Effect of obesity on sinonasal disease in asthma.

OBJECTIVE: Sinonasal disease can contribute to poor asthma control. There are reports that link obesity with an increased prevalence of sinonasal disease, but no studies evaluating the severity of sinonasal disease in obese asthmatics, and how this impacts asthma control. The purpose of the current study was to determine if obesity is associated with increased severity of sinonasal disease, and/or affects response to nasal corticosteroid treatment in asthma. METHODS: This study included 236 adults participating in a 24-week randomized, double-masked, placebo-controlled study of nasal mometasone for the treatment of poorly controlled asthma. Sinonasal disease severity was assessed using validated questionnaires, and compared in participants of differing BMIs. Eosinophilic inflammation was assessed using markers in nasal lavage, serum and exhaled nitric oxide. Response to treatment was compared in different BMI groups. RESULTS: Obesity had no effect on the severity of sinonasal disease symptoms in asthmatics (Sino-Nasal Outcome Test 22 (SNOT 22) score [mean ± SD] 35.4 ± 18.5, 40.2 ± 22.8, and 39.1 ± 21.7, p = 0.43, in lean, overweight and obese participants), nor on nasal, bronchial or systemic markers of allergic inflammation. Nasal steroids had some limited effects on symptoms, lung function and inflammatory markers in lean participants, but no detectable effect was found in obese patients. CONCLUSIONS: Obesity does not affect severity of sinonasal disease in patients with asthma; the association of sinonasal disease symptoms with increased asthma severity and markers of Type 2 inflammation are consistent across all BMI groups. The response of obese patients to nasal corticosteroids requires further study.

[EVALUATION OF NUTRIENT MEDIA TO GROW SOME INFECTION DISEASES CAUSATIVE AGENTS].

The detection methods for microbial agents that have eidemiological significance are diversity but cultivation on nutritional media remains the gold standard in microbiological diagnostics. Choice of medium depends on the conditions in which bacteria were early and is present. The nature life determines its physiological peculiarity then a metabolic plasticity promote to survive and to save the virulence. In this review on the example of Yersihia pestis and Vibrio cholerae performed evaluations of the efficient decisions for the bacterial media development. It is declared advantage of baker's yeast hydrolisate as the nutrition media base.

Single photon emission computerized tomography with capromab pendetide plus computerized tomography image set co-registration independently predicts biochemical failure.

PURPOSE: We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy. MATERIALS AND METHODS: Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116). RESULTS: Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group. CONCLUSIONS: Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression.

Opioids were originally discovered because of their ability to induce analgesia, but further investigation has shown that the opioids regulate the function of cells involved in the immune response. We suggest that the regulation of cytokine, chemokine, and cytokine receptor expression is a critical component of the immunomodulatory activity of the opioids. In this paper we review the literature dealing with the regulation of cytokine and cytokine receptor expression by agonists for the three major opioid receptor types (mu, kappa, and delta), and nociceptin, the natural agonist for the orphanin FQ/nociceptin receptor. Although the opioid receptors share a high degree of sequence homology, opposing roles between the kappa opioid receptor (KOR) and the mu opioid receptor (MOR) have become apparent. We suggest that activation of the KOR induces an anti-inflammatory response through the down-regulation of cytokine, chemokine and chemokine receptor expression, while activation of the MOR favors a pro-inflammatory response. Investigation into the opioid receptor-like (ORL1)/nociceptin system also suggests a role for this receptor as a down-regulator of immune function. These effects suggest a broad role for opioids in the modulation of the function of the immune system, and suggest possible targets for the development of new therapeutics for inflammatory and infectious diseases.

Cytokine changes after a marathon race.

The influence of carbohydrate (1 l/h of a 6% carbohydrate beverage), gender, and age on pro- and anti-inflammatory plasma cytokine and hormone changes was studied in 98 runners for 1.5 h after two competitive marathon races. The marathoner runners were randomly assigned to carbohydrate (C, n = 48) and placebo (P, n = 50) groups, with beverages administered during the races in a double-blind fashion using color codes. Plasma glucose was higher and cortisol was lower in the C than in the P group after the race (P < 0.001). For all subjects combined, plasma levels of interleukin (IL)-10, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 rose significantly immediately after the race and remained above prerace levels 1.5 h later. The pattern of change in all cytokines did not differ significantly between the 12 women and 86 men in the study and the 23 subjects > or =50 yr of age and the 75 subjects <50 yr of age. The pattern of change in IL-10, IL-1ra, and IL-8, but not IL-6, differed significantly between the C and the P group, with higher postrace values measured for IL-10 (109% higher) and IL-1ra (212%) in the P group and for IL-8 (42%) in the C group. In conclusion, plasma levels of IL-10, IL-1ra, IL-6, and IL-8 rose strongly in runners after a competitive marathon, and this was not influenced by age or gender. Carbohydrate ingestion, however, had a major effect in attenuating increases in cortisol and two anti-inflammatory cytokines, IL-10 and IL-1ra.

