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ObjectiveTo determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects.DesignA 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement.SubjectsSixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months.MeasurementsEfficacychanges in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices.Safetyblood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms.ResultsForty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality.ConclusionA dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.

Background Zileuton, a leukotriene pathway inhibitor, was compared with slowly absorbed theophylline in a randomized, double-blind study of patients with chronic asthma. The primary efficacy measure was improvement in forced expiratory volume in 1 second (FEV1). Methods Eligibility criteria included FEV1 of 40% to 80% of predicted, documented reversibility of airway disease, and age 18 to 60 years. Initially, the theophylline dosage was titrated to achieve trough concentrations of 8 to 15 µg/mL. After washout and 1-week placebo lead-in, patients were randomly assigned to 13 weeks of the appropriate theophylline dose or zileuton, 400 or 600 mg 4 times daily. The FEV1 was measured before the morning dose at 2-week intervals and serially after the dose on days 36 and 92. Patients kept daily diaries of asthma symptoms, β-agonist usage, and peak expiratory flow rate; on days 36 and 92, they completed quality-of-life questionnaires. Results Of 471 eligible patients at 38 centers, 377 were randomly assigned to the study; 313 completed the study. On first-dose administration, all groups showed 11% to 13% improvement in FEV1 within 30 minutes. Patients who received zileuton, 400 mg, had significantly greater improvement at several points than did theophylline-treated patients. The range of long-term maximum improvement in FEV1 in the groups was 30% to 34% (P=.40 for zileuton 600 mg; P=.90 for zileuton 400 mg vs theophylline). Initially, the theophylline group improved significantly more in symptom scores, β-agonist usage, and peak expiratory flow rate, but at maximal effect there was no significant difference. All groups showed significant improvement in quality of life. No overall differences were observed between the zileuton dosage groups. Adverse events were comparable in all groups. Conclusion Zileuton appears as effective and safe as theophylline in patients with chronic asthma. [ABSTRACT FROM AUTHOR]

Azathioprine, an analog of 6-mercaptopurine has been used as a steroid-sparing agent in the treatment of inflammatory bowel disease for over 30 years. Hypersensitivity reactions to azathioprine including fever, myalgia, arthralgia, rash are well documented in the literature. Here, we report 2 cases of azathioprine hypersensitivity in patients with inflammatory bowel disease manifesting with the unusual symptom of profound muscular weakness resulting in inability to perform simple tasks such as lifting even light objects, sitting upright, and walking a few steps. Development of severe weakness raised concern about myositis, rhabdomyolysis, myopathy, and sepsis in these patients. Discontinuation of azathioprine resulted in prompt improvement of muscular weakness, and rechallenge led to recurrence of similar symptoms within hours. These observations suggest that the development of muscular weakness in patients on azathioprine should be considered as an adverse effect of the drug. Failure to recognize this adverse outcome can lead to prolonged periods of muscular weakness in this group of patients.

The use of high-frequency (5 MHz) ultrasonography was studied in 11 jennies (7 non-pregnant and 4 pregnant) to characterize the reproductive organs and follicular activities at different stages of reproduction. The result showed close similarity with the mare. The visibility of endometrial folds increased towards ovulation. A positive correlation (p < 0.001; tau = 0.79) was found between the score of the folds and the size of the dominant follicle. The diameter of the uterus and the size of the dominant follicle were significantly correlated (p < 0.001; r = 0.80). In pregnant jennies, an embryonic vesicle was detectable at 14 days. Follicular growth was characterized by more than one wave. The smallest ovarian follicle was 2 mm and the largest 40mm. Depending on the reproductive stage, up to 13 follicles were detected per ovary. After monitoring 84 cycles, a mean (+/- SD) diameter of 34.4 +/- 3.6 mm (27.5-40.2 mm) of the preovulatory follicle and 67.85% incidence of single ovulation were found. The mean (+/-SD) interovulatory interval was 25.7 +/- 6 days. This study proved that high-frequency ultrasonography is highly effective in characterizing the reproductive organs and follicular activity of jennies and could be useful in the reproductive management of donkeys.

Serial ultrasonography was performed on seven jennies to study the effect of seasonally fluctuating body condition on ovarian activity during the dry, short rainy and long rainy seasons. Kendall Tau correlations and differences of least square mean values were compared. A distinct seasonal pattern was observed both in body condition and ovarian activity. The mean (+/-SD) Body Condition Score (BCS) was lowest during the dry season 2.6 +/- 0.45 when compared with 3.5 +/- 0.52 and 3.9 +/- 0.58 during the short and long rainy seasons, respectively. The mean (+/-SD) number of total follicles was also proportionally low 7.3 +/- 1.6 during the dry season compared with 9.6 +/- 2.4 and 11.3 +/- 3.3 found during the short and the long rainy seasons, respectively. The BCS was positively correlated to the total number of follicles and the diameter of the largest follicle during all seasons. Periods of increasing BCS and transition between seasons with both increasing and decreasing body conditions were strongly correlated to the number and size of ovarian follicles. Seasonal fluctuation in the body condition was found to be the result of variation in feed resource and ovarian activity was also closely following this seasonal pattern. The improvement in body condition has generally, a positive impact on emergence of small growing follicles there by having influence on the total count of ovarian follicles.

