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Biomedical subjects

S Barr

Publications and source records attributed to S Barr.

At least 19 recordsLinked to original sources
PubMed2006

Prosthetic rehabilitation for older dysvascular people following a unilateral transfemoral amputation.

BACKGROUND: Dysvascularity accounts for 75% of all lower limb amputations in the UK. Around 37% of these are at transfemoral level (mid-thigh), with the majority of people being over the age of 60 and having existing co-morbidities. A significant number of these amputees will be prescribed a lower limb prosthesis for walking. However, many amputees do not achieve a high level of function following prosthetic rehabilitation. OBJECTIVES: We aimed to identify and summarise the evidence from randomised controlled trials evaluating rehabilitation interventions for prosthetic ambulation following unilateral transfemoral amputation in older dysvascular people, whether community dwelling or institutionalised. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group Specialised Register (July 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 3), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006), CINAHL (1982 to December 2005), AMED (1985 to December 2005), several more specialised databases and reference lists of articles. We also searched the UK National Research Register (Issue 2, 2005) for ongoing trials and contacted experts in the field. No language restrictions were applied. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials testing prosthetic rehabilitation interventions following a unilateral transfemoral or transgenicular amputation in older (aged 60 years or above) dysvascular people. DATA COLLECTION AND ANALYSIS: Two authors independently scanned the search results for potentially eligible studies and then, on obtaining full reports of these, selected studies for inclusion and exclusion. Two authors independently assessed methodological quality and extracted data. No data pooling was possible. MAIN RESULTS: Of 38 full reports obtained for consideration, one trial was included and four were excluded. The sole included trial was a short-term crossover randomised trial which tested the effects of adding three seemingly identical prosthetic weights (150 g versus 770 g versus 1625 g) to the prostheses of 10 participants with unilateral dysvascular transfemoral amputation. Eight participants were over 60 years of age. The trial found that four participants preferred the lightest weight (150 g), five preferred the middle weight (770 g) and one preferred the addition of the heaviest weight (1625 g). AUTHORS' CONCLUSIONS: There is a lack of evidence from randomised controlled trials to inform the choice of prosthetic rehabilitation, including the optimum weight of prosthesis, after unilateral transfemoral amputation in older dysvascular people. A programme of research, including randomised controlled trials to examine key interventions, is urgently required in this area.

Aged↗
PubMed2006

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Adolescent↗
PubMed2006

RAT CYP3A and CYP2B1/2 were not associated with nevirapine-induced hepatotoxicity.

Nevirapine is an antiretroviral drug that is used for treatment as well as for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV). Unfortunately, its adverse effects, mainly hypersensitivity skin reactions and hepatotoxicity, have hampered the use of nevirapine. Since nevirapine-induced hepatotoxicity commonly occurs between 2-12 weeks of treatment, and nevirapine is a known inducer of human CYP3A and CYP2B6 isozymes, it was envisaged that the hepatotoxicity was due to activation of nevirapine to toxic metabolites by the induced enzymes. Therefore, the aim of this study was to use a rat model and determine the role of the rat analogues, rat CYP3A and CYP2B1/2, in nevirapine-induced hepatotoxicity. This was tested by the extent at which hepatotoxicity could be prevented when ketoconazole or thiotepa, known inhibitors of CYP3A and CYP2B1/2, respectively, were given one hour prior to administration of a hepatotoxic dose of nevirapine. It was shown here that nevirapine-induced hepatotoxicity only occurred in animals that were pretreated with an enzyme inducer (dexamethasone or nevirapine); that ketoconazole and thiotepa did not prevent the occurrence of nevirapine-induced hepatotoxicity; and that histopathologic examinations were more accurate than the use of liver enzymes in detecting the liver damage. This suggested that nevirapine-induced hepatotoxicity is closely associated with enzyme induction, and that liver function tests alone might not be good markers for determining nevirapine-induced hepatotoxicity. In conclusion, rat CYP3A and CYP2B1/2 may not be involved in the pathogenesis of nevirapine-induced hepatotoxicity, suggesting that a different enzyme inducible by nevirapine or dexamethasone may be responsible. However, this is yet to be proven in humans.

Administration, Oral↗
PubMed2005

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Adult↗
PubMed2005

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

Adult↗
PubMed2004

Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms.