Distal lung dysfunction at night in nocturnal asthma.

We have previously shown that patients with nocturnal worsening of asthma (nocturnal asthma) exhibit increased parenchymal inflammation at night. To evaluate the functional significance of this parenchymal inflammation, 10 subjects with nocturnal asthma (NA), four subjects with non-nocturnal asthma (NNA), and four normal control subjects underwent bronchoscopy with measurement of peripheral airways resistance (Rp) at 4:00 P.M. and at 4:00 A.M. Employing a wedged bronchoscope technique, Rp was measured. Flow was stopped, and the pressure reached after 10 s of decay was termed the plateau pressure. The time constant of this decay (tau) was measured, and the peripheral compliance (Cp) was calculated as tau/Rp. The NA group exhibited the highest Rp values at 4:00 P.M. and at 4:00 A.M. as compared with the NNA and control groups, but all groups were significantly different from each other at 4:00 P.M.: NA, 0.113 +/- 0.02 cm H(2)O/ml/min; NNA, 0.033 +/- 0.005 cm H(2)O/ml/min; Control subjects, 0.010 +/- 0.001 cm H(2)O/ ml/min; p = 0.0001; and at 4:00 A.M.: NA, 0.129 +/- 0.023 cm H(2)O/ ml/min; NNA, 0.035 +/- 0.007 cm H(2)O/ml/min; Control subjects, 0.009 +/- 0.002 cm H(2)O/ml/min; p = 0.0003. None of the groups exhibited statistically significant differences in Rp between 4:00 P.M. and 4:00 A.M. The plateau pressure increased significantly from 4:00 P.M. to 4:00 A.M., but only in the NA group (7.7 +/- 0.9 cm H(2)O at 4:00 P.M. versus 16.9 +/- 4.6 cm H(2)O at 4:00 A.M.; p = 0.0004). Cp was decreased in the NA group as compared with the NNA and control groups at both 4:00 P.M. (p = 0.0003) and 4:00 A.M. (p = 0.003). The Rp positively correlated with the residual volume at both 4:00 P.M. (r = 0.71, p = 0.004) and 4:00 A.M. (r = 0.59, p = 0.03). We conclude that the distal lung units, specifically the collateral channels, and may be functionally altered at night in NA.

New insights from lung function.

Asthma is a disease that is, in large part, defined by abnormalities of pulmonary function. Failure of any new treatment modality to improve objective measures of lung function suggests a limited usefulness of such new therapies. The clear dissociation between inflammation and airways responsiveness indicates the latter is not solely dependent on the former. Recent long-term treatment trials suggest that monitoring the degree of airways responsiveness, and returning responsiveness toward a normal value should be an obtainable goal of therapy. The effects of large inhalations and loss of lung volume dependence suggest that linkage between the airways and lung parenchyma are a key to maintenance of airway patency. Measurement of lung function remains the most practical means for the assessment of permanent changes in lung structure. New developments in monitoring lung function, especially using forced oscillation approaches, show particular promise in assessing the lung function of the asthmatic person.

Pulmonary capillary blood volume in hyperpnea-induced bronchospasm.

Reactive hyperemia of the bronchial circulation has been postulated to contribute to the airway narrowing that occurs following exercise or hyperpnea in subjects with asthma with hyperpnea-induced bronchospasm (HIB). Changes in lung parenchymal mechanics also occur in HIB, including increases in peripheral airway resistance. Since the peripheral airways and lung parenchyma are supplied by the pulmonary circulation, and changes in the pulmonary circulation could alter airway resistance or tissue mechanics, we hypothesized that pulmonary capillary blood flow would increase in association with HIB, resulting in increases in pulmonary capillary blood volume (VC). We measured VC by using two test gases of varying oxygen concentration to determine the diffusing capacity of the lung for carbon monoxide (DL(CO)) before and after a period of hyperpnea in 13 subjects with asthma with HIB and 10 control subjects without asthma. Despite subjects with asthma having a significant fall in FEV(1) following hyperpnea compared with control subjects (DeltaFEV(1) = -26 +/- 12 versus -4 +/- 4%, mean +/- SD, p < 0.001), there was no change in the DL(CO) or VC from baseline values. We conclude that pulmonary capillary blood volume does not change following hyperpnea, and therefore that changes in pulmonary blood flow are not associated with HIB.

Effects of cool, dry air stimulation on peripheral lung mechanics in asthma.

