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Biomedical subjects

R Burt

Publications and source records attributed to R Burt.

At least 19 recordsLinked to original sources

Stakeholder involvement facilitates decision making for UK nuclear accident recovery.

The importance of major stakeholders participating in the formulation of strategies for maintaining food safety and agricultural production following a nuclear accident has been successfully demonstrated by the UK 'Agriculture and Food Countermeasures Working Group' (AFCWG). The organisation, membership and terms of reference of the group are described. Details are given of the achievements of the AFCWG and its sub-groups, which include agreeing management options that would be included in a recovery handbook for decision-makers in the UK and tackling the disposal of large volumes of contaminated milk, potentially resulting from a nuclear accident.

Agriculture↗

Meat intake and the recurrence of colorectal adenomas.

A large multicenter randomized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (T0) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence.

Adenoma↗

Hematopoietic stem cell transplantation for severe rheumatoid arthritis.

The substantial morbidity and mortality associated with rheumatoid arthritis (RA), while not widely appreciated, provide adequate justification for consideration of high-dose immunoablative therapy followed by hematopoietic stem cell transplantation. While some patients with RA follow a benign course, selected subsets of patients have been identified with 5-year survival rates of 40-70%. A number of factors that can be easily determined serve as useful prognostic indicators for poor outcome. These include the presence of many involved joints (total joint count), the degree of functional disability as measured by the health assessment questionnaire and the presence of rheumatoid factor. This article summarises the present status of hematopoietic stem cell transplantation for rheumatoid arthritis and proposes future directions for research.

Arthritis, Rheumatoid↗

Hematopoietic stem cell transplantation for cardiac and peripheral vascular disease.

Recent studies have suggested that marrow and blood hematopoietic stem cells may contribute to nonhematopoietic tissue repair in multiple organ systems. In animal models and more recently in limited human trials, unpurified marrow mononuclear cells and/or subsets of adult hematopoietic stem cells have been reported to contribute to neoangiogenesis. Since the subset of hematopoietic stem cells (HSCs) that are both CD34+ and AC133+ are endothelial cell precursors, clinical trials using autologous AC133+ HSCs isolated with the Miltenyi CLIMACS cell separator and transplanted into patients with ischemic and refractory peripheral vascular or coronary artery disease are being implemented at Northwestern University.

Animals↗

Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL.

ABX-CBL, an immunoglobulin M murine monoclonal antibody, recognizes CD147 and initiates cell killing through complement-mediated lysis. In a dose-finding trial, 27 patients with steroid-refractory acute graft-versus-host disease (GVHD) received ABX-CBL at 0.01 (presumed no effect dose), 0.1, 0.2, or 0.3 mg/kg per day, and an additional 32 patients were given ABX-CBL at 0.2 or 0.15 mg/kg per day. All patients had undergone allogeneic transplantation for malignant or nonmalignant disorders and received GVHD prophylaxis, generally with methotrexate- and cyclosporine-containing regimens. None responded to methylprednisolone, given for a minimum of 3 days. ABX-CBL was started 20 to 236 (median, 47) days after transplantation; it was given for 7 consecutive days and was followed by 2 infusions per week for 2 more weeks. Among 51 patients evaluable for efficacy, 26 (51%) responded, including 13 with complete responses (CR) and 13 with partial responses (PR). CR lasting 14 days or longer or PR lasting 7 days or longer occurred in 21 (41%; 8 CR, 13 PR) patients, including 19 of 43 (44%) patients who received 0.1 to 0.3 mg/kg ABX-CBL and 2 of 8 (25%) patients given 0.01 mg/kg per day. Myalgias at doses 0.2 mg/kg or greater were dose limiting and resolved without sequelae. Causes of death included organ failure, progressive GVHD, and infection. No death was attributed to ABX-CBL. At 6 months after the initiation of ABX-CBL therapy, 26 (44%) patients were surviving. These results are encouraging. Further studies on the use of ABX-CBL in the management of GVHD are warranted.

Acute Disease↗

CD34(+) cell collection efficiency does not correlate with the pre-leukapheresis hematocrit.

