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Biomedical subjects

R A Simon

Publications and source records attributed to R A Simon.

At least 19 recordsLinked to original sources
PubMed2001

Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma.

BACKGROUND: Patients with aspirin-sensitive respiratory disease experience cross-reactions to all nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase enzymes. With the introduction of antiarthritis drugs, which selectively inhibit cyclooxygenase-2, questions are raised as to whether cross-reactivity occurs between aspirin and these new cyclooxygenase-2 inhibitors. OBJECTIVE: The goal of this study was to determine whether rofecoxib cross-reacts in aspirin-sensitive patients with asthma. METHODS: Sixty patients with asthma underwent doubleblinded, placebo-controlled oral challenges with rofecoxib (12.5 mg, 25 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, aspirin sensitivity was proven in each of the 60 patients through use of single-blinded oral aspirin challenges. RESULTS: None of the 60 patients experienced any symptoms, changes in nasal examination findings, or declines in FEV(1) values during their challenges with rofecoxib. All 60 patients experienced typical naso-ocular and asthmatic reactions to aspirin with a mean provoking dose of 61 mg. The exact 1-sided CI for the probability of rofecoxib inducing crossreactions in aspirin-sensitive patients with asthma is calculated to be between 0% and 0.05%. CONCLUSION: Given that none of the 60 patients reacted to rofecoxib and given the statistical power of this large sample size, we conclude that cross-reactivity between aspirin and rofecoxib does not occur in patients with aspirin-sensitive respiratory disease. This does not exclude rofecoxib from participating in other types of reactions, including immune recognition after prior treatment with the drug. From the standpoint of the mechanisms involved in aspirin-induced respiratory reactions, this study strongly supports inhibition of cyclooxygenase-1 as the essential initiator of these types of reactions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Lack of effect of the 5-lipoxygenase inhibitor zileuton in blocking oral aspirin challenges in aspirin-sensitive asthmatics.

BACKGROUND: Leukotrienes (LTs) have been implicated as major mediators of aspirin-(ASA)-induced respiratory reactions. It was therefore logical to assume that an inhibitor of 5-lipoxygenase (5-LO), such as zileuton, given before and during oral challenges with ASA, might prevent ASA-induced respiratory reactions. Indeed, in prior studies, pretreatment of ASA-sensitive respiratory disease patients with leukotriene modifiers eliminated or attenuated respiratory reactions upon re-challenge with the previously established provoking dose of ASA. However, doses higher than the provoking doses were not administered during these reported studies. OBJECTIVE: We wished to determine whether zileuton pretreatment could prevent ASA-induced respiratory reactions in our six volunteers with aspirin-sensitive respiratory disease when ASA challenge doses were started below the usual provoking dose of 60 mg and then increased until a respiratory reaction occurred. METHOD: Aspirin sensitivity was established previously in all six patients during a prior ASA oral challenge. In this study, pretreatment with zileuton 600 mg qid was initiated 7 days prior to, and continued during oral ASA challenges. Patients underwent single-blind oral ASA challenges with escalating doses of ASA, every 3 hours, according to our standard protocol. RESULTS: All six patients reacted to doses of ASA between 45 and 325 mg. Four patients experienced bronchospasm (FEV1 declined 19% to 53%) while receiving zileuton. All six had naso-ocular reactions. Concentrations of urine LTE4 also increased significantly (mean 334 pg/mg Cr at baseline, increasing to 1024 pg/mg Cr at respiratory reactions). CONCLUSIONS: During ASA challenges, zileuton, in standard doses of 600 mg qid was associated with increased synthesis of LTs in five of six patients and naso-ocular reactions in all six patients, as well as bronchospasm in four patients.

Administration, Oral↗
PubMed2000

Montelukast is only partially effective in inhibiting aspirin responses in aspirin-sensitive asthmatics.

