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Biomedical subjects

E Israel

Publications and source records attributed to E Israel.

At least 55 records · Page 3Linked to original sources
PubMed1998

Expired nitric oxide after bronchoprovocation and repeated spirometry in patients with asthma.

Compared with normal individuals, subjects with asthma have elevated levels of expired nitric oxide (NO). These levels are hypothesized to reflect the degree of airway inflammation. Expired NO levels rise during the late phase of allergen challenge and decrease in asthmatics after steroid treatment. Isocapnic cold air hyperventilation (ISH) is believed to cause airway narrowing through noninflammatory mechanisms. We measured mixed expired NO in 10 individuals with atopic asthma who underwent both ISH challenge and allergen challenge, and compared these measurements with the change in expired NO that occurred after serial spirometry alone. We found that ambient NO levels affected mixed expired NO. Controlling for inspired NO, we found that repeated spirometry alone produced a significant fall in mixed expired NO (p < 0.01) that was maximal after 30 min (36.6 +/- 8.5% fall). After allergen and ISH challenges, expired NO was elevated relative to levels after repeated spirometry (p < 0.01 and p = 0.065, respectively). In addition, we found that prechallenge expired NO levels were significantly correlated with the magnitude of the late fall in FEV1 following allergen challenge (r = 0.80, p < 0.01). These data demonstrate that repeated spirometry results in reduced mixed expired NO and suggest that both ISH and allergen-induced bronchoconstriction share pathobiologic mechanisms that produce increases in mixed expired NO.

Adult↗
PubMed1997

Antileukotrienes in the treatment of asthma.

PURPOSE: To review the activity in clinical models, the efficacy, and the safety of antileukotrienes as a new class of antiasthma treatment. DATA SOURCES: English-language trials identified from the archival literature, including the MEDLINE database, through 1996; bibliographic references; and textbooks. STUDY SELECTION: Reports from placebo-controlled, double-blind, randomized trials were selected. DATA EXTRACTION: Study designs and results were extracted from the clinical trial reports. Statistical evaluation of combined results was not attempted. DATA SYNTHESIS: The various classes of antileukotrienes have shown activity in clinical models of asthma, including exercise-induced, cold air hyperventilation-induced, allergen-induced, and aspirin-induced bronchoconstriction. In addition, the antileukotrienes partially reverse spontaneous bronchoconstriction in asthmatic persons, an effect additive to that of inhaled beta 2-agonists. Clinical trials of the antileukotrienes have shown clinical benefit, as measured by reductions in asthma symptom scores, improvements in air flow obstruction, and reductions in the rescue use of inhaled beta 2-agonists. Some, but not all, of the antileukotrienes have been shown to cause liver microsomal activation with increases in hepatic aminotransferase levels. CONCLUSIONS: Antileukotrienes are an important new therapy for asthma. Inhibition of leukotriene synthesis or action has a beneficial effect in the treatment of both induced and spontaneous asthma. These results show that leukotrienes are important mediators of the asthmatic response. In addition, encouraging results have been obtained from clinical trials of antileukotrienes; however, these results do not yet provide guidelines for the optimal clinical use of antileukotrienes in asthma treatment. Such recommendations await the results of further studies.

Animals↗
PubMed1997

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Alleles↗
PubMed1997

Influence of closed head injury on isoflurane MAC in the rat.

We designed the present study to determine whether the minimum alveolar concentration (MAC) for isoflurane is decreased after closed head trauma (CHT) in rats and, if so, whether the decrease of MAC is related to the severity of neurological impairment following CHT. Isoflurane MAC was determined in 36 Sprague-Dawley rats. Then, at time = 0 h, animals were grouped. Group 1 (n = 8) received no CHT, group 2 (n = 14) received moderate CHT, and group 3 (n = 14) received severe CHT. Neurological severity score (NSS, 0 = no deficit and 25 = maximal impairment) and MAC were determined at 1, 4, 24, and 48 h. In groups 1 and 2, isoflurane MAC at 1, 2, 24, and 48 h (1.0-1.1 +/- 0.8-1.2%, median +/- range) was not significantly different from baseline (1.0-1.1 +/- 1.0-1.1%). In group 3, isoflurane MAC at 1, 2, 24, and 48 h (0.4 +/- 0.2-0.5%) was decreased as compared to baseline (1.1 +/- 1.0-1.1%). In group 2, NSS at 1 h was 18 +/- 11-21 and improved by 48 h to 9 +/- 4-15. In group 3, NSS at 1 h was 24 +/- 22-25 and was not significantly different from NSS at 48 h (24 +/- 24-25). Thus, moderate CHT does not significantly alter isoflurane MAC, whereas severe CHT equivalent to a Glasgow Coma Scale score of 3 to 6 significantly decreases isoflurane MAC.

