Interleukin-4 and interleukin-4 soluble receptor alpha levels in bronchoalveolar lavage from children with asthma.

BACKGROUND: In asthma there is increased expression of the Th2-type cytokine interleukin-4 (IL-4). IL-4 is important in immunoglobulin isotype switching to immunoglobulin E and adhesion of eosinophils to endothelium. OBJECTIVE: We hypothesized that levels of IL-4 in bronchoalveolar lavage (BAL) fluid would be increased in stable, atopic asthmatic children compared with controls and that levels of its physiologic inhibitor IL-4 soluble receptor alpha (IL-4sR alpha) would be correspondingly decreased. METHODS: One hundred sixteen children attending a children's hospital for elective surgery were recruited. A nonbronchoscopic BAL was performed, and IL-4 and IL-4sR alpha were measured in the BAL supernatants. RESULTS: There was no significant difference in IL-4 concentrations between atopic asthmatic children, atopic normal controls, and nonatopic normal controls [0.13 pg/mL (0.13 to 0.87) vs 0.13 pg/mL (0.13 to 0.41) vs 0.13 pg/mL (0.13 to 0.5), P = 0.65]. IL-4sR alpha levels were significantly increased in asthmatic patients compared with atopic controls [6.4 pg/mL (5.0 to 25.5) vs 5.0 pg/mL (5.0 to 9.9), P = 0.018], but not when compared with the nonatopic controls [5.2 pg/mL (5.0 to 10.6), P = 0.19]. CONCLUSIONS: Contrary to expectation, IL-4sR alpha levels are increased in BAL from stable asthmatic children compared with nonatopic controls, and we speculate that IL-4sR alpha is released by inflammatory cells in the airways to limit the proinflammatory effects of IL-4.     

Chronic Hepatitis C Infection in a Rural Medicaid HMO

CONTEXT: Chronic hepatitis C infection (CHCI) is an increasingly common problem, affecting about 2% of the US population. The cost and complexity of treatment and difficulties in communicating with the infected population are of concern to insurers and health planners. PURPOSE: To describe the clinical features of patients with CHCI in a rural Medicaid-covered population and to describe a method developed for treating CHCI in an underserved rural community. METHODS: We developed a disease management approach to patients with CHCI receiving insurance coverage through a Medicaid HMO in rural Oregon. A locally based multidisciplinary hepatitis committee was formed to develop a management protocol and a process for selecting patients for treatment. The committee met monthly to develop the treatment plan for individual patients. Day-to-day treatment was provided by a nurse under the supervision of the committee. FINDINGS: One hundred forty-three adults with CHCI were identified by their primary care physicians. About half the patients had a type 1 genotype. Treatment with pegylated interferon and ribavirin was completed on 21 persons, 11 (52%) of whom had a virologic cure. Problems with treatment toxicity were common. Patient satisfaction with the treatment by the nurse was high. CONCLUSIONS: CHCI is common in this rural, nonminority Medicaid-insured population. A locally based disease management model was developed that was well received by patients and was successful in delivering a high quality of care for people with CHCI in a rural area.     

Defunding preoperative histories and physical exams: putting the cart before the evidence?

Objective

Several Canadian health authorities have defunded preoperative cataract history and physical examinations performed by general practitioners. While these authorities suggest that such decisions are evidence-based, we are unaware of reviews addressing this topic, nor have health authorities been forthcoming with evidence used in their decision-making processes. The objective of this study is to perform a comprehensive review of the literature regarding the value of preoperative histories and physical examinations in cataract surgery.

Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model

OBJECTIVES: To identify an accurate and reproducible method to define myocardial infarct (MI) size, we conducted a study in a closed-chest canine model of acute myocardial infarction, in which MI size was measured using different thresholding techniques and by imaging at different delay times after contrast administration. BACKGROUND: The MI size by contrast-enhanced magnetic resonance imaging (CE-MRI) is directly related to long-term prognosis. However, previous measurements were done using nonuniform methods and tended to overestimate nonviable areas. METHODS: Thirteen animals underwent 90 min of coronary artery occlusion, followed by reperfusion. The CE-MRI data were acquired within 24 h after reperfusion and compared with triphenyltetrazolium chloride pathology. In the first nine animals, images were obtained approximately 15 min after gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) using an inversion-recovery gradient-echo pulse sequence. To identify the most accurate method, MI size by CE-MRI was measured visually and by semi-automatic thresholding techniques, using different criteria. In four additional animals, images were acquired every 6 min until 30 min after Gd-DTPA. RESULTS: Postmortem MI size was 13.5 +/- 2.6% of left ventricular volume. Semi-automatic techniques, using full-width at half-maximum (FWHM) criterion, correlated best with postmortem data (r(2) = 0.94, p < 0.001; results confirmed by Bland-Altman plots). Using FWHM, there was no difference in MI size between different delay times after contrast (15.2 +/- 2.9% to 14.5 +/- 4.2% at 6 and 30 min, respectively; p = NS). CONCLUSIONS: When an objective technique is used to define MI size by CE-MRI, accurate infarct size measurements can be obtained from images obtained up to 30 min after contrast administration.     