In a retrospective analysis of our patient population, 20 difficult-to-treat patients with asthma were found to have clinical and laboratory evidence of specific antibody deficiency, and several had mild hypogammaglobulinemia. Intravenous immunoglobulin replacement therapy at 400-600 mg/kg every 3-4 weeks gave remarkable clinical benefits, with reduction in morbidity, number of hospitalizations, steroid therapy, and number of respiratory infections. We believe that, in this group of patients, the use of intravenous immunoglobulin perhaps allows the achievement of asthma prevention rather than an amelioration of inflammation.

Diabetes mellitus is a heterogeneous group of diseases characterized by high blood glucose levels due to defects in insulin secretion, insulin action, or both. With the number of cases expected to increase rapidly in the years to come, diabetes is a growing health challenge worldwide. Of the approximately 16 million diabetics in the United States, about 1.5 million suffer from type 1 diabetes. In this catabolic disorder afflicting predominantly young individuals, blood insulin is almost completely absent, leading to hyperglycemia and alterations in lipid metabolism. Type 1 diabetes is thought to be induced by a toxic or infectious insult that occurs in genetically predisposed individuals. With recent advances in the understanding of the involved immunology and cellular and molecular mechanisms, researchers strive to battle the disease with new preventive and corrective strategies.

Two possible uses exist for intravenous gamma-globulin (IVIG) therapy in asthma. First, it has been suggested that high-dose IVIG can serve as an anti-inflammatory, immunomodulatory agent in steroid-dependent asthma patients. Second, IVIG can be used as a replacement treatment in those asthma patients with frank hypogammaglobulinemia or more subtle antibody deficiencies. The mechanisms by which IVIG functions are widely different in these two potential uses. Clear characterization of the patients' immune status is pivotal in choosing whether to use IVIG. The assessment should not be limited to simple determination of serum immunoglobulin A (IgA), IgG, IgM, and IgG subclass levels. When clinically warranted, the specific antibody response to active immunization with antigens such as those in Pneumovax may be invaluable in identifying patients with subtle antibody-deficiency disorders. Asthma in those patients may be improved markedly if infection is prevented by antibody-replacement therapy with IVIG.

Although anaphylaxis continues to be recognized as a life-threatening clinical problem, efforts to develop in-vitro methods for diagnosis and verification continue. The results have been interesting but not yet definitive, so that the necessity for clinical diagnosis remains pivotal.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease with uncertain pathology. Studies have suggested a pathogenic role for T(H)2 cells. Previously, we demonstrated, in a small group of patients, that T(H)2 reactivity to a major Aspergillus fumigatus antigen was restricted by HLA-DR2 or HLA-DR5 alleles., Objectives: We sought to confirm whether susceptibility to ABPA is exclusively associated with HLA-DR locus and to investigate the involvement of HLA-DQ genes in the development of ABPA., Methods: Genomic DNA was extracted from patients with ABPA, patients without ABPA but with positive A fumigatus skin test responses and asthma or cystic fibrosis, and healthy control subjects. HLA-DR and HLA-DQ genes were detected by using low-resolution typing; high-resolution typing was done only on HLA-DR2- and HLA-DR5-positive individuals by using sequence-specific primers (PCR-SSP)., Results: A significantly higher frequency of HLA-DR2 was observed in patients with ABPA versus those without ABPA (corrected P <.01) or healthy control subjects (corrected P <.01). Genotype analysis revealed that susceptibility to ABPA is associated with HLA-DR2 alleles DRB1*1503 and DRB1*1501 and, to a lesser extent, with the HLA-DR5 allele DRB1*1104. The presence of DR4 or DR7 alleles in non-DR2/5 patients with ABPA suggests that these alleles may also be contributing factors in this disease. Another striking observation was the significantly high frequency of HLA-DQ2 in patients without ABPA (67. 4%) compared with patients with ABPA (20.5%) and normal control subjects (37.7%), suggesting that these alleles may confer protection in the population without ABPA., Conclusion: These genetic studies suggest that HLA-DR molecules DR2, DR5, and possibly DR4 or DR7 contribute to susceptibility while HLA-DQ2 contributes to resistance and that a combination of these genetic elements determines the outcome of ABPA in patients with cystic fibrosis and asthma.