Anesthetics, Inhalation↗
PubMed1997

Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold dry air.

BACKGROUND: Leukotrienes have been implicated in the mediation of airway obstruction induced by hyperventilation of cold dry air in asthmatic subjects. The effect of a novel inhibitor of 5-lipoxygenase activating protein, BAYx 1005, on the bronchospastic response to cold dry air hyperventilation was investigated in asthmatic patients. METHODS: After a screening cold dry air hyperventilation challenge to document cold air responsiveness, 16 asthmatic subjects (baseline forced expiratory volume in one second (FEV1) > 60% of predicted) underwent cold air challenge three hours after receiving 750 mg of BAYx 1005 or placebo using a randomised, double blind, crossover design. Leukotriene synthesis inhibition was estimated by measuring the concentration of leukotriene B4 in whole blood stimulated with calcium ionophore A21387. RESULTS: Treatment with BAYx 1005 produced a 34% (95% CI 11 to 63) increase in the amount of cold air minute ventilation required for a 10% decrease in FEV1 (PD10VE) compared with placebo (mean (SE) 37.6 (1.12) 1/min compared with 28.0 (1.13) 1/min, p < 0.006). The PD20VE increased 19% (95% CI 8 to 31) after treatment with BAYx 1005 compared with placebo (57.3(1.10)1/min versus 48.1 (1.10) 1/min, p < 0.002). Treatment with BAYx 1005 produced a 15.4% decrease in ionophore-stimulated LTB4 production, while treatment with placebo produced a 7.1% increase in ex vivo LTB4 (p < 0.02). CONCLUSIONS: Treatment with BAYx 1005, a novel inhibitor of leukotriene synthesis, produced a significant blunting of cold dry air responsiveness consistent with the hypothesis that leukotrienes mediate part of the bronchoconstriction induced by hyperventilation of cold dry air.

Adolescent↗
PubMed1997

An evaluation of colchicine as an alternative to inhaled corticosteriods in moderate asthma. National Heart, Lung, and Blood Institute's Asthma Clinical Research Network.

Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 microg daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomized to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81+/-1.38 versus 2.11+/-2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions.

Administration, Inhalation↗
PubMed1996

Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network.

BACKGROUND: Inhaled beta-agonists are the most commonly used treatment for asthma, but data suggest that regularly scheduled use of these agents may have deleterious effect on the control of asthma. We compared the effects of regularly scheduled use of inhaled albuterol with those of albuterol used only as needed in patients with mild chronic, stable asthma. METHODS: In a multicenter, double-blind study, we randomly assigned 255 patients with mild asthma to inhale albuterol either on a regular schedule (126 patients) or only as needed (129 patients). The patients were followed for 16 weeks. RESULTS: The primary outcome indicator, peak expiratory air flow measured in the morning, did not change significantly during the treatment period in the scheduled (416 liters per minute after the run-in period and 414 liters per minute after the treatment period) or the as-needed (424 liters per minute at both times) treatment groups (P=0.71). There were no significant differences between the two groups in peak flow variability, forced expiratory volume in one second, the number of puffs of supplemental albuterol needed, asthma symptoms, asthma quality-of-life score, or airway responsiveness to methacholine. The statistically significant differences between the groups in evening peak flow and in the short-term bronchodilator response to inhaled albuterol were small and judged to be clinically unimportant. CONCLUSIONS: In patients with mild asthma, neither deleterious nor beneficial effects derived from the regular use of inhaled albuterol beyond those derived from use of the drug as needed. Inhaled albuterol should be prescribed for patients with mild asthma on an as-needed basis.