BACKGROUND: Leukotrienes have been implicated as major mediators of ASA-induced respiratory reactions. In several prior studies, pretreatment of ASA-sensitive respiratory disease (ASRD) patients with leukotriene modifiers have sometimes allowed subjects to tolerate previously established provoking doses of oral ASA or inhalation ASA-lysine, without respiratory reactions. OBJECTIVE: The purpose of this study was to examine whether ASA-provoked respiratory reactions would be blocked or attenuated by pretreatment with a cystLT1 receptor antagonist, montelukast, particularly if ASA doses were increased above their threshold doses. METHODS: Baseline ASA oral challenges were performed. Eight to 12 days later, following pretreatment with montelukast 10 mg daily, threshold and then escalating doses of ASA were used during repeat oral ASA challenges. The differences in responses between baseline and montelukast protected ASA oral challenges were then compared. RESULTS: Nine of 10 patients, despite pretreatment with montelukast, experienced at least naso-ocular reactions during their second oral ASA challenges. In four of nine patients, asthmatic reactions also occurred. In comparing baseline and montelukast protected ASA challenges, there were no statistically significant differences in their responses. CONCLUSIONS: Pretreatment with montelukast allowed only one patient to proceed through all challenge doses of ASA without any reactions. The remaining nine patients enjoyed only partial protection from respiratory reactions. Montelukast pretreatment was generally not effective in altering upper airway reactions and only partly effective in altering lower airway reactions.

Acetates↗
PubMed2000

Additive-induced urticaria: experience with monosodium glutamate (MSG).

In patients with chronic urticaria, the incidence of reactions to any additives, including monosodium glutamate (MSG), is unknown. Although many studies have investigated the association of additives and urticaria, most have been poorly designed. This study sought to determine the prevalence of reactions to additives, including MSG, in patients with chronic urticaria using a rigorous protocol. We studied 65 subjects (44 women, 21 men; ages 14-67). All had urticaria for >6 wk without discernible etiology. Subjects with active urticaria were studied while they were taking the lowest effective dose of antihistamine. Screening challenges to the 11 additives most commonly associated with exacerbations of chronic idiopathic urticaria were performed in a single-blind fashion. The dose of MSG given was 2500 mg. Skin scores were obtained to determine a positive reaction in an objective manner. Subjects with a positive screening challenge were rechallenged (at least 2 wk later) with a double-blind, placebo-controlled protocol as in-patients in our General Clinical Research Center. Two subjects had positive single-blind, placebo-controlled challenges, but neither had a positive double-blind, placebo-controlled challenge. We conclude, with 95% confidence, that MSG is an unusual (<3% at most) exacerbant of chronic idiopathic urticaria.

Adolescent↗
PubMed1999

Monosodium glutamate sensitivity in asthma.

BACKGROUND: Questions have been raised since the early 1980s about monosodium glutamate (MSG) and provocation of asthma. Because MSG is widely available as a chemical in both natural foods and as an additive in many prepared foods, the need to define the relationship of MSG to asthma is of great importance. OBJECTIVE: The purpose of this study was to determine whether MSG ingestion induces asthma attacks in asthmatic subjects. METHODS: With single-blind, placebo-controlled screening challenges, 100 subjects with asthma (30 subjects with a history of Oriental restaurant asthma attacks; 70 subjects with a negative history) were challenged with 2.5 g of MSG. A total of 78 patients were proved to have aspirin-sensitive asthma. RESULTS: No patient had a significant fall in FEV(1 ) value or the development of asthma symptoms during the MSG challenge. The mean change in FEV(1 ) with MSG challenge was no different from that of placebo challenge. Subjects with an MSG-positive history showed no significant percent decrease in FEV(1 ) values after placebo challenges compared with MSG 2.5 g oral challenge (P =.28). In the group with an MSG-negative history, there was no statistical difference in the change in lowest FEV(1 ) values between the placebo and MSG challenges (P =.44). The exact 1-sided 95% confidence interval (CI) for the probability of MSG sensitivity in individuals with aspirin-sensitive asthma (negative history) is 0% to 0.04%. When combined with previous studies that did not demonstrate MSG-provoked asthma, the 95% CI is 0% to 0.03%. For patients with an MSG-positive history, the exact 1-sided 95% CI for the probability of MSG sensitivity in this study was 0% to 0.07%, which is somewhat wider because of the smaller sample size. CONCLUSIONS: MSG challenges in subjects with and without a perceived sensitivity to MSG failed to induce signs or symptoms of asthma. Therefore in view of the poorly conducted studies that proposed that MSG induced asthma and the subsequent studies that failed to confirm those findings, it is important to maintain a healthy skepticism about the existence of MSG sensitivity in individuals with asthma.

