Biomedical subjects

S Wenzel

Publications and source records attributed to S Wenzel.

At least 55 records · Page 3Linked to original sources

PubMed2001

Tetracycline residues in meat and bone meals. Part 1: methodology and examination of field samples.

The incidence of tetracycline residues in commercially available samples of meat meals and meat and bone meals was investigated. Four different methods were used on each of the 87 samples from nine different rendering plants in Germany: examination using a screening fluorescence test; examination by high performance liquid chromatography analysis using three different extraction procedures (succinate buffer, hydrochloric acid, hydrochloric acid after sedimentation of bone particles). Tetracyclines were found in 100% of the samples by one or more of the extraction procedures. The highest concentrations found in meat meals were 2048 microgkg(-1), 1393 microgkg(-1) and 608 microgkg(-1) for oxytetracycline, tetracycline and chlortetracycline, respectively. In meat and bone meals the highest concentrations were 2295 microg oxytetracycline kg(-1) 848 microg tetracycline kg(-1) and 1274 microg chlortetracycline kg(-1). The extraction after sedimentation was the most effective of the applied extraction procedures and exposed the highest total tetracycline concentrations. The results of this investigation showed that considerable amounts of tetracyclines have to be expected in field samples. Further research has to be done on the heat stability of bound tetracycline residues.

Animal Feed↗

PubMed2001

Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality.

AIM: Add-on therapy with omalizumab, an anti-immunoglobulin E antibody, is effective in improving disease control in patients with allergic asthma of varying severity. The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality. METHODS: A meta-analysis was performed of three randomised, double-blind, placebo-controlled studies (studies 1, 2 and 3) that enrolled 1412 patients with moderate or severe allergic asthma, all requiring daily treatment with inhaled corticosteroids (ICS). Omalizumab was administered subcutaneously every 2 or 4 weeks at a total 4-weekly dose of at least 0.016 mg/kg/IgE [IU/ml]. Each study consisted of a 16-week steroid-stable phase and a 12-16-week steroid-reduction phase, followed by a 24-week extension phase (studies 1 and 2 only). The primary outcome measure was the annualised rate of significant asthma exacerbation episodes (sAEEs) during the steroid-stable phase for the pooled subgroup of 254 high-risk patients (omalizumab, n = 135; placebo, n = 119). sAEEs were those requiring a doubling of baseline ICS dose (studies 1 and 2 only) or use of systemic steroids (all three studies). RESULTS: Overall, the number of patients with at least one sAEE during the steroid-stable phase was reduced from 35% (42/119) with placebo to 18% (24/135) with omalizumab. Mean sAEE rates were 1.56 and 0.69 per patient-year, respectively, a reduction of 56% with omalizumab (p = 0.007). Similar reductions in exacerbations in favour of omalizumab were observed for the whole study period and for all AEEs. In those with a history of hospitalisation in the last year, 6/49 (12%) on placebo vs. 2/44 (4.5%) on omalizumab were re-hospitalised during the study period. Patients treated with omalizumab also showed significantly greater improvements from baseline in PEFR (p = 0.026), overall AQoL (p = 0.042) and mean nocturnal (p = 0.007) and mean total (p = 0.011) asthma symptom scores compared with placebo. CONCLUSIONS: In patients at high risk of serious asthma-related morbidity and mortality, treatment with omalizumab offers the potential to halve the rate of asthma exacerbations and improve disease control.

Adolescent↗

PubMed2000

Expression, release, and biological activity of parathyroid hormone-related peptide from coronary endothelial cells.