Background: Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy., Methods: We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met immunologic and pulmonary-function criteria for corticosteroid-dependent allergic bronchopulmonary aspergillosis. A response was defined as a reduction of at least 50 percent in the corticosteroid dose, a decrease of at least 25 percent in the serum IgE concentration, and one of the following: an improvement of at least 25 percent in exercise tolerance or pulmonary-function tests or resolution or absence of pulmonary infiltrates. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks., Results: There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). The rate of adverse events was similar in the two groups. In the subsequent open-label phase, 12 of the 33 patients who had not had a response during the double-blind phase (36 percent) had responses, and none of the patients who had a response in the double-blind phase of the trial had a relapse., Conclusions: For patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole can lead to improvement in the condition without added toxicity.

Background: There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta2-agonists versus low-dose inhaled corticosteroids in the treatment of asthma., Objective: To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma., Methods: Salmeterol (42 microg twice daily), BDP (84 microg four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV1) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed., Results: There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV1 of 0.28 L (SE = 0.04) and 0.23 L (SE = 0.04), respectively, compared with 0.08 L (SE = 0.04); P < or = .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo (P < or = .033; changes from baseline of 1.29 (SE = 0.26) and 1.42 (SE = 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE = 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments., Conclusions: Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.

The worldwide incidence of asthma and of allergic respiratory diseases is increasing (Akiyama K. 'Environmental allergens and allergic diseases.' Rinsho Byori 1997;45(1):13. D'Amato G, Liccardi G, D'Amato M. Environment and development of respiratory allergy. II. Indoors. Monaldi Arch Chest Dis 1994;49(5):412. Weeke AR. Epidemiology of allergic diseases in children. Rhinol Suppl 1992;13:5. Ulrik CS, Backer V, Hesse B, Dirksen A. Risk factors for development of asthma in children and adolescents: findings from a longitudinal population study. Respir Med 1996;90(10):623.) This has been attributed to several factors, including lifestyle changes and an expanding variety of potential causative allergens. Management of asthma entails preventive and acute medications, immunologic therapies, and removal of the identified allergen(s) from the patient's environment. Without the latter, patients may not experience full symptomatic relief. This case report describes a patient who developed bronchial asthma subsequent to an infection of tinea pedis and pedal onychomycosis; antifungal management resulted in full resolution of his tinea pedis, onychomycosis and asthma.

Background: Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma., Objectives: We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction., Methods: Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (>/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results., Results: Zafirlukast was significantly (P <.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P /=0.5-unit change from baseline; P

Objectives: Specific recommendations for administering the influenza vaccine to patients with egg allergy are based on limited scientific data. The objectives of this investigation were to determine the safety of a 2-dose administration of an influenza vaccine to patients with egg allergy and to evaluate the usefulness of skin testing with the influenza vaccine before administration., Study Design: In this multicenter clinical trial, clinical histories of egg allergy were confirmed by skin testing with egg and, if possible, by oral challenges with egg. Subjects with egg allergy received the vaccine in 2 doses, 30 minutes apart; the first dose was one tenth and the second dose nine tenths of the recommended dose as determined by age. Subjects without egg allergy were recruited as control subjects and received 1 age-determined dose of the vaccine. Skin prick tests with the influenza vaccine were performed on all subjects., Results: From 1994 to 1997, 83 subjects with egg allergy and 124 control subjects were evaluated. The content of ovalbumin/ovomucoid was 0.1, 1.2, and 0.02 micrograms/mL, respectively in the 1994-95, 1995-96, and 1996-97 influenza vaccines. Results of vaccine skin prick tests were positive in 4 subjects with egg allergy and in 1 control subject. All patients with egg allergy tolerated the vaccination protocol without any significant allergic reactions., Conclusions: These results demonstrate that patients with egg allergy, even those with significant allergic reactions after egg ingestion, can safely receive an influenza vaccine in a 2-dose protocol when the vaccine preparation contains no more than 1.2 micrograms/mL egg protein.

