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Biomedical subjects

S Wright

Publications and source records attributed to S Wright.

At least 73 records · Page 4Linked to original sources

Assessment of an extracorporeal life support to LVAD bridge to heart transplant strategy.

BACKGROUND: Extracorporeal life support (ECLS) is an effective technique for providing emergent circulatory assistance. However, its use in adult patients is associated with poor survival when myocardial function fails to recover. Due to the prolonged waiting times for heart transplantation, ECLS as a bridge to transplant is associated with poor survival. In addition, ECLS has been reported to be a significant risk factor for death after bridging to an implantable left ventricular assist device (LVAD). After acquisition of the HeartMate LVAD (Thermo Cardiosystems, Inc) in October 1996, we began using ECLS as a bridge to an implantable LVAD and subsequently transplantation in selected high-risk patients. METHODS: From October 1, 1996 to December 1, 1999, 60 adult patients presenting with cardiogenic shock were evaluated for circulatory assistance. RESULTS: Twenty-five patients (group 1) with cardiac arrest or severe hemodynamic instability and multiorgan failure were placed on ECLS. Eight patients survived to LVAD implant, 1 was bridged directly to transplant, and 4 weaned from ECLS. Nine patients in group 1 survived to discharge. Thirty patients (group 2) underwent LVAD implant without ECLS. Twenty-three were bridged to transplant, with 22 surviving to discharge. Five patients (group 3) were placed on extracorporeal ventricular assist with 3 bridged to transplant and all surviving to discharge. One-year actuarial survival from the initiation of circulatory support was 36% (group 1), 73% (group 2), and 60% (group 3). One-year actuarial survival from the time of LVAD implant in group 1, conditional on surviving ECLS, was 75% (p = NS compared with group 2). CONCLUSIONS: In selected high-risk patients, LVAD survival after initial ECLS was not different from survival after LVAD support alone. An initial period of resuscitation with ECLS is an effective strategy to salvage patients with cardiac arrest or extreme hemodynamic instability and multiorgan injury.

Actuarial Analysis↗

Varieties of secrets and secret varieties: the case of biotechnology.

This article examines several trends that have combined to veil the new field of biotechnology in secrecy: the transformation of biotechnology from an essentially academic field characterized by strong norms of openness to a field with extensive corporate connections that have reached even to research in leading universities; the establishment of intellectual property rights for life-forms initiated by the landmark Supreme Court decision, Diamond v. Chakrabarty; and the limiting of public access to information about the genetically altered organisms whose use in agriculture, industry, and medicine falls under government controls. The article also examines the effects of the U.S. biotechnology industry's demand for secrecy on the negotiations for a protocol to the 1972 Biological Weapons Convention, particularly the turn from requirements for transparency to protection of opacity with respect to biotechnology and other biological processes, equipment, and production.

Access to Information↗

Energy disposal during desorption of D2 from the surface and subsurface region of Ni(111).

The recombination of surface and subsurface D atoms on Ni(111) has been studied using resonance-enhanced multiphoton ionisation (REMPI) to measure the internal state and translational energy distributions of the desorbing product. By detecting D2 formed during temperature-programmed desorption we were able to examine the reaction between subsurface and surface D atoms, and the recombination of two D atoms chemisorbed on the surface. Translational energy distributions for D2 formed by recombination of surface D are very sensitive to coverage. Desorption from a low coverage surface produced a translational energy release of 2.6 kT, but a thermal rotational distribution, reflecting an entrance channel barrier to dissociative chemisorption on the clean Ni(111) surface. Sticking probabilities predicted from detailed balance are consistent with molecular beam adsorption measurements. Desorption from D coverages above 0.5 ML resulted in a sub-thermal energy release, desorption being mediated by a molecular precursor state with D2 dissociation occurring via a non-activated, trapping-dissociation channel. In contrast, the reaction of subsurface D produces translationally hot D2, with a mean energy approaching 8 kTs at 180 K. This is consistent with the energetics for direct recombination of a chemisorbed D atom with a metastable subsurface D atom, which overcomes an activation barrier to resurface of between 0.35 and 0.47 eV depending on D concentration. The energy release decreases at higher temperature, probably as a result of a reduction in the energy of resurfacing D as the subsurface D concentration drops. This low energy component is attributed to accommodation of resurfacing D which is unable to react directly, followed by slow thermal desorption via the high coverage, surface D recombination channel. No internal rotational or vibration excitation was found in D2 formed by reaction of subsurface D.

