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Biomedical subjects

E Jones

Publications and source records attributed to E Jones.

At least 91 records · Page 5Linked to original sources

Electron spin resonance spectroscopy, exercise, and oxidative stress: an ascorbic acid intervention study.

Oxygen free radicals are highly reactive species that are produced in increased quantities during strenuous exercise and can damage critical biological targets such as membrane phospholipids. The present study examined the effect of acute ascorbic acid supplementation on exercise-induced free radical production in healthy subjects. Results demonstrate increases in the intensity of the alpha-phenyl-tert-butylnitrone adduct (0.05 +/- 0.02 preexercise vs. 0.19 +/- 0.03 postexercise, P = 0.002, arbitrary units) together with increased lipid hydroperoxides (1.14 +/- 0.06 micromol/l preexercise vs. 1.62 +/- 0.19 micromol/l postexercise, P = 0.005) and malondialdehyde (0.70 +/- 0.04 micromol/l preexercise vs. 0.80 +/- 0.04 micromol/l postexercise, P = 0.0152) in the control phase. After supplementation with ascorbic acid, there was no significant increase in the electron spin resonance signal intensity (0.02 +/- 0. 01 preexercise vs. 0.04 +/- 0.02 postexercise, arbitrary units), lipid hydroperoxides (1.12 +/- 0.21 micromol/l preexercise vs. 1.12 +/- 0.08 micromol/l postexercise), or malondialdehyde (0.63 +/- 0.07 micromol/l preexercise vs. 0.68 +/- 0.05 micromol/l postexercise). The results indicate that acute ascorbic acid supplementation prevented exercise-induced oxidative stress in these subjects.

Adolescent↗

Detection and treatment of depression in a VA primary care clinic.

The Veterans Health Administration clinical guideline for major depressive disorder was used in screening 574 male veterans treated in primary care settings in the Department of Veterans Affairs health care system. Thirteen percent (N=73) screened positive for depression, and 33 percent of those patients showed evidence of a major depressive episode. Pre- and posttreatment assessment of a sample of 16 patients treated for depression in a primary care setting revealed statistically significant improvement with treatment.

Adult↗

PDX-1 and Msx-2 expression in the regenerating and developing pancreas.

We have observed pancreatic duct cell proliferation and islet regeneration in transgenic mice whose pancreata produce interferon gamma (IFNg mice). We have previously demonstrated that new islet cells derive from endocrine progenitor cells in the pancreatic ducts of this model. The current study was initiated to define these endocrine progenitor cells further and to identify novel markers associated with pancreatic regeneration. Importantly, we have found that PDX-1, a transcription factor required for insulin gene transcription as well as for pancreatic development during embryogenesis, is expressed in the duct cells of IFNg mice. This striking observation suggests an important role for PDX-1 in the marked regeneration observed in IFNg mice, paralleling its critical function during ontogeny. Also demonstrated was elevated expression of the homeobox-containing protein Msx-2 in the pancreata of fetal mice as well as in adult IFNg mice, identifying this molecule as a novel marker associated with pancreatic development and regeneration as well. The identification of PDX-1 and Msx in the ducts of the IFNg transgenic pancreas but not in the ducts of the non-transgenic pancreas suggests that these molecules are associated with endocrine precursor cells in the ducts of the IFNg transgenic mouse.

Animals↗

Increased HLA-DR and CD44 antigen expression in the gut: evidence of extraarticular immunological activity in rheumatoid arthritis.