Ventricular cardiomyocytes have previously been identified as potential target cells for parathyroid hormone-related peptide (PTHrP). Synthetic PTHrP peptides exert a positive contractile effect. Because systemic PTHrP levels are normally negligible, this suggests that PTHrP is expressed in the ventricle and acts as a paracrine mediator. We investigated the ventricular expression of PTHrP and its expression in cultured cells isolated from the ventricle, studied the release of PTHrP from hearts and cultures, and investigated whether this authentic PTHrP mimics the biological effects previously described for synthetic PTHrP on ventricular cardiomyocytes. We found PTHrP expressed in ventricles of neonatal and adult rat hearts. In cells isolated from adult hearts, we found PTHrP expression exclusively in coronary endothelial cells but not in cardiomyocytes. The latter, however, are target cells for PTHrP. PTHrP was released from isolated perfused hearts during hypoxic perfusion and from cultured coronary endothelial cells under energy-depleting conditions. This PTHrP was biologically active; ie, it exerted a positive contractile and lusitropic effect on cardiomyocytes. Authentic PTHrP was glycosylated and showed a slightly higher potency than synthetic PTHrP. These results suggest that PTHrP is an endothelium-derived modulator of ventricular function.

Animals↗

PubMed2000

[Tumor oxygenation in combined whole body hyperthermia and polychemotherapy. Studies exemplified by recurrent carcinoma of the mouth cavity].

BACKGROUND AND OBJECTIVE: Previous studies have reported synergistic effects of combined hyperthermia and chemotherapy and/or irradiation. The response to irradiation and chemotherapy of well-oxygenated and vascularized tumors generally is better than that of hypoxic tumors. Therefore, tumor oxygenation is recognized as an important predictive factor in the therapy of malignant tumors. In practice, the head and neck area remains outside of the hyperthermia chamber during whole-body hyperthermia. It was the aim of this study to evaluate if the head and neck region receives sufficient warmth and, if so, if tumor oxygenation increases accordingly. PATIENTS/METHODS: Whole-body hyperthermia, as heat radiation (Enthermics Medical Systems RHS-7500), was applied to the narcotised 60-year-old male patient with a local recurrence tumor pT3 pN2b M0 squamous cell carcinoma of the oral cavity. Tumor oxygenation and temperature were measured by LICOX catheters via one-point measurement during the entire hyperthermia treatment (3.5 h). Parallelly, chemotherapy (ifosfamide/Carboplatin) was given in four cycles (one cycle/month). RESULTS: With a latency of 10 min the increase of intratumoral temperature was comparable to temperatures achieved in the esophagus. The maximum intratumoral temperature was 41.8 degrees C. The average increase in tumor oxygenation was more than 100%. The clinical outcome in the case presented was a partial tumor remission (PR). CONCLUSIONS: During combined whole-body hyperthermia and polychemotherapy, tumor oxygenation is also significantly improved in the head and neck area, despite the fact that the head and neck area remained outside the hyperthermia chamber. The intratumoral temperature was comparable to esophageal and rectal temperatures.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[Studies of the histomorphology and function of the uvula].

BACKGROUND: Alternations in pharyngeal structure and function are considered fundamental in the pathogenesis of snoring or obstructive sleep apnea (OSA). The physiological function of the uvula as a dynamic sealing of the nasopharynx prevents a "craniocaudal aspiration" during deglutition. The oropharyngeal soft tissues and the uvula are known to play an important role in affecting the oropharyngeal airflow resistance but studies about alterations in the histomorphological uvula structure are controversial. METHODS: We studied the histomorphological tissue composition of the uvula (midsagittal and transversal sections) in 142 patients who underwent uvulopalatopharyngoplasty (UPPP) or uvulopalatoplasty (UPP) for snoring and by autopsy in 30 normal subjects not known to have been snoring. Statistical comparisons were controlled for differences caused by age and body mass index. RESULTS: The uvula was found to be significantly longer in patients with snoring than in control subjects. Patients with snoring had a significantly greater percentage of fat content and connective tissue in combination with a muscle atrophy in the uvula than did normal subjects. CONCLUSIONS: The disturbance of the specific muscular composition and formation causes a reduction of muscular tonus and a loss of muscular contraction. The uvula is destabilized on the basis of a missing skeletal and cartilaginous brace. The uvula destabilization causes a narrowing of the pharyngeal airway that could lead to an increased oropharyngeal airflow resistance with an intensified passive uvula movement and vibration during mouth breathing.