Background: Therapy with salmeterol, a long-acting, selective, inhaled beta 2-adrenergic agonist, is effective and safe for patients with persistent asthma; however, few long-term studies comparing salmeterol with current combination treatment regimens have been reported., Methods: A multicenter, randomized, placebo-controlled, double-blind study was conducted in 386 patients over 41 to 46 weeks in 27 medical centers (two thirds of the investigators were primary care physicians). Patients were randomized to receive either salmeterol or placebo, and further randomized to weaning or nonweaning from current asthma therapies (except inhaled corticosteroids). Treatment groups were: salmeterol/weaning (S + W), placebo/weaning (P + W), salmeterol/no weaning (S + NW), and placebo/no weaning (P + NW). Attempts at active weaning were carried out at the discretion of the investigator for 2 to 6 weeks. Pulmonary function, albuterol use, and asthma symptoms were measured., Results: The clinical benefits of salmeterol occurred despite weaning off existing nonsteroidal asthma medications. The mean morning peak expiratory flow rate was significantly increased in the S + W group (32.3 L/min) compared with both the P + W (4.9 L/min) and P + NW (6.8 L/min) groups (P < .001). Compared with the P + W and P + NW groups, the S + W group experienced significant (P < .05) improvements in overall mean asthma symptom scores, mean number of puffs of supplemental albuterol, the percentage of days with no supplemental albuterol use, and the mean number of awakenings caused by asthma (except for the P + NW comparison, P = .090). No significant differences were noted between treatment groups in any safety evaluation, including 12-lead electrocardiograms., Conclusions: The addition of salmeterol in the treatment of persistent asthma resulted in sustained improvement in pulmonary function and symptoms. The long-term use of salmeterol is safe and improves the clinical course and stability of asthma following reductions in nonsteroidal asthma therapy.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by the mold Aspergillus fumigatus. We previously reported that the majority of T cell clones (TCC) isolated from three ABPA patients, and specific for a dominant Ag of A. fumigatus, Asp f 1, were IL-4-producing CD4+ Th2 cells capable of responding to Ag in association with the HLA-DR subtypes DRB1*1501, *1503, and *1601 for HLA-DR2, and DRB1*1101, *1104, and *1202 for HLA-DR5. In the present study we extended the previous findings to determine whether the observed restriction with the HLA-DR2/5 subtypes held importance in a larger patient population. Serotyping revealed that 16 of 18 ABPA patients were either HLA-DR2, HLA-DR5, or both. Compared with a normal control population, the frequencies of HLA-DR2 (50 vs 22.3%) and HLA-DR5 (44.4 vs 19.8%) were significantly increased in these ABPA patients. Genotype analyses of an additional 15 patients identified the same HLA-DR subtypes previously shown functional for Asp f 1 Ag presentation. The relative avidities of Asp f 1 peptides for the purified HLA-DR subtypes, DRB1*1501 (functional) and DRB1*1502 (nonfunctional), were examined to determine whether differential binding to the HLA-DR subtypes explains successful Ag presentation. Similar low binding avidities were detected for both HLA-DR subtypes, indicating that the functionality cannot be simply explained by differences in binding affinities. Thus, the limited number and their role in Ag presentation emphasizes the possibility that the six identified HLA-DR subtypes are important in the pathophysiology of ABPA.

Chronicity and high therapeutic cost prompted this study to determine a cost-effective and efficacious regimen in treating narcotic-induced constipation. The efficacy of lactulose was compared with polyethylene glycol 3350/electrolyte solution for relief of methadone-induced constipation. This was a randomized, triple cross-over after control run-in (no treatment) study conducted at a methadone maintenance program in Baltimore, Maryland in 57 patients who are affected by opiate-induced constipation. The study was measured by self-reported frequencies, consistency, and ease of defecation during a 1 week run-in control period, followed by 3 treatment phases of 2 weeks each. Polyethylene glycol 3350/electrolyte solution and lactulose produced more "nonhard" stools than the placebo (P < 0.01) and control (P < 0.003). Polyethylene glycol 3350/electrolyte solution produced the loosest stool (P < 0.0001) compared with the control, whereas lactulose had the most adverse effects. There were no significant differences in reducing hard stool formation in either experimental group, but both were better than having nothing or just the placebo. Polyethylene glycol/electrolyte solution resulted in the loosest (diarrheal) stool. It is also likely that polyethylene glycol/electrolyte solution is the most cost effective.

Both suppressor oncogene and proliferative activity are believed to indicate colon cancer risk. The retinoblastoma (Rb) gene is a suppressor oncogene affecting cell differentiation. Retinoblastoma gene inactivation is associated with tumour development. However, the relation of the Rb protein to cell proliferation and colon tumour formation is unknown. Retinoblastoma protein quantity was correlated with proliferative activity in flat, unaffected mucosa specimens from 36 cancer patients, 21 non-cancer control subjects and in 29 tumour tissue samples from cancer patients. Nuclear Rb protein was measured by using automated CAS-200 image analysis of monoclonal antibody labelled frozen sections from fresh, surgically removed tissue. All colon cells within 15 whole crypts were imaged. Proliferative activity was also measured by using analysis with Ki-67 monoclonal antibody. Retinoblastoma protein content correlated directly with proliferative activity in flat mucosa of non-cancer control subjects (r = 0.63; P < 0.001; n = 21). A significant correlation was also found in flat mucosa specimens of non-metastatic (Duke's stages A and B) cancer patients (r = 0.52; P < 0.01; n = 22). However, Rb protein did not correlate with proliferation in flat mucosa from metastatic (Duke's stages C and D) cancer patients (r = 0.03; NS; n = 14) or in cancer tissue (r = 0.068; NS; n = 29). Mucosal Rb protein in the colon normally increases as proliferation increases. Dissociation between Rb protein and colon proliferation may occur in flat mucosa in patients with a higher risk of metastatic tumour growth. Future studies comparing Rb protein quantity and proliferative activity may help identify high-risk colon cancer patients.

