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Biomedical subjects

K Bradley

Publications and source records attributed to K Bradley.

At least 19 recordsLinked to original sources
PubMed2004

Investigation of nasal disease in the cat--a retrospective study of 77 cases.

A retrospective study was undertaken to determine the prevalence of different diseases in cats referred for investigation of chronic nasal disease, to identify historical, clinical and diagnostic features which may assist in making a diagnosis, and to provide information pertaining to outcome in these cats. Diagnoses included neoplasia (30 cases), chronic rhinitis (27), foreign body (8), nasopharyngeal stenosis (5), Actinomyces infection (2), nasal polyps (2), stenotic nares (2), and rhinitis subsequent to trauma (1). The most common neoplasia was lymphosarcoma (21 cases), with a median survival of 98 days for cats treated with multiagent chemotherapy. Cats with neoplasia were older on average than the other cats, and were more likely to be dyspnoeic and have a haemorrhagic and/or unilateral nasal discharge than cats with chronic rhinitis. Cats with neoplasia were more likely to have radiographic evidence of nasal turbinate destruction, septal changes, or severe increases in soft tissue density than cats with chronic rhinitis. It was unusual for cats with diseases other than neoplasia to be euthanased as a result of their nasal disease.

Animals↗
PubMed2001

Impact of troponin T determinations on hospital resource utilization and costs in the evaluation of patients with suspected myocardial ischemia.

The evaluation and triage of patients with suspected myocardial ischemia in the emergency department remains challenging and costly. Previous studies of cardiac troponins have focused predominantly on patients with chest pain and have not randomized patients to different diagnostic strategies. Eight hundred fifty-six patients with suspected myocardial ischemia were prospectively randomized to receive a standard evaluation, including serial electrocardiographic and creatine phosphokinase-MB determinations (controls) or a standard evaluation with the addition of serial troponin T determinations (troponin group). The primary end points were length of stay and hospital charges. Significant reductions in length of hospital stay were seen in troponin T patients both with (3.6 vs 4.7 days; p = 0.01) and without (1.2 vs 1.6 days; p = 0.03) acute coronary syndromes compared with controls. Total hospital charges were reduced in a similar fashion in troponin patients with and without acute coronary syndromes ($15,004 vs $19,202; p = 0.01, and $4,487 vs $6,187; p = 0.17, respectively) compared with controls. Troponin patients without acute coronary syndromes had fewer hospital admissions (25% vs 31%; p = 0.04), whereas troponin patients with acute coronary syndromes had shorter telemetry and coronary care unit lengths of stay (3.5 vs 4.5 days; p = 0.03) compared with controls. Thus, utilization of troponin T in a broad spectrum of emergency department patients with suspected myocardial ischemia improves hospital resource utilization and reduces costs.

Adult↗
PubMed2001

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

Journal Article↗
PubMed2001

Creutzfeldt-Jakob disease in unusually young patients who consumed venison.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) in humans and chronic wasting disease (CWD) in deer and elk occur in the United States. Recent reports of 3 unusually young patients with CJD who regularly consumed deer or elk meat created concern about the possible zoonotic transmission of CWD. OBJECTIVE: To examine the possible transmission of CWD to humans. PATIENTS: Three unusually young patients (aged 28, 28, and 30 years) with CJD in the United States during 1997-2000. METHODS: We reviewed medical records and interviewed family members and state wildlife and agriculture officials. Brain tissue samples were tested using histopathologic, immunohistochemical, immunoblot, or prion protein gene analyses. MAIN OUTCOME MEASURES: Presence or absence of established CJD risk factors, deer and elk hunting in CWD-endemic areas, and comparison of the evidence for the 3 patients with that of a zoonotic link between new variant CJD and bovine spongiform encephalopathy. RESULTS: None of the patients had established CJD risk factors or a history of travel to Europe. Two patients hunted game animals and 1 was a daughter of a hunter. Unlike patients with new variant CJD, the 3 patients did not have a unique neuropathologic manifestation, clinicopathologic homogeneity, uniformity in the codon 129 of the prion protein gene, or prion characteristics different from those of classic variants. CONCLUSIONS: Although the occurrence of 3 unusually young patients with CJD who consumed venison suggested a possible relationship with CWD, our follow-up investigation found no strong evidence for a causal link. Ongoing CJD surveillance remains important for continuing to assess the risk, if any, of CWD transmission to humans.