One hundred and seventy-seven large-volume leukapheresis procedures performed on 91 patients over a 15 month period were reviewed to see if the pre-apheresis hematocrit (Hct) affected the CD34(+) cell collection efficiency (CE) of the Fenwal CS 3000 Plus cell separator. The Hct was 0.174-0.461 (median 0.317), and the peripheral blood CD34(+) cell count 2-2487 per microl (median 21). The total CD34(+) cell quantity collected was 3.0-2677.2 x 10(6) (median 113.0). Based on the number of CD34(+)cells contained in the blood volume processed (23.3-37303.2 x 10(6); median 318.0), the CE was 1.7-87.5% (median 30.3). No correlation was found between the Hct and CE (r(2) = 0.0034; P = 0.44) or the total CD34(+) cell quantity collected (r2 = 0.0040; P = 0.40). CEs for Hct <0.25 (median CE 36%), Hct 0.25-0.299 (median CE 30%) and Hct 0.30 (median CE 30%) were comparable. As expected, highly significant correlations were seen between the CD34(+) cell quantities collected and quantities processed (r2 = 0.59; P < 10(-6)) as well as the peripheral blood CD34(+) cell counts (r2= 0.60; P < 10(-6)). We conclude that the minimum acceptable Hct or hemoglobin level for leukapheresis should be dictated by clinical circumstances because it does not affect stem cell collection.

Antigens, CD34↗

Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group.

BACKGROUND: We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. METHODS: We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. RESULTS: A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups. CONCLUSIONS: Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.

Adenoma↗

Work-related respiratory symptoms and lung function in New Zealand mussel openers.

Our objectives were to measure the prevalence of work-related and nonwork-related respiratory symptoms in a group of New Zealand mussel openers who open green-lipped mussels, and to relate these to demographic factors, work history, smoking history, and pulmonary function measurements. A cross-section study of respiratory symptoms and lung function was performed on 224 New Zealand mussel openers (99.6% of the study population) at nine work sites. In addition, peak expiratory flow (PEF) change across-shift was measured at one work site in 19 workers. The mean age of all mussel openers was 33.4 years and the mean duration of mussel opening was 5.0 years; 25% were male, 54.7% were current smokers, and 13.9% were ex-smokers. The reported symptom prevalences were: any wheeze, 35%; work-related wheeze, 23%; any chest tightness, 30.5%; work-related chest tightness, 20.2% (work-related symptoms were defined as symptoms improving on rest days or worse at work). Seventy-two mussel openers (32.3%) answered positively to at least 1 of 4 questions concerning work-related symptoms. The mean predicted FEV1 (SD) for this group was 74.3% (14.5), and the mean predicted FVC (SD) was 79.2 (16.0). Nineteen workers completed serial PEF, and the mean percentage change was +1.5% at 7 hr, but 8 workers had falls ranging between 1.1-14% after either 1 or 7 hr of work. Duration of mussel opening of greater than 2 years, but less than 7 years (OR = 2.29; 95% CI, 1.07-4.91), and duration of mussel opening greater than 7 years (OR = 3.72; 95% CI, 1.52-9.11), were significant predictors of work-related respiratory symptoms. Female sex (OR = 1.73; 95% CI, 0.83-3.60) was also associated with the presence of work-related symptoms. No relationship was found with measured hygiene parameters of cleaning agents used. In conclusions, duration of work as a mussel opener was associated with the present of work-related respiratory symptoms, after adjustment of age, sex, and smoking habit. There were marked abnormalities in mean FEV1 and FVC, although no consistent changes across working shift were noted.

Adult↗

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? The Polyp Prevention Trial.

BACKGROUND & AIMS: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas. METHODS: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. RESULTS: Four hundred sixty patients (46.9%) had >/=1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or >/=1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas. CONCLUSIONS: Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma. Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable.

Adenoma↗

Dual isotope F-18 FDG and Tc-99m RBC imaging for lung cancer.

PURPOSE: To produce fluorodeoxyglucose (FDG) images with markers for normal organs and large blood vessels in patients with suspected lung cancer. METHODS: Dual isotope SPECT images were made using F-18 FDG- and Tc-99m-labeled autologous red cells. RESULTS: FDG-positive lesions are localized in relation to major structures when they are viewed in a fused rotating three-dimensional display or in cross sections. CONCLUSIONS: Tc-99m red cell and FDG fusion imaging provides relative location information for lung tumors.

