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Biomedical subjects

W Holden

Publications and source records attributed to W Holden.

15 recordsLinked to original sources
PubMed2000

The accuracy of oral predictive and infrared emission detection tympanic thermometers in an emergency department setting.

OBJECTIVE: To assess the accuracy of an oral predictive thermometer and an infrared emission detection (IRED) tympanic thermometer in detecting fever in an adult emergency department (ED) population, using an oral glass mercury thermometer as the criterion standard. METHODS: This was a single-center, nonrandomized trial performed in the ED of a metropolitan tertiary referral hospital with a convenience sample of 500 subjects. The temperature of each subject was taken by an oral predictive thermometer, an IRED tympanic thermometer set to "oral" equivalent, and an oral glass mercury thermometer (used as the criterion standard). A fever was defined as a temperature of 37.8 degrees C or higher. The subject's age, sex, triage category, and diagnostic group were also recorded. Sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, and corresponding 95% confidence intervals were calculated. Logistic regression was used to identify predictors of fever. RESULTS: The sensitivities and specificities for detection of fever of the predictive and the IRED tympanic thermometers were similar (sensitivity 85.7%/88.1% and specificity 98.7%/95.8%, respectively). The predictive thermometer had a better positive predictive value (85.7%) compared with the IRED tympanic thermometer (66.1%). The positive and negative likelihood ratios for the predictive oral thermometer were 65 and 0.14, respectively, and for the IRED tympanic thermometer 21 and 0.12, respectively, indicating that the predictive thermometer will "miss" 1 in about 7 fevers and the IRED tympanic thermometer will "miss" 1 in about 8 fevers. CONCLUSIONS: Although quick and convenient, oral predictive and IRED tympanic thermometers give readings that cannot always be relied on in the detection of fever. If we are to continue using electronic thermometers in the ED setting, we need to recognize their limitations and maintain the importance of our clinical judgment.

Emergency Service, Hospital↗
PubMed1997

CD40 ligand induces an antileukemia immune response in vivo.

Leukemia cells may express tumor specific antigens in association with Class I and II major histocompatability complex (MHC) molecules. However, lack of expression of conventional costimulator molecules means that these cells tend to induce specific T-cell anergy rather than activation. CD40 ligand (CD40L) is a costimulator molecule that directly activates T cells and may promote antigen presentation by CD40-expressing cells, which include professional antigen presenting cells and B-acute lymphoblastic leukemia (ALL) cells from many patients. We determined whether transgenic expression of CD40L could enhance an antileukemia immune response using a CD40+ murine lymphoblastic (A20) leukemia and a CD40- myeloblastic (WEHI-3) leukemia in a tumor treatment model. Injection of otherwise nonimmunogenic A20 cells in the presence of CD40L induced an immune response active against preexisting A20 tumor at a distant site. Moreover, concomitant local secretion of transgenic interleukin-2 (IL-2) further amplified the antileukemic response induced and increased protection against preexisting tumor. In ex vivo studies, CD40 activation of A20 cells enhances the antigen presenting potential of A20 cells by upregulating expression of B7.1 (CD80), Class I and II MHC molecules, and increases expression of fas antigens. The importance of CD40 activation to the resulting antitumor response is further emphasized by the failure of transgenic CD40L to protect against the CD40- WEHI myeloblastic leukemia. Depletion studies showed the protective effects against A20 cells to be mediated by a combination of CD4+ and CD8+ T lymphocytes and by natural killer (NK) cells. These results suggest a means by which CD40+ leukemia cells may be rendered immunogenic in vivo.

Animals↗
PubMed1997

A novel herpes vector for the high-efficiency transduction of normal and malignant human hematopoietic cells.

Herpes simplex viruses (HSVs) would offer numerous advantages as vectors for gene transfer, but as yet they have not proved capable of transducing hematopoietic cells. Using a genetically inactivated form of HSV that is restricted to a single cycle of replication (disabled single-cycle virus, [DISC-HSV]), we have transduced normal human hematopoietic progenitor cells and primary leukemia blasts with efficiencies ranging from 80% to 100%, in the absence of growth factors or stromal support. Toxicity was low, with 70% to 100% of cells surviving the transduction process. Peak expression of transferred genes occurred at 24 to 48 hours after transduction with the DISC-HSV vector, declining to near background levels by 14 days. Despite this limitation, sufficient protein is produced by the inserted gene to permit consideration of the vector for applications in which transient expression is adequate. One example is the transfer of immunostimulatory genes, to generate leukemia immunogens. Thus, murine A20 leukemia cells transduced with a DISC-HSV vector encoding granulocyte-macrophage colony-stimulating factor were able to stimulate a potent antitumor response in mice, even against pre-existing leukemia. The exceptional transducing ability of the DISC-HSV vector should therefore facilitate genetic manipulation of normal and malignant human hematopoietic cells for biological and clinical investigation.