Administration, Inhalation↗
PubMed1996

Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group.

OBJECTIVE: To study the effect of 3 months of treatment with zileuton, an inhibitor of the enzymatic pathway (5-lipoxygenase) leading to leukotriene formation, on disease control in patients with mild to moderate asthma. DESIGN: Randomized, double-blind, parallel-group study in 401 patients. A 10-day placebo lead-in was followed by a double-blind treatment period of 13 weeks. SETTING: Asthma study clinics in university hospitals and private practices. PATIENTS OR OTHER PARTICIPANTS: Patients with mild to moderate asthma (forced expiratory volume in the first second [FEV1], 40% to 80% of predicted) whose only treatment was inhaled beta-agonists. INTERVENTIONS: Treatment with 600 mg or 400 mg of zileuton or placebo (each taken four times daily.) MAIN OUTCOME MEASURES: Frequency of asthma exacerbation requiring treatment with corticosteroids, use of inhaled beta-agonists, pulmonary function tests, asthma symptom assessment, and quality-of-life evaluation. Safety was evaluated by monitoring adverse events. RESULTS: Only eight (6.1%) of 132 patients receiving 600 mg of zileuton four times a day required corticosteroid treatment for asthma vs 21 (15.6%) of 135 patients receiving placebo (P=.02), giving a relative risk of 2.6. At the time of expected peak drug concentration, the average FEV1 improved 15.7% in the 600-mg zileuton group vs 7.7% in the placebo group (P=.006). Quality-of-life assessments significantly improved in the 600-mg zileuton group and not in the placebo group (P=.007 for the overall score). Elevations in liver function tests (more than three times normal), all of which reversed with drug withdrawal, occurred in five patients (P=.03 vs placebo), three patients (P=.12 vs placebo), and no patients treated with 600 mg of zileuton, 400 mg of zileuton, or placebo, respectively. CONCLUSIONS: Three months of 5-lipoxygenase inhibition produced a significant improvement in asthma control. These data indicate that 5-lipoxygenase products of arachidonic acid metabolism are mediators of inflammation with an important role in the biology of asthma.

Adrenergic beta-Agonists↗
PubMed1996

Lyme disease surveillance in Maryland, 1992.

The incidence of Lyme disease (LD) reported to the Maryland Department of Health and Mental Hygiene during 1992 was 6.5/100,000 population, ranging from 29.3 cases/100,000 on the Eastern Shore (74.4% of all cases) to no cases in the mountains of western Maryland. Among the 317 reported patients, 44.4% gave a history of tick exposure and 78.9% had positive serologic test results. For the 187 (59.0%) patients meeting the Centers for Disease Control and Prevention (CDC) surveillance case definition, erythema migrans (EM) occurred in 69.5%, with arthritic (26.7%), neurologic (13.4%), and cardiac (2.1%) manifestations being less frequent. Patients not meeting the surveillance case definition were significantly more likely to have influenza-like symptoms, a smaller rash, and arthralgia. Patients meeting the CDC criteria were more likely to have an onset during the major transmission season in the summer (odds ratio (OR): 2.1; confidence interval (CI): 1.2 to 3.6) since this was the time when most (115/130) patients with EM were detected. Positive serologic results were more likely (OR: 2.2; CI: 1.2 to 4.2) in those not meeting the case definition. The treatment given to patients thought to have LD was almost always that recommended in the literature and there was no difference between treatment prescribed for patients meeting and those not meeting the case definition. These data show that physicians in Maryland are treating many patients for LD who are clinically diagnosed as having LD (e.g., febrile patients with flulike symptoms, patients with arthralgias or erythematous rashes < 5 cm in size) and who have positive serologic test results but who do not meet the CDC surveillance case definition. These patients and the large number of unreported patients being seen and treated for LD or tick bites must be added to the overall burden of LD in the state.

Adolescent↗
PubMed1996

The public health impact of Lyme disease in Maryland.