Aged↗

Stepwise approaches for estimating the intakes of chemicals in food.

Estimating intakes of chemicals in food requires residue data, giving the concentration of the chemical in food, and consumption data for foods which could contain the chemical. Residue data are often restricted to only a few foods and even then may not be representative of the foods of interest due to limitations in the sampling or analytical procedures. Obtaining reliable consumption data can also be complex. People normally eat a wide range of different foods, which may each contain a range of concentrations of the chemical of interest. Both sets of data can be combined using one of several approaches. This paper reviews the nature and relevance of the factors affecting the collection of these two data sets and the procedures available for combining them to estimate consumer exposure. Considerable expertise and judgment are necessary to obtain an estimate of exposure that is robust enough for risk management purposes.

Animals↗

Palliative medicine: providing care when cure is not possible. A roundtable discussion: Part I.

Palliative medicine describes the care of patients with advanced disease. When cure is no longer possible, the goal becomes control of pain, other symptoms, and psychological distress. In the United States, palliation has been pioneered by the hospice movement for patients with disseminated cancer and AIDS. Palliative care is also appropriate for patients with many of the chronic diseases of aging. For medical, humanitarian, financial, and legal reasons, physicians are being called on to provide palliative care when they make the diagnosis of all illness that is unresponsive to curative treatment.

Acquired Immunodeficiency Syndrome↗

A peaceful death: how to manage pain and provide quality care. A roundtable discussion: Part 2.

One of the most important components of a peaceful death is adequate control of pain and other distressing symptoms, such as dyspnea, agitation, and restlessness. Pain is an important symptom in 75 to 80% of noncancer patients in the last year of life. Opioid analgesics are often the mainstay of pain treatment for dying patients. A primary care physician also needs to know about anesthetic and neurosurgical approaches, the use of cognitive behavioral approaches, and the availability of specialized pain experts. A sizeable minority of physicians receive requests for an assisted death, which should be seen as a cry for help. The most useful function of advance directives is that they open an avenue for discussion between the doctor and the patient about a difficult subject.

Analgesics, Opioid↗

Characterization of the autoreactive T cell repertoire in cyclosporin-induced syngeneic graft-versus-host disease. A highly conserved repertoire mediates autoaggression.

Syngeneic graft-vs-host disease (SGVHD) is a MHC class II-restricted T cell-mediated autoimmune syndrome that occurs following syngeneic bone marrow transplantation and the administration of cyclosporin (CsA). The present studies evaluated the V beta repertoire of T lymphocytes that mediate SGVHD. To facilitate analysis, SGVHD effector cells were adoptively transferred into thymectomized syngeneic recipients reconstituted with T cell-depleted bone marrow to provide an environment that allows for the selective clonal expansion of autoreactive T cells. Analysis of target tissues and PBL by reverse transcriptase PCR using oligonucleotide V beta-specific primers revealed a predominance of V beta 8.5+ T cells and a minor population expressing V beta 10. The majority of infiltrating lymphocytes in target tissues was confirmed to be V beta 8.5+ by in situ hybridization and by immunoperoxidase staining. A small population of V beta 10+ cells could also be detected. Furthermore, SGVHD effector T splenocytes depleted of lymphocytes expressing either the TCR-alpha beta or the V beta 8.5 determinant could not adoptively transfer SGVHD. Depletion of T cells expressing the V beta 10 determinant delayed the onset of this autoaggression syndrome. Subset analysis of the autoreactive T cell compartment revealed that the V beta 8.5 determinant was expressed on both CD4+ and CD8+ lymphocytes whereas the V beta 10 determinant was principally expressed on a minor population of CD4+ autoreactive T cells. These data were confirmed by limiting dilution analysis. Additional studies examining the effect of CsA on thymic differentiation revealed that although V beta 8.5 is not normally clonally deleted, there was a pronounced shift in the expression of this determinant between CD4 and CD8 single positive thymocytes, suggesting that CsA may inhibit normal positive selection processes for MHC class I and class II reactive T cells.

Animals↗

Symptom-limited arm exercise increases detection of ischemia during dipyridamole tomographic thallium stress testing in patients with coronary artery disease.

