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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 37 records · Page 2Linked to original sources

[Enterococci; increase in infection rate and antibiotic resistance].

Enterococci (mainly Enterococcus faecalis and E. faecium) are increasingly isolated as causative agents of infections, notably in hospitalised patients. Most infections are urinary tract infections, septicaemia and endocarditis. Dutch figures indicate that 10.8% of all bacteria isolated in seven regional microbiological laboratories were enterococci; the samples came not only from hospital infections. Of the isolates 34% were from faecal samples, 14% from urinary tract samples and 14% from genital organ samples. Antibiotic resistance is an increasing problem. Enterococci are moderately resistant to the antibiotics commonly used to treat Gram positive infections. The infections may be treated with (high dose) penicillin and (or) in combination with an aminoglycoside or with a glycopeptide. Unrestricted use of antibiotics increases the risk of resistance. Recently enterococci have been isolated which are resistant to ampicillin, gentamycin and vancomycin: such infections are virtually untreatable.

Drug Resistance, Microbial

Cardiopulmonary effects of combinations of medetomidine hydrochloride and atropine sulphate in dogs.

Medetomidine and xylazine are alpha 2 adrenoceptor agonists which are used as sedatives and premedicants in small animals. However, bradycardia is a side effect and the use of atropine sulphate has been recommended to counteract it. This study investigated the effects of combining medetomidine (40 micrograms/kg) and atropine (30 micrograms/kg) on the cardiopulmonary function of six dogs. Medetomidine administered alone caused severe bradycardia, but hypertension was mild and transient. Medetomidine and atropine administered together caused an initial bradycardia, but within 15 minutes there was tachycardia accompanied by a mean arterial blood pressure of 210 mm Hg. When atropine was administered 30 minutes before medetomidine, tachycardia and hypertension were observed within five minutes of the medetomidine injection. Thus, although atropine will counteract medetomidine-induced bradycardia, its use results in prolonged and severe hypertension, in association with the tachycardia. Although atropine may be life-saving when bradycardia is profound, its indiscriminate use in combination with alpha 2 adrenoceptor agonists may be disadvantageous.

Adrenergic alpha-Agonists

A CD66a-specific, activation-dependent epitope detected by recombinant human single chain fragments (scFvs) on CHO transfectants and activated granulocytes.

Antibodies to CD66 recognize at least five members (CD66a-e) of the carcinoembryonic antigen (CEA) family. Recombinant human single-chain Fv fragments (scFvs) that bind specifically to CD66a (biliary glycoprotein) were obtained from a naive human scFv library. The scFvs bound to the N-domain of CD66a on Chinese hamster ovary (CHO) transfectants but did not bind to freshly isolated peripheral granulocytes or to dimethylsulfoxide-treated HL-60 cells. In contrast, scFvs bound well to granulocytes that were short-term activated with N-formyl-Met-Leu-Phe or phorbol 12-myristate 13-acetate and to human HL-60 cells that were treated with all-trans-retinoic acid to induce granulocytic differentiation. Quantification of antigenic sites showed that the activation-dependent CD66a epitopes were expressed on nearly all of the CD66a molecules on CHO-biliary glycoprotein transfectants, but they were detected only on a portion of the molecules on activated polymorphonuclear neutrophils and differentiated HL-60 cells. Binding of CD66a scFvs to their neoepitopes on prestimulated PMNs induced respiratory burst, suggesting that CD66a is capable of delivering transmembrane signals in these cells.

Animals

Exercise and the oxidation and storage of glucose, maize-syrup solids and sucrose determined from breath 13CO2.

