Environmental PCB exposure and risk of endometriosis.

BACKGROUND: Hormonally active environmental agents have recently been associated with the development of endometriosis. METHODS: We undertook a study to assess the relationship between endometriosis, an estrogen-dependent gynaecological disease, and 62 individual polychlorinated biphenyl (PCBs) congeners. We enrolled 84 eligible women aged 18-40 years undergoing laparoscopy for study, which included an interview and blood specimen (n=79; 94%). Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not. Blood specimens were run in batches of 14 including four quality control samples for toxicological analysis. Each PCB congener was adjusted for recovery; batch-specific reagent blanks were subtracted. All PCB concentrations were log transformed and expressed in ng/g serum first as a sum and then as tertiles by purported estrogenic or anti-estrogenic activity of PCB congeners. RESULTS: Using unconditional logistic regression analysis, a significantly elevated odds ratio (OR) was observed for women in the third tertile of anti-estrogenic PCBs [OR 3.77; 95% confidence interval (CI) 1.12-12.68]. Risk remained elevated after controlling for gravidity, current cigarette smoking and serum lipids (OR 3.30; 95% CI 0.87-12.46). CONCLUSIONS: These data suggest that anti-estrogenic PCBs may be associated with the development of endometriosis.

Allergen immunotherapy for asthma.

BACKGROUND: Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct another systematic review of allergen specific immunotherapy for asthma. OBJECTIVES: The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register up to June 2001, MEDLINE, Dissertation Abstracts, Current Contents and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed eligibility of studies for inclusion. Two reviewers independently performed quality assessment of studies. MAIN RESULTS: Seventy-five trials were included (52 of 54 previously included trials and 23 new trials). A total of 3,506 participants (3,188 with asthma) were involved. There were 36 trials of immunotherapy for house mite allergy; 20 pollen allergy trials; ten animal dander allergy trials; two Cladosporium mould allergy, one latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 15 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.72, 95% confidence interval -0.99 to -0.33) and it would have been necessary to treat 4 (95%CI 3 to 5) patients with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat 5 (95%CI 4 to 6) patients with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. REVIEWER'S CONCLUSIONS: Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of adverse effects (such as anaphylaxis) must be considered.

Comparison of information processing technologies.

OBJECTIVE: To examine the type of information obtainable from scientific papers, using three different methods for the extraction, organization, and preparation of literature reviews. DESIGN: A set of three review papers was identified, and the ideas represented by the authors of those papers were extracted. The 161 articles referenced in those three reviews were then analyzed using 1) a formalized data extraction approach, which uses a protocol-driven manual process to extract the variables, values, and statistical significance of the stated relationships; and 2) a computerized approach known as "Idea Analysis," which uses the abstracts of the original articles and processes them through a computer software program that reads the abstracts and organizes the ideas presented by the authors. The results were then compared. The literature focused on the human papillomavirus and its relationship to cervical cancer. RESULTS: Idea Analysis was able to identify 68.9 percent of the ideas considered by the authors of the three review papers to be of importance in describing the association between human papillomavirus and cervical cancer. The formalized data extraction identified 27 percent of the authors' ideas. The combination of the two approaches identified 74.3 percent of the ideas considered important in the relationship between human papillomavirus and cervical cancer, as reported by the authors of the three review articles. CONCLUSION: This research demonstrated that both a technically derived and a computer derived collection, categorization, and summarization of original articles and abstracts could provide a reliable, valid, and reproducible source of ideas duplicating, to a major degree, the ideas presented by subject specialists in review articles. As such, these tools may be useful to experts preparing literature reviews by eliminating many of the clerical-mechanical features associated with present-day scientific text processing.

Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant.