Adult↗
PubMed1999

A pilot study examining the role of zileuton in atopic dermatitis.

BACKGROUND: Atopic dermatitis is a common chronic inflammatory skin condition. Current therapies are often insufficient to control the degree of inflammation and pruritus seen in this disease. OBJECTIVE: To examine the efficacy of zileuton in treating atopic dermatitis by measuring both subjective and objective outcome parameters. METHODS: This was an open-label pilot study using zileuton to treat atopic dermatitis. Following a 1-week run-in period off all corticosteroids and antihistamines, six adult patients received 6 weeks of zileuton 600 mg po QID. Subjects were not allowed to use their usual atopic dermatitis medications during the study. At baseline, and at 2, 4, and 6 weeks into the zileuton course, patients were asked to report on their disease dissatisfaction and their pruritus. Objective skin scoring was also performed by an examiner at these visits. RESULTS: Disease dissatisfaction score decreased from a mean of 8 (out of a possible 10) to 4.4 over the 6-week period (P = .03). Pruritus scores showed a trend toward improvement during the study, decreasing from a mean of 7.3 to 4.3 (out of a possible 10, P = .06). Objective skin erythema scores decreased from a baseline mean of 24 (out of a possible 60) to 14 following zileuton treatment (P = .03). CONCLUSIONS: In this pilot study, zileuton showed efficacy in significantly improving the symptoms and objective skin findings seen in atopic dermatitis. The encouraging results seen in this trial should encourage larger, placebo-controlled studies looking at this novel approach toward treating this condition.

Adult↗
PubMed1996

Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes.

BACKGROUND: Aspirin-sensitive patients with asthma experience continuous inflammation of their nasal and sinus tissues, complicated by recurrent sinusitis, which frequently leads to asthma attacks. Systemic corticosteroid therapy and sinus or polyp surgery are currently required to control underlying rhinosinusitis, and bursts of corticosteroids are used for asthma control. OBJECTIVE: After aspirin desensitization therapy, objective measures of respiratory disease activity, linked to the need for systemic corticosteroids and sinus surgery, were studied to determine whether any changes occurred. METHODS: Sixty-five aspirin-sensitive patients with asthma underwent aspirin challenge, followed by aspirin desensitization and daily treatment with aspirin over 1 to 6 years (mean, 3.1 years). Clinical outcome measurements before aspirin desensitization treatment and during follow-up were analyzed for the larger group of 65 patients and subgroups (29 patients receiving therapy for 1 to 3 years and 36 patients receiving therapy for 3 to 6 years). RESULTS: In the larger group of 65 patients, there were significant reductions in numbers of sinus infections per year (median, 6 to 2), hospitalizations for treatment of asthma per year (median, 0.2 to 0), improvement in olfaction (median, 0 to 2), and reduction in use of systematic corticosteroids (mean, 10.2 to 2.5 mg) with p values less than 0.0001. Numbers of sinus and polyp operations per year were significantly reduced (median, 0.2 to 0; p = 0.004), and doses of nasal corticosteroids (in micrograms) were significantly reduced (mean dose, 139 to 106 micrograms, p = 0.01). Emergency department visits and use of inhaled corticosteroids were unchanged. CONCLUSIONS: The results support a role for aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma.

Adult↗
PubMed1995

Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects.

