Treating mild asthma--when are inhaled steroids indicated?
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Administration, Inhalation↗
Biomedical subjects
E Israel
Publications and source records attributed to E Israel.
Capsaicin-induced airway obstruction in tracheally perfused guinea pig lungs.
The neurokinin receptors responsible for transducing the airway obstruction resulting from capsaicin infusion were defined in the tracheally perfused guinea pig lung. In this lung preparation, buffer is perfused via the trachea and allowed to exit the lung through numerous small holes in the pleural surface; airway obstruction is monitored as the backpressure (Pao) generated at a constant perfusion flow rate. Infusion of the specific NK1 receptor agonist, Sar-9 Met02(11) substance P, resulted in an increase in Pao; this effect was prevented by the NK1 receptor antagonist CP 99,994 but not by the NK2 receptor antagonist SR 48,968. Infusion of the specific NK2 receptor agonist Nle10-neurokinin A 4-10 resulted in an increase in Pao; this effect was prevented by the NK2 receptor antagonist SR 48,968 but not by the NK1 receptor antagonist CP 99,994. In the absence of NK receptor antagonists, infusion of capsaicin resulted in a significant increase in Pao, 31 +/- 4 cm H2O. In the presence of the NK1 receptor antagonist, the capsaicin response was not diminished, but in the presence of the NK2 receptor antagonist, the Pao response diminished to only 10 +/- 2 cm H2O, p < 0.001. These data indicate that when capsaicin is presented to the epithelial surface of the lung the resulting airway obstruction is mediated predominantly by NK2 receptor stimulation.
Animals↗
The influence of age, diagnosis, and gender on proper use of metered-dose inhalers.
Metered dose inhalers (MDIs) are widely used in clinical practice for administering pharmaceuticals targeted to the lung. It is well known that the inhalation technique used with MDIs can substantially influence the clinical response to inhaled medications. To determine the acceptability of MDI maneuvers, we studied 59 subjects (26 females and 33 males; age, 20 to 81 yr; mean age, 38 yr) to determine whether the MDI technique used by these individuals complied with published recommendations for acceptable inhalation technique. Measurements were made with an MDI adapter that contained an unobtrusive, lightweight, miniature sensing system. Inspiratory flow at the moment of MDI actuation (Va), the volume (integrated from airflow) at actuation as a fraction of total inspiratory volume (Va/VI), breath-holding time (tBH), and inspiratory volume as a fraction of FVC (VI/FVC) were determined from 59 uncoached inhalations. We defined an acceptable maneuver, based on published data, by four components: (1) inspiratory flow at actuation (Va) between 25 and 90 L/min; (2) actuation during early inspiration (0 < Va/VI < or = 0.20); (3) adequate breath-holding time (tBH > 4 s), and (4) a deep inhalation (VI/FVC > 0.50). For all subjects, only 25% of inhalation maneuvers met all four criteria for acceptability. We found that a significantly higher proportion of male than female subjects performed an acceptable MDI maneuver (43% versus 4%, p < 0.001). There were no significant differences in technique between younger and older subjects or between patients with a diagnosis of asthma or chronic obstructive pulmonary disease (COPD). We conclude that most patients use their MDIs incorrectly; females of all ages are much more likely to have improper MDI technique than are males.
Adult↗
Inhaled diuretics in asthma: the search for the mechanism of action.
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Administration, Inhalation↗
[Handling of Foley catheter regarding urinary retention syndrome following vaginal surgery].
The post surgical urinary retention syndrome is a frequent problem after vaginal surgery. In many medical centers it is used a transurethral vesical drainage for three to five days with or without vesical reeducation to prevent it. In order to determine the importance of the time of drainage and vesical reeducation in the presence of this syndrome 106 patients submitted to vaginal surgery were studied at random and prospectively, in our service. Patients were distributed in three groups: the first one, with 37 women in which the drainage was withdrawn at 24 hours; in the second group it was retired at 72 hours and in the third group the drainage was removed at 72 hours with previous vesical reeducation. The results show that those patients who were less time under vesical drainage presented a minor frequency of urinary retention after surgery (24.3% vs 30.7% and 43.7%).
Adult↗
Role of cysteinyl leukotrienes in spontaneous asthmatic responses.
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Asthma↗
Maryland physicians' survey on Lyme disease.
In a survey of 252 physicians practicing in Maryland, 170 responders diagnosed 142 cases of Lyme disease (LB) during 1990 and 1991. About 80% of the cases were diagnosed by primary care physicians. The most common clinical finding, erythema migrans (EM), was reported in half the cases and arthritis was reported in a quarter. Only 22.2% had a history of a tick bite; serological tests were ordered in a third of the cases. EM was treated with oral antibiotics for 10-21 days. Most physicians treated Lyme arthritis with the same therapy, although some used intravenous ceftriaxone. The most commonly used treatment for neurologic or cardiac complications was intravenous ceftriaxone. These preliminary data suggest that LB may be diagnosed by Maryland physicians more frequently than syphilis and tuberculosis. The data also indicate LB is a much larger problem in Maryland than suggested by official reports to the Centers for Disease Control. The clinical characteristics of the illness and the antibiotics prescribed for it in Maryland are similar to those reported in northeastern states.
