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Biomedical subjects

S Welsh

Publications and source records attributed to S Welsh.

At least 19 recordsLinked to original sources

Early carotid surgery in acute stroke: a multicentre randomised pilot study.

BACKGROUND: Standard practice has been to delay carotid endarterectomy (CEA) for 2 months following acute stroke to avoid a perceived risk of cerebral haemorrhage. We investigated whether early CEA reduces early recurrent stroke and improves outcome in partial anterior circulation infarction (PACI). METHODS: Patients with PACI and a Barthel score of >18 before stroke underwent carotid duplex and CT imaging within 7 days of stroke. Forty consenting patients fit for surgery with greater than 70% ipsilateral carotid stenosis were randomised, 19 to 'early' (within 24 h) and 21 to 'delayed' surgery (at 8 weeks). Modified Rankin and Barthel scores were recorded at 1 week, 2 months, 6 and 12 months. RESULTS: Rankin scores improved more rapidly following 'early' surgery to a score of 1 (0-4) at 2 and 6 months compared with 2.5 and 2 (1-4), respectively, for delayed surgery (p < 0.05). Barthel scores were also significantly improved following 'early' CEA at 7 days but both groups reached a median score of 20 by 2 months. Four 'delayed' and 3 'early' patients suffered extension or recurrence of neurological deficits with 1 death in each group. CONCLUSIONS: Early CEA within 7 days of ischaemic stroke improved functional outcome with earlier hospital discharge. A large multicentre study is needed to exclude the possibility that 'early' CEA increases the risk of cerebral haemorrhage or death.

Activities of Daily Living↗

Big brother is watching you--the ethical implications of electronic surveillance measures in the elderly with dementia and in adults with learning difficulties.

Electronic surveillance has insidiously seeped into the fabric of society with little public debate about its moral implications. Perceived by some as a sinister Orwellian tool of repression and social control, the new technologies offer comfort and security to others; a benevolent parental watchful eye. Nervousness at being watched has been replaced increasingly by nervousness if we're not. These technologies are now becoming widely available to health care professionals who have had little opportunity to consider their ethical and moral ramifications. Electronic tagging and tracking devices may be seen as away of creating a more secure environment for vulnerable individuals such as the elderly with dementia or people with learning disabilities. However, the proponents of surveillance devices have met with considerable resistance and opposition,from those who perceive it as contrary to human dignity and freedom, with its connotations of criminal surveillance. In addition, they cite increased opportunity for abuse through, for example, the withdrawal of staff and financial resources from the care of people with complex needs. Implementing these technologies, therefore, has ethical implications for human rights and civil liberties. Optional alternatives to long-term and/or restrictive care, in the context of the practical difficulties involved in caring for those who represent a risk to themselves from wandering, demands rigorous exploration of pragmatic questions of morality, with reference to risk versus benefit strategies. Like reproductive cloning techniques, the mere existence of surveillance technologies is morally neutral. Rather it is the use (in this instance that of health and social care settings) to which it is put which has the potential for good or bad.

Aged↗

Comparative analysis of the Cosmed Quark b2 and K4b2 gas analysis systems during submaximal exercise.

AIM: The purpose of this study was to compare the Cosmed K4b2 portable gas analysis system with the Cosmed Quark b2 metabolic cart. METHODS: Twenty-one subjects attended one testing session that consisted of duplicate measurements of gas volumes and concentrations using both Cosmed gas analysis systems at 3 treadmill work rates; 1) 80m x min(-1), 0% grade, 2) 80m x min(-1), 5% grade, and 3) 80m x min(-1), 10% grade. Subjects walked for 3 min at each rate with one of the gas analysis systems attached to the facemask. The order of the procedures was randomized so that one system was used during both phases (1st or 2nd) of each work rate. RESULTS: The results indicated that oxygen consumption (VO2) was significantly higher in the K4b2 compared to the Quark at 80m x min(-1), 0% grade (14.3+/-1.2 vs 13.6+/-1.2ml x kg(-1) x min(-1), respectively), (p<0.01). The fractional concentration of oxygen in expired air was also significantly lower in the K4b2 at 80 m x min(-1), 0% grade and 80 m x min(-1), 10% grade (p<0.05). There were no significant differences between systems for minute ventilation or carbon dioxide production. Despite the small mean bias in mean VO2 values (0.5-1.0ml x kg-1 x min(-1) higher) in the K4b2, all individual values were within the limits of agreement (mean difference+/-2 SD) as determined by the Bland-Altman technique. CONCLUSION: The findings show a minimal bias in respiratory and metabolic parameters during bi-pedal locomotor activities at low to moderate exercise intensities in the two gas analysis systems.