In order to determine which of maize syrup solids, glucose and sucrose were more readily oxidised during exercise and least readily oxidised afterwards, the rates of oxidation of three almost identical isoenergetic solutions of carbohydrates (330 ml of 18.5% w/v solutions of glucose, maize syrup solids and sucrose, 989-1050 kJ total energy) naturally enriched with 13C were examined at rest and during and after 1 h uphill walking at 75% maximum oxygen uptake (VO2max) in nine subjects [mean (SEM) VO2max, 45.4 (0.9) ml.kg-1.min-1]. Rates of production of expired 13CO2 were used to estimate rates of oxidation of each exogenous substrate. Energy expenditure and the contributions from total carbohydrate and fat oxidation were calculated from whole-body gas exchange. At rest, maize syrup solids were oxidised less than sucrose during the 1st h [glucose 2.7 (0.2) g.h-1, maize syrup solids 1.9 (0.3) g.h-1, sucrose 3.7 (0.2) g.h-1; maize syrup solids vs sucrose P < 0.01], but this difference disappeared after a further 3 h at rest [glucose 8.3 (0.5) g.h-1, maize syrup solids 7.7 (0.5) g.h-1, sucrose 8.1 (0.4) g.h-1]. During exercise, all the carbohydrates were oxidised to the same extent [glucose 23.0 (2.8) g.h-1, maize syrup solids 23.9 (3.4) g.h-1, sucrose 27.5 (2.6) g.h-1) but during 4 h of recovery after exercise, maize syrup solids were oxidised least [glucose 4.6 (0.1) g.h-1, maize syrup solids 3.7 (0.1) g.h-1, sucrose 6.4 (0.1) g.h-1; P < 0.05] suggesting that it may be stored to a greater extent. The results suggest that 18.5% glucose, maize syrup solids and sucrose solutions were equally well oxidised during exercise. During recovery from exercise maize syrup solids were oxidised less than glucose, which in turn was oxidised less than sucrose.

Adult

Biochemical markers of bone turnover reflect femoral bone loss in elderly women.

Although over 90% of hip fractures occur in patients over age 70, few data are available on femoral bone loss in this age group. To examine the relationship between biochemical markers of bone turnover and femoral bone loss in the elderly, 36 female and 17 male, healthy, community-dwelling elderly over age 65 (mean +/- SD age: women 71 +/- 4 years, men 75 +/- 5 years) were followed for 3 years. Annual bone mineral density measurements of the hip and lumbar spine by dual-energy x-ray absorptiometry (DXA) were obtained and biochemical markers of bone resorption (urinary N-telopeptide crosslinks, free pyridinoline, total pyridinoline, total deoxypyridinoline, and hydroxyproline) and bone formation (serum osteocalcin, bone-specific alkaline phosphatase) were obtained at the end of year 3. In elderly women, longitudinal bone loss at the total hip was negatively correlated with markers of bone resorption (r = -0.39 to -0.52, P < 0.05), bone formation (r = -0.38, P < 0.05), and age (r = -0.39, P < 0.05). Markers of bone resorption were correlated with markers of bone formation (r = 0.63 to 0.74, P < 0. 01). In multiple regression analysis, urinary N-telopeptide crosslinks (marker of resorption), serum osteocalcin (marker of formation), and serum parathyroid hormone explained 43% of the variability of bone loss at the total hip in women. These parameters were not related to bone loss in men. We conclude that femoral bone loss increases with age in women over 65. Measurements of specific biochemical markers of bone turnover are correlated with longitudinal bone loss in elderly women. These markers may help identify women at greatest risk for bone loss who would benefit most from therapeutic interventions.

Aged

Characterization of a human ubiquitin-conjugating enzyme gene UBE2L3.

Ubiquitin-conjugating enzymes (E2s) are essential components of the post-translational protein ubiquitination pathway, mediating the transfer of activated ubiquitin to substrate proteins. We have identified a human gene, UBE2L3, localized on Chromosome (Chr) 22q11. 2-13.1, encoding an E2 almost identical to that encoded by the recently described human L-UBC (UBE2L1) gene present on Chr 14q24.3. Using chromosome-specific vectorette PCR, we have determined the intron/exon structure of UBE2L3. In contrast to the intronless UBE2L1 gene, the coding sequence of UBE2L3 is interrupted by three large introns. UBE2L3-derived mRNA appears to be the predominant species in most tissues rather than the transcript from UBE2L1 or another homologous gene UBE2L2, which maps to Chr 12q12. We also present additional evidence that these genes are members of a larger multigene family. The primary sequence of the protein encoded by UBE2L3 is identical to partial peptide sequence derived from the rabbit E2 'E2-F1,' suggesting that we have identified the human homolog of this protein. This latter E2 has been demonstrated to participate in transcription factor NF-kappaB maturation, c-fos degradation, and human papilloma virus-mediated p53 degradation in vitro.