Adult↗
PubMed2001

The Fas-FasL death receptor and PI3K pathways independently regulate monocyte homeostasis.

Peripheral blood-derived monocytes spontaneously undergo apoptosis mediated by Fas-Fas ligand (FasL) interactions. Activation of monocytes by LPS or TNF-alpha prevents spontaneous monocyte apoptosis through an unknown mechanism. Here, we demonstrate that LPS and TNF-alpha up-regulate Flip and suppress spontaneous Fas-FasL mediated monocyte apoptosis and caspase 8 and 3 activation. Flip was responsible for this protection, since inhibition of Flip by antisense oligonucleotides in the presence of LPS or TNF-alpha restored monocyte sensitivity to spontaneous apoptosis. We also investigated whether the PI3K pathway contributes to the suppression of spontaneous monocyte apoptosis mediated by LPS and TNF-alpha. Monocytes treated with a reversible PI3K inhibitor (LY294002) displayed enhanced apoptosis, while LPS and TNF-alpha partially protected against apoptosis mediated by LY294002. However, direct suppression of Fas-FasL interactions by addition of neutralizing anti-FasL antibody did not further suppress LY294002-induced apoptosis in the presence of LPS or TNF-alpha. Collectively, these data demonstrate that LPS or TNF-alpha protect monocytes from death receptor-mediated apoptosis through the up-regulation of Flip, but not apoptosis initiated by inhibition of the PI3K pathway.

Animals↗
PubMed2001

A simple strategy for improving patient contact after ED discharge.

The purpose of this study was to assess strategies to improve telephone contact with adult patients discharged from the emergency department (ED). The basic procedure was a prospective, randomized, interventional trial of a convenience sample of patients 18 years or older being discharged from the ED. Patients were excluded if they had altered mental status or were unable to communicate with the College Research Associates (RAs). RAs asked intervention subjects a set of scripted questions confirming patients' telephone numbers and times for a follow-up call. Control subjects received routine discharge instructions from the ED staff. Subjects were called back within 4 days of ED discharge. Eighty-seven control subjects and 76 intervention subjects were enrolled. There were no significant demographic differences between the 2 groups. Forty-seven (54%) control subjects were contacted versus 58 (77%) in the intervention group (P <.003; Chi-square test). A simple patient interview conducted immediately before discharge confirming the patient's telephone number and setting a time for a follow-up call significantly improved patient follow-up contact rates.

Adult↗
PubMed2000

Is the intrinsic thermoelectric power of carbon nanotubes positive?

The thermoelectric power (TEP) of single-walled carbon nanotubes (SWNTs) is extremely sensitive to gas exposure history. Samples exposed to air or oxygen have an always positive TEP, suggestive of holelike carriers. However, at fixed temperature the TEP crosses zero and becomes progressively more negative as the SWNTs are stripped of oxygen. The time constant for oxygen adsorption/desorption is strongly temperature dependent and ranges from seconds to many days, leading to apparently "variable" TEP for a given sample at a given temperature. The saturated TEP can be accounted for within a model of strong oxygen doping of the semiconducting nanotubes.

Journal Article↗
PubMed2000

Extreme oxygen sensitivity of electronic properties of carbon nanotubes

The electronic properties of single-walled carbon nanotubes are shown here to be extremely sensitive to the chemical environment. Exposure to air or oxygen dramatically influences the nanotubes' electrical resistance, thermoelectric power, and local density of states, as determined by transport measurements and scanning tunneling spectroscopy. These electronic parameters can be reversibly "tuned" by surprisingly small concentrations of adsorbed gases, and an apparently semiconducting nanotube can be converted into an apparent metal through such exposure. These results, although demonstrating that nanotubes could find use as sensitive chemical gas sensors, likewise indicate that many supposedly intrinsic properties measured on as-prepared nanotubes may be severely compromised by extrinsic air exposure effects.

