential therapeutic effect of clonidine in heart failure.

Adrenergic alpha-Agonists↗

Norepinephrine release in the human forearm: effects of epinephrine.

It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.

Adult↗

Report on primate supply for biomedical scientific work in the UK. EUPREN UK Working Party.

A Working Party of the UK group of European Primate Resources Network (EUPREN) considered primate supply for scientific work in the UK. Through a questionnaire, which achieved a very good response, it obtained details of primate use, sources and breeding in the UK and it put forward options to ensure that animal welfare is the best possible whilst ensuring continued supply. The questionnaire showed that contract research laboratories and pharmaceutical companies use about 80% of the 4233 primates used annually at the moment, with the rest accounted for by academic establishments and public sector laboratories. Fifty-four per cent are cynomolgus macaques (Macaca fascicularis), of which nearly 90% are captive-bred outside the European Union (EU), the remainder being bred in the UK. Nearly 90% of cynomolgus macaques are used by only five institutions. Thirty-seven per cent of primates used are marmosets (Callithrix jacchus jacchus), all of which are bred in the UK. Most of the rest are rhesus macaques (Macaca mulatta), about half of which are captive-bred outside the EU, the other half being bred in the UK. Overall primate use has increased from about 3000 per year in 1990 and users predict that requirements for all species except baboons (Papio sp.) will be maintained or increase. Marmoset breeding in the UK is already closely matched to use, and it could be increased reasonably easily if necessary. Some of the existing breeding centres of macaques in the UK would be prepared to consider expanding to supply others, although investment and imported breeding stock would be needed and it is likely that a large investment would be needed to breed a significant fraction of the macaque use in the UK. A further problem is that the users of only about 10% of the cynomolgus macaques said that they could replace this species by rhesus macaques, which are easier to breed in the UK. The questionnaire showed that much of the use of macaques would be transferred to other countries equally remote from the natural source countries of the animals, if constraints on primate use became more severe in the UK. Users felt that it is unlikely that much of the work could be transferred to the natural source countries themselves. A review of the literature revealed a paucity of information on the effects of transport on primate welfare. The importance of obtaining this information before making decisions about alternative means of supply is stressed. Current schemes for the accreditation of primate breeders were reviewed. A list of options is presented for discussion. Users vary so much in their requirements that it is unlikely that one means of supply will be applicable to all. Animal welfare will benefit and supply will be more certain if cooperation between those concerned (preferably through the UK group of EUPREN) is maintained.

Animal Welfare↗

Telementoring: pushing the telemedicine envelope.

Telemedicine offers significant advantages in bringing consulting support to distant colleagues. Our aim in this study was to evaluate the role of telementoring in the training of advanced laparoscopic surgical procedures. Student surgeons received a uniform training format to enhance their laparoscopic skills and intracorporeal suturing techniques and specific procedural training in laparoscopic colonic resections and Nissen fundoplication. Subsequently, operating rooms were equipped with three cameras. A telestrator (teleguidance device), instant replay (to critique errors), and CD-ROM programs (to provide reference information) were used as intraoperative, educationally assistant tools. In phase 1, four colonic resections were performed with the mentor in the operating room (group A), and four colonic resections were performed with the mentor on the hospital grounds but not in the operating room (group B). The voice and video signals were received at the mentor's location using coaxial cable. In phase 2, two Nissen fundoplications were performed with the mentors in the operating room (group C), and two Nissen fundoplications were performed with the mentors 5 miles away from the operating room (group D) using existing land lines at the T1 level. We found no differences in the performances of the surgeons or the outcomes of the operations between groups A and B and groups C and D. Intraoperative problems were tackled effectively. Preliminarily, we conclude that the telementoring concept is potentially a safe and cost-effective option for advanced training in laparoscopic operations. Further investigation is necessary before routine transcontinental patient applications are attempted.

Colectomy↗

Soybean (Glycine max) agglutinin binds to corneal endothelial cells during wound repair and alters their microfilament pattern.

In the present study we have examined soybean (Glycine max) agglutinin (SBA) binding to cells of the rat corneal endothelium during wound repair. Circular transcorneal freeze injuries were given to the endothelia and the tissues were organ cultured at 37 degrees C in basal media Eagle with 10% serum for up to 72 hrs. SBA failed to bind to the surface of non-injured corneal endothelium, but strongly bound to cells involved in the wound repair process. Punctate surface binding was detected 24 hrs. post-injury, but stronger binding was observed at 48 hrs. after wounding. In this case, binding appeared to be distinctly distributed around the cell periphery. To investigate SBA binding during wound repair, endothelia were cultured in the presence of SBA (100 and 200 micrograms/ml). Cell migration into the wound area, and hence subsequent wound repair, was not affected at these concentrations. However, both concentrations altered cell morphology and microfilament patterns. Phalloidin staining of cells 24 hrs. after injury revealed that microfilaments appeared thinner and less in number. In addition, distinct aggregations of actin-positive material were detected at cell-to-cell contacts. Cells around the tissue periphery do not partake in the repair process but displayed an SBA concentration dependent fragmentation of their circumferential microfilament bundles. At 48 hrs. post-injury, SBA-treated cells within the wound area, unlike their control counterparts, did not exhibit stress fibers. These results suggest that a SBA binding surface component is associated with the reorganization of actin during corneal endothelial wound repair, and that these cells can migrate across their natural basement membrane without the benefit of a highly organized microfilament cytoskeleton.