Background: A patient with complaints of rhinitis and asthma occurring at work presented for consultation., Objectives: To evaluate the role of the foods and spices with which he worked, in the causation of his complaints, and to evaluate his immune reactivity to these materials., Methods: Allergy skin testing and in vitro RAST assays were carried out. After demonstrating specific reactivity to fennel, SDS-PAGE electrophoreses was carried out., Results: Positive skin tests to grass, ragweed, and freshly prepared fennel seed were found. Serum IgE antibodies to fennel were quite high. Immunoblotting studies showed reactions to two components in fennel extract as well as to components in mugwort, paprika, short ragweed and black pepper., Conclusion: This case of occupational rhinitis and asthma in an atopic individual involves sensitivity to unique allergens in fennel, with molecular weights of 67 to 75 KD.

Background: Allergic fungal sinusitis has been described since 1983 but has been a diagnostic problem due to the lack of agreed upon criteria that should be met for diagnosis: such criteria have recently been proposed by deShazo and Swain., Objectives: The findings in ten patients previously diagnosed as having allergic fungal sinusitis were reviewed and compared with the recently proposed criteria., Methods: A detailed review of each of these ten previously diagnosed cases was undertaken in order to compare their findings with these newly proposed criteria., Results: The newly proposed criteria were found to be highly valid standards for the diagnosis of allergic fungal sinusitis; no significant discrepancies were found., Conclusion: The criteria proposed by deShazo and Swain for the diagnosis of allergic fungal sinusitis should be widely adopted. Utilizing these criteria, a broadly based study of the true prevalence of this disease should be undertaken.

Nedocromil sodium and cromolyn sodium are the only two currently available nonsteroid anti-inflammatory agents for treatment of asthma. Clinical differences between the two agents remain under continuous investigation with reports differentiating the two on the basis of atopy of the patient and reversibility of bronchoconstriction. This study investigated the efficacy of nedocromil sodium (4 mg, qid) for treatment of mild-to-moderate asthma in comparison to placebo using cromolyn sodium (2 mg, qid) as an active control treatment. Patients were primarily allergic asthmatics (with at least 15% reversibility) previously maintained on a regimen of regular bronchodilator therapy. During a 2-week run-in period, the patient's slow-release theophylline therapy was removed, and the patients were randomized to treatment after deterioration of asthma control (asthma symptom summary score of 3 for 7 of the 14 days). After 8 weeks of treatment, patients were returned to as occasion requires bronchodilator therapy, as per the 2-week baseline period. The results demonstrate that patients treated with nedocromil sodium showed statistically significant improvements during the primary time period (mean weeks 3 through 8) over placebo-treated patients as evidenced by all indexes of asthma symptoms, pulmonary function measures, and decreased bronchodilator reliance (p<0.05). Patients treated with cromolyn sodium demonstrated similar improvements over placebo-treated patients. Comparisons between nedocromil sodium and cromolyn sodium showed the two agents to be comparable in this group of primarily allergic patients with reversible disease. Between-group differences were noted for 3 of the 13 variables (nighttime asthma, FEV1, and forced expiratory flow rate between 25 % and 75% of the FVC) in favor of cromolyn sodium when the data were pooled during the primary time period. The number of patients missing 1 or more days from work/school/regular activity due to asthma was significantly fewer compared with placebo, and favoring nedocromil sodium over cromolyn sodium. No differences were observed among the three treatments for adverse events. This study demonstrated that in primarily allergic patients with reversible airways disease, nedocromil sodium and cromolyn sodium are both significantly more effective than placebo for treatment of mild-to-moderate asthma.

Objective: To identify risk factors associated with bicycling injuries, and to further define the magnitude of this problem., Design: Information from the database of the Kingston and Region Injury Surveillance Program (KRISP)-the Kingston reporting centre for the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP)-was used to identify all bicycling injuries in children who were treated at participating emergency departments in 1994. A follow-up mail survey was then used to obtain further information about the incidents., Setting: Two southeastern Ontario emergency departments that serve a regional population of 125,000 people. FOCUS POPULATION: Children and youth aged 0-19., Results: The KRISP database documented 348 bicycling injuries in this population. Mail surveys were sent to 280 subjects and completed by 163 of these children or their parents. Our descriptions of the circumstances of the injury events and of the most frequent resulting injuries are similar to patterns in previously published reports. Sixty percent of the children who returned surveys indicated they were injured on bicycles they had been riding for less than one year, even though most of these children were experienced bicycle riders. We estimated that there were 9.4 injury events per 1000 children in the Kingston region., Conclusions: Bicycling injuries remain a significant cause of childhood morbidity and mortality. We found that many children were injured on bicycles with which they were not familiar. Consequently, we propose as a preventive measure that children be targeted at the time of purchasing a new bicycle for helmet purchase, bicycle fitting and enrollment in safety courses.