OBJECTIVE: Cross-sensitivity between aspirin and acetaminophen in aspirin-sensitive asthmatic patients has been reported with frequencies ranging from 0% to 29%. The relationship is dose-dependent for acetaminophen challenges, ranging between 300 and 100 mg. METHODS: To determine the prevalence of cross-sensitivity to high-dose acetaminophen, we performed single-blind acetaminophen oral challenges with 1000 mg and 1500 mg in 50 aspirin-sensitive asthmatic patients and in 20 non-aspirin-sensitive asthmatic control subjects. RESULTS: Overall, 17 of 50 (34%) of aspirin-sensitive asthmatic patients reacted to acetaminophen in doses of 1000 to 1500 mg (95% confidence interval: 20% to 49%). By contrast, none of the 20 non-aspirin-sensitive asthmatic patients reacted to acetaminophen (95% confidence interval: 0% to 14%). This difference was highly significant (p = 0.0013), supporting the hypothesis that cross-sensitivity between aspirin and acetaminophen is unique in aspirin-sensitive asthmatic patients. CONCLUSION: Although high-dose ( > 1000 mg) acetaminophen cross-reactions with aspirin were significant with respect to frequency (34%), such reactions included easily reversed bronchospasm in only 22%, and were generally mild. We recommended that high doses of acetaminophen (1000 mg or greater) should be avoided in aspirin-sensitive asthmatic patients.

Acetaminophen↗
PubMed1995

Hydrocortisone sodium succinate does not cross-react with aspirin in aspirin-sensitive patients with asthma.

BACKGROUND: Bronchospasm after intravenous hydrocortisone treatment has been reported in some patients with aspirin-sensitive respiratory disease. OBJECTIVE: This study was designed to determine the prevalence of sensitivity to hydrocortisone among patients with aspirin-sensitive respiratory disease. METHODS: We performed double-blind, placebo-controlled challenges with aspirin and 100 mg of hydrocortisone sodium succinate administered intravenously in 53 subjects. RESULTS: Forty-five of the 53 subjects (85%) undergoing oral aspirin challenge experienced respiratory reactions to aspirin. Forty-four of these 45 patients had neither naso-ocular, cutaneous, nor respiratory reactions to hydrocortisone sodium succinate. One aspirin-sensitive subject had bronchospasm and a naso-ocular reaction to hydrocortisone sodium succinate and a naso-ocular reaction with minimal bronchospasm to methylprednisolone sodium succinate. After desensitization to aspirin, and while receiving maintenance aspirin therapy, this subject again reacted to hydrocortisone sodium succinate with bronchospasm and naso-ocular reaction. CONCLUSION: We conclude that aspirin-sensitive patients with asthma are not preferentially sensitive to hydrocortisone and that hydrocortisone sodium succinate does not cross-react or cross-desensitize with aspirin.

Adult↗
PubMed1995

How patients determine when to replace their metered-dose inhalers.

BACKGROUND: One factor that has been suggested as a possible contributing factor to the rise in asthma morbidity and mortality in the United States is utilization of metered-dose inhalers after the canister has reached its specified maximum number of actuations. METHODS: We surveyed patients using inhalers as to their awareness of the manufacturer's listed maximum number of actuations for the inhalers they were using, their methods for determining when to replace their inhalers, and the replacement methods they thought were best. We also determined the number of actuations existing in inhalers beyond the specified maximum number listed by the manufacturer, and determined the flotation status of the inhalers after that listed number had been actuated. RESULTS: Fifty-four percent of patients surveyed were unaware of the specified maximum number of actuations listed by the manufacturer for the inhalers they were currently using. Only 8% reported tallying the number of actuations used. All canisters tested contained a greater number of total actuations than the number listed by the manufacturer. There was no universal flotation status that accurately reflected when these canisters had reached their respective specified maximum number. CONCLUSIONS: Both lack of knowledge and inhaler replacement practices likely cause patients to extend the use of their metered-dose inhalers beyond the specified maximum number of actuations. This practice may well contribute to the documented rise in asthma morbidity and mortality.

Asthma↗
PubMed1994

Childhood intussusception in a regional hospital.