We have previously demonstrated that peripheral airway resistance (Rp) rises more in asthmatics than in nonasthmatic control subjects after segmental challenge with cool, dry air. To better understand this rise in Rp, we used a stop-flow method to measure the decay of segment pressure with time that yielded information on airway resistance (Raw), final plateau pressure (Pp), and peripheral lung compliance (Cp). After stop-flow maneuvers in all seven asthmatics and all seven normal subjects, pressure decayed smoothly without an initial sudden drop. This finding suggests that Raw was negligible and that the predominant site of flow resistance was the collateral pathways of the obstructed segment. Asthmatics had a significantly higher Pp and lower Cp at baseline than did normal subjects, but neither Pp nor Cp changed after challenge. Pp and Rp were significantly correlated. When interpreted in terms of a single-compartment nonlinear model, we concluded that Rp is predominantly determined by the resistance of the collateral airways rather than the more proximal airways. We also concluded that, compared with normal subjects, asthmatics have (1) more collateral airway narrowing and closure and lower segmental compliance, and (2) after challenge, increased collateral airway narrowing or closure without a change in compliance of the distal lung parenchyma. These results reflect the fundamental differences in peripheral lung mechanics between asthmatic and nonasthmatic subjects and in their response to directly instilled cool, dry air.

Pulmonary leukostasis mimicking pulmonary embolism.

We report a case of a 32-year-old woman who presented with shortness of breath and pleuritic chest pain, and mismatched perfusion defects on a ventilation-perfusion scan suspicious for pulmonary embolism. However, subsequent data revealed the diagnosis of acute myelogenous leukemia with hyperleukocytosis and associated pulmonary leukostasis. Unfortunately, the patient died despite urgent leukopheresis. Autopsy examination revealed extensive infiltration of leukemic cells in all major organs with no evidence of pulmonary embolism. This case highlights the clinical, radiographic and histologic features of pulmonary leukostasis, and reminds the clinician that not all ventilation-perfusion mismatching is due to thromboembolic disease.

The invaluable pressure-volume curve.

We present a case in which the pressure-volume (P-V) curve proved invaluable in the diagnostic workup of a patient. The patient was a 43-year-old man who presented with progressive dyspnea on exertion, restrictive spirometry, exercise desaturation, and an unremarkable CT scan. Because of the unexpected finding of an unremarkable CT scan, we wanted more data assuring the presence of an indication for lung biopsy. Detailed pulmonary function tests, including a P-V curve, were administered. The P-V curve was abnormal, thus prompting a biopsy, which revealed hypersensitivity pneumonitis. In this report, we discuss the use of P-V curves and the clinical presentation of hypersensitivity pneumonitis.

Nitrotyrosine formation in the airways and lung parenchyma of patients with asthma.

BACKGROUND: Recent evidence has shown that nitric oxide (NO) levels are increased in asthmatic airways. Although the role of NO in asthma is unknown, reactive metabolites of NO may lead to nitrotyrosine formation and promote airway dysfunction. OBJECTIVE: The aim of this study was to determine whether nitrotyrosine, as a marker of nitrating species, could be found in the airways and lung parenchyma of subjects with asthma who died of status asthmaticus or other nonrespiratory causes. METHODS: Lung tissue specimens were obtained from 5 patients who died of status asthmaticus, 2 asthmatic patients who died of nonrespiratory causes, and 6 nonasthmatic control subjects who died of nonrespiratory causes. Lung sections were stained for immunofluorescence with use of an antinitrotyrosine antibody, followed by a indiocarbocyanine (Cy5, Jackson Immunochemicals, Westgrove, Pa)-conjugated secondary antibody. RESULTS: Nonasthmatic lungs showed little or no nitrotyrosine staining, whereas asthmatic lungs demonstrated significantly more staining of nitrotyrosine residues distributed in both the airways and lung parenchyma. CONCLUSION: This study demonstrates the presence of nitrotyrosine, and hence evidence of formation of nitrating species, in the airways and lung parenchyma of patients with asthma who died of status asthmaticus or other nonrespiratory causes. This finding supports the concept that widespread airway and parenchymal inflammation occurs in asthma, and, more specifically, that NO and its reactive metabolites may play a pathophysiologic role in asthma.

Substance use among street children in Honduras.

The hypothesis that drug use among Honduran street children is a function of developmental social isolation from cultural and structural influences is examined. Data from 1,244 children working and/or living on the streets of Tegucigalpa are described, separating "market" children from "street" children. The latter group is then divided into those who sniff glue and those who do not to identify salient distinguishing factors. An OLS regression of drug usage on these variables results in a model that explains 75% of the variance, where family relations, length of time on the street, and delinquency are the most important factors.