The purpose of this study was to estimate the health burden imposed by Lyme disease (LD) in Maryland during 1992 and 1993. A cross-sectional 1-in-15 survey of physicians (total, 1200) in Maryland was conducted to estimate the incidence of diagnosed LD, presumptive cases of LD, patients with tick bites, and diagnostic tests ordered for LD. Results show that LD is underreported by 10- to 12-fold in Maryland, that 80% of cases are managed by primary care physicians, and that there is discordance between the actual clinical treatment of patients and the recommended approach. In addition, the much greater numbers of patients treated for presumptive LD, seen and given prophylaxis for tick bites, and having diagnostic tests indicate that real and perceived LD is a far greater public health problem and uses more medical resources than official surveillance data suggest.

Animals↗
PubMed1996

Diagnostic yield of bronchoalveolar lavage and bronchoscopic lung biopsy for detection of Pneumocystis carinii.

OBJECTIVE: To assess the need to perform a bronchoscopic lung biopsy (BLB) in addition to bronchoalveolar lavage (BAL) to obtain a definitive diagnosis of Pneumocystis carinii pneumonia. DESIGN: We retrospectively reviewed the results of concurrently collected paired BAL and BLB specimens to determine the diagnostic yield of both methods for the detection of P. carinii organisms. MATERIAL AND METHODS: During a 3-year period, the BAL fluid specimens stained with a commercially available direct immunofluorescence monoclonal antibody (DFA) reagent and the BLB specimens stained with Grocott methenamine-silver nitrate (GMS) were assessed for the presence of P. carinii. BAL fluid was routinely collected from multiple sites and combined into a single specimen for testing. RESULTS: During the 3-year period of study, 119 patients were identified who had paired BAL fluid and BLB specimens tested for the presence of P. carinii. Of the 119 patients, 16 had either BAL fluid that could not be interpreted or BLB tissue that was inadequate. Of the other 103 patients, 21 had P. carinii pneumonia. The sensitivity of the DFA method on BAL fluid and of the GMS method on BLB was 95% and 43%, respectively. CONCLUSION: For detection of P. carinii, the diagnostic yield is significantly higher for DFA-stained BAL specimens than for GMS-stained BLB specimens.

Biopsy↗
PubMed1996

Identification of childhood vaccine providers in Maryland.

The purpose of the study was to compare the utility of an American Medical Association (AMA)-derived list and a Maryland State Department of Health and Mental Hygiene (state)-derived list of potential childhood vaccine providers (CVPs) in identifying true childhood vaccine providers for the Vaccines for Children (VFC) program in Maryland. A telephone survey of a sample of physicians from the two lists was used to determine their status as providers of routine vaccinations to children. Results showed a significant difference between the two lists. The state-derived list was composed of an estimated 60.7% CVPs, whereas the AMA-derived list was composed of an estimated 36.7% CVPs. Using the capture-recapture method, it was estimated that there are about 2077 CVPs in Maryland. Based on this figure, the state-derived list would have identified 71.7% of the state's CVPs, and the AMA-derived list would have identified 59.4%. Using the AMA-derived list would have required contacting approximately 1800 extra providers to identify the additional 350 CVPs (16.8%) not identified in the state-derived list. Accurate, up-to-date lists of providers that include pertinent practice characteristics would enhance the ability to contact specific providers for VFC program enrollment and for other clinical and public health purposes.

Adolescent↗
PubMed1995

Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma.