Objective: To determine the inhibitory constant, Ki, of cocaine for a number of the different genetic variants of human plasma cholinesterase., Design: In vitro analysis of plasma cholinesterase activity in the presence of cocaine as a competitive inhibitor., Methods: Six normal (UU) control sera and seven sera with the following plasma cholinesterase genotypes were assayed: AA, UA, AS, UF, US, AF and SS. Plasma cholinesterase activity was determined in the samples by colorimetric measurement of propionylthiocholine metabolism over a range of concentrations. Competitive activities were then determined in the presence of varying concentrations of cocaine. Double reciprocal plots (1/v vs 1/S) were used to calculate Km and Vmax for propionylthiocholine, and Ki for cocaine for each genotype., Results: The variant forms of the plasma cholinesterase had high cocaine Ki values--all were approximately ten times greater than the Ki for normal plasma cholinesterase., Conclusions: Since the inhibitory constant is an indirect measure of an enzyme's affinity for a competing substrate, a high Ki for cocaine at recreational or therapeutic concentrations would translate into a longer in vivo half-life. Our results support the growing evidence that low plasma cholinesterase activity predisposes to cocaine toxicity.

Two studies have been carried out specifically to examine the speed of onset of action of intranasal nedocromil sodium 1% (Tilarin) for the relief of symptoms due to ragweed allergic rhinitis. One, a multicentre placebo-controlled comparative study using a QID regimen, 1 spray per nostril, was designed to assess the speed of onset of action of nedocromil sodium during the first week of treatment in patients with rhinitis symptoms, and to evaluate the efficacy and safety of nedocromil sodium during 6 weeks of treatment (1). A 1-week baseline, the start of which was timed to coincide with the start of the ragweed season, was followed by 6 weeks double-blind trial treatment; only patients (n = 166) who were symptomatic at the end of baseline were included in the double-blind phase. Non-parametric analyses of all variables including a summary score (stuffy nose, runny nose, itchy nose and sneezing) showed that the onset of action of nedocromil sodium occurred on the first day of treatment. Further, patients using nedocromil sodium had less symptoms during the 10 days of peak pollen, at which time physician assessment showed reduced mucosal oedema and nasal discharge, and both patient and clinician opinions favoured nedocromil sodium. No significant adverse events were reported during this 6-week study. In the second study (2), 104 patients were randomly allocated to receive either nedocromil sodium or placebo, QID. They then spent 10 hours per day for 2 consecutive days in Iowa City Park during the peak of the ragweed season. Only patients showing significant symptoms of seasonal allergic rhinitis (SAR) during 3 hourly baseline assessments were included. Over the 2-day period, symptom scores for stuffy nose, runny nose, itchy nose and sneezing, and global symptom summary scores, were recorded at 19 hourly time points. At home in the evening, patients recorded symptom scores for the post-exposure period. In comparison with placebo, nedocromil sodium significantly improved rhinitis symptoms within 2 hours, and this reduction in SAR symptoms was maintained throughout the 2-day exposure period. Post exposure symptom summary scores were also significantly lower in patients treated with nedocromil sodium than in those patients treated with placebo. Overall, very few adverse events were reported, none of them serious. In conclusion, nedocromil sodium 1% nasal spray acts rapidly, within 2 hours on the first day of treatment, to reduce ongoing symptoms of SAR. Relief of rhinitis symptoms is maintained throughout the peak pollen period with nedocromil sodium QID, which appears to be a safe and well tolerated treatment for ragweed SAR.

The labeling index (LI), a microscopic measurement of proliferative activity in colonic crypts, is proposed as an indicator of colonic cancer risk. Computed image analysis of proliferative regions is less labor intensive and more objective than is direct microscopy but has not been validated for labeling indices by direct comparison. The authors compared colonic crypt proliferation in 26 cancer and 13 noncancer patients by using Ki-67 monoclonal antibody (McAb) labeling of flat mucosa obtained from surgically removed, frozen specimens. In cancer patients, the mucosa specimen was excised 10 cm away from the tumor, and the LI was determined microscopically for the whole crypt, the upper two thirds, and the upper one third of 15 crypts. Nuclear antigen levels of 15 whole crypts were determined by using the CAS-200 computed image analyzer (Cell Analysis Systems, Elmhurst, IL). Cancer and noncancer specimens were compared as were microscopically determined LI and stained nuclei specimens by using image analysis. No statistically significant difference in proliferative activity of whole crypts, or the upper two thirds of crypts, was observed between cancer specimens and noncancer specimens from using either technique. However, a significant correlation existed between microscopic analysis and computed image analysis of labeled nuclei. Computed image analysis using Ki-67 McAb labeling can be used instead of microscopy to determine crypt LI, but neither method can be used to distinguish cancer specimens from noncancer specimens.