Journal Article↗

Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition.

Tissue plasminogen (plgn) activator (tPA) modulates neuronal death in models of stroke, excitotoxicity, and oxidative stress. Amyloid-beta (Abeta) appears central to Alzheimer's disease and is neurotoxic to neurons in vitro. Here, we evaluate tPA effects on Abeta toxicity. We report that tPA alone had no effect on Abeta toxicity. However, in combination with plgn, tPA reduced Abeta toxicity in a robust fashion. Moreover, the combined tPA and plgn treatment markedly inhibited Abeta accumulation. The addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to a sample of tPA, plgn, and Abeta resulted in a marked reduction of Abeta degradation. We interpret the actions of tPA and plgn within the context of the ability of plasmin to degrade Abeta.

Amyloid beta-Peptides↗

Does a glass of red wine improve endothelial function?

AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease.

Adult↗

Disseminated fungal infection following falciparum malaria.

Falciparum malaria can cause immune suppression sufficient to allow opportunistic infection during the recovery phase. A patient is described who died from a disseminated infection with Aspergillus flavus and Absidia corymbifera, unresponsive to treatment with amphotericin and voriconazole.

Absidia↗

Effect of training frequency on face-name recall by adults with traumatic brain injury.

Many TBI survivors have difficulty recalling the names of people with whom they frequently interact. Researchers have established that mnemonics and visual imagery strategies are often effective in facilitating encoding and recall of such information; however, no research exists pertaining to the frequency that such training should occur. The purpose of this study was to assess the relative effectiveness of three frequencies of intervention sessions--once per day, two times per week, and five times per day--on TBI survivors' ability to recall face-name associations. Results showed that sessions held daily and twice a week were more effective than sessions held five times per day. Mnemonics and visual imagery strategies were effective for four of the seven participants, regardless of frequency of intervention sessions. Implications for treatment and future research are discussed.

Adult↗

Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.

OBJECTIVE: To determine effects of conjugated linoleic acid (CLA) on establishment and progression of experimentally-induced atherosclerosis in rabbits. METHODS: For establishment of atherosclerosis, New Zealand White rabbits were fed a semipurified diet containing 0.1% to 0.2% cholesterol for 90 days. Some groups were fed diet and CLA. For effects on progression of atherosclerosis, rabbits with established atherosclerosis were fed a semipurified diet +/- CLA for 90 days. RESULTS: At dietary levels as low as 0.1%, CLA inhibited atherogenesis. At dietary levels of 1%, CLA caused substantial (30%) regression of established atherosclerosis. This is the first example of substantial regression of atherosclerosis being caused by diet alone. CONCLUSION: Dietary CLA is an effective inhibitor of atherogenesis and also causes regression of established atherosclerosis.

Animals↗

Lip and vermilion reconstruction with the facial artery musculomucosal flap.

The lips are a complex laminated structure. When lost through injury or disease, they present a complex reconstructive challenge. The facial artery musculomucosal (FAMM) flap is a composite flap with features similar to those of lip tissue. In this article, the anatomy, dissection, and clinical applications for the use of the FAMM flap in lip and vermilion reconstruction are discussed. A series of 16 FAMM flaps in 13 patients is presented. Seven patients had upper-lip reconstruction and six had lower-lip reconstruction. Superiorly based FAMM flaps were used in eight patients, and eight inferiorly based flaps were performed in five patients. Three patients had bilateral, inferiorly based flaps. In summary, the FAMM flap is a local flap that can be used for lip and vermilion reconstruction. Although not identical to the lip, it has many similar features, which make it an excellent option for lip reconstruction.

Adolescent↗

Exercise-induced hyponatremia in ultradistance triathletes is caused by inappropriate fluid retention.