OBJECTIVE: To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for evidence of activation. METHODS: Duodenal biopsies from 25 patients with RA were obtained by endoscopy. Single cell suspensions from the epithelial layer and lamina propria were prepared. Flow cytometry was used to examine the expression of CD4, CD8, T cell receptor-gammadelta (TCR-gammadelta), TCR-alphabeta, HLA-DR, CD44, and interleukin 2 receptor on gut T lymphocytes. Fifteen disease control (DC) individuals and 6 patients with osteoarthritis (OA) taking longterm nonsteroidal antiinflammatory drug (NSAID) therapy were also investigated. Peripheral blood T lymphocytes from all individuals were examined for the expression of these surface molecules. RESULTS: HLA-DR expression was significantly increased on intraepithelial lymphocytes (IEL) and enterocytes from patients with RA (n = 13) compared with the 2 control groups (p<0.01). Immunohistochemistry also revealed increased expression of HLA-DR on enterocytes from patients with RA. RA IEL (n = 6) expressed significantly higher levels of CD44 (p<0.02). In the lamina propria, a small but significant gammadelta T lymphocyte population (mean 5.5%, range 2-12%) was detected in rheumatoid factor positive RA patients (n = 8) compared with RF negative RA patients (n = 8, mean 2%, range 0.4-6%; p<0.01) and the disease control group (n = 15, mean 2%, range 0.5-5%; p<0.01). None of these changes were detectable in peripheral blood lymphocytes from patients with RA. CONCLUSION: This study demonstrates evidence of activation of specific components of the GI immune system in RA. Peripheral blood T lymphocytes from patients with RA did not show increased expression of activation markers, suggesting that changes in the RA GI tract are not systemic but localized. Moreover, these changes appear to be independent of NSAID therapy.

Adult↗

Randomized, double-blind crossover study to investigate the effects of amlodipine and isosorbide mononitrate on the time course and severity of exercise-induced myocardial stunning.

BACKGROUND: Myocardial stunning may cause prolonged left ventricular dysfunction after exercise-induced ischemia that can be attenuated by calcium antagonists in animal models. To assess their effects in humans, we performed a randomized, double-blind crossover study comparing the calcium antagonist amlodipine (10 mg once daily) versus isosorbide mononitrate (ISMN, 50 mg once daily) on postexercise stunning. METHODS AND RESULTS: Twenty-four men with chronic stable angina and normal left ventricular function underwent serial quantitative exercise stress echocardiography after 3 weeks on each treatment to assess the degree of postexercise stunning with simultaneous sestamibi single-photon emission computed tomography perfusion scans at peak stress to quantify the ischemic burden. Exercise time (P=1), maximum ST depression (P=0.48), and sestamibi single-photon emission computed tomography scores (P=0.17) were unchanged between treatments. Stunning occurred more often with ISMN than amlodipine (82% versus 48%). The global and segmental stress echocardiography parameters of stunning were attenuated in patients while taking amlodipine compared with ISMN. Shortening fractions and ejection fractions were less impaired 30 minutes after exercise in patients receiving amlodipine (3.5+/-1.4% versus 2.5+/-1.4%, P=0.014, and 59.7+/-5.4% versus 54.5+/-8%, P<0.001); similarly, the isovolumic relaxation period was less prolonged with amlodipine (93+/-15.5 versus 106.3+/-14.9 ms, P=0.018). CONCLUSIONS: Despite comparable levels of ischemia, amlodipine attenuated stunning when compared with ISMN. This beneficial effect may relate to a prevention of the calcium overload implicated in the pathogenesis of stunning.

Aged↗

Visceral abdominal-fat accumulation associated with use of indinavir.

BACKGROUND: After the addition of the protease inhibitor indinavir to combination drug regimens for HIV-1 infection, some patients have experienced an increase in abdominal girth with symptoms of abdominal fullness, distension, or bloating. We aimed to find out whether this collection of symptoms was associated with changes in abdominal fat and whether such changes were associated with indinavir use. METHODS: Abdominal computed tomography was used in ten HIV-1-positive patients who had such abdominal symptoms to measure total adipose tissue (TAT) and visceral adipose tissue (VAT) at the umbilicus (L4 vertebral level). The VAT:TAT ratio in the ten cases was compared with that in ten HIV-1-infected patients who had been using indinavir without abdominal symptoms for at least 6 months and ten HIV-1-infected patients who were not using indinavir. FINDINGS: The mean VAT:TAT ratios for the three groups-non-users, symptom-free indinavir users, and symptomatic indinavir users-were 0.40 (SD 0.15), 0.59 (0.18), and 0.70 (0.20), respectively (p=0.004). The VAT:TAT ratio correlated with duration of indinavir use (r=0.47, p=0.01). The mean areas of VAT for the three groups were 106 cm2 (SD 72), 141 cm2 (65) and 202 cm2 (93), respectively (p=0.03). The mean body-mass index of the groups was similar, and patients in the two indinavir groups did not gain a significant amount of weight after starting the drug. Serum triglyceride values increased after starting indinavir and correlated with VAT:TAT ratios. INTERPRETATION: Our data suggest that some HIV-1-infected patients on indinavir treatment accumulate intra-abdominal fat that may cause abdominal symptoms. Recent evidence suggests that other HIV-1 protease inhibitors may be associated with changes in body-fat distribution. Larger studies of protease-inhibitor treatment are needed to investigate this association further and to investigate metabolic or endocrine mechanisms that may underlie this phenomenon.