Data Collection↗
Moderating the inflammation of asthma: inhibiting the production or action of products of the 5-lipoxygenase pathway.
The products of the 5-lipoxygenase pathway of arachidonic acid metabolism, particularly the leukotrienes, can mediate bronchoconstriction, mucous secretion, airway mucosal edema, chemotaxis, and mobilization of cells into the airway in the inflammatory process of asthma. This paper will review the current data on the efficacy of available leukotriene antagonists or inhibitors that act on the 5-lipoxygenase pathway in induced bronchoconstriction in humans and in clinical studies in asthma. Studies of asthmatic responses to antigen and cold air hyperventilation and exercise will be discussed. Data will be reviewed from investigations regarding the effects of these pharmacological agents as they relate to increased airway tone in asthmatic patients and, finally, as they relate to clinical and physiological improvement in mild to moderate asthma. These studies suggest that the antagonists and inhibitors that affect the 5-lipoxygenase products of arachidonic acid may provide a new approach in the pharmacologic treatment of asthma. Further clinical studies will be required to define the precise role of these agents.
Arachidonate 5-Lipoxygenase↗
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↗
Agonist-induced lipoxin A4 generation: detection by a novel lipoxin A4-ELISA.
Lipoxin A4 (LXA4) possesses potent bioactions. To facilitate its detection, an enzyme-linked immunosorbent assay (ELISA) was developed that proved sensitive and selective. Quantitation by ELISA of LXA4 generated from cellular sources strongly correlated (r = 0.99) with values obtained by high-pressure liquid chromatography (HPLC). We used this LXA4-ELISA to examine parameters influencing LXA4 generation from endogenous substrates during human platelet-neutrophil (PLT-PMN) interactions in vitro. Agonist-induced LXA4 production was clearly evident at a PLT-PMN ratio of 10:1, and recombinant human granulocyte/monocyte colony stimulating factor-priming of PMN augmented LXA4 generation 5-6 fold. The chemotactic peptide formylmethionyl-leucyl-phenylalanine, platelet-derived growth factor and arachidonic acid (20:4n-6) each stimulated formation of immunoreactive LXA4 (iLXA4) in these co-incubations. The presence of iLXA4 was also evaluated in vivo in aspirin-sensitive asthmatic patients who, in a randomized, double-blind crossover design, underwent nasal lavage after they each ingested a predetermined threshold dose of aspirin or placebo. Aspirin challenge provoked statistically significant increases in iLXA4 in each patient (P < 0.005). These results validate the use of a solid-phase ELISA for detection of LXA4. Furthermore, the use of this ELISA has allowed the first documentation of iLXA4 formation in human subjects with aspirin-sensitive asthma following specific antigenic challenge.
Adult↗
The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin.
A subset of persons with asthma develop bronchospasm, naso-ocular, gastrointestinal, and/or dermal reactions after ingesting aspirin (ASA) or agents with the capacity to inhibit cyclooxygenase. The bronchopulmonary reactions have been associated with a rise in urinary LTE4. We examined the effects of an inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients with known sensitivity to ASA accompanied by LTE4 hyperexcretion. We first confirmed ASA sensitivity and an increase in urinary LTE4 after ASA ingestion in these patients using a placebo-controlled ASA challenge. Subjects were then randomized to a double-blind, crossover trial to examine the effects of zileuton versus placebo on the response to ASA. Zileuton treatment decreased baseline urinary LTE4 excretion from a mean of 469 +/- 141 pg/mg creatinine to 137 +/- 69 pg/mg creatinine (p < 0.02) and blunted the maximum increase in urinary LTE4 after ingestion of ASA (3,539 +/- 826 pg/mg creatinine versus 1,120 +/- 316 pg/mg creatinine [p < 0.01]). The pre-ASA challenge FEV1 was unchanged by zileuton (3.41 +/- 0.15 L versus 3.35 +/- 0.17 L, zileuton versus placebo). Zileuton prevented the fall in FEV1 in response to ingestion of ASA; post-ASA ingestion the mean of the minimal FEV1 fell to 2.72 +/- 0.18 L on the placebo day while there was no significant fall on the zileuton day (3.26 +/- 0.17 L; p < 0.014). Zileuton also prevented the development of the nasal, gastrointestinal (p < 0.006 and p < 0.025, respectively), and dermal symptoms which developed after ASA ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Medical handling of the tubal pregnancy: results].
We report the outcome of the treatment with intratubal methotrexate (25 mg) administered via laparoscopy in 8 patients with ectopic pregnancy who where treated according to a preestablished protocol. A successful treatment was achieved in 6 patients (75%). Hysterosalpingography was performed in 5 of the patients, and in 4 of them we found bilateral tubal patency. Currently 3 patients have a normal intrauterine pregnancy.
Adult↗
[Gestational choriocarcinoma in a tubal pregnancy].