This study reviews all childhood intussusceptions treated over a 6 year period in a regional centre with six visiting general surgeons and two paediatricians. Clinical presentation, management, complications and outcomes were noted and an attempt was made to follow up all cases. There were 20 patients, with a median age of 6 months (range 10 weeks to 17 months). Only one patient had all four classical features of intussusception (pain, vomiting, 'red currant jelly' stools and abdominal mass). Seven patients were managed successfully by barium enema reduction, but 14 required operation, four following failed radiological reduction. There was one intestinal perforation due to attempted barium enema reduction and one patient required a reoperation for ileal gangrene following operative reduction. There were no deaths and there have been no subsequent recurrent intussusceptions although three cases were lost to follow up. There was a delay in diagnosis in some cases (average duration from onset to diagnosis was 34 h). Although delay was incurred by parents in some cases and in peripheral hospitals in others, there is a need for greater awareness by surgeons of the significance of subtle features such as pallor and lethargy in a child with persistent vomiting. Delay in diagnosis is likely to lead to an increased need for primary surgical intervention. Adverse features (age > 3 months or < 2 years; symptoms > 24 h; small bowel obstruction; dehydration > 5%) were predictive of an increased likelihood of surgical resection, and may help avoid inappropriate attempts at radiological reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Barium Sulfate↗
PubMed1994

Oral challenges to detect aspirin and sulfite sensitivity in asthma.

Oral challenge with aspirin or potential cross-reacting substances (including other nonsteroidal anti-inflammatory drugs [NSAIDs] or food and drug additives) is an effective method for establishing the presence of sensitivity to these substances in asthmatic subjects. Sulfite challenges can be performed in a similar manner. However, many of these subjects have concomitant active irritable airways that could make testing both inaccurate and potentially dangerous. This paper contains strategies for dealing with these problems as well as other important details in conducting oral challenges in asthmatic subjects in a manner which will lead to valid data and conclusions.

Administration, Oral↗
PubMed1991

Safety and possible efficacy of fiberoptic bronchoscopy with lavage in the management of refractory asthma with mucous impaction.

Mucous impaction may be suspected in asthmatic exacerbation when, despite aggressive medical management, patients continue to produce sputum containing mucous plugs and exhibit prominent rhonchi and/or wheezes on chest auscultation. Spirometric measurements in this setting corroborate lack of improvement and reveal significant impairment in indices that may reflect small airways function (FEF25-75). We hypothesized that clearance of inspissated secretions by fiberoptic bronchoscopy with lavage (FOBwL) may promote or hasten the clinical improvement of such patients. Fifty-one therapeutic FOBwL were accomplished in 19 patients during 20 episodes of stabilized yet refractory asthma with mucous impaction. No significant complications were encountered. After FOBwL, spirometric measurements of FEV1, FEF25-75, and FVC increased significantly (P less than .01, paired t test), and correlated with relief of dyspnea and mobilization of secretions with cough. FOBwL can be safely performed in stabilized, refractory asthma, and with apparent efficacy. Further investigation is needed to document the therapeutic utility of FOBwL in refractory asthma.

Adult↗
PubMed1990

Long-term effects of aspirin desensitization--treatment for aspirin-sensitive rhinosinusitis-asthma.

One hundred seven known aspirin (ASA)-sensitive patients with rhinosinusitis-asthma were studied from 1975 to 1988. Forty-two of the patients avoided ASA and served as the control group. Thirty-five patients were desensitized to ASA and treated with daily ASA treatment (Rx) for as long as 8 years (mean, 3.75 years) to May 1988 and were designated the continuous group. Thirty patients, initially desensitized to ASA and treated with daily ASA, who stopped Rx permanently after a mean duration of 2 years, were designated the discontinued group. Retrospective analyses of baselines revealed that both continuous and discontinued groups during ASA Rx demonstrated statistically significant reduction in number of hospitalizations per year, emergency room visits per year, outpatient visits per year, upper respiratory infections-sinusitis-antibiotics per year, need for nasal polypectomies and additional sinus operations, and improvement in sense of smell compared to the control group. Simultaneously, the ASA-Rx groups were able to significantly reduce systemic corticosteroid dosage, corticosteroid bursts per year, and, in the continuous group only, significantly reduce inhaled corticosteroids. All three groups maintained control of respiratory symptoms. ASA desensitization followed by long-term daily ASA Rx appears to improve ASA-sensitive rhinosinusitis-asthma and concomitantly allows reduction of systemic corticosteroids.

Adrenal Cortex Hormones↗