Adult↗

Complementary and alternative groups contemplate the need for effectiveness, safety and cost-effectiveness research.

OBJECTIVE: To examine the views of complementary and alternative medicine (CAM) groups on the need to demonstrate the effectiveness, safety and cost-effectiveness of their therapies and practices. DESIGN: Qualitative interviews were conducted with 22 representatives of three CAM groups (chiropractic, homeopathy and Reiki). Qualitative content analysis was used to identify similarities and differences among and across groups. SETTING: Ontario, Canada. RESULTS: There were striking differences in the views of the three sets of respondents. The chiropractors agreed that it was essential for their group to provide scientific evidence that their interventions work, are safe and cost-effective. The leaders of the homeopathic group were divided on these points and the Reiki respondents showed virtually no interest in undertaking such research. CONCLUSIONS: CAM groups that are more formally organized are most likely to recognize the importance of scientific research on their practices and therapies.

Attitude of Health Personnel↗

Selective behaviors altered in plasminogen-deficient mice are reconstituted with intracerebroventricular injection of plasminogen.

In vitro studies demonstrate a role for the plasminogen (Plg) system in neurological function and recently in vivo studies show a role of the Plg system in neurodegeneration after the injection of an excitotoxic agent. Differences in the development of neurological function, however, have not been demonstrated in the Plg-deficient (Plg-/-) mice compared to wild-type (WT) mice. The role of Plg system in neurological function may relate to remodeling which occurs in response to various environmental challenges. In this study, behaviors (open field, grooming, hind-leg gait, water maze, and acoustic startle reflex) were tested in the Plg-deficient and WT mice at 6-8 weeks of age. Grooming, a response to the stress of an open field or fur moistening, was increased in the Plg-/--deficient mice compared to WT mice, and the acoustic startle reflex (ASR) was markedly decreased in the Plg-/- mice. The reduced ASR in Plg-/- mice occurred in mice with a mixed C57BL:129 background or in mice with a C57BL background. Plg was required for the ASR, since a deficiency of the Plg activators, urokinase (uPA) or tissue Plg activator (tPA), did not cause a reduction in the ASR compared to their WT control. Infusion of Plg directly into the brain was effective in restoring the ASR in the Plg-/- mice, but had no effect on the ASR of WT mice. Peripheral bolus injections of Plg or infusion into the jugular vein were ineffective in restoring the ASR in the Plg-/- mice. These results indicate that Plg is required for the appropriate response to the environmental challenge of a sudden loud sound, and that the response can be restored in Plg-/- mice by directly infusing Plg into the brain.

Animals↗

In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B.

Halichondrin B is a highly potent anticancer agent originally found in marine sponges. Although scarcity of the natural product has hampered efforts to develop halichondrin B as a new anticancer drug, the existence of a complete synthetic route has allowed synthesis of structurally simpler analogues that retain the remarkable potency of the parent compound. In this study, we show that two macrocyclic ketone analogues of halichondrir B, ER-076349 and ER-086526, have sub-nM growth inhibitory activities in vitro against numerous human cancer cell lines as well as marked in vivo activities at 0.1-1 mg/kg against four human xenografts: MDA-MB-435 breast cancer, COLO 205 colon cancer, LOX melanoma, and NIH: OVCAR-3 ovarian cancer. ER-076349 and ER-086526 induce G2-M cell cycle arrest and disruption of mitotic spindles, consistent with the tubulin-based antimitotic mechanism of halichondrin B. This is supported further by direct binding of the biotinylated analogue ER-040798 to tubulin and inhibition of tubulin polymerization in vitro by ER-076349 and ER-086526. Retention of the extraordinary in vitro and in vivo activity off halichondrin B in structurally simplified, fully synthetic analogues establishes the feasibility of developing halichondrin B-based agents as highly effective, novel anticancer drugs.

Animals↗

A randomised trial comparing cytomegalovirus antigenemia assay vs screening bronchoscopy for the early detection and prevention of disease in allogeneic bone marrow and peripheral blood stem cell transplant recipients.