We report a gestational choriocarcinoma arising in a tubal ectopic pregnancy. Unilateral salpingectomy and single agent methotrexate chemotherapy achieved a cure. A follow up of two years revealed no evidence of recurrence.
Adult↗
Tuberculosis: optimism, pessimism, frustration.
The re-emergence of tuberculosis as a serious public health threat has captured the nation's attention. Tuberculosis more frequently affects the ethnic minorities and the socially and economically disadvantaged residents of Maryland. Effective regimens are available to treat and prevent tuberculosis. Consistent application of proven infection control measures and of treatment and prevention regimens will prevent the development and spread of multidrug-resistant tuberculosis.
Humans↗
Characteristics of epidemic hepatitis A in Baltimore City: implications for control measures.
In 1988, a hepatitis A epidemic began in Baltimore, Maryland. A total of 607 cases were reported to the Baltimore City Health Department between the period November 1, 1988, and December 31, 1989. The health department conducted case investigations to identify factors important to the development of control measures. Immunoglobulin was given to appropriate contacts, and an educational campaign was initiated. Of the 607 reported cases, 63% were white and 57% were male. Cases were geographically clustered within 5 of Baltimore's 23 zip codes. Among the 242 adults interviewed, 43% self-reported drug use and 44% were unemployed. Twenty-one percent of the adults and 56% of the children reported contact with either a suspected or confirmed case of hepatitis. Despite control efforts, the epidemic continued through 1990. Barriers to implementing traditional control measures resulted in continuing transmission of hepatitis A in the community.
Adolescent↗
Lyme disease in outdoor workers on Assateague Island: high tick-exposure but low disease risk.
Lyme disease is endemic to the Assateague Island area. Using a questionnaire and serosurvey, we examined the extent of tick exposure, compliance with recommended Lyme disease personal preventive activities, and risk of the disease in 86 outdoor workers on Assateague Island before and after the summer of 1989. Despite high self-reported tick exposure and relatively long employment durations on the island, there was no evidence of current or past infection with Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease knowledge and use of several personal strategies were high, but compliance with these preventive strategies was not universal. These data suggest that even in this high-risk population, intensive educational efforts are necessary to encourage Lyme disease preventive behavior, but the current level of compliance may have decreased the risk of Lyme disease on the island.
Adult↗
Epizootic of rabies in raccoons in Maryland from 1981 to 1987.
The epizootic of rabies in raccoons entered Maryland in 1981 and systematically moved through the state affecting raccoons in all counties except those of the lower Eastern Shore. A precoded surveillance form was provided to all county and city health departments and data were requested for each animal head submitted for testing for the year 1985. The disease persisted and, in 1987, all counties previously reporting rabies in raccoons also had documented cases in other species. The incidence of rabies in raccoons increased in late winter and peaked in March. Most human exposures occurred during daylight hours and in private yards. Agricultural areas were similarly affected by rabid animals. Analysis of vaccination status of animals exposed to rabid animals gave estimations of statewide vaccination rates for dogs (70%) and cats (28%). The danger of rabies in cats was emphasized by the large number of animals exposed by each rabid cat. The spillover of rabies in raccoons to other species persisted in all jurisdiction through 1992, with periodic upsurges of disease at 3- to 4-year intervals as the raccoon population is replenished. Rabies was not diagnosed in any human beings.
Animals↗
A serosurvey of pathogens associated with shellfish: prevalence of antibodies to Vibrio species and Norwalk virus in the Chesapeake Bay region.
Recent concerns regarding the safety of shellfish consumption have focused on the risk posed by naturally occurring marine bacteria such as Vibrio species and by viruses such as Norwalk and related agents. Despite the widespread environmental presence of Vibrio species in the Chesapeake Bay, the rate of reported infections remains low; there have also been no reports of major Norwalk outbreaks associated with shellfish in this area. As infections with these agents may not always be recognized because of difficulties in making the diagnosis and/or their mild or subclinical presentation, a serosurvey was conducted among healthy volunteers living in the Chesapeake Bay region. Serum and questionnaire data were collected during the fall of 1987 from 267 persons with varying levels of exposure to shellfish: shellfish industry workers, persons attending a local seafood festival, and Seventh-day Adventists (who traditionally abstain from eating shellfish). In comparisons among groups, a significant association could not be demonstrated between shellfish consumption or contact and antibody response to Vibrio cholerae O1 or Norwalk virus. Rates of seropositivity were high for both agents (up to 22% seropositive with a V. cholerae O1 Inaba vibriocidal assay, 14% with an enzyme-linked immunosorbent assay for cholera toxin, and up to 70% seropositive with an enzyme-linked immunosorbent assay for antibodies to Norwalk virus); the basis for these responses in population-based studies remains to be determined. Shellfish industry workers did have a significantly elevated antibody response to the unencapsulated phase variant of Vibrio vulnificus as compared with the other groups studied. Infection with V. vulnificus may be relatively common among persons with high levels of exposure to shellfish.
Adult↗