Adult↗

PubMed1999

Microvascular and tumor cell alterations during continuous hyperfractionated irradiation: an electron microscopic investigation on the rat R1H rhabdomyosarcoma.

PURPOSE: Conventionally fractionated y-irradiation results in severe damage of tumor capillaries associated with decreasing oxygen partial pressure within the tumor. The present study was undertaken to assess whether vasculo-connective changes are less pronounced after continuous hyperfractionated irradiation, implying better tumor oxygenation and improved radiosensitivity. MATERIALS AND METHODS: Twenty rats with an isotransplanted R1H rhabdomyosarcoma were irradiated for 12 days with 2 daily fractions of 2.5 Gy (delta t = 6 h). After 0, 15, 30, 45, and 60 Gy, tumor tissue of 4 rats each was analyzed histologically and electron-microscopically. RESULTS: Untreated rhabdomyosarcomas were composed of spindle-shaped tumor cells with numerous mitoses. There were many apoptotic nuclei and a large central necrosis. Tumor capillaries showed a continuous lining of flattened endothelial cells with broad overlapping cell contacts overlying a delicate continuous basal lamina. During irradiation, mean tumor volume declined from 1.9 cm3 to 1.2 cm3. The number of atypical mitoses and apoptoses increased and numerous giant tumor cells appeared. The proportion occupied by necrotic tumor tissue rose from 30% to 60%. After 15 Gy (3 days), a marked vasodilatation was apparent accompanied by an interstitial edema. Occasionally, endothelial cells were rounded up and showed indented nuclei, with the underlying basal lamina disintegrated. These changes progressed with increasing radiation doses. After 30 Gy (6 days), leukocytes started to adhere to the endothelial wall. Electron-dense fine fibrillar and basal lamina-like deposits appeared in the perivascular space. Endothelial cell edema was only observed after 60 Gy (12 days). Cell contact areas were shortened, however, the endothelial lining was not interrupted. No signs of radiation fibrosis were observed. CONCLUSION: Continuous hyperfractionated irradiation induces relatively discrete alterations of the vasculo-connective tumor tissue as compared to conventional irradiation. This may be an advantage with respect to tumor blood flow, oxygenation, and thus, radiosensitivity.

Animals↗

PubMed1999

Associations between homeless women's intimate relationships and their health and well-being.

The purpose of this study was to describe the associations between intimate relationships, characterized in terms of presence or absence of conflictive interaction with the partner, and the health and well-being of homeless women. A sample of 558 homeless women were administered structured interviews by trained nurses or outreach workers of the participants' ethnicity. Women answered questions about their general physical health, health-threatening behaviors (i.e., risky drug and sexual behaviors), health-promoting behaviors (i.e., TB and Pap testing), psychological well-being and symptomatology, self-esteem, coping, and life satisfaction. Women in nonconflictive relationships reported significantly greater psychological well-being, self-esteem, and life satisfaction and less hostility and noninjection drug use than women with conflictive relationships or those without an intimate partner. Women with conflictive relationships were significantly more anxious and depressed than those with nonconflictive relationships. Results suggest that, when possible, it is advisable to involve the intimate partner in programs to facilitate the emotional well-being of homeless women.

Adaptation, Psychological↗

PubMed1999

Utilization of mental health and substance abuse services among homeless adults in Los Angeles.