BACKGROUND: There are many reports of allergic reactions, including anaphylaxis, following exposure to chlorhexidine. Reactions may occur via contact with the skin and mucous membranes or from catheters treated with the antibacterial agent. Apart from implicating chlorguanide in immunoglobulin (Ig) E antibody-binding studies on serum from an anaphylactic patient, little work has been done on the molecular basis of recognition of the agent in sensitive subjects. OBJECTIVES: The molecular basis of IgE-binding to chlorhexidine was closely examined with the view of defining its fine structural recognition features by antibodies from a subject who experienced anaphylaxis following contact with the antiseptic. METHODS: Tryptase determinations, different drug-solid phases, immunoassays and quantitative hapten inhibition studies with chlorhexidine and selected structural analogues were employed together with serum from the anaphylactic patient. Results were analysed to define the complete drug allergenic determinant and to identify the important structural features complementary to the IgE antibody combining sites. RESULTS: The subject's serum tryptase levels sampled after the reaction were elevated and employment of a chlorhexidine-EA Sepharose solid phase showed the presence of serum IgE antibodies to the drug. Lack of inhibition by 4-chlorophenol and other selected substituted phenyl compounds showed that the terminal groups at each end of the chlorhexidine molecule, alone, did not account for antibody recognition of the antibacterial agent. Although chlorguanide and alexidine, the structures of which each comprise part of the chlorhexidine molecule, showed significant inhibition of the binding of IgE antibodies to chlorhexidine, neither compound was as potent an inhibitor as chlorhexidine itself. Two molecules of chlorguanide make up the symmetrical molecule of chlorhexidine while the interior structure of alexidine (that is excluding the terminal 2-ethylhexyl groups) is identical to part of the chlorhexidine molecule. CONCLUSIONS: Taken together, for this patient, these results lead to the conclusion that the whole chlorhexidine molecule is complementary to the IgE antibody combining sites and that the 4-chlorophenol, biguanide and hexamethylene structures together comprise the allergenic determinant. Hence, like one of the trimethoprim determinants identified, but unlike most drug allergenic determinants identified so far, the chlorhexidine allergenic determinant identified here encompasses the entire molecule.

Allergen immunotherapy for asthma.

BACKGROUND: Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct a systematic review of allergen specific immunotherapy for asthma. OBJECTIVES: Allergen specific immunotherapy involves injecting an extract of the allergen under the skin. It is also known as hyposensitisation or desensitisation, and carries a risk of potentially fatal anaphylaxis. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register up to 1997, Dissertation Abstracts, WorldCat and ArticleFirst. SELECTION CRITERIA: Randomised trials using various forms of allergen specific immunotherapy to treat asthma. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion was decided by three reviewers independently. Quality assessment of studies was performed by two reviewers independently. MAIN RESULTS: Fifty-four trials were included. There were 25 trials of immunotherapy for house mite allergy; 13 pollen allergy trials; eight animal dander allergy trials; two Cladosporium mould allergy and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 11 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication following immunotherapy. There was also a significant improvement in asthma symptom scores (standardised mean difference -0.52, 95% confidence interval -0.70 to -0.35). People receiving immunotherapy were less likely to report a worsening of asthma symptoms than those randomised to placebo (odds ratio 0.27, 95% confidence interval 0.21 to 0.35). People randomised to immunotherapy were less likely to require medication than those randomised to placebo (odds ratio 0.28, 95% confidence interval 0.19 to 0.42). Allergen immunotherapy reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. REVIEWER'S CONCLUSIONS: Immunotherapy may reduce asthma symptoms and use of asthma medications, but the size of the benefit compared to other therapies is not known. The possibility of adverse effects (such as anaphylaxis) must be considered.

Innovative multidisciplinary research in environmental epidemiology: the challenges and needs.

The ability of epidemiology to determine the relationships between health and environmental insults has become exceedingly difficult. The multifactorial nature of disease and the diversity of the insults, which include biologic, physical, social and cultural factors, combined with genetic susceptibility, suggest the need to develop better models of multidisciplinary epidemiologic investigation. This paper highlights the needs of an environmental epidemiologic team, discusses ways to incorporate new ideas across disciplines and to integrate constructs and paradigms of social, ecological, cultural and population determinants with individual-based exposure assessments. Innovation will be the key to the survival and increasing importance of epidemiology in addressing the public health needs of the future, but what are the ways to enhance and encourage creativity in environmental epidemiology? The process of self-renewal and continuing education will be highlighted. Additionally, the complexity of the problems and the need for clear supervision and control of multidisciplinary research efforts require a forum of communication and an 'information-processing approach' beyond those in traditional epidemiologic studies. New approaches in data management and medical informatics must be incorporated into the epidemiologic investigative framework. Methods to be included should focus on opportunities for computer-supported sharing of ideas. Such capabilities minimise the geographic distances and the disparate knowledge and training of the investigators and bring the team closer to the objectives and functions inherent in multidisciplinary investigation.

Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials.

OBJECTIVE: To determine whether intranasal corticosteroids are superior to oral H1 receptor antagonists (antihistamines) in the treatment of allergic rhinitis. DESIGN: Meta-analysis of randomised controlled trials comparing intranasal corticosteroids with oral antihistamines. SETTING: Randomised controlled trials conducted worldwide and published between 1966 and 1997. SUBJECTS: 2267 subjects with allergic rhinitis in 16 randomised controlled trials. MAIN OUTCOME MEASURES: Nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, nasal discomfort, total nasal symptoms, nasal resistance, and eye symptoms and global ratings. Outcomes measured on different scales were combined to determine pooled odds ratios (categorical outcomes) or standardised mean differences (continuous outcomes). Assessment of heterogeneity between studies, and subgroup analyses of eye symptoms, were undertaken. RESULTS: Intranasal corticosteroids produced significantly greater relief than oral antihistamines of nasal blockage (standardised mean difference 0.63, 95% confidence interval - 0.73 to - 0.53), nasal discharge (-0.5, - 0.6 to - 0.4), sneezing (- 0.49, - 0.59 to - 0.39), nasal itch (- 0.38,- 0.49 to - 0.21), postnasal drip (- 0.24,- 0.42 to - 0.06), and total nasal symptoms (- 0.42,- 0.53 to - 0.32), and global ratings gave an odds ratio for deterioration of symptoms of 0.26 (0.08 to 0.8). There were no significant differences between treatments for nasal discomfort, nasal resistance, or eye symptoms. The effects on sneezing, total nasal symptoms, and eye symptoms were significantly heterogeneous between studies. Other combined outcomes were homogeneous between studies. Subgroup analysis of the outcome of eye symptoms suggested that the duration of assessment (averaged mean score over the study period versus mean score at end of study period) might have accounted for the heterogeneity. CONCLUSION: The results of this systematic review, together with data on safety and cost effectiveness, support the use of intranasal corticosteroids over oral antihistamines as first line treatment for allergic rhinitis.

The effects of monosodium glutamate in adults with asthma who perceive themselves to be monosodium glutamate-intolerant.

BACKGROUND: Many previous clinical studies of food-induced asthma suffer from inadequate baseline or control data. A statistically valid, randomized, double-blind, placebo-controlled, monosodium glutamate (MSG)-challenge protocol was developed for identifying early and late asthmatic reactions in an individual. OBJECTIVE: We sought to determine whether MSG would induce bronchoconstriction in a group of adults with asthma who perceived that they were MSG sensitive. METHODS: Twelve subjects (seven women, mean age 35.3 years) with clinically documented asthma and a perception of MSG-induced asthma were recruited. FEV1 and peak expiratory flow data were obtained for 3 whole control days, as well as time-matched data for 3 separate challenge days (1 gm MSG, 5 gm MSG, and 5 gm lactose [placebo]). Opaque capsule challenges were given as a single dose in the morning after an overnight fast. Subjects complied with an elimination diet throughout the study. Nonspecific bronchial hyperresponsiveness was measured at baseline, after the control days, and at the conclusion of the challenges. Venous blood samples were taken at baseline and on each challenge day to determine soluble inflammatory marker (eosinophil cationic protein and tryptase) activity. RESULTS: No immediate or definite late asthmatic reactions occurred. One subject's FEV1 declined more than 15% on MSG challenge, but 95% confidence limits for the control-day spirometry showed that this decline was within her daily variation, hence the challenge was deemed to be negative. No significant changes in bronchial hyperresponsiveness or soluble inflammatory markers were found. CONCLUSIONS: MSG-induced asthma was not demonstrated in this study. This study highlighted the importance of adequate baseline and control data and indicated that such a rigorous protocol for individual assessment is feasible.

Reported food intolerance and respiratory symptoms in young adults.

