Cataract extraction by phacoemulsification in a sympathizing eye.
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Biomedical subjects
Publications and source records attributed to A Leznoff.
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OBJECTIVE: To review the pathophysiology of chronic urticaria in light of recent evidence for it being an autoimmune disease, and to recommend appropriate management. QUALITY OF EVIDENCE: An extensive literature review was supplemented with a MEDLINE search. Articles from easily available journals were preferred. These consisted of the most recent basic articles on autoimmunity in relation to chronic urticaria and a selection of previous articles on pathophysiology, which illustrate consistencies with recent evidence. The investigation and management protocol is supported by original and relevant literature. MAIN FINDINGS: The histopathology and immunohistology of chronic urticaria and certain clinical studies were a prelude to definitive evidence that most instances of chronic urticaria are autoimmune. Although allergic and other causes are uncommon, these must be sought because identification can lead to cure or specific treatment. Management of the much more common autoimmune urticaria is based on principles derived from the demonstrated pathogenesis and on results of published clinical trials. CONCLUSIONS: In most instances, chronic urticaria is an autoimmune disease, but uncommon allergic or other causes must be considered.
Whether multiple chemical sensitivity (MCS) is an organic disease initiated by environmental exposure or a psychologic disorder is a subject of controversy. The identification of pathophysiologic or psychophysiologic mechanisms occurring in patients with MCS after provocative challenges should be illuminating. Fifteen patients with MCS were challenged with their trigger substances and observed clinically. Prechallenge and postchallenge pulmonary function tests and PCO2, PO2, and oxygen saturation were measured. All of the patients whose symptoms were reproduced by the challenge (11 of 15) showed clinical evidence of acute hyperventilation with a rapid fall in PCO2 and no change or a rise in oxygen saturation. The symptoms and signs were consistent with an anxiety reaction with hyperventilation. Pulmonary function was unchanged; and recovery was rapid, aided in two cases by rebreathing into a paper bag. The most logical conclusion is that in these patients the MCS disorder is a manifestation of an anxiety syndrome triggered by their perception of an environmental insult, with at least some of their symptoms induced by hyperventilation.
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Eighteen patients with severe, progressive nonmicrobial inflammatory ophthalmic disease (including five with intermediate uveitis, four with sympathetic ophthalmia and three with serpiginous choroiditis) that had not responded to conventional therapy were treated with cyclosporine. Three of the four patients with sympathetic ophthalmia responded quickly and maximally, and the fourth showed partial improvement. One patient, with several corneal graft failures in the right eye, started cyclosporine therapy after undergoing left corneal transplantation; at the last follow-up visit the graft had been clear for almost 3 years. The response was inconsistent in patients with other types of eye disease. In general, the drug was well tolerated; however, two patients stopped treatment because of unpleasant side effects. No serious or irreversible complications developed. The results suggest that cyclosporine therapy is useful in the treatment of sympathetic ophthalmia and in high-risk corneal transplantation.
Four patients treated with fluoxetine alone developed generalized urticaria. One also suffered polyarthritis. These reactions subsided when fluoxetine was stopped. After 6-12 months, because of progressive psychiatric problems, fluoxetine was reintroduced using a desensitization protocol. In each case this was well tolerated, and fluoxetine has been continued without adverse affects for 3-10 months.
Forty-five patients with classic food-allergic symptoms and/or subjective food-related complaints not traditionally associated with food allergy underwent evaluation. On the basis of a comprehensive clinical history, skin testing, and placebo-controlled, double-blind food challenges, patients were assigned to one of two groups: patients with reactions highly suggestive of IgE-mediated food hypersensitivity (group A, N = 22) and patients with atypical adverse food reactions that could not be confirmed by double-blind food challenge (group B, N = 23). Most patients in both groups were female, 77.3% and 91.3% of patients in group A and B, respectively. In group B, onset of symptoms occurred at an older age than in group A, 28.9 years +/- 17.2 versus 17.1 +/- 12.1 (p = 0.0015), respectively, and involved more foods, 25.6 +/- 22.1 versus 5.2 +/- 5.5 (p = 0.0002). Foods causing most prominent symptoms among patients in group A included legumes, tree nuts, crustaceans, and fish. In group B, milk, white sugar, wheat, egg, smoked/cured meat, and yeast were among the most troublesome foods. All but one patient in group A gave a positive skin test response to food; only four patients in group B had a positive response. We conclude that a subset of patients with food-related complaints can be accurately predicted to have a negative double-blind challenge with suspected foods on the basis of information obtained by history and skin testing.