Amino Acid Sequence

N2-methyl-8-oxoguanine: a tRNA urinary metabolite--role of xanthine oxidase.

DNA damage produces a series of oxidation products including 8-oxo-2'-deoxyguanosine and 8-oxoguanine, whose urinary excretion have been used to estimate in vivo oxidative injury. A monoclonal antibody to 8-oxoguanine was used to measure these adducts in urine taken from ill infants. In the process of this investigation we observed a large chromatographic peak that did not correspond to any of the known 8-oxoguanine adducts. A combination of liquid chromatography with electrochemical detection and gas chromatography/mass spectrometry allowed isolation and identification of the previously undescribed oxidation product, N2-methyl-8-oxoguanine. The excretion of this compound is increased in ill and growing infants but is also found in the urine of adult rats and humans. Experiments with allopurinol, a xanthine oxidase inhibitor, show that in humans, N2-methyl-8-oxoguanine is formed from the tRNA modified base N2-methylguanine. This is in contrast to the nonmethylated bases, which are converted to 8-oxo derivatives as a result of oxidative damage to nucleic acids and do not appear to be substrates for xanthine oxidase.

Animals

AORN sales professional course.

The sales professional course "Introduction to the Operating Room" offered by the AORN Center for Nursing Practice, Health Policy, and Research is an introductory program in OR etiquette. Its purpose is to provide sales professionals a working knowledge of OR protocol for them to function appropriately in OR settings. Sales professionals who have completed this course establish mutually beneficial perioperative partnerships with OR personnel. Sales professionals' effectiveness is strengthened as a result of their newly acquired knowledge of OR protocol, and patient safety is protected. An AORN Certificate of Recognition is awarded on completion of the course.

Commerce

AORN's multisite clinical study of bloodborne exposures in OR personnel.

Perioperative nurses are participating in a multisite clinical study to identify risk factors for blood and body fluid exposures in OR settings and to create a surveillance database that can be used to assess the benefits of strategies to prevent these exposures. The project is funded by a grant from Becton Dickinson, Franklin Lakes, NJ, to the AORN Foundation and is coordinated by an AORN Headquarters nurse in collaboration with the primary investigator at the University of Virginia Medical Center, Charlottesville. This article reports the study's implementation and current status.

Blood-Borne Pathogens

Predicted and measured resting metabolic rate of male and female endurance athletes.

OBJECTIVE: To measure the resting metabolic rate (RMR) of a group of endurance-trained male and female athletes and to compare it with values predicted using published equations. DESIGN: RMR was measured twice: 1 week apart for the men and approximately 1 month apart for the women. RMR was predicted using equations of Harris and Benedict, Owen et al, Mifflin et al, and Cunningham. SUBJECTS/SETTING: Subjects were 37 trained endurance athletes (24 men, 13 women) who had participated in studies previously completed in our laboratory. MAIN OUTCOME MEASURES: The primary outcome measure was the comparison of predicted RMR with measured RMR. An exploratory procedure for the determination of predictive variables in these athletes was also performed. STATISTICAL ANALYSES PERFORMED: The Root Mean Squared Prediction Error method was used to compare predicted RMR with measured RMR. The maximum R2 procedure method was used to determine the best possible combination of four variables that explained the largest amount of variance in RMR. RESULTS: The Cunningham equation was found to predict measured RMR most accurately (within 158 kcal/d for men and 103 kcal/d for women). Fat-free mass was the best predictor of RMR in men, whereas energy intake was the best predictor in women. APPLICATIONS/CONCLUSIONS: The Cunningham equation provides an accurate estimate of RMR when determining energy needs of highly active people. Equations specific to athletes need to be developed. Factors in addition to body weight, height, and age should be investigated as possible predictor variables in athletes.