Animals↗
PubMed1996

Combined chemokine and cytokine gene transfer enhances antitumor immunity.

The probability of producing a specific antitumor response should be increased by multiplying the number of T lymphocytes that encounter the malignant cells. We tested this prediction in a murine model, using a recently discovered T-cell chemokine, lymphotactin (Lptn). This chemokine increased tumor cell infiltration with CD4+ lymphocytes but generated little antitumor activity. Coexpression of the T-cell growth factor interleukin-2, however, greatly expanded the T lymphocytes attracted by Lptn, affording protection from the growth of established tumor in a CD4+ and CD8+ T cell-dependent manner. Lesser synergy was seen with GM-CSF. Hence coexpression of a T-cell chemokine and T-cell growth factor potentiates antitumor responses in vivo, suggesting a general strategy to improve cancer immunotherapy.

Animals↗
PubMed1996

Feasibility study of respiratory questionnaire and peak flow recordings in autobody shop workers exposed to isocyanate-containing spray paint: observations and limitations.

Diisocyanates, highly reactive monomers which cross-link polyurethane, are the most widely recognized causes of occupational asthma. Many exposed workers are end-users, including autobody spray painters who form a large population at risk. Neither the factors which determine incidence rate nor strategies for control have been adequately studied in this setting. We have conducted a cross-sectional survey of 23 (about one in five) autobody shops in the New Haven area to determine the feasibility of clinical epidemiological studies in this population. Among 102 workers, there was a high rate of airway symptoms consistent with occupational asthma (19.6%). Symptoms were most prevalent among those with the greatest opportunity for exposure (dedicated spray painters) and least among office workers; part-time painters had intermediate rates. Atopy was not associated with risk while smoking seemed to correlate with symptoms. Regular use of air-supplied respirators appeared to be associated with lower risk among workers who painted part- or full-time. We were unable to validate the questionnaire responses with peak expiratory flow record data attempted on a 1/3 sample of the workers. Despite intensive training and effort, subject compliance was limited. Among those who provided adequate data (24 of 38), only two demonstrated unequivocal evidence of labile airways; two others demonstrated lesser changes consistent with an occupational effect on flow rates. There was no clear association between these findings and either questionnaire responses or exposure classification. Overall, the survey suggests that there is a high prevalence of airway symptoms among workers in autobody shops, at least in part due to work-related asthma. However, there is need for both methodological and substantive research in this setting to document rates of occupational asthma and to develop a scientific basis for its effective control.

Asthma↗
PubMed1989

Alterations in complement-induced shape change and stimulus-specific superoxide anion generation by neonatal calf neutrophils.

Increased susceptibility of neonates to infection may be related to defects in newborn neutrophil (PMN) functional activities, including altered responses to complement fragments (Cf) and defective microbicidal activity. We therefore compared the kinetics of newborn and adult bovine PMN membrane shape change responses following stimulation with zymosan-activated plasma (ZAP) as a source of Cf. Measurement of PMN membrane shape change was a rapid, sensitive, and reproducible measure of Cf stimulation within a population of PMNs; a maximum of 67-85% of the PMNs exhibited easily detectable membrane ruffling, lamellipodia formation, and polarity within 2 min. Newborn PMNs exhibited significantly increased (P less than 0.01) membrane shape change at 20, 30, 60, 120, and 300 sec after Cf stimulation. A maximum of 85.8 +/- 3.2% of newborn PMNs exhibited such Cf-induced shape changes by 120 sec. which was significantly greater (P less than 0.01) than the maximum stimulation (67.7 +/- 4.3%) attained with adult PMNs. These data indicate enhanced kinetics of induced newborn PMN membrane shape change in response to Cf stimulation. We also compared stimulus-specific superoxide anion (O2-) generation as a measure of respiratory burst activity after incubation of newborn and adult PMNs with soluble (phorbol myristate acetate, PMA) and particulate (opsonized zymosan, OZ) stimuli. When PMA was used as the stimulus, newborn PMNs generated significantly less O2- (9.3 +/- 0.5 nmol O2-/10(6) PMN, P less than 0.05) than did adult PMNs (12.4 +/- 0.3 nmol O2-/10(6) PMN). This finding was reversed when OZ was used as the stimulus; newborn PMNs generated significantly more O2- (7.7 +/- 0.4 nmol O2-/10(6) PMN, P less than 0.05) than did adult PMNs (5.5 +/- 0.5 nmol O2-/10(6) PMN). These findings collectively document biochemical and morphological differences between newborn and adult PMNs as determined by stimulus-specific O2- generation and Cf-induced membrane shape change. Such differences may be important to neonatal disease susceptibility.

Animals↗
PubMed1989

Inflammatory aneurysm: a cause of obstructive nephropathy.