Abdomen↗

The effect of hysterectomy on ano-rectal physiology.

Hysterectomy is associated with severe constipation in a subgroup of patients, and an adverse effect on colonic motility has been described in the literature. The onset of irritable bowel syndrome and urinary bladder dysfunction has also been reported after hysterectomy. In this prospective study, we investigated the effect of simple hysterectomy on ano-rectal physiology and bowel function. Thirty consecutive patients were assessed before and 16 weeks after operation. An abdominal hysterectomy was performed in 16 patients, and a vaginal procedure was performed in 14. The parameters measured included the mean resting, and maximal forced voluntary contraction anal pressures, the recto-anal inhibitory reflex, and rectal sensation to distension. In 8 patients, the terminal motor latency of the pudendal nerve was assessed bilaterally. Pre-operatively, 8 patients were constipated. This improved following hysterectomy in 4, worsened in 2, and was unchanged in 2. Symptomatology did not correlate with changes in manometry. Although, the mean resting pressure was reduced after hysterectomy (57 mmHg-53 mmHg, P = 0.0541), the maximal forced voluntary contraction pressure was significantly decreased (115 mmHg-105 mmHg, P = 0.029). This effect was more pronounced in those with five or more previous vaginal deliveries (P = 0.0244, n = 9). There was no significant change in the number of patients with an intact ano-rectal inhibitory reflex after hysterectomy. There was no change in rectal sensation to distension, and the right and left pudendal nerve terminal motor latencies were unaltered at follow-up. Our results demonstrate that hysterectomy causes a decrease in the maximal forced voluntary contraction and pressure, and this appears to be due to a large decrease in a small group of patients with previous multiple vaginal deliveries.

Adult↗

Electron spin resonance spectroscopic detection of oxygen-centred radicals in human serum following exhaustive exercise.

Free radicals or oxidants are continuously produced in the body as a consequence of normal energy metabolism. The concentration of free radicals, together with lipid peroxidation, increases in some tissues as a physiological response to exercise - they have also been implicated in a variety of pathologies. The biochemical measurement of free radicals has relied in the main on the indirect assay of oxidative stress by-products. This study presents the first use of electron spin resonance (ESR) spectroscopy in conjunction with the spin-trapping technique, to measure directly the production of radical species in the venous blood of healthy human volunteers pre- and post-exhaustive aerobic exercise. Evidence is also presented of increased lipid peroxidation and total antioxidant capacity post-exercise.

Adolescent↗

Continuous-infusion granisetron compared to ondansetron for the prevention of nausea and vomiting after high-dose chemotherapy.