Preemptive antiviral therapy is often employed for CMV prevention following allogeneic BMT. Two common strategies are a screening bronchoscopy for CMV post-BMT or regular CMV antigenemia testing with ganciclovir administration for a positive result. In a randomised trial, we prospectively compared the efficacy of these two preemptive strategies. Consecutive patients were randomised to either a bronchoscopy for CMV on day 35 post BMT or weekly CMV antigenemia testing. If the bronchoscopy was positive for CMV, patients received preemptive ganciclovir for 8-10 weeks. If the antigenemia was positive for CMV, patients received a minimum of 2 weeks of preemptive ganciclovir. The primary endpoint was the development of active CMV disease. One hundred and eighteen allogeneic BMT patients were enrolled (60 in the antigenemia arm and 58 in the bronchoscopy arm). The two groups were comparable with respect to baseline demographic data, underlying disease, conditioning regimen, and immunosuppression. Active CMV disease developed in 7/58 (12.1%) patients in the bronchoscopy arm vs 1/60 patients (1.7%) in the CMV antigenemia arm (P = 0.022). Based on the screening test, 13.8% of patients received preemptive ganciclovir in the bronchoscopy arm vs 48.3% of patients in the antigenemia arm (P < 0.001). There was no significant difference in the rate of graft-versus-host disease, bacteremia, invasive fungal infections or mortality between the two groups. Preemptive therapy based on regular CMV antigenemia monitoring is superior to screening bronchoscopy for the prevention of CMV disease after allogeneic BMT.

Adult↗

Effects of pattern orientation and number of symmetry axes on the detection of mirror symmetry in dot and solid patterns.

It has been postulated that as the number of axes of symmetry in a pattern increases, so pattern 'goodness' increases. Recently, a distinction was made between two different theoretical accounts of regularity or 'goodness' in relation to patterns with mirror symmetry: the 'transformational' and the 'holographic' models. It was argued that the former predicts a 'goodness' ordering of four > three > two > one whereas the latter predicts four > two > three > one, where '>' means greater regularity or goodness. In three experiments, we have tested these predictions. In experiment 1, we measured percentage correct and reaction time to dot patterns which had one, two, three, or four axes of symmetry and were flashed for 150 ms. Experiment 2 was identical except that patterns were presented for 2000 ms. In experiment 3, dot patterns were replaced by solid shapes which also had one, two, three, or four axes of symmetry. Although it was found that stimuli with four axes clearly allowed superior performance to that of stimuli with one axis, results obtained with stimuli with two and three axes were almost identical and in between those obtained with one and four axes. The data thus support the suggestion that extra axes add 'goodness' to symmetrical patterns but not in a monotonic fashion.

Computer Graphics↗

Reporter gene expression for monitoring gene transfer.

The use of reporters such as green fluorescent protein (GFP) and firefly luciferase permit highly sensitive and nondestructive monitoring of gene transfer and expression. Modifications in GFP which increase intensity and thermostability, as well as alter its spectral qualities, have facilitated the use of GFP in a variety of gene transfer methods. Improvements in imaging technologies and their increased application in biological research have allowed the expanded use of luciferase-based reporters in gene transformation, particularly in genetic screens and in monitoring temporal changes in gene expression.

Animals↗

Achieving dietary recommendations: whole-grain foods in the Food Guide Pyramid.

The Food Guide Pyramid illustrates USDA's food guide developed to help people follow the Dietary Guidelines for Americans. Unlike earlier food guides, the new food guide specifies foods for a total diet; that is, it addresses both concerns about adequacy and moderation. The food guide recommends increased intakes of the vegetable, fruit, and grain groups with special emphasis on dark-green leafy vegetables, legumes, and whole-grain products. These foods are important sources of several vitamins and minerals, complex carbohydrates, and dietary fiber, and they are generally low in fat. Analyses of expected nutrient levels provided by the food guide diet patterns indicate that the nutrient contribution of whole-grain products is particularly important for diets at lower calorie levels. In these diets, it is recommended that at least half the number of servings in the grain group be whole-grain products. In all diets, it is recommended that several servings of whole-grain products be included each day. Average intakes of vegetables, fruits, and grain products are less than recommended. The pyramid graphic has been especially helpful in emphasizing to the public the importance of increased consumption of vegetables, fruits, and grain products for a healthful diet.

Diet↗

Atwater to the present: evolution of nutrition education.