Journal Article↗
PubMed2000

Femur length and trisomy 21: impact of gestational age on screening efficiency.

OBJECTIVE: This study assesses two methods used to define relatively short femur in screening for trisomy 21 and examines changes in performance of screening with gestational age. DESIGN: Retrospective analysis of data on menstrual age, femur length (FL) and biparietal diameter (BPD) in 49 trisomy 21 pregnancies and 6069 normal controls. Reference ranges were derived for BPD/FL versus menstrual age and for FL versus BPD. Two methods of defining short femur (BPD/FL and observed-to-expected FL ratio) were examined for false-positive rates and detection rates for trisomy 21 at different gestational ages. RESULTS: In the control group the BPD/FL ratio and its standard deviation decreased with menstrual age. Trisomy 21 was associated with a significantly higher BPD/FL ratio (P < 0.001) and the deviation increased significantly with menstrual age (P < 0.05). Eleven percent of 28 fetuses examined at 15-17 weeks had a BPD/FL above the 95th centile compared with 24% of 21 fetuses examined at 18-20 weeks (P = 0.40). The median observed-to-expected FL ratio in the control group was 1.0 throughout the gestational age range but the standard deviation decreased significantly with menstrual age (P < 0.01). Trisomy 21 was associated with a significantly reduced observed-to-expected FL ratio (P < 0.001) and the deviation increased significantly with menstrual age (P < 0.05). A fixed cut-off of 0.91 for observed-to-expected FL ratio provided a false-positive rate of 12% at 15-17 weeks compared with 6% at 18-20 weeks of gestation (P < 0.001) with detection rates of 29 and 38%, respectively (P = 0.73). CONCLUSION: Irrespective of the definition used to define the condition, relatively short femur is a poor marker for trisomy 21 particularly when the assessment takes place before 18 weeks of gestation.

Adult↗
PubMed1999

Effect of erythromycin on myocardial repolarization in patients with community-acquired pneumonia.

BACKGROUND: Erythromycin has been associated with prolongation of myocardial repolarization and torsades de pointes (TdP). METHODS: To determine the frequency, dose-response, and risk factors for erythromycin-associated prolongation of myocardial repolarization, we observed data of patients admitted to our hospital with pneumonia who were treated with erythromycin. RESULTS: In 35 women and 28 men enrolled in this study, the QTc increased from 434 +/- 4 milliseconds at baseline to 464 +/- 5 milliseconds after receiving a cumulative dose of 3.2 +/- 0.2 g of erythromycin. Neither age, sex, presence of preexistent congestive heart failure/coronary artery disease, electrolyte values, nor cumulative dose of erythromycin was associated with QTc prolongation. In 27 patients who received intravenous erythromycin for 3 days, the QTc increased from 427 +/- 5 milliseconds before to 461 +/- 8 milliseconds at 24 hours but did not increase further by day 3 (457 +/- 10 milliseconds). No patient in this cohort had TdP. CONCLUSIONS: Erythromycin therapy is associated with prolongation of myocardial repolarization that manifests after the first few doses in a majority of patients.

Administration, Oral↗
PubMed1998

Local treatment with IL-12 is an effective inhibitor of airway hyperresponsiveness and lung eosinophilia after airway challenge in sensitized mice.