Cerebral Segmental Polyarteritis of Unknown Aetiology in Sheep

Vasculitis affecting the meningeal elastic arteries was identified in six sheep of various breeds during routine diagnostic investigation. The lesions consisted of multifocal intimal proliferation, thickening of the tunica media, multifocal infiltration of the media by inflammatory cells and more extensive perivascular accumulation of lymphocytes and plasma cells within the tunica adventitia. Fibrinoid necrosis affected an intergyral artery in one sheep. Immunohistochemistry failed to demonstrate pestivirus antigen associated with the lesions and no alternative aetiology was defined. Possible causes of meningeal segmental polyarteritis in sheep are discussed.     

Optimizing ventilation in conjunction with phased chest and abdominal compression-decompression (Lifestick) resuscitation.

The best method for employment of phased chest and abdominal compression-decompression (Lifestick) cardiopulmonary resuscitation (CPR) has yet to be determined. Of particular concern with using this technique is the combining of ventilation with the phased compressions and decompressions. Twenty domestic swine (50+/-1 kg) were equally divided into four groups. Following 10 min of untreated VF, CPR was begun. Group 1 received Lifestick (LS) CPR with only passive ventilation ('passive'); Group 2 received LS-CPR with synchronized positive pressure ventilations (ppv) at a chest compression ratio of 15:2 (15:2 S); Group 3 had LS-CPR with synchronized ppv at 5:1 (5:1 S); and Group 4 received LS-CPR with asynchronous ppv at 5:1 (5:1 A). Endpoints included hemodynamics, blood gases, minute ventilation, and 24 h outcome. Asynchronous ventilation (5:1 A) had significantly worse hemodynamics including aortic and right atrial systolic, aortic diastolic, and coronary perfusion pressures than the other groups (P<0.05). Passive ventilation had the poorest arterial and mixed venous blood gases (P<0.05), but did not differ from 15:2 S in minute ventilation produced (8 vs 10 l/min). No differences in outcome were seen. The ventilation technique combined with LS-CPR can make a significant difference in hemodynamics as well as ventilation. Optimizing other forms of basic and advanced cardiac life support through different ventilation methods deserves new consideration, including a re-examination of the current single rescuer recommendation of a 15:2 ratio. Optimal ventilation strategy when using the LS device at 60 compressions per min appears to be 5:1 S. Such data is important for conducting clinical trials with this new CPR adjunct.     

Antioxidants and oxidative stress in BAL fluid of atopic asthmatic children

Earlier studies in adults have indicated that increased oxidative stress may occur in the blood and airways of asthmatic subjects. Therefore the aim of this study was to compare the concentrations of antioxidants and protein carbonyls in bronchoalveolar lavage fluid of clinically stable atopic asthmatic children (AA, n = 78) with our recently published reference intervals for nonasthmatic children (C, n = 124). Additionally, lipid peroxidation products (malondialdehyde) in bronchoalveolar lavage fluid and several antioxidants in plasma were determined. Bronchoalveolar lavage concentrations (median and interquartile range) of ascorbate [AA: 0.433 (0.294-0.678) versus C: 0.418 (0.253-0.646) micromol/L], urate [AA: 0.585 (0.412-0.996) versus C: 0.511 (0.372-0.687) micromol/L], alpha-tocopherol [AA: 0.025 (0.014-0.031) versus C: 0.017 (0.017-0.260) micromol/L], and oxidized proteins as reflected by protein carbonyls [AA: 1.222 (0.970-1.635) versus C: 1.243 (0.813-1.685) nmol/mg protein] were similar in both groups (p > 0.05 in all cases). The concentration of protein carbonyls correlated significantly with the number of eosinophils, mast cells, and macrophages in AA children only. Concentrations of oxidized proteins and lipid peroxidation products (malondialdehyde) correlated significantly in AA children (r = 0.614, n = 11, p = 0.044). Serum concentrations of ascorbate, urate, retinol, alpha-tocopherol, beta-carotene, and lycopene were similar in both groups whereas alpha-carotene was significantly reduced in asthmatics. Overall, increased bronchoalveolar lavage eosinophils indicate ongoing airway inflammation, which may increase oxidatively modified proteins as reflected by increased protein carbonyl concentrations.