Adult

Routine use of the piggyback technique in pediatric orthotopic liver transplantation.

The theoretical advantages of the piggyback technique over conventional orthotopic liver transplantation are as follows. (1) Continuous venous decompression during the anhepatic phase is provided without venovenous bypass. (2) Warm ischemia time can be shortened because there is no need for the infrahepatic vena cava anastomosis. The following report is a review of the authors' experience with this method in children during the past year at their institution. Analyses of intraoperative hemodynamics and blood loss, postoperative renal function, patient and graft survival, and length of hospital stay have shown excellent results. There were no intraoperative deaths, and causes of death and graft loss were not related to the technique. The authors conclude that children who undergo liver transplantation can be very satisfactorily managed with the piggyback operation, and this technique may be more advantageous than the conventional method.

Adolescent

Cardiopulmonary effects of medetomidine in sheep and in ponies.

Medetomidine was administered intravenously to six sheep at 5, 10 and 20 micrograms kg-1 and to one horse and four ponies at 5 and 10 micrograms kg-1. In both species medetomidine resulted in significant decreases in heart rate and cardiac output and, initially, in an increase in arterial blood pressure. In the ponies this increase in blood pressure was followed by a significant and prolonged decrease, but in the sheep the secondary decrease in blood pressure was not statistically significant. In the sheep, the three doses of medetomidine resulted in profound and significant decreases in arterial oxygen tensions, which were significantly dose related, but in the ponies the arterial blood oxygen tensions were not significantly decreased. In both species medetomidine caused a small but significant increase in arterial blood carbon dioxide tensions.

Animals

Oxygen free radical and cytokine generation during endovascular and conventional aneurysm repair.

OBJECTIVES: Endovascular aneurysm repair has been proposed as a "minimally invasive" alternative to conventional aneurysm resection. One of the most important potential benefits of endoluminal surgery is the avoidance of aortic cross clamping, which may attenuate the ischaemia-reperfusion injury that complicates open aneurysm repair. This study aimed to quantify the metabolic response to both conventional and endovascular aortic surgery. DESIGN: Prospective clinical study. SETTING: University hospital. METHODS: Femoral vein blood samples (pre-clamp, during aneurysm repair and 5 and 30 min post reperfusion) were obtained from 12 patients undergoing aortoaortic aneurysm repair, six by conventional transperitoneal inlay replacement (median age 71 years, median aneurysm diameter 5.8 cm), and six by endoluminal deployment of a straight endograft (median age 73 years, median aneurysm diameter 5.5 cm). All endovascular procedures were completed satisfactorily with no conversions to conventional surgery. OUTCOME MEASURES: Venous blood samples were analysed for oxygen free radical (OFR) production using the quantifiable oxidation of IgG in plasma, and cytokine (IL-1 beta and TNF-alpha) generation by radioimmunoassay. [table: see text] RESULTS: The results are given as median values with interquartile ranges: CONCLUSIONS: These results suggest that the ischaemia-reperfusion response associated with conventional aneurysm surgery may be largely negated by endovascular techniques. This may have significant consequences as the generation of oxygen free radicals and cytokines have been implicated in the development of systemic organ failure following aortic surgery.

Aged

A randomized controlled study of iron supplementation in patients treated with erythropoietin.