The aim of the study was to assess the ability of the European Community Respiratory Health Survey (ECRHS) questionnaire to provide data on the prevalence, type and reported symptoms associated with food intolerance from a group of young adults in Melbourne. Six hundred and sixty nine randomly selected subjects completed the questionnaire with 553 attending the laboratory for skin-prick tests, anthropometry, and ventilatory function tests. A further 207 symptomatic participants completed the questionnaire, with 204 of them attending the laboratory. Seventeen per cent of all respondents reported food intolerance or food allergy. A wide variety of food items was cited as being responsible for food-related illnesses. Those with current asthma did not report food-related illness more frequently than those without asthma. Respondents who reported respiratory symptoms following food ingestion were more likely to be atopic, to have used inhaled respiratory medications in the previous 12 months, reported less exposure to regular passive smoking over the past 12 months and weighed more. These associations between respiratory symptoms and food intolerance require further prospective investigation and verification. The importance of using appropriate dietary methodology in future studies for determining diet-disease relationships was highlighted by this study.

Anaerobic benzene degradation in petroleum-contaminated aquifer sediments after inoculation with a benzene-oxidizing enrichment.

Sediments from the sulfate-reduction zone of a petroleum-contaminated aquifer, in which benzene persisted, were inoculated with a benzene-oxidizing, sulfate-reducing enrichment from aquatic sediments. Benzene was degraded, with apparent growth of the benzene-degrading population over time. These results suggest that the lack of benzene degradation in the sulfate-reduction zones of some aquifers may result from the failure of the appropriate benzene-degrading sulfate reducers to colonize the aquifers rather than from environmental conditions that are adverse for anaerobic benzene degradation.

Do dairy products induce bronchoconstriction in adults with asthma?

BACKGROUND: Dairy products have often been implicated as a cause of exacerbation of asthma, but there is little scientific evidence to support this hypothesis. OBJECTIVE: We sought to determine whether dairy products induce bronchoconstriction in a group of adults with asthma. METHODS: Twenty subjects with asthma (13 women and 7 men) were recruited from respondents who had previously completed a food and asthma questionnaire. Ten subjects perceived that their asthma became worse with ingestion of dairy products (positive perceivers), whereas ten were negative perceivers. None of the subjects had positive skin prick test results with cow's milk. The study was a randomized, cross-over, double-blind, placebo-controlled trial. Subjects complied with a dairy-free diet throughout the study. The active challenge was a single-dose drink equivalent to 300 ml of cow's milk. A positive reaction was defined as a 15% reduction in both FEV1 and peak expiratory flow (PEF) on the active challenge day compared with results obtained at the same time on the placebo day. RESULTS: For both FEV1 and PEF there were no statistically significantly differences in group means between active challenge and placebo challenge, between sequence of administration, or between perceptions. Nine subjects showed FEV1 or PEF changes that were greater than 15% of baseline values: four patients showed changes after both active and placebo treatment; two after treatment with placebo only; and three after active treatment alone. Of the latter group, two subjects showed changes only in PEF, and when one of these subjects underwent a further detailed study, no asthmatic reaction could be demonstrated. CONCLUSION: It is unlikely that dairy products have a specific bronchoconstrictor effect in most patients with asthma, regardless of their perception.

Precipitants of brain infarction. Roles of preceding infection/inflammation and recent psychological stress.

BACKGROUND AND PURPOSE: Antecedent febrile infection and psychological stress are described as predisposing risk factors for brain infarction. We examined the temporal relationship between preceding infection/inflammation and stroke onset as well as the role of recent psychological stress as a potential precipitant for brain infarction. METHODS: In this case-control study, a standardized evaluation including a signs/symptoms-based questionnaire was used to characterize the prevalence and timing of recent prior (< 1 month) infectious and inflammatory syndromes in 37 adults with acute brain infarction, 47 community control subjects, and 34 hospitalized nonstroke neurological patient controls. Recent psychological stress was measured with scales of stressful life events and negative affect. RESULTS: The prevalence of infection/inflammation was significantly higher in the stroke group only within the preceding 1 week compared with either community control subjects (13/37 versus 6/47, P < .02) or hospitalized neurological patient controls (3/34, P < .02). Upper respiratory tract infections constituted the most common type of infection. A substantial proportion of stroke patients with preceding (< 1 week) infection/inflammation (5/13) had no accompanying fever or chills. There were no significant differences between the stroke and control groups in the levels of stressful life events within the prior 1 month or in negative-affect scale scores within the prior 1 week. CONCLUSIONS: Our data suggest that both febrile and nonfebrile infectious/inflammatory syndromes may be a common predisposing risk factor for brain infarction and that the period of increased risk is confined within a brief temporal window of less than 1 week. Results of this study argue against a role for recent psychological stress as a precipitant for cerebral infarction.