BACKGROUND: Bone marrow cell therapy is reported to contribute to collateral formation through cell incorporation into new or remodeling vessels. However, the possible role of a paracrine contribution to this effect is less well characterized. METHODS AND RESULTS: Murine marrow-derived stromal cells (MSCs) were purified by magnetic bead separation of cultured bone marrow. The release of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and monocyte chemoattractant protein-1 (MCP-1) was demonstrated by analysis of MSC conditioned media (MSC-CM). MSC-CM enhanced proliferation of endothelial cells and smooth muscle cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partly attenuated these effects. Balb/C mice (n=10) underwent distal femoral artery ligation, followed by adductor muscle injection of 1x10(6) MSCs 24 hours later. Compared with controls injected with media (n=10) or mature endothelial cells (n=8), distal limb perfusion improved, and mid-thigh conductance vessels increased in number and total cross-sectional area. MSC injection improved limb function and appearance, reduced the incidence of auto-amputation, and attenuated muscle atrophy and fibrosis. After injection, labeled MSCs were seen dispersed between muscle fibers but were not seen incorporated into mature collaterals. Injection of MSCs increased adductor muscle levels of bFGF and VEGF protein compared with controls. Finally, colocalization of VEGF and transplanted MSCs within adductor tissue was demonstrated. CONCLUSIONS: MSCs secrete a wide array of arteriogenic cytokines. MSCs can contribute to collateral remodeling through paracrine mechanisms.

Animals↗
PubMed2004

Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.

We recently demonstrated that marrow stromal cells (MSCs) augment collateral remodeling through release of several cytokines such as VEGF and bFGF rather than via cell incorporation into new or remodeling vessels. The present study was designed to characterize the full spectrum of cytokine genes expressed by MSCs and to further examine the role of paracrine mechanisms that underpin their therapeutic potential. Normal human MSCs were cultured under normoxic or hypoxic conditions for 72 hours. The gene expression profile of the cells was determined using Affymetrix GeneChips representing 12 000 genes. A wide array of arteriogenic cytokine genes were expressed at baseline, and several were induced >1.5-fold by hypoxic stress. The gene array data were confirmed using ELISA assays and immunoblotting of the MSC conditioned media (MSC(CM)). MSC(CM) promoted in vitro proliferation and migration of endothelial cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partially attenuated these effects. Similarly, MSC(CM) promoted smooth muscle cell proliferation and migration in a dose-dependent manner. Using a murine hindlimb ischemia model, murine MSC(CM) enhanced collateral flow recovery and remodeling, improved limb function, reduced the incidence of autoamputation, and attenuated muscle atrophy compared with control media. These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects.

Adult↗
PubMed2004

The role of cytochrome-P450 inhibitors in the prevention of hepatotoxicity after paracetamol overdose in rats.

Despite the understanding that some cytochrome P450 isoforms are responsible for activation of paracetamol to the hepatotoxic metabolite, N-acetyl-p-benzoquinineimine (NAPQI), the use of enzyme inhibitors for prevention and/or treatment of paracetamol hepatotoxicity is still not well researched. Here, a mixture of ketoconazole, isoniazid and caffeine (inhibitor solution), known inhibitors of CYP3A, CYP2E1 and CYP1A2, was investigated for prevention of hepatotoxicity after paracetamol over-dose in rats. The appropriate doses of paracetamol (1000 mg/kg/day) and the 'inhibitor solution' (ketoconazole 5 mg/kg, isoniazid 5 mg/kg and caffeine 10 mg/kg; =KIC-5-50), were selected in preliminary experiments. Thereafter, two groups of 15 male Sprague-Dawley rats each were treated with the toxic dose of paracetamol intraperitoneally to induce severe hepatotoxicity. But one of the two groups was treated with the KIC-5-50 intraperitoneally 5 min after administration of paracetamol. Five rats were killed at 24, 48 and 72 hours after paracetamol administration. Plasma concentrations of paracetamol were determined by the polarization fluorescent immunoassay and a piece of liver was sent for histopathology examination. Liver function tests at 48 hours were higher in the 'paracetamol only' treated group than in the 'KIC-5-50 + paracetamol' treated group' (P < 0.05), i.e., median (range) AST 2025 (530-4329) i.u./L, ALT 1174 (662-2395) i.u./L versus AST 194 (81-494) i.u./L, ALT 311 (201-945) i.u./L, respectively. The corresponding plasma concentrations of paracetamol were 0.26 (0.13-1.02) microg/mL for the 'paracetamol only' treated group versus 0.17 (0.07-0.33) microg/ml for the 'KIC-5-50 + paracetamol' treated group. Centrilobular necrosis, the pathogmonomic feature of paracetamol hepatotoxicity, was demonstrated only in the 'paracetamol only' treated group. In conclusion, coadministration of paracetamol with inhibitors of cytochrome P450 prevented the development of paracetamol-induced hepatotoxicity in rats, and this calls for research for enzyme inhibitors that may be of therapeutic value.