BACKGROUND: Systemic administration of IL-12 can prevent airway hyperresponsiveness (AHR) in mice after sensitization and repeated allergen challenge. However, systemic IL-12 has been associated with severe adverse effects. OBJECTIVE: We determined whether IL-12 administration to the airways in a dose sufficiently low so as not to result in systemic effects can modify allergic inflammation and AHR after allergen challenge. METHODS: Mice were sensitized to ovalbumin by intraperitoneal injection and challenged with ovalbumin aerosol on 3 consecutive days. During the period of challenge, IL-12 was administered intranasally following 2 regimens, designated high (1500 ng) or low (150 ng). We monitored airway responsiveness to inhaled methacholine by barometric body plethysmography, lung inflammatory cells, local cytokine production, and, to assess systemic effects of IL-12 treatment, spleen weights and numbers of eosinophils in the bone marrow. RESULTS: Allergen challenge resulted in increases in airway responsiveness and in numbers of lung eosinophils. These increases were prevented by both high- and low-dose IL-12. Additionally, IL-12 administration resulted in enhanced local interferon-gamma production and prevented the increases in local IL-4 and IL-5 production after airway challenge. A high dose, but not a low dose, of IL-12 resulted in increased spleen weights and prevented the increase in numbers of bone marrow eosinophils after allergen challenge. CONCLUSION: These data indicate that local administration of IL-12 can prevent AHR and reduce lung eosinophilia after allergen challenge in sensitized mice without eliciting systemic adverse effects. IL-12 exerts these effects by inducing local T(H1)-type responses in the airways in a setting that is normally dominated by T(H2)-type responses.

Allergens↗
PubMed1997

Posttranscriptional regulation of T-cell IL-2 production by human pooled immunoglobin.

We evaluated the mechanism by which human pooled gamma-globulin for intravenous use (hIVIG) inhibits interleukin-2 (IL-2) production by human T cells. hIVIG reduced by 70-95% the amount of IL-2 in culture supernatants from mitogen-stimulated peripheral blood T cells or Jurkat cells. This reduction was not apparent at the transcriptional level: hIVIG had no effect on the levels of IL-2 mRNA or on the accumulation of firefly luciferase when its gene was linked to the IL-2 promoters. In contrast, hIVIG inhibited IL-2 protein synthesis, and the intracellular IL-2 was not restored by monensin. Our results indicate that the inhibition of IL-2 production by hIVIG occurred post-transcriptionally, and also suggest that secretion was unaffected, and that this effect of hIVIG was specific for IL-2 (and possibly other related cytokines). The data identify a previously uncharacterized regulatory mechanism of IL-2 production and predict that this immunomodulatory effect of hIVIG may be significant for its therapeutic actions in immune-mediated diseases.

Adult↗
PubMed1997

Efficacy of atropine sulfate in combination with albuterol in the treatment for acute asthma.

OBJECTIVE: To determine the efficacy of combination therapy using atropine sulfate and albuterol in the treatment for an acute exacerbation of asthma. METHODS: A prospective, randomized double-blind, placebo-controlled study was performed in the ED of a large, inner-city, university-affiliated teaching hospital. Participants were a convenience sample of patients presenting to the ED between September 1993 and March 1994 with acute exacerbations of their asthma. Patients judged to be in extremis were excluded. All patients received 3 nebulized treatments with 2.5 mg of albuterol at 0, 30, and 60 minutes. Patients were randomized into 1 of 3 groups with the following added to their nebulizer solutions: 1) saline placebo during all 3 treatments; 2) 2.0 mg atropine sulfate added to the first nebulizer and saline in the second and third; or 3) 2.0 mg atropine to the first and third treatments (with saline in the second). No other medication was administered during the study period. At 90 minutes, the patients were evaluated for admission or release from the ED according to predetermined criteria, and additional medications were given as necessary. Vital signs, peak expiratory flow rate (PEFR), degree of wheezing, level of distress, and side effects were measured before and after each nebulizer treatment. RESULTS: Of the 153 patients eligible for the study, 126 completed the entire study protocol. There was no significant difference between the 3 groups on any parameter studied, including improvement of PEFR, vital signs, or level of distress. There was no difference in the admission rate between the 3 groups, nor was there a difference in the incidence of side effects among the groups. CONCLUSION: In this study population, combination therapy with atropine sulfate and albuterol offered no significant benefit over the use of albuterol alone in the treatment for acute exacerbation of asthma.