Actin Cytoskeleton↗

Cross-linking hybridization assay for direct detection of factor V Leiden mutation.

A nucleic acid photocross-linking technology was used in the development of a direct assay for factor V Leiden, a point mutation in the factor V gene (G1691A) that is the most common inherited risk factor for thrombosis. This cross-linking hybridization assay included two allele-specific capture probes and six signal-generating reporter probes; all were modified with a photoactivated cross-linking compound. By using two different capture probes complementary to a 16-base sequence at the factor V Leiden mutation site, but differing in the nucleotide opposite the mutation site (C vs T), wild-type and factor V Leiden alleles were differentiated in purified DNA specimens. The assay was also successfully applied to genomic DNA in leukocytes isolated from whole blood; the factor V status of 122 patients as determined by this method was in complete concordance with a standard PCR-based assay and clearly discriminated between healthy individuals and factor V Leiden heterozygotes.

Alleles↗

Stress in mental health nursing: findings from the Mental Health Care survey.

Organisational and administrative concerns topped the list of stressors reported by a national sample of hospital and community mental health nurses. Seven of the ten top stressors were listed by both groups. Community nurses also listed inadequate service provision and lack of time to plan treatment. Hospital nurses were most stressed by inadequacy of staffing cover in potentially dangerous situations and low morale at work. Jerome Carson et al believe the findings indicate an urgent need for change at senior NHS management and administration level.

Adult↗

An investigation of the mechanism responsible for fluoxetine-induced hypophagia in rats.

The effect of fluoxetine on feeding in p-chlorophenylalanine (PCPA) pretreated rats and the nature of its interaction with 5-HT2C receptors have been investigated. Animals that received 3 days PCPA (150 mg/kg i.p.) pretreatment and vehicle on the test day consumed a similar amount as control, saline pretreated animals under the test paradigm used in this study. Fluoxetine (20 and 30 mg/kg p.o.) significantly reduced food intake in PCPA and control pretreated animals to a similar extent, despite an approximately 90% reduction in the levels of brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the PCPA-pretreated animals. Thus, hypophagia is unlikely to be caused by inhibition of 5-HT reuptake. In the pig choroid plexus in vitro, fluoxetine and norfluoxetine inhibited specific [3H] mesulergine binding with pKI's (+/- S.E.M.) of 6.45 +/- 0.09 (n = 4) and 6.05 +/- 0.05 (n = 3), and slope factors (+/- S.E.M.) of 1.06 +/- 0.14 and 0.99 +/- 0.13, respectively. In slices of piglet choroid plexus fluoxetine (1, 10 and 33 microM) caused a rightward shift in the dose-response curve produced by 5-HT with no effect on the maximal response, and a mean pKB of 5.94 +/- 0.09. Norfluoxetine (10 microM) also produced a rightward shift in the 5-HT dose-response curve with no effect on the maximal response, and a pKB of 6.20. Thus, both compounds acted as surmountable antagonists with no agonist efficacy at 5-HT2C receptors present in choroid plexus. The hypophagic effect of fluoxetine (20 mg/kg p.o.) was also unaffected by the non-specific 5-HT2C receptor antagonist metergoline (2 and 5 mg/kg i.p.). These findings suggest that the hypophagic effect of fluoxetine is not likely to be dependent upon intact brain 5-hydroxytryptaminergic presynaptic function, nor is it mediated by an agonist action at the 5-HT2C receptor, but by an additional, unknown mechanism.

Animals↗

Functional MRI of lateral occipitotemporal cortex during pursuit and motion perception.

We performed functional imaging with a conventional 1.5-T magnetic resonance scanner in 9 normal subjects. We used a gradient-echo technique to examine changes in signal between periods when subjects viewed a stationary black-and-white grating, a moving grating, and when they followed a moving spot. We located image pixels with significant differences between the viewing conditions. In 7 subjects, these occurred in the lateral occipitotemporal cortex, a region previously identified as a putative human homologue of the motion-sensitive middle temporal area (MT, or V5) of monkeys. Signal intensity was greater during pursuit of the moving dot than during viewing of the moving grating with the eyes still, despite the fact that the moving grating generated more retinal image motion. In contrast, signal intensity in striate cortex was least during pursuit of the moving dot. These findings suggest that the lateral occipitotemporal cortex has extraretinal signals during pursuit. Such signals may include attentional input, corollary eye movement information, or even a pursuit command. Extraretinal signals suggest that the lateral occipitotemporal cortex may contain a human homologue not only of MT but also of other components of the monkey V5 complex, such as the medial superior temporal area.

Adult↗