OBJECTIVES: Even though psychiatric disorders are disproportionately present among the homeless, little is known about the extent to which homeless people receive treatment for those problems or the factors that are associated with receiving treatment. This article examines utilization and predictors of mental health and substance abuse treatment among a community-based probability sample of homeless adults. METHODS: The data analyzed here were collected through face-to-face interviews with 1,563 homeless individuals. Bivariate analyses examined differences between homeless men and women in (1) the prevalence of major mental illnesses and substance dependence and (2) utilization of inpatient and outpatient treatment services for those with specific diagnoses. Logistic regression analyses identified predictors of mental health treatment among those with chronic mental illness and substance abuse treatment among those with recent substance dependence. RESULTS: Two-thirds of these homeless adults met criteria for chronic substance dependence, whereas 22% met criteria for chronic mental illness, with substantial overlap between those two disorders: 77% of those with chronic mental illness were also chronic substance abusers. Only one-fifth of each of those two groups reported receiving treatment for those disorders within the last 60 days. Mental health service utilization was predicted largely by factors related to need (eg, diagnosis, acknowledgment of a mental health problem), whereas substance abuse service utilization was predicted by myriad additional factors, reflecting, in part, critical differences in the organization and financing of these systems of care. CONCLUSIONS: More attention must be directed at how to better deliver appropriate mental health and substance abuse services to homeless adults.

Adolescent↗

PubMed1999

Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells.

A hallmark of asthma is mucin overproduction, a condition that contributes to airway obstruction. The events responsible for mucin overproduction are not known but are thought to be associated with mediators of chronic inflammation. Others have shown that T-helper 2 (Th2) lymphocytes are required for mucous cell metaplasia, which then leads to mucin overproduction in animal models of allergy. We hypothesized that Th2 cell mediators are present in asthmatic airway fluid and directly stimulate mucin synthesis in airway epithelial cells. Results in cultured airway epithelial cells showed that samples of asthmatic fluid stimulated mucin (MUC5AC) synthesis severalfold more potently than non-asthmatic fluid. Consistent with this, lavage fluid from the airways of allergen-challenged dogs stimulated mucin synthesis severalfold more potently than that from non-allergen-challenged dogs. Fractionation of dog samples revealed 2 active fractions at <10 kDa and 30-100 kDa. Th2 cytokines in these molecular weight ranges are IL-9 (36 kDa), IL-5 (56 kDa), and IL-13 (10 kDa). Antibody blockade of ligand-receptor interaction for IL-9 (but not IL-5 or IL-13) inhibited mucin stimulation by dog airway fluid. Furthermore, recombinant IL-9, but not IL-5 or IL-13, stimulated mucin synthesis. These results indicate that IL-9 may account for as much as 50-60% of the mucin-stimulating activity of lung fluids in allergic airway disease.

Adult↗

PubMed1998

[Effect of various forms of metastatic lymph node involvement on prognosis of squamous epithelial carcinomas of the upper aerodigestive tract].

BACKGROUND: Based on a new histo-morphological rating scheme, we assessed the impact on patient prognosis of lymph node metastasis of squamous cell carcinoma (SCC) in the head/neck area. Special attention was given to possible capsular rupture. METHOD: In a retrospective study, 111 patients with squamous cell carcinoma of the head and neck with concomitant cervical lymph node metastases were evaluated to determine the importance of lymph node capsular rupture on the occurrence of disseminated disease, loco-regional recurrence as well as survival rate. To cover the broad morphological spectrum of cervical metastatic disease, a newly developed scheme (differentiating seven different histo-morphological types of lymph node metastasis) was applied. On the basis of this scheme, every single metastatic lymph node received a score from one to seven. These single scores were then added to obtain a total score for every individual patient. These total scores were then divided into four groups. RESULTS: Synthesis of histo-morphological pattern of metastasis in combination with the number of metastatic lymph nodes showed highest concordance/significance in respect of disseminated disease (p = 0.0029), local recurrence (p = 0.0008) and regional lymph node metastasis (p = 0.0000) as well as survival rate (p = 0.0000). CONCLUSION: The newly introduced histological scheme seems to provide more accuiate and detailed information on the prognosis of SCC in the head and neck area.

Aged↗

PubMed1998

Identification and characterization of Arcobacter isolates from broilers by biochemical tests, antimicrobial resistance patterns and plasmid analysis.