Atwater charted a new course for nutrition education 100 years ago by using the scientific process to develop dietary guidance to improve public health and well being. Each of the areas of research to which Atwater gave leadership--nutrient requirements, food composition, food consumption, and consumer economics--are essential components in the development of dietary guidance. The emerging science of nutrition was translated into recommendations for a healthful diet by Caroline Hunt in 1916 in the first USDA food guide. Other familiar food guides were the "Basic-7" developed in the 1940's and the "Basic-4" from the 1950's. These early guides focused primarily on getting enough nutrients. By 1970, research was providing evidence of the role of excessive intakes of certain food components in the etiology of chronic disease. With the release of the "Dietary Guidelines for Americans" in 1980, work began on a new food guide to address both concerns about nutritional adequacy and overconsumption. Research involved development of a new food guide and a graphic to illustrate it. Although the time since the release of the new Food Guide Pyramid has been short, its wide acceptance by the professional community, industry, and the media promises to make it an effective nutrition education tool.

Female↗

Parotid function and composition of parotid saliva among elderly edentulous African-American diabetics.

This study examined parotid salivary flow rate and composition in three groups of differently treated diabetics and a control group of non-diabetics. The study population was composed of edentulous African-Americans at least 65 years of age. Group A was the control, Group B insulin-dependent (Regular Iletin, U-100 qd.), Group C controlled by oral medication (Tolbutamide, 500 mg qd.), and Group D was diet controlled. All diabetic patients had serum glucose values under 250 mg/dl. Salivary flow rates, secretory IgA, electrolytes (Na+, Cl-, K+, Ca++) and total protein concentrations were evaluated. The results showed no significant differences between groups with respect to salivary flow rates, electrolytes and IgA concentrations. Additionally, all diabetic groups demonstrated a significantly lower salivary total protein concentration when compared to the controls. There appears to be no evident decrease in salivary flow rate in these three differently controlled diabetic groups compared with healthy non-diabetics.

Aged↗

Triazolam blocks the initial rotational effects of quinpirole but permits the later developing reduction of dopamine D2-mediated rotational behavior and dopamine D2 receptors.

Continuous infusion of the dopamine D2 receptor agonist quinpirole into mice with unilateral striatal 6-hydroxydopamine lesions initially produces a supersensitive rotational behavior. This is followed by reductions of dopamine D2-mediated behavior and dopamine D2 receptors. In this study we attempted to determine if it is possible to inhibit the acute increase in D2-mediated behavior while still allowing the reduction of D2-mediated behavioral responses and dopamine D2 receptors to occur. Mice were implanted with Alzet minipumps containing either quinpirole alone or quinpirole combined with the GABA receptor modulator triazolam or the dopamine D2 receptor antagonist sulpiride, and rotational behavior was monitored for the 6 days of infusion. The pumps were then removed, and D2 receptors in striatal membranes were determined. Triazolam completely blocked the initial rotational behavior normally induced by implanting quinpirole. However, the quinpirole-induced reduction of D2-mediated behavioral responses and D2 receptors still occurred. Continuous infusion of sulpiride also inhibited the rotational behavior produced by quinpirole, but it prevented the reduction of dopamine D2 receptors. We conclude that up-regulated dopamine receptors and dopaminergic behaviors can be reversed by the continuous administration of a dopamine receptor agonist and that this reversal can occur without producing an initial exacerbation of dopaminergic responses. These results suggest that this type of treatment regimen might be useful for treating clinical conditions associated with dopaminergic supersensitivity.

Analysis of Variance↗

A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy.

Although neuropeptides have been demonstrated to be hippocampal neuromodulators in laboratory animals, their role in human hippocampal physiology or pathophysiology remains to be defined. The concentrations of somatostatin, cholecystokinin octapeptide, vasoactive intestinal polypeptide, and dynorphin A 1-17 were determined in hippocampal tissue resected from patients with cryptogenic temporal lobe epilepsy, a common seizure disorder originating in or near the hippocampus. Control tissue was obtained from cadavera or epilepsy patients in whom the hippocampus was removed during the resection of temporal lobe tumors. Peptide determinations were performed on extracts of punch biopsy specimens taken from six different hippocampal regions. A significant decrease in immunoreactive somatostatin concentration was identified in the dentate gyrus and in region cornu ammonis 4 of cryptogenic temporal lobe epilepsy specimens. No significant changes were present in any other hippocampal region or in the levels of other peptides. In situ hybridization studies performed on cryostat sections from similar patients confirmed a marked loss of neurons expressing the somatostatin gene, which was restricted to the dentate hilus. The density of specific 125I-somatostatin binding to cryostat sections, as determined by semiquantitative in vitro autoradiography, was significantly increased in the dentate gyrus of the cryptogenic epilepsy patients, compared with tumor control specimens. We conclude that a loss of somatostatin-producing interneurons with an upregulation of dentate somatostatin receptors is a specific and characteristic element in the pathophysiology of human cryptogenic temporal lobe epilepsy.

Adolescent↗