PURPOSE: The serotonin receptor antagonists effectively prevent emesis with little toxicity when employed with standard doses of emetogenic chemotherapy. The optimal approach to the prevention of the emesis associated with the high doses of chemotherapy used for autologous stem cell transplantation is not known. A randomized controlled trial was designed to assess the relative efficacy and toxicity of granisetron compared to ondansetron in the setting of autologous stem cell transplantation. METHODS: A group of 48 patients with breast cancer were randomized in a double-blind fashion to receive either (1) granisetron as a 0.5-mg i.v. bolus 30 min. before chemotherapy followed by a continuous infusion of 0.04 mg/h (1 mg/day) for 7 days or (2) ondansetron as an 8-mg i.v. bolus 30 min before chemotherapy followed by a continuous infusion of 1 mg/h (24 mg/day) for 7 days. All patients also received 10 mg dexamethasone/day i.v. for 7 days. Chemotherapy consisted of 1500 mg cyclophosphamide per m2/day, 125 mg thiotepa m(-2) day(-1), and 200 mg carboplatin per m2/day all as a continuous infusion for 4 consecutive days. The two study arms were then compared for the incidence and severity of nausea, incidence of emesis, number of salvage anti-emetics required, cost, and toxicity. RESULTS: A total of 46 patients were evaluable. The treatment arms were well-balanced for known risk factors for chemotherapy-induced nausea and vomiting. Compliance with self-reporting of nausea and vomiting was poor but indicated no difference between the two treatment arms. The average number of anti-emetics required was 15.8 in both treatment arms and the average time to the first dose of a salvage anti-emetic was 2.8 days in the granisetron arm and 2.9 days in the ondansetron arm. The incidence of headache was 36 % in the granisetron arm and 39 % in the ondansetron arm. None of these differences was statistically significant. The use of granisetron resulted in a cost saving of 6.5 %. CONCLUSION: There was no significant difference between granisetron and ondansetron in either efficacy or toxicity. At our institution, the use of granisetron resulted in a moderate cost saving.

Adult↗

Service support to people in Wales with severe intellectual disability and the most severe challenging behaviours: processes, outcomes and costs.

A survey of people with severe intellectual disability and the most severe challenging behaviour in Wales identified five adults living in family homes, 17 in new specialist community housing and 19 in traditional services. With the omission of two people from the latter group and with a restricted collection of data for people living in the family home, the present study explored service input, outcome and costs across the three setting types. Process and outcome indicators for the family home group, who received little service input, were better than those for the traditional service group, although less good than those for the community house group. The specialist community home model produced significant gains over the traditional services in virtually all areas. Across the residential data set as a whole, there was no association between staff:resident ratios and severity of disability or between costs and severity of disability. This was largely true of the service types separately. There was a relationship between costs and service quality. However, this association was underpinned by gross differences between community houses and traditional settings. Costs, processes and outcomes ceased to be related when the two residential types were considered separately. Although higher costs of new community services compared to traditional services may be set against improved outcomes, high costs within the former could not be related to benefit. Outcome indicators were generally related to each other, suggesting that high quality in one sense was matched by high quality in other senses. Outcome was significantly associated with the ability of residents. Outcome indicators also tended to be related to observed staff performance, which was independent of resident ability. Therefore, outcome may be considered as dually determined by differences in resident ability and in what staff did.

Adult↗

The characteristics and residential situations of people with severe intellectual disability and the most severe challenging behaviour in Wales.

A total population study of people in Wales with severe intellectual disability and the most severe challenging behaviour was undertaken to identify their characteristics, and the nature of their residential arrangements and service support. Forty-one participants were identified: five living in family homes, 17 in community housing, 17 in hospitals and two in hostels. The family home group had slightly higher adaptive behaviour scores than residents in community housing. Both groups had significantly higher scores than the hospital and hostel residents combined. Assessments of challenging behaviour showed the groups to be similar and to have a considerable range and extent of severely problematic behaviour. Co-occurrence of several forms of frequent severe problem behaviour was the norm and there was a marked association with social impairment. The five people living in their family homes had nominated service keyworkers, but reported professional input was low. The residential situations comprised two main service types: (1) traditional services, which were characterized by large living unit and facility size, atypical architectural design, relative isolation from the community, a greater level of buildings adaptations, low staff:resident ratios, a relatively high percentage of qualified staff, and a relative absence of systematic approaches to goal planning and structured activity; and (2) new community houses, which were characterized by small size, domestic design, location within the community, a lower level of buildings adaptations, much higher staff:resident ratios, and less emphasis on qualified staff but a greater emphasis on systematic working methods. Community settings were similar in having 'specialist' resident groupings based on challenging behaviour or conditions like autism in which challenging behaviours are common. A policy to provide for people with these characteristics being resettled from traditional settings in this way seems to have been established.

Adult↗