Adrenergic beta-Agonists↗
PubMed1997

New-onset bronchospasm or recrudescence of asthma associated with cocaine abuse.

OBJECTIVE: To determine whether the occurrence of new-onset bronchospasm or the recrudescence of asthma is associated with the use of cocaine. METHODS: A consecutive sample of patients presenting to an inner-city adult ED with new-onset bronchospasm or recrudescence of bronchospasm after > 5 years were prospectively enrolled in a case-control prevalence study. The bronchospasm patients were queried as to their exposure to illicit drugs, and urine was obtained to screen for cocaine and its metabolite, benzoylecgonine. An age- and sex-matched control group was composed of randomly chosen subjects without respiratory complaints or a history of asthma. The control group was also screened by urine toxicology for cocaine and its metabolite, benzoylecgonine. RESULTS: In the asthma group, 21/59 (36%) had a urine toxicologic screen positive for cocaine metabolite (benzoylecgonine). Of the 21 with a positive screen for cocaine, 8 denied illicit drug abuse. Among the 13 patients reporting drug use, 10 said that they smoked crack and 3 snorted cocaine. In the control group, 8/53 (15%) were positive. Multivariate logistic regression analysis, with adjustment for age and sex, indicated that the use of cocaine was associated with a 3-fold higher prevalence of new-onset bronchospasm or recrudescence of asthma (OR = 3.28, 95% CI: 1.26 to 8.50). CONCLUSIONS: There appears to be an association between cocaine use and new-onset bronchospasm or recrudescence of asthma in this inner-city ED population. Further study is necessary to determine the basis for this association.

Adult↗
PubMed1997

Allergen-specific IgE and IL-5 are essential for the development of airway hyperresponsiveness.

The mechanisms underlying the development of airway hyperresponsiveness are not fully delineated. We addressed this question by studying the effects of passive sensitization with anti-OVA IgE on the development of altered airway responsiveness (AR) following local challenge with OVA in normal and athymic mice. Both normal and athymic BALB/c mice developed allergen-specific immediate cutaneous hypersensitivity after passive sensitization with anti-OVA IgE. In contrast, the combination of local challenge with allergen via the airways and passive sensitization triggered the development of airway hyperresponsiveness only in normal but not in athymic mice. Treatment of athymic mice with IL-5 significantly increased eosinophil accumulation in the lungs after local challenge with OVA; increased airway reactivity was only observed in athymic mice which received anti-OVA IgE, not an unrelated IgE, plus IL-5 treatment and airway challenge with OVA. These findings identify the requirement for allergen-specific IgE and IL-5 for the development of airway hyperresponsiveness following allergen challenge via the airways.

Allergens↗
PubMed1996

Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization.

To study the role of CD8+ T cells in allergic sensitization, we examined the effects of in vivo depletion of CD8+ T cells prior to sensitization on IgE production, immediate type cutaneous hypersensitivity and development of altered airway responsiveness. BALB/c mice were thymectomized and treated with anti-CD8 antibody resulting in depletion of CD8+ T cells (<1%) in spleen and lymphoid tissues. In these mice, sensitization to ovalbumin (OVA) via the airways still resulted in IgE anti-OVA responses and immediate cutaneous reactions to OVA, but the animals were unable to develop airway hyperresponsiveness, eosinophil infiltration of the lung parenchyma, or IL-5 production in the local lymph nodes of the airway. Transfer of CD8+ T cells from naive animals during sensitization (on day 8 of the 10-d protocol) fully restored the ability to develop airway hyperresponsiveness and this was accompanied by IL-5 production and eosinophil accumulation in the lung. These data indicate a critical role for CD8+ T cells in the production of IL-5 and the development of altered airway responsiveness after antigen sensitization through the airways.

Allergens↗