Background: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is difficult; a prerequisite for one approach is the detection of IgE sensitivity to A. fumigatus., Objective: The purpose of the present study was to examine skin test extracts of A. fumigatus from five different extract manufacturers to evaluate their reliability for detecting IgE reactivity., Methods: A total of 26 patients with previously diagnosed ABPA underwent intradermal skin testing with A. fumigatus skin test reagents obtained from five separate extract manufacturers from the USA, at 1,000 pnu/mL., Results: A marked disparity in skin test reactivity was seen in patients, such that the diagnosis would have been missed in a substantial number of patients if extracts from manufacturers A, B, or C would have been used in the initial skin test screening., Conclusion: It is clear that this finding of disparate skin test reactivity rates with extracts from different manufacturers can account for some degree of false negative skin test reactivity in patients suspected of having either ABPA or other mold sensitivity syndromes. A standardized skin test extract of A. fumigatus is badly needed for diagnostic purposes.

Efforts at understanding the patterns and prevalence rates of various causes of anaphylaxis are needed. This report is a first effort to address the issue and review the experiences of one voluntary hospital emergency room, where records from 326 (1.4%) of 23,647 emergency room reports for 1992 were analyzed. These results are compared to other already published results. Further study, on a national basis, is clearly necessary. It was remarkable that only 13/48 (27%) bee sting allergic patients were given self-injectable epinephrine and only 6/48 (12.5%) of these patients were referred to an allergist. Further, none of 165 other patients was referred to an allergist.

Background: Serum tryptase levels reflect mast cell activation and correlate with anaphylactic reactions. Elevated post-mortem serum tryptase levels have been found in witnessed fatal anaphylaxis., Objective: This study was designed to examine whether or not unwitnessed anaphylaxis may be a hitherto unrecognized cause of sudden unexplained death., Methods: Mast cell tryptase was measured by immunoassay in 68 post-mortem sera remaining from a previous study which reported elevated venom-specific IgE antibodies in 22 (23%) of 94 victims of sudden unexpected death. Autopsies were performed in all cases. The cause of death was independently reported by pathologists unfamiliar with the nature of this study., Results: Serum tryptase levels were elevated (> 10 ng/mL) in nine of 68 cases. The levels could not be predicted from the clinical circumstances surrounding death. Sera from four individuals contained both elevated tryptase and previously reported elevated venom-specific IgE., Conclusions: We conclude that mast cell activation may accompany up to 13% of sudden unexpected deaths in adults. Measurement of both tryptase and specific IgE antibody levels in post-mortem sera from persons experiencing sudden, unexpected death may identify a small subset of cases due to clinically unrecognized fatal anaphylaxis, including those due to insect stings.

Background: Food allergies are usually recognized by historical triggers; yet, on occasion, objective testing may be needed to demonstrate allergic causes more convincingly., Objective: Two atopic adult patients presented with respiratory and/or ocular symptoms with an unusual association to handling or eating of vegetables. A third atopic patient presented without attribution of symptoms to vegetable exposure. In all, work-up had revealed positive skin tests and in vitro assays for specific IgE to carrot and/or lettuce; none had gastrointestinal complaints., Methods: To assess further these unusual histories and/or IgE antibody findings, laboratory challenge was performed with nasal resistance being used as a monitor of rhinitic reaction., Results: The first two patients had prolonged nasal objective responses to challenge; the third had a transient response to one of two challenges., Conclusion: We conclude that lettuce and carrot can account for clinically significant IgE-mediated allergic reactions, manifested by nasal obstruction. This laboratory reaction to foodstuffs appears to correlate with patient-reported upper airway and ocular symptoms.