Exercise combined with dipyridamole during thallium stress testing in patients with coronary artery disease (CAD) increases the frequency of angina and ischemic ST changes in the electrocardiogram. Evidence for an increase in thallium abnormalities has been inconclusive. We prospectively examined 54 consecutive patients who underwent coronary angiography and tomographic thallium with dipyridamole (0.57 mg/kg) alone and combined with symptom-limited dynamic arm exercise. Most patients presented with a history of chest pain and 49 had angiographic evidence of significant coronary stenosis (50% diameter narrowing). Thallium abnormalities were scored blindly by consensus. The number of abnormal segments (total and ischemic) and indexes of left ventricular dysfunction, such as increased lung uptake or ischemic dilation, were compared in the 49 patients with CAD. During arm exercise more patients had evidence of ischemia (39 vs 30; p < 0.001), and the number of ischemic segments increased significantly from 1.3 +/- 1.5 to 2.5 +/- 2.2 (p < 0.001). There was also a significant increase in the indexes of left ventricular dysfunction, ischemic dilation (10 vs 4 patients; p < 0.03) and increased lung uptake (16 vs 5 patients; p < 0.001). Patients who exercised had increased thallium evidence of extent and severity of ischemia and more frequent indexes of left ventricular dysfunction. Thus, symptom-limited arm exercise improves detection of extent and severity of ischemia in patients with CAD undergoing dipyridamole thallium stress testing.

Aged↗

Disseminated intravascular coagulation associated with granulocyte colony-stimulating factor therapy in a child with human immunodeficiency virus infection.

We report a case of disseminated intravascular coagulopathy, apparently caused by exposure to granulocyte colony-stimulating factor (G-CSF). The medical records of patients treated for more than 30 consecutive days with subcutaneously administered G-CSF were reviewed for the occurrence of thrombocytopenia or coagulation abnormalities. New-onset thrombocytopenia with a platelet count less than 100 x 10(9) cells/L (< 100,000 cells/mm3) developed in 9 of 23 patients (39%) after a median of 11 weeks of treatment with G-CSF at dosages between 1 and 10 micrograms/kg per day.

Adolescent↗

Enhancement of pain control with ketorolac tromethamine in patients with sickle cell vaso-occlusive crisis.

Twenty one patients with sickle cell disease admitted to the hospital with the pain of vaso-occlusive crisis (VOC) were treated by continuous IV infusion of ketorolac or normal saline for up to 5 days. All patients received supplemental IM injections of meperidine, 100 mg, as necessary, but not more frequently than every 3 hr. Over the 5 days the ketorolac treated patients (KT) required 33% less meperidine than did the placebo treated patients (PL), P = 0.04, and had significantly better pain relief as assessed by categorical, visual analog, and pain relief scales. By the end of 5 days infusions had been discontinued in six KT and one PL. The time to discontinuation of the infusion was significantly shorter in KT, (P = 0.009). The median duration of hospital stay from the start of treatment was 3.3 days for KT and 7.2 days for PL, P = 0.027. Adverse events were mainly related to the digestive system. This study showed that continuous infusion of ketorolac significantly reduced total meperidine requirement and that the analgesia produced by this combination was superior to that produced by meperidine alone. Further evaluation of this drug in the management of sickle cell VOC is warranted.

Adult↗

A CA-repeat polymorphism close to the adenomatous polyposis coli (APC) gene offers improved diagnostic testing for familial APC.

Presymptomatic genetic testing for the presence of a mutant allele causing familial adenomatous polyposis coli (APC) has been difficult to perform effectively in the past because DNA markers surrounding the APC gene on chromosome 5q have not been very informative. We report results of genetic linkage studies on both research families and clinical families by using D5S346, a highly polymorphic dinucleotide (CA)-repeat locus 30-70 kb from the APC gene. Linkage analysis with this marker in a large APC pedigree showed an increase of at least 9.0 LOD units, in likelihood of linkage of the disease-causing allele to the APC locus, when compared with the highest LOD score attained with any other closely linked marker. When the first 14 APC families that requested genotypic analysis by the DNA Diagnostic Laboratory at the University of Utah were tested with D5S346, 20 of the 31 at-risk individuals were identified as either carriers or noncarriers of an APC-predisposing allele. We see this marker as an important tool for research studies and for the presymptomatic diagnosis of APC.

Adenomatous Polyposis Coli↗