A total of 89 Arcobacter butzleri isolates obtained from freshly slaughtered broilers was investigated for their biochemical capacities by using the API CAMPY system as well as additional growth and tolerance tests, for their antimicrobial resistance patterns and their plasmid content. Among these techniques, biochemical profiling and antimicrobial resistance testing proved to be the most discriminatory methods as confirmed by the calculation of discriminatory indices. These two methods might represent valuable tools for epidemiological analysis of A. butzleri isolates. Small plasmids of up to 5 kbp were detectable in only 21 of the 89 isolates while the remaining 68 A. butzleri isolates were plasmid-free.

Abattoirs↗

PubMed1998

Surface EMG and myosonography in the detection of fasciculations: a comparative study.

Surface electromyography (EMG) and muscle sonography both facilitate the detection of fasciculations. This study was conducted to evaluate the prevalence of fasciculations in 10 lower extremity muscles in 58 subjects 47 +/- 18 years of age without and 54 patients 52 +/- 15 years of age with various neuromuscular diseases (3 with inflammatory myopathy, 15 with lower motor neuron disease, 22 with acquired and 11 with hereditary motor and sensory neuropathy (HMSN), and 3 with adrenomyeloneuropathy). When each muscle was screened by means of myosonography for 10 seconds, fasciculations were found in up to 8 muscles in 11 control subjects (19%) and in up to 10 muscles in 41 patients (76%). Within the same recording period surface EMG revealed fasciculations in 5 control subjects (9%) and 30 patients (56%), whereas during a recording time of 20 minutes fasciculations were detected in 55 (95%) control subjects and all patients. An amplitude of 400 microV proved to be the optimum cutoff between fasciculations for healthy subjects and patients with neuromuscular disease (accuracy, 74%). Myosonography allowed differentiation of both groups with an accuracy of 79%. Surface EMG was more liable to artifacts than myosonography. The average interval between subsequent fasciculations cannot be used to differentiate patients with acquired and hereditary polyneuropathy and with lower motor neuron disease. Long-term surface EMG recording indicates fasciculations to occur in almost all patients with neuromuscular disease and the vast majority of healthy subjects. Muscle ultrasonography was more convenient and reliable than surface EMG in differentiating patients and healthy subjects.

Adult↗

PubMed1998

Safety and clinical efficacy of zileuton in patients with chronic asthma.

Zileuton, a leukotriene pathway inhibitor used to treat asthma, improves lung function, relieves symptoms, and is well tolerated. The purpose of this 12-month, parallel-group, open-label study was to assess the efficacy of zileuton and evaluate liver function in patients treated with this drug (approximately 2% of patients treated with zileuton in controlled trials had reversible liver enzyme elevations). A total of 2,947 patients at 233 centers in the United States were randomly assigned in a 5:1 ratio to treatment with zileuton plus usual asthma care or usual asthma care alone. Efficacy variables included asthma exacerbations; need for alternative treatment, steroid rescue, emergency care, and hospitalizations; forced expiratory volume in 1 second (FEV1); and asthma symptom scores. The safety evaluation included measurement of alanine aminotransferase levels. Patients treated with zileuton had significantly fewer corticosteroid rescues (P < 0.001), required less emergency care (P < 0.05), had fewer hospitalizations, and had greater increases in FEV1 (P = 0.048). They also had significantly greater improvements in asthma symptoms. Increases in alanine aminotransferase levels to three times or more the upper limit of normal occurred in 4.6% of patients treated with zileuton and 1.1% of those receiving usual care (P < 0.001); most increases occurred during the first 2 to 3 months. Alanine aminotransferase levels decreased to less than two times the upper limit of normal or to baseline levels during zileuton treatment or after drug cessation. Jaundice or chronic liver disease did not develop in any patient. Adding zileuton to the therapeutic regimens of patients with asthma is likely to improve asthma control and lower utilization of healthcare resources.