In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin (EPO), a prospective randomized controlled study was designed to investigate this issue. All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were randomized into three groups with different iron supplementation: Group 1, i.v. iron dextran 5 ml every 2 weeks; Group 2, oral ferrous sulphate 200 mg tds; Group 3, no iron. All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously. The hemoglobin concentration, reticulocyte count, serum ferritin, transferrin saturation, and EPO dose were monitored every two weeks for the first four months. Thirty-seven patients entered the study (12 i.v., 13 oral, 12 no iron). The three groups were equivalent with regard to age, sex, and other demographic details. Even allowing for dosage adjustments, the hemoglobin response in the group receiving i.v. iron (7.3 +/- 0.8 to 11.9 +/- 1.2 g/dl) was significantly greater than that for the other two groups (7.2 +/- 1.1 to 10.2 +/- 1.4 g/dl and 7.3 +/- 0.8 to 9.9 +/- 1.6 g/dl for Groups 2 and 3, respectively; P < 0.005 for both groups vs. Group 1 at 16 weeks). There was no difference between the groups supplemented with oral iron and no iron. Serum ferritin levels remained constant in those receiving i.v. iron (345 +/- 273 to 359 +/- 140 micrograms/liter), in contrast to the other two groups in which ferritin levels fell significantly (309 +/- 218 to 116 +/- 87 micrograms/liter and 458 +/- 206 to 131 +/- 121 micrograms/liter for Groups 2 and 3, respectively; P < 0.0005 for Group 1 vs. Group 2, and P < 0.005 for Group 1 vs. Group 3 at 16 weeks). Dosage requirements of EPO were less in Group 1 (1202 +/- 229 U/kg/16 weeks) than in Group 2 (1294 +/- 314 U/kg/16 weeks) or Group 3 (1475 +/- 311 U/kg/16 weeks; P < 0.05 vs. Group 1). The results of this study suggest that, even in iron-replete patients, those supplemented with i.v. iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO, compared with those patients receiving oral iron and no iron supplementation.

Cost-Benefit Analysis

Expression and characterization of a divalent chimeric anti-human CD3 single chain antibody.

Murine anti-CD3 monoclonal antibodies (MoAbs) are used in clinical practice for immunosuppression. However, there are two major drawbacks to this treatment: the associated cytokine release syndrome and human anti-mouse antibody response. To overcome these side-effects, the authors generated a chimeric anti-human CD3 single chain antibody, scUCHT1. It is an IgM variant of UCHT1, a mouse IgG1 MoAb directed against human CD3. scUCHT1 consists of the light and heavy variable chain binding domains of UCHT1 and a human IgM Fc region (CH2 to CH4). scUCHT1 was produced by COS-7 and SP2/0 transfectants, and mainly assembled in a dimeric form. It retained the binding specificity and affinity of the parental MoAb UCHT1. In contrast to UCHT1, scUCHT1 did not induce T-cell proliferation and cytokine release (TNF-alpha and IFN-gamma) in in vitro assays. These results suggest that the engineered chimeric anti-CD3 single chain antibody (scUCHT1) may be useful in clinical immunosuppressive treatment.

Animals

Increased frequency of TCR gamma delta + T cells in disease-free survivors following T cell-depleted, partially mismatched, related donor bone marrow transplantation for leukemia.

Recent interest has focused on the function of gamma delta + T cells in immune responses. However, their role in allogeneic bone marrow transplantation (BMT) remains undefined. We report on a group of 43 leukemia patients who survived for at least 100 days following transplantation using partially HLA-mismatched grafts from related donors that were T cell depleted with the anti-TCR alpha beta monoclonal antibody T10B9.1A-31 and complement. Ten patients (23.2%) were found to have an increased (> or = 10%) proportion of gamma delta + T cells in the peripheral blood at 60-270 days after BMT. All of these patients remain alive, and 9 (90% of patients with > or = 10% gamma delta + cells) are free of disease at 2.5 years compared with a disease-free survival probability of 31% among patients with a normal proportion and concentration of gamma delta + T cells. No other factor was found to be independently associated with improved survival in these patients. These data suggest a possible association between an increase in the percentage and number of gamma delta + T cells and improved disease-free survival following transplantation from a partially mismatched related donor.

Bone Marrow Transplantation