BACKGROUND: Leukotriene E4 (LTE4) and histamine excreted into the urine reflect the in vivo synthesis and release of cysteinyl leukotrienes and histamine, respectively. We examined the diurnal variation of the excretion rate of these mediators over 4 consecutive days in normal subjects (n = 5) and patients with stable mild-to-moderate asthma (n = 8). METHODS: Sixteen consecutive 6-hour urine samples were collected over 4 days. Urinary LTE4 concentrations were determined by reverse-phase high-pressure liquid chromatography, followed by ELISA. Urinary histamine concentrations were measured by ELISA. The excretion rates of these compounds were normalized relative to urinary creatinine content. RESULTS: The mean urinary LTE4 excretion rate was 83.8 +/- 38.2 pg/mg creatinine (mean +/- SD) in normal subjects; in patients with asthma, the urinary LTE4 excretion rate (110.0 +/- 59.2 pg/mg creatinine) was significantly higher than that in normal subjects (p < 0.05). The urinary histamine excretion rate was not different between normal subjects (24.0 +/- 12.5 ng/mg creatinine) and patients with asthma (31.5 +/- 25.8 ng/mg creatinine). A robust and systematic within-day variation (p < 0.01), but no day-to-day variation, was observed in histamine excretion rate. Although the magnitude of variation in LTE4 excretion within a day was significantly greater in patients with asthma than in normal subjects (p < 0.05), we could not identify any specific diurnal variation pattern in either the normal or the asthma group. No significant correlation was observed between urinary LTE4 and histamine excretion rate within any subject. CONCLUSIONS: Patients with asthma excrete LTE4 in the urine at a greater rate than normal subjects. Although no systematic variation in urinary LTE4 excretion rates over the course of a day was observed in either normal subjects or patients with stable asthma, the presence of a systematic diurnal variation of urinary histamine excretion exists in both groups.

Adult↗
PubMed1995

Effect of chronic 5-lipoxygenase inhibition on airway hyperresponsiveness in asthmatic subjects.

The leukotrienes are known bronchoactive agonists with potential proinflammatory effects that may be involved in mediating airway hyperresponsiveness. We investigated the effects of zileuton, an inhibitor of 5-lipoxygenase (5-LO), on airway responsiveness to cold, dry air in patients with moderate asthma. A group of 10 asthmatic patients underwent cold, dry air hyperventilation challenge; challenges were performed before drug treatment and 1 to 10 d after the completion of treatment with study drugs. The cold air minute ventilation required to cause a 15% decrease in FEV1 (PD15 VE) increased by 58% compared with the response before treatment, 1 to 10 d after the completion of 13 wk of treatment with zileuton. The geometric mean (geometric mean/SEM and geometric mean x SEM) PD15 VE increased from 24.5 (20.4, 29.5) L/min to 38.8 (34.7, 43.7) L/min (p = 0.01). Zileuton treatment inhibited 5-LO as measured ex vivo by ionophore-stimulated LTB4 levels in whole blood. In four of seven subjects, LTB4 levels before zileuton ingestion fell from 110.88 +/- 25.42 to 5.40 +/- 1.95 ng/ml 2 h post-zileuton dosing (p = 0.02, pre- versus 2 h postzileuton ingestion). Consistent with the short half-life of zileuton, 6 h postzileuton dosing the ionophore-stimulated, LTB4 levels in whole blood had increased to 89.68 +/- 35.54 ng/ml (p = 0.41, pre- versus 6 h postzileuton ingestion). Based on the first-order kinetics of zileuton, its effect on 5-LO activity should have been dissipated less than 16 h postingestion. Thus, chronic zileuton treatment decreased airway hyperresponsiveness as determined by reactivity to cold, dry air.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Environmental risk factors for Lyme disease identified with geographic information systems.

OBJECTIVES: A geographic information system was used to identify and locate residential environmental risk factors for Lyme disease. METHODS: Data were obtained for 53 environmental variables at the residences of Lyme disease case patients in Baltimore County from 1989 through 1990 and compared with data for randomly selected addresses. A risk model was generated combining the geographic information system with logistic regression analysis. The model was validated by comparing the distribution of cases in 1991 with another group of randomly selected addresses. RESULTS: In crude analyses, 11 environmental variables were associated with Lyme disease. In adjusted analyses, residence in forested areas (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.2, 11.8), on specific soils (OR = 2.1, 95% CI = 1.0, 4.4), and in two regions of the county (OR = 3.5, 95% CI = 1.6, 7.4) (OR = 2.8, 95% CI = 1.0, 7.7) was associated with elevated risk of getting Lyme disease. Residence in highly developed regions was protective (OR = 0.3, 95% CI = 0.1, 1.0). The risk of Lyme disease in 1991 increased with risk categories defined from the 1989 through 1990 data. CONCLUSIONS: Combining a geographic information system with epidemiologic methods can be used to rapidly identify risk factors of zoonotic disease over large areas.

Environmental Exposure↗