Asthma↗

PubMed1996

Interleukin-10 regulation in normal subjects and patients with asthma.

Interleukin-10 or cytokine synthesis inhibitory factor has important antiinflammatory activities in immune diseases. We speculated that diminished IL-10 production in asthma would permit the unopposed synthesis of proinflammatory cytokines, contributing to the development and severity of asthma. Our data demonstrate constitutive secretion of IL-10 into bronchoalveolar lavage (BAL) fluid of normal, nonasthmatic subjects (130 +/- 61 pg/ml; n = 8). Asthmatic patients' BAL fluid was characterized by diminished concentrations of IL-10 (9 +/- 18 pg/ml; n = 8; p < 0.01 compared with that of normal subjects). By using the RNA-based polymerase chain reaction, we demonstrated that diminished IL-10 occurred as a result of inhibition of transcription. IL-10 transcription, but not protein, was observed at the time of the late asthmatic response. We speculate that the subsequent appearance of IL-10 protein could contribute to the resolution of the late asthmatic response. Similar to what was observed in the BAL fluid, peripheral blood mononuclear cells of patients with asthma demonstrated decreased spontaneous (0.01 +/- 0.01 ng/ml-asthmatic and 0.09 +/- 0.04 ng/ml-normal; p < 0.05) and stimulated (0.60 +/- 0.22 ng/ml-asthmatic and 1.69 +/- 0.49 ng/ml-normal; p < 0.05) IL-10 production compared with normal subjects. In support of the hypothesis that IL-10 mitigates the development of inflammation, we demonstrated that the addition of a neutralizing anti-IL-10 antibody to resting peripheral blood mononuclear cell cultures of normal subjects stimulated the spontaneous production of interferon-gamma (10.4 +/- 4.3 to 152.4 +/- 23.6 ng/ml; p < 0.01). Finally, we reasoned that corticosteroids might exert at least part of their antiinflammatory activity through the induction of IL-10 secretion. However, methylprednisolone inhibited the lipopolysaccharide-stimulated production of IL-10 (2.34 +/- 0.49 ng/ml IL-10 with lipopolysaccharide alone to 1.11 +/- 0.38 ng/ml in the additional presence of 10(-6) mol/L methylprednisolone; p < 0.05).

Adult↗

PubMed1996

Effects of silibinin and antioxidants on high glucose-induced alterations of fibronectin turnover in human mesangial cell cultures.

To elucidate the primary mechanism of high glucose cytotoxicity, the cytoprotective properties of antioxidants against metabolical disorders were assessed in human mesangial cell (HMC) cultures. An 8-day incubation of HMC with high glucose concentration (30 mM) resulted in an extracellular accumulation of the matrixprotein fibronectin (FN), owing to both an expansion of the matrix-associated pericellular FN and a 60% increase of the soluble molecule in the culture medium. The high glucose-induced FN alterations were not due to osmotical effects, as assessed by an iso-osmotic mannitol control. Rather, they are mediated by oxygen-free radicals because the combined treatment of HMC with high glucose and either the antioxidative flavonoid silibinin (given as the water soluble derivative silibinin-C-2,3-dihydrogensuccinate disodium salt) or a radical scavenger cocktail totally prevented the extracellular FN accumulation. This is corroborated further by the determination of malondialdehyde, a product of lipid peroxidation. Incubation of HMC with high glucose resulted in an increase of malondialdehyde in cell homogenates which was completely counteracted by either silibinin or a radical scavenger cocktail. Silibinin alone had no effects on protein synthesis and culture growth. The data presented are compatible with oxidative stress induced by high glucose concentration in HMC cultures. The study further substantiates the proposed role of silibinin in the amelioration of glucose cytotoxicity in renal cells.

Antioxidants↗

PubMed1995

Fibronectin expression in human mesangial cell cultures and its alterations by adriamycin.