Inflammatory aortic aneurysms are aneurysms that are surrounded by a variable amount of periaortic fibrosis. This periaortic fibrosis may involve abdominal viscera, such as the duodenum, inferior vena cava, renal veins, or ureters, to a variable degree. On ultrasonographic images, the periaortic fibrosis appears as a hypoechoic mass surrounding the anterior and anterolateral aspects of a dilated aorta. Computed tomography scans reveal a periaortic mass of inflammatory tissue surrounding a dilated atherosclerotic and thickened aorta. The inflammatory mass may enhance to the same extent or slightly less than the aortic lumen following intravenous administration of a contrast agent. Magnetic resonance imaging scans may show the periaortic mass of inflammatory tissue to have a pseudocapsule of compressed fat at its periphery. Recognition of this entity and the extent of the inflammatory process is important to the definitive management of this condition, as illustrated by the case presented.

Aged↗
PubMed1986

Metabolic and ventilatory responses to steady state exercise relative to lactate thresholds.

The metabolic and ventilatory responses to steady state submaximal exercise on the cycle ergometer were compared at four intensities in 8 healthy subjects. The trials were performed so that, after a 10 min adaptation period, power output was adjusted to maintain steady state VO2 for 30 min at values equivalent to: (1) the aerobic threshold (AeT); (2) between the aerobic and the anaerobic threshold (AeTAnT); (3) the anaerobic threshold (AnT); and (4) between the anaerobic threshold and VO2max (AnTmax). Blood lactate concentration and ventilatory equivalents for O2 and CO2 demonstrated steady state values during the last 20 min of exercise at the AeT, AeAnT and AnT intensities, but increased progressively until fatigue in the AnTmax trial (mean time = 16 min). Serum glycerol levels were significantly higher at 40 min of exercise on the AeAnT and the AnT when compared to AeT, while the respiratory exchange ratios were not significantly different from each other. Thus, metabolic and ventilatory steady state can be maintained during prolonged exercise at intensities up to and including the AnT, and fat continues to be a major fuel source when exercise intensities are increased from the AeT to the AnT in steady state conditions. The blood lactate response to exercise suggests that, for the organism as a whole, anaerobic glycolysis plays a minor role in the energy release system at exercise intensities upt to and including the AnT during steady state conditions.

Adult↗
PubMed1979

The clinical usefulness of a screening test to detect static pulmonary blood using a multiple-breath analysis of diffusing capacity.

We devised a screening test to detect static blood in the lungs (e.g., with pulmonary vascular obstruction or pulmonary hemorrhage). A back pressure to CO will develop in static blood as the concentration of carboxyhemoglobin increases with time, and diffusing capacity (DLCO) will decrease. Instead of obtaining a single value for DLCO, we calculated DLCO over small decrements of the exhaled vital capacity during 4 sequential breaths using a modification of a method developed in our laboratory. In each of 5 healthy subjects there was no difference in DLCO during the 4 sequential breaths in the sitting, supine, or lateral decubitus positions. However, in a patient with a proved pulmonary embolus, DLCO decreased with sequential breaths, expecially at low lung volumes. In a patient with angiographic evidence of kinking of the left pulmonary artery when he assumed the right lateral decubitus position, DLCO showed a sequential decrease in this position only. Three patients with pulmonary hemorrhage also showed decreases in DLCO during sequential breaths during episodes of active bleeding.

Adult↗
PubMed1978

Characterisation of heart rate response to exercise in the sick sinus syndrome.

Patients with sick sinus syndrome have abnormalities of the sinoatrial node. We have measured the heart rate response to exercise in 7 patients with sick sinus syndrome without significant associated heart disease (group A) mean age 53.4 years, and compared this with 7 'normal' patients who were age-matched to within 5 years (group B), and 7 younger, well-trained subjects (group C). All underwent maximal treadmill exercise. Although maximum oxygen consumption (VO2max), 1/min per kg, in group A was not significantly different from group B (23.8 +/- 4.7 vs 19.9 +/- 0.8, mean +/- SE) maximum heart rate, beats/min, in group A was significantly lower than in group B (124 +/- 8.9 vs 163 +/- 3.7, P less than 0.001). At the end of 3 minutes of Bruce Stage I exercise, group A patients had a heart rate less than 130/minute (95% confidence level), whereas group B patients had heart rates greater than 134/minute. VO2 was plotted against heart rate (HR). Patients in group A had a significantly lower slope (deltaHR 5.20 +/- 0.33/delta1 ml VO2/kg per min, P less than 0.001). There was no significant difference in the slopes between groups A and C. On exercise patients with sick sinus syndrome have a normal VO2, but a reduced heart rate response as compared with age-matched normal patients. This abnormal heart rate response to the physiological stimulus of exercise may be of help in the evaluation of patients with sick sinus syndrome who do not have significant underlying heart disease.

Arrhythmia, Sinus↗