Acetaminophen↗
PubMed2003

The treatment of de novo acromegalic patients with octreotide-LAR: efficacy, tolerability and cardiovascular effects.

AIM: Somatostatin analogues are normally used as adjunctive therapy to surgery and radiotherapy in management of acromegaly. We studied the effects of de novo OCT-LAR treatment on growth hormone (GH) suppression, tumour size, cardiovascular function, clinical symptoms, signs and quality of life in 9 newly diagnosed acromegalic patients. METHODS: Patients commenced OCT-LAR 20 mg IM monthly for 2 months. Dose increased to 30 mg monthly if mean serum GH (MGH) > 5 mU/l (2 microg/litre) (7 patients). Treatment continued for 6 months. Cardiac function assessed by echocardiography at baseline and day 169. Left ventricular (LV) mass and ejection fraction (EF) calculated from 2D M-mode studies. RESULTS: Serum GH demonstrated suppression in 8/9 patients (mean suppression 64.9% +/- 29.7%, range; 4-95.2%). MGH suppressed < 5 mU/ (2 microg/litre) in 3 (33%) patients. IGF-I and IGFBP3 normalised in 1 (12.5%) and 3 (38%) patients respectively. Tumour shrinkage seen in 30% patients. Eight patients were assessed by echocardiography. At baseline, 7 patients demonstrated abnormalities in LV mass and EF. At day 169, 6 patients demonstrated a fall and 1 an increase in LV mass. Overall there was no significant change in LV mass. A significant increase in EF was observed (p = 0.02). There were significant improvements in health perception (p = 0.01), fatigue (p < 0.05) and perspiration (p = 0.0039). CONCLUSIONS: These data demonstrate OCT-LAR provides adequate control of acromegaly in a proportion of patients treated over 6 months. This is associated with improved LV function, evidenced by increased EF. Improved results are expected with longer-term treatment. OCT-LAR may be considered as primary treatment for acromegaly in selected patients.

Acromegaly↗
PubMed2001

Living with lupus: a prospective pan-Canadian study.

OBJECTIVE: To portray life with lupus for women affected by this disease and to identify predictors of fatigue, a common symptom that compromises patients' quality of life. METHODS: A sample of 120 female patients (mean age 42.5 yrs) with systemic lupus erythematosus (SLE) from 9 rheumatology clinics across Canada were followed prospectively for 15 months. Assessments of psychosocial functioning took place at baseline, and at 3, 9, and 15 months. Physician examinations were conducted at baseline and 15 months. RESULTS: Significant time effects were found for: global psychological distress (p < 0.001), stress (p < 0.01), emotion-oriented coping (p < 0.001), physical health status (p < 0.001), and fatigue (p < 0.001), indicating that patients improved from baseline to 15 months. Disease activity worsened for 40.3%, improved for 50.8%, and remained the same for 8.8% of the patients from baseline to 15 months. Controlling for baseline disease activity and fatigue, and considering sleep problems, decreases in stress and depression predicted less fatigue at 15 months (p < 0.001; adjusted R2 = 0.43). CONCLUSION: Despite fluctuations in disease activity, patients with SLE, as a group, cope adequately with their disease over time. There is, nonetheless, a subset of patients (about 40%) who remain distressed and who may benefit from psychosocial interventions.

Adolescent↗
PubMed1999

Quality of life in systemic lupus erythematosus patients during more and less active disease states: differential contributors to mental and physical health.