OBJECTIVE: To study fluid and sodium balance during overnight recovery following an ultradistance triathlon in hyponatremic athletes compared with normonatremic controls. CASE CONTROL STUDY: Prospective descriptive study. SETTING: 1997 New Zealand Ironman Triathlon (3.8 Km swim, 180 Km cycle, 42.2 Km run). PARTICIPANTS: Seven athletes ("subjects") hospitalized with hyponatremia (median sodium [Na] = 128 mmol L(-1)). Data were compared with measurements from 11 normonatremic race finishers ("controls") (median sodium = 141 mmol L(-1)). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Athletes were weighed prior to, immediately after, and on the morning after, the race. Blood was drawn for sodium, hemoglobin, and hematocrit immediately after the race and the following morning. Plasma concentrations of arginine-vasopressin (AVP) were also measured post race. RESULTS: Subjects were significantly smaller than controls (62.5 vs. 72.0 Kg) and lost less weight during the race than controls (median -0.5% vs. -3.9%, p = 0.002) but more weight than controls during recovery (-4.4% vs. -0.8%, p 0.002). Subjects excreted a median fluid excess during recovery (1,346 ml): controls had a median fluid deficit (521 ml) (p = 0.009). Estimated median sodium deficit was the same in subjects and controls (88 vs. 38 mmol L(-1), p = 0.25). Median AVP was significantly lower in subjects than in controls. Plasma volume fell during recovery in subjects (-5.9%, p = 0.016) but rose in controls (0.76%, p = NS). CONCLUSIONS: Triathletes with symptomatic hyponatremia following very prolonged exercise have abnormal fluid retention including an increased extracellular volume, but without evidence for large sodium losses. Such fluid retention is not associated with elevated plasma AVP concentrations.

Adult↗

Neosporosis. Aspects of epidemiology and host immune response.

Neospora caninum is a recently recognized protozoan parasite which has been described as causing a neuromuscular paralysis in dogs and is emerging as a major cause of bovine infertility and abortion worldwide. The parasite is known to infect a range of warm blooded animals but the disease predominates in dogs and cattle. It is not yet known if N. caninum can infect and cause disease in people. The dog has recently been identified as the definitive host and the parasite may be transmitted through the ingestion of oocysts or congenitally from mother to fetus. N. caninum is known to infect red foxes (Vulpes vulpes) and coyotes (Canis latrans) and the role of wildlife species as reservoirs of infection requires further investigation. Little is known about the range of parasite genotypes within the environment or the variation in virulence between different strains. RAPD-PCR analysis of geographically distinct bovine and canine isolates has revealed little genetic variation. Epidemiological studies from different areas of the world have investigated the importance of N. caninum as an abortifacient agent and longitudinal studies have shown the high rate (approximately 80%) of congenital transmission within infected herds. Information on the rates of repeat abortion due to neosporosis are less well defined however current estimates put this at 5% suggesting that cattle may develop some form of protective immunity against N. caninum-induced abortion. Diagnosis of the disease is based upon detection of the parasite in the tissues, most commonly using immunohistochemistry with additional information provided by serology. However, although positive fetal serology is a strong indicator of exposure to the parasite, care should be taken in the interpretation of maternal serology. As we understand more about the epidemiology of neosporosis we are also better able to interpret the results of diagnostic tests. The mere presence of the parasite does not necessarily infer that this was the primary cause of abortion. CD4+ T-cells, interferon gamma and macrophages have all been found to significantly inhibit multiplication of N. caninum tachyzoites. The nature of a protective immune response and its modulation in the pregnant animal is discussed.

Animals↗

Faster top running speeds are achieved with greater ground forces not more rapid leg movements.

We twice tested the hypothesis that top running speeds are determined by the amount of force applied to the ground rather than how rapidly limbs are repositioned in the air. First, we compared the mechanics of 33 subjects of different sprinting abilities running at their top speeds on a level treadmill. Second, we compared the mechanics of declined (-6 degrees ) and inclined (+9 degrees ) top-speed treadmill running in five subjects. For both tests, we used a treadmill-mounted force plate to measure the time between stance periods of the same foot (swing time, t(sw)) and the force applied to the running surface at top speed. To obtain the force relevant for speed, the force applied normal to the ground was divided by the weight of the body (W(b)) and averaged over the period of foot-ground contact (F(avge)/W(b)). The top speeds of the 33 subjects who completed the level treadmill protocol spanned a 1.8-fold range from 6.2 to 11.1 m/s. Among these subjects, the regression of F(avge)/W(b) on top speed indicated that this force was 1.26 times greater for a runner with a top speed of 11.1 vs. 6.2 m/s. In contrast, the time taken to swing the limb into position for the next step (t(sw)) did not vary (P = 0.18). Declined and inclined top speeds differed by 1.4-fold (9.96+/-0.3 vs. 7.10+/-0.3 m/s, respectively), with the faster declined top speeds being achieved with mass-specific support forces that were 1.3 times greater (2.30+/- 0.06 vs. 1.76+/-0.04 F(avge)/ W(b)) and minimum t(sw) that were similar (+8%). We conclude that human runners reach faster top speeds not by repositioning their limbs more rapidly in the air, but by applying greater support forces to the ground.