Human mesangial cell (HMC) cultures synthesize cellular fibronectin (FN), which is secreted and incorporated into a fibrillar extracellular matrix (ECM). The anticancer drug adriamycin (ADR) induces changes in extracellular FN deposition. As revealed by immunofluorescence staining, a 24 h incubation of the cells with 2 micrograms ADR/ml resulted in a marked expansion of the pericellular FN fibers, which may be due to either an increased synthesis or a decreased FN degradation. The effects of ADR on FN mRNA were analysed by northern hybridization and in vitro translation. Steady-state FN mRNA levels were significantly increased by 60% following ADR administration. However, yields of radioactivity incorporated into FN by cell-free translation remained constant (2.3 +/- 0.7%, n = 24, vs controls 2.2 +/- 0.8% of total radioactivity, n = 23). The quality of translation products was not affected by the drug, whereas translation efficiency of total RNA from ADR-treated HMC was only 75% of controls. The data presented suggest a negative feedback control of FN expression on the level of translation. Extracellular FN accumulation in the experimental model of ADR-induced progressive glomerulopathy therefore cannot be explained by an increased FN synthesis, but is rather regarded a consequence of proteinase inhibition. This assumption is compatible with a diminished number of FN fragments recently demonstrated in the culture medium of ADR-treated HMC, and is further corroborated by the loss of urinary FN degradation products accompanying the onset of proteinuria in ADR-treated rats.

Blotting, Northern↗

PubMed1995

Accelerating momentum for change!

As we develop strategies to compete globally, we are challenged with integrating our resources to execute these strategies effectively. Many companies are in the midst of dramatic shifts in corporate cultures, giving more responsibility to employees while raising expectations for their performance. The extent of these changes is far reaching and brings significant challenges to both employees and corporations. This article is a continuation of the evolution (over five years) of a corrective action/continuous improvement process implemented at Exide Electronics. It discusses organizational structures, including steering committees, corrective action teams, task teams, and work cells. Specific expectations, goals, and results of the teams are presented, along with ground rules for functioning within the organization. After structuring the organization and coordinating the resources effectively, the next challenge is accelerating momentum for change. The presentation also discusses the evolutionary process required to make a culture focused on change, including ongoing communication and feedback, constant evaluation and direction of the process, and measuring and paying for performance.

Communication↗

PubMed1993

The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma.

OBJECTIVE: To evaluate the effectiveness of inhibiting the formation of the 5-lipoxygenase products of arachidonic acid by the 5-lipoxygenase inhibitor zileuton in the treatment of mild-to-moderate asthma. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University hospitals and private allergy and pulmonary practices. PATIENTS: A total of 139 persons with asthma who had a forced expiratory volume in 1 second (FEV1) of 40% to 75% of the predicted value and who were not being treated with inhaled or oral steroids. INTERVENTION: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks. MEASUREMENTS: Airway function, beta-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4). RESULTS: Zileuton produced a 0.35-L (95% CI, 0.25 to 0.45 L) increase in the FEV1 within 1 hour of administration (P < 0.001 compared with placebo), equivalent to a 14.6% increase from baseline. After 4 weeks of zileuton therapy, airway function and symptoms improved, with the greatest improvements occurring in the 2.4 g/d group: This group's FEV1 increased by 0.32 L (CI, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (CI, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of beta-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (CI, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (CI, 6.6 to 46.5 pg/mg creatinine) in the 2.4 g/d and 1.6 g/d groups, respectively, compared with a slight increase in the placebo group (P = 0.007 and P = 0.05). No difference was noted in the number of adverse events among treatment groups. CONCLUSIONS: Inhibition of 5-lipoxygenase can improve airway function and decrease symptoms and medication use in patients with asthma, suggesting that this inhibition can be useful therapy for asthma. Also, 5-lipoxygenase products may mediate part of the baseline airway obstruction in patients with mild-to-moderate asthma.

Adult↗