Impairments of the protein C system and fibrinolysis in infection-associated stroke.

BACKGROUND AND PURPOSE: Infection/inflammation appears to be an important predisposing risk factor for brain infarction, but little is known regarding underlying molecular mechanisms. We examined the hypothesis that patients with brain infarction preceded by infection/inflammation within 1 week could be identified by a distinctive procoagulant laboratory profile characterized by abnormalities in the protein C system and endogenous fibrinolysis. METHODS: We performed a case-control study examining the relationship between preceding systemic infectious/inflammatory syndromes and selected immunohematologic variables in 36 patients with acute brain infarction and 81 control subjects (community control subjects [n = 47] and hospitalized nonstroke neurological patient controls [n = 34]). RESULTS: The stroke group had a lower mean level of the circulating antithrombotic enzyme activated protein C (APC) (4.33 +/- 0.34% [log-transformed percentage of control value, mean +/- SD]) than community control subjects (4.51 +/- 0.27%, P < .02) or hospitalized neurological patient controls (4.57 +/- 0.31%, P < .005). The lowest circulating APC levels were found in the stroke group with antecedent infection/inflammation within 1 week preceding index brain infarction (4.23 +/- 0.4%, n = 12). Within the stroke group, circulating APC levels were inversely related to IgG isotype anticardiolipin antibody titers (r = -.55, P < .001). Only the stroke group with infection/inflammation within 1 week had elevated plasma C4b binding protein compared with control subjects (141 +/- 61% versus 112 +/- 44%, P < .05). Stroke patients with antecedent infection/inflammation had a distinctively lower ratio of active tissue plasminogen activator to plasminogen activator inhibitor (0.11 +/- 0.04, n = 9) than other stroke patients (0.19 +/- 0.06, n = 9, P < .01) and control subjects (0.22 +/- 0.16, n = 17, P < .02). CONCLUSIONS: Impairments in the protein C pathway and endogenous fibrinolysis may contribute to the increased risk for brain infarction after recent (< or = 1 week) infection/inflammation. A decrease in the circulating anticoagulant APC may be related to elevated antiphospholipid antibody titers.

Effect of fluconazole on fungicidal activity of flucytosine in murine cryptococcal meningitis.

Both animal and in vitro studies have demonstrated that combinations of flucytosine with amphotericin B and with fluconazole have significantly improved activity against cryptococcal meningitis compared with the activity of each drug used alone. However, very few dose levels of these agents have been tested in combination. This study evaluated the efficacy of fluconazole plus flucytosine in a murine model of cryptococcal meningitis over a broad range of dose combinations (fluconazole, 0 to 40 micrograms/g of body weight per day; flucytosine, 0 to 200 micrograms/g/day). Both drugs were dissolved in drinking water, with treatment on days 2 to 11. In this highly reproducible model, fluconazole had a dramatic effect on the fungicidal activity of flucytosine. Flucytosine at dose levels of as much as 200 micrograms/g/day alone or in combination with low doses of fluconazole had minimal fungicidal activity, whereas in combination with fluconazole at 24 to 40 micrograms/g/day, flucytosine showed fungicidal activity in the range of 45 to 65% of the animals treated at doses of 40 to 100 micrograms/g/day. This striking effect of fluconazole is consistent with the results of both in vitro and clinical studies. In the clinic, the use of flucytosine is often limited by severe toxicity, while toxicity is rarely observed with fluconazole. These results suggest that when flucytosine is given with higher doses of fluconazole, the maximum therapeutic effect of the former in the clinic may be observed at dose levels that are far less than the doses commonly employed (150 micrograms/g daily).