OBJECTIVE: To identify determinants of mental and physical health as a function of disease state in patients with systemic lupus erythematosus (SLE). METHODS: A sample of 129 SLE patients (mean age 42.01 years; SD 11.09) was recruited from 9 immunology/rheumatology clinics across Canada. Patients completed questionnaires assessing psychological distress, social support, coping, stress, and health-related quality of life. Physicians rated disease activity (using the revised Systemic Lupus Activity Measure; SLAM-R) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). Mental and physical health composite scores were derived from the Medical Outcomes Study Short Form 36. Patients were subdivided into more active (SLAM-R > or = 10; n = 38) or less active disease states (n = 91). RESULTS: Better mental health was predicted by more education and less emotion-oriented coping in the patients in a more active disease state (P = 0.0001; R2 = 0.46). Better mental health was predicted by less stress, less emotion-oriented coping and more task-oriented coping in patients during a less active disease state (P = 0.0001; R2 = 0.45). Better physical health was predicted by more emotion-oriented coping in patients in a more active disease state (P = 0.04; R2 = 0.11). Better physical health was predicted by less stress and younger age in patients during a less active disease state (P = 0.0001; R2 = 0.20). CONCLUSION: The positive association between emotion-oriented coping and better physical health in patients during a more active disease state suggests that this style of coping may be more adaptive in situations that are considered uncontrollable (e.g., SLE flare). Predictors of mental health were similar to those found in the literature, especially for SLE patients in a less active disease state.

Acute Disease↗
PubMed1997

The effects of health beliefs on weight loss in individuals at high risk for NIDDM.

OBJECTIVE: To determine whether perceived risk and other health beliefs held by individuals at high risk for developing NIDDM predict weight loss and behavior change during a behavioral weight loss program to reduce the risk of NIDDM. RESEARCH DESIGN AND METHODS: Health beliefs and objective risk factors for diabetes were examined in 154 overweight men and women with a family history of NIDDM. The effects of these factors on adherence, dietary intake, weight loss, and changes in glucose levels were examined in a subset of 79 of these subjects who participated in a 2-year behavioral weight control program. RESULTS: Those subjects who perceived themselves at highest risk of developing diabetes had a stronger family history of the disease and were more likely to be women than subjects considering themselves at more moderate risk. These participants also rated diabetes as a more serious disease, but were less likely to believe that weight loss would lower their risk. None of these health beliefs were related to attendance at meetings, dietary intake, weight loss, or fasting glucose, but higher perceived seriousness predicted larger reductions in BMI at 1 year. Of the objective risk factors for NIDDM, higher baseline BMI predicted larger weight losses throughout the program, and a stronger family history of diabetes was related to greater weight regain after an initial weight loss. CONCLUSIONS: Perceived risk of developing diabetes and other health beliefs did not predict performance in a behavioral weight loss program. These data suggest that efforts to modify health beliefs by educating high-risk individuals about their risk and benefits of weight loss may not be effective in improving long-term weight loss results.

Adult↗
PubMed1996

Thirty years on.

Explore the source record for details and available documents.

Adolescent↗
PubMed1996

The 1990 Florida Dental Investigation: is the case really closed?

In 1994, a magazine article, a newspaper article, and a segment of the television newsmagazine 60 Minutes presented information that cast doubt on the Centers for Disease Control and Prevention's conclusion that a dentist in Florida had infected six of his patients with the human immunodeficiency virus (HIV). These reports were based on previously unavailable documentary evidence, which suggested that the infected patients had unreported or undetected risk factors for HIV infection and that the molecular analyses used to determine that the dentist and his patients had the same strains of HIV had potentially serious flaws. A recent article in this journal sought to dismiss the relevance of this information in the eyes of the scientific community. That report, however, failed to respond directly to many key pieces of evidence, and it offered no rebuttal beyond personal invective and a reassertion of previously published material. Although scientists and clinicians should not rely solely on media reports when drawing conclusions about this complex and controversial case, they deserve a chance to consider and reflect on this material in a meaningful way.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in acute canine Chagas' disease.

UNLABELLED: The effect of verapamil treatment on the myocardial beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease was investigated. Relative to uninfected animals, 30 days of infection with T. cruzi reduced myocardial adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the infection-associated reduction in adenylyl cyclase activity was less than 50%. The individual components of the beta-adrenergic receptor complex were characterized. INFECTION: (1) increased right ventricular (RV) beta-adrenergic receptor (beta AR) density five-fold; (2) decreased left ventricle beta AR density by 20%; (3) reduced the proportion of high-affinity beta AR receptors to the same extent in both left and right ventricles; (4) reduced alpha s by 50% as determined by Western blot analysis, increased alpha 11-3 but did not change alpha 0; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated in alpha 0. Verapamil treatment of infected animals restored RV beta AR receptor density, alpha s and alpha i1-3 to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increased beta-adrenergic adenylyl cyclase activity; (2) increased beta AR density in the RV but not the LV; (3) reduced high- to low-affinity beta-adrenergic receptors; and (4) affected only alpha i2 (50% decrease). The results indicate that the major actions of verapamil on the beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to account for its cardioprotective effects.

Adenylyl Cyclases↗