Adolescent↗

Could a low-cost audio-visual link be useful in rheumatology?

We have investigated prospectively the diagnostic accuracy, specialist satisfaction and patient-specialist rapport of a low-cost audio-visual link between a junior doctor with a patient and a consultant rheumatologist. Using a telephone link and subsequently a video-phone link, 20 patients, with various rheumatological problems, were presented by a junior doctor to the consultant rheumatologist for provisional diagnosis. All patients were then seen face to face by the consultant, when a final diagnosis was made. An independent consultant rheumatologist made a 'gold standard' diagnosis. Thirty-five per cent of diagnoses were made correctly over the telephone and 40% over the video-phone--there was no significant difference in the diagnostic accuracy between these two methods of communication. Rapport over the video-phone was universally poor. Where it was important, clinical signs could not be visualized over the video-phone and in more than 85% of cases small joint swellings could not be seen clearly.

Adolescent↗

The impact of a structured programme of asthma care in general practice.

The impact of a new GP programme of asthma care was examined using: a) a retrospective pre- and post-casenote survey of 400 asthma patients, comparing patients in practices using the health board programme (HBP) and other programmes (OP); and b) a patient satisfaction questionnaire, completed by 532 people on asthma clinic lists in HBP and OP practices. Outcomes assessed were health service use, perceived change in symptoms and asthma self-management. The casenote survey indicated improved health service use by patients in HBP practices, with fewer patient-initiated (p < 0.05), emergency (p < 0.05) and other chest-related attendances (p < 0.01) and increased clinic attendance (p < 0.05) post intervention. OP practices also showed reduced patient-initiated (p < 0.01) and increased asthma clinic use (p < 0.01). Increased use of management plans (p < 0.01) and peak flow diaries (p < 0.01) was noted post intervention for HBP practices. Responders to the questionnaire survey perceived that clinic attendance improved asthma symptoms, including severity and control, sleep disturbance and early morning wheeze. People in HBP practices were more likely than those in OP practices to possess a peak flow meter, a diary and a personal management plan (all p < 0.01 or above) but were not more likely to use a peak flow diary. Notwithstanding methodological difficulties in the selection of practices, both studies showed trends towards improvement in health service use and asthma self-management. The HBP was associated with greater improvement in self-management processes and outcomes, and greater patient satisfaction with asthma care.

Adolescent↗

Detection of T. gondii in tissues of sheep and cattle following oral infection.

It has been reported in the literature that cattle are more resistant to toxoplasmosis than sheep. Congenital disease due to T. gondii infection is rarely reported in cattle whereas the parasite is a major cause of abortion and neonatal mortality in sheep. It is believed that sheep remain chronically infected for life. Undercooked meat from infected sheep is an important source of infection for man. In contrast cattle are thought to harbour fewer parasite tissue cysts which may not persist for the lifetime of the host. Therefore, cattle are believed to pose less of a risk for human infection. In this study we examined the presence of T. gondii within a range of tissues in sheep and cattle at 6 weeks and 6 months following oral infection with 10(3) or 10(5) sporulated oocysts of T. gondii. The presence of parasite was determined by bioassay in mice and using polymerase chain reaction (PCR). The results from this study show that T. gondii was more frequently and consistently detected in sheep, in particular within brain and heart tissues, whereas parasites were not detected in the samples of tissues taken from cattle. T. gondii was more frequently detected in sheep given the higher dose of T. gondii. Examination of tissues at either 6 weeks or 6 months after infection did not appear to affect the distribution of T. gondii. The polymerase chain reaction has more specificity and sensitivity when detecting the presence of T. gondii in large animals than histological detection.

Animals↗

ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease.

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.

Aged↗