Summary: Parturitions of 338 among humid-zone ewes and 690 among subhumid-zone ewes gave rise to 361 and 797 live-born lambs, respectively. Mean age and weight at first parity were 431.3 days and 15.6 kg for the humid-zone ewes while those for the subhumid-zone ewes were 429.4 days and 17.0 kg. Early age at first parity is related to physiological age and growth of body weight which is closely related to early sexual maturity. The monthly distribution of parturitions is discussed with considerably higher peaks in October, April and May in the humid zone while in the subhumid zone, high frequencies were recorded in July, August, February and March. Higher parities significantly shortened the successive parturition intervals within and between the climatic zones with general intervals of 234.2 and 208.7 days among the humid- and the subhumid-zone ewes, respectively, at the fifth parity. The shortest parturition intervals (242.6 days) were recorded during the dryspell-minor wet season (August-October) in the humid zone and the major-wet season (May-July; 223.9 days) in the subhumid zone. Higher annual reproduction rates of 1.95 (1st year) and 1.79 (2nd year) lambs among the free-range ewes while subnormal rates of 1.72 (1st year) and 1.68 (2nd year) lambs among the humid-zone ewes were recorded. These differences are related to the natural service, parturition intervals, litter size and the availability of fodder plants as influenced by management (semi-tethering as against free-range). ZUSAMMENFASSUNG: Untersuchungen über traditionelle Schafproduktion in der humiden und sub-humiden Asante Region Ghanas II. Reproduktionsleistungen und Fruchtbarkeitsraten Gegenüber 690 Lebendgeburten bei 338 Mutterschafen in der humiden Zone (H) wurden in der semi-humiden Zone (SH) 797 Geburten bei 361 Mutterschafen erfaßt. Mit einem Erstlammalter zwischen 431,3 (H) und 429,4 (SH) Tagen und Körpergewichten von 15,6 kg (H) und 17,0 kg (SH) sind Mutterschafe zu diesem Zeitpunkt in der semi- humiden Zone schwerer. Das höhere Körpergewicht bestimmt weitgehend die sexuelle Frühreife. Die monatliche Verteilung der Ablammungen zeigte deutliche Häufungen in den Monaten Oktober, April und Mai (H) und Juli, August, Februar und März (SH). Eine höhere Anzahl von Ablammungen führte zu einer signifikanten Verkürzung der aufeinanderfolgenden Ablammungsintervalle innerhalb und zwischen den Klimazonen. Die Zwischenlammzeit zur fünften Ablammung reduzierte sich in der humiden Zone auf 234,2 Tage und in der subhumiden Zone auf 208,7 Tage. Die kürzesten Zwischenlammzeit wurden während der kleinen 'Dryspell'-Regenzeit (August-Oktober) in der humiden Zone (242,6 Tage) bzw während der Haupt-regenzeit (Mai-Juli) in der sub-humiden Zone (223,9 Tage) beobachtet. Während höhere Reproduktionsraten von 1,95 Lämmern (1. Jahr) und 1,79 Lämmern (2. Jahr) bei den freilaufenden Mutterschafen in der sub-humiden Zone festgestellt wurden, sind niedrigere Reproduktionsraten von 1,72 Lämmern (1. Jahr) und 1,68 Lämmern (2. Jahr) beim Tüdern in der humiden Zone zu verzeichenen. Als Gründe wurden die Haltungsformen (Tüdern bzw. freie Weidegang), die Wurfgröße und die verfügbare Futtergrundlage mit ihrem Einflüssen auf die Zwischenlammzeiten analysiert. Insgesamt unterschieden sich hier die Mutterschafe der humiden Zone mit 112,2 % von Mutterschafen der sub-humiden Zone mit 120,4%. RÉSUMÉ: Analyse de la production traditionnelle d'ovins dans les zones humide et sub-humide de la région d'Asante, Ghana II. Rendements de reproduction et taux de fertilité Par rapport aux 690 naissances vives ches 338 brebis dans la zone humide (H), on a enregistré 797 naissances chez 361 brebis dans la zone semi-humide (SH). Avec un age de premier agnelage entre 431,3 (H) et 429,4 (SH) jours et avec un poids vif de 15,6 (H) et 17,0 kg (SH), les brebis, vers ce temps-là, ont plus de poids dans la zone semi-humide. Le poids plus élevé détermine largement la maturité sexuelle précoce. La distribution mensuelle des agnelages montre des fréquences plus élevées aux mois d'octobre, d'avril et de mai (H), et mois de juillet, d'août, de février et de mars (SH). Un nombre plus élevé d'agnelages menait à une diminution significative des intervalles successives d'agnelages non seulement dedans mais aussi entre les zones climatiques. La période entre le quatrième et le cinquième agnelage se réduisait à 234,2 jours dans la zone humide et à 208,7 jours dans la zone sub-humide. La période la plus courte entre deux agnelages qu'on a observée était de 242,6 jours pendant la courte période des pluies, nommée 'dry spelle' (août à octobre) dans la zone humide, et de 223,9 jours pendant la période principale des pluies (mai à juillet) dans la zone sub-humide. On a enregistré des taux plus élevées de reproduction (1,95 agneaux pendant la première année, et 1,79 agneaux pendant la deuxième) chez les brebis pâturant librement, dans la zone sub-humide, et des taux plus bas de reproduction (1,72 agneaux/la première année et 1,68/la deuxième) chez les brebis pâturant au piquet, dans la zone humide. Les formes d'entretien (pâturage au piquet ou pâturage libre), la taille de la portée et la disponibilité de fourrage ont été analysés comme des facteurs importants sur les périodes entre les agnelages., (1994 Blackwell Verlag GmbH.)