Hyperpnea-induced changes in parenchymal lung mechanics in normal subjects and in asthmatics.

The effects of hyperpnea on parenchymal lung mechanics are unknown, but they may contribute to the resultant airflow limitation commonly seen in asthma. To investigate these effects, we measured the following parameters in seven asthmatic and six normal subjects before and after 5 min of hyperpnea: specific conductance, upstream resistance, static compliance, the coefficient of retraction, lung volumes, lung hysteresis, and the ratio of maximal to partial flow rates (the M:P ratio, an indicator of the effect of deep inhalation on airflow, and a measure of relative airway and parenchymal hysteresis). In addition to a central effect on the airways, as shown by significant falls in specific conductance, hyperpnea in asthmatics, but not in normal subjects, resulted in significant increases in residual volume and pressure-volume hysteresis, suggestive of changes in parenchymal lung mechanics. The M:P ratio also increased in the asthmatics, consistent with greater increases in airway than in parenchymal hysteresis after hyperpnea. We conclude that hyperpnea has significant effects on the lung parenchyma that contribute to airflow limitation in asthmatics, and we hypothesize that these effects may be due to alterations in peripheral airway smooth muscle tone and surfactant function.

Urinary leukotriene E4 levels in high-altitude pulmonary edema. A possible role for inflammation.

STUDY OBJECTIVES: Inflammation may contribute to the pathogenesis of high-altitude pulmonary edema (HAPE). This study was designed to determine whether a marker of inflammation, urinary leukotriene E4 (LTE4), is elevated in patients with HAPE. DESIGN: We conducted a case-control study to collect clinical data and urine samples from HAPE patients and healthy control subjects at moderate altitude (> or = 2727 m), and follow-up urine samples from HAPE patients following their return to low altitude (< or = 1,600 m). SETTING: Five medical clinics in Summit County, Colorado. PATIENTS: Questionnaire data were evaluated in 71 HAPE patients and 36 control subjects. Urinary LTE4 levels were determined from a random subset of 38 HAPE patients and 10 control subjects presenting at moderate altitude, and on 5 HAPE patients who had returned to low altitude. MEASUREMENTS AND RESULTS: Using an enzyme immunoassay technique, urinary LTE4 levels were found to be significantly higher in HAPE patients (123 [16 to 468] pg/mg creatinine, geometric mean [range]) than in control subjects (69 [38 to 135]), p = 0.02. Following return to low altitude, urinary LTE4 levels fell significantly from 122 (41.8 to 309) to 53.6 (27.6 to 104) pg/mg creatinine (p = 0.05). Urinary LTE4 levels were not related to age, sex, time at altitude, physical condition or habitual exercise, recent use of alcohol or nonsteroidal anti-inflammatory drugs (NSAIDs), or oxygen saturation. Clinical factors associated with HAPE included male sex, regular exercise, and recent use of NSAIDs. CONCLUSIONS: We conclude that urinary LTE4 levels are elevated in patients with HAPE, supporting the view that HAPE involves inflammatory mechanisms.

Treating alcoholism through a narrative approach. Case study and rationale.

A case study illustrates the narrative or story-telling approach to treating alcoholism. We discuss the rationale for this method and describe how it could be useful in family practice for treating people with alcohol problems.

Peripheral airways responsiveness to cool, dry air in normal and asthmatic individuals.

Peripheral airways resistance (Rp) has been shown to be increased in asymptomatic asthmatic patients with normal spirometric values, and to be correlated with airways hyperresponsiveness to methacholine. We investigated whether Rp in asthmatic subjects with exercise-induced bronchospasm (EIB) would rise in response to cool, dry air. Using a wedged bronchoscope technique, we challenged an isolated lung segment with high flows (500 to 1,000 ml/min) of cool (22 degrees C) dry 5% CO2 in air for 5 min in eight asthmatic subjects with EIB and eight normal subjects. Baseline Rp and Rp following challenge were measured with saturated air at 37 degrees C at a flow rate of 100 ml/min. Baseline Rp was significantly greater in the asthmatic (0.09; [0.05 to 0.23] cm H2O/ml/min; median [interquartile range]) than in the normal subjects (0.05; [0.03 to 0.07] cm H2O/ml/min) (p = 0.04). The asthmatic, but not the normal subjects, had a significant absolute maximal increase in Rp following cool, dry air (0.10 [0.03 to 0.15] cm H2O/ml/min) (p < 0.01). In the asthmatic subjects, baseline Rp correlated with airways hyperresponsiveness to exercise (r = -0.76, p = 0.03). We conclude that the peripheral airways of asthmatic individuals with EIB are responsive to cool, dry air, and may play an important role in EIB.