From a pool of 624 patients with idiopathic chronic urticaria and angioedema, 90 patients had evidence of associated thyroid autoimmunity (TA). Since the number expected by chance alone is 37, given that less than 6% of normal subjects have TA, the association is significant (p less than 0.01; chi-square test). Age and sex distribution was typical of patients with TA. Clinically, most patients suffered relentless and severe urticaria and/or angioedema. With the exception of thyroid function and thyroid antibody tests, other laboratory tests were not rewarding. In most cases, treatment with 1 thyroxine did not improve urticaria or angioedema, but a few patients demonstrated a dramatic response. Awareness of the association resulted in the identification of previously undiagnosed thyroid disease. The authors hypothesize that a subset of idiopathic chronic urticaria and angioedema may be an autoimmune disease.
A six-month double-blind controlled trial compared a 2,000 microgram per day dose of beclomethasone dipropionate aerosol (BDP), with current upper level doses of 800 micrograms per day of the standard BDP, in asthmatics requiring oral corticosteroids in addition to BDP and bronchodilators. Both groups showed a significant reduction in their oral steroid requirements during the study, with a 34 percent reduction in the lower dose group and a 57 percent reduction in the high dose BDP group while maintaining good symptomatic control of asthma; there was an associated improvement in baseline serum cortisol levels. Over the same period, the pulmonary function of the lower dose group showed significant worsening relative to that of the group receiving the high dose BDP which improved. There was no increase in dysphonia or oropharyngeal candidiasis among those using the concentrated BDP. We conclude that high dose concentrated BDP appears to be a safe medication in long-term steroid-dependent asthma, and is effective in reducing dependence on the use of oral corticosteroid with associated improvement both in pulmonary and adrenal function.
This double-blind, randomized, crossover study compared the incidence of nasal burning and stinging, as well as overall tolerability of the currently marketed formulation of Rhinalar (original formulation) to a new formulation of Rhinalar containing less propylene glycol. In addition, patient and investigator subjective evaluations were used to compare the effectiveness of the test medications in controlling the nasal symptoms of seasonal allergic rhinitis. A total of 122 patients were enrolled in this 4-week trial. Each patient received one formulation of Rhinalar for 2 weeks and then crossed over to receive the alternate formulation for an additional 2 weeks. Eighteen patients withdrew from the trial prematurely. Ten patients were lost to follow-up and eight withdrew due to side effects and/or inadequate therapeutic response. Statistical comparisons of patient evaluations of nasal burning and stinging with the two formulations of Rhinalar showed a very significant difference in terms of severity (P less than .001), duration (P less than .001), and tolerability (P = .006) in favour of the new formulation. A reduction in severity of throat irritation with the new formulation was also shown to be statistically significant (P = .006). Nausea, headache, and other side effects including watery eyes, taste perversion, and runny nose were seldom reported with either test medication. Both formulations were shown to be equally effective in relieving the nasal symptoms of seasonal allergic rhinitis. The considerable reduction in nasal burning and stinging and throat irritation with the new formulation of Rhinalar was shown to enhance patient acceptability and may lead to better compliance.
An open long-term trial of inhaled beclomethasone dipropionate was carried out in 32 asthmatic patients chronically dependent on systemic corticosteroids. Our objectives were to study the efficacy and safety of beclomethasone and to determine the proportion of patients in whom systemic steroids could be replaced by the new drug. All subjects had a clear history and physical findings of asthma as well as significant improvement in respiratory function after inhalation of salbutamol. Patients were followed for 4 to 8 years. Compared with a baseline period, patients receiving beclomethasone had reduced symptoms and needed less bronchodilator therapy, but their pulmonary function was unchanged. Bronchial biopsy specimens from seven patients who had been taking beclomethasone for as long as 8 years did not differ histologically from specimens from five asthmatic patients who had never taken the drug. Nine patients were able to stop taking systemic corticosteroids within 9 months, eight required them occasionally, and in eight the requirement was substantially reduced; the requirement did not change appreciably in the remaining seven. Inhaled beclomethasone is a safe and effective drug for chronic administration to asthmatic patients, and in 78% of our subjects the need for systemic steroids was substantially reduced or eliminated.
This report describes a case of reversible obstructive sleep apnea caused by occupational exposure to an inhaled allergen, guar gum powder. The patient, a pet food plant employee, also experienced severe cough, rhinitis, and conjunctivitis. Skin tests confirmed the specific guar allergy. Pharyngeal cross-sectional area was smaller than normal. Pulmonary function studies, histamine challenge tests, nasal air-flow resistance measurements, and nocturnal polysomnography were performed on 3 separate occasions: while the patient was working at his usual occupation, at the end of a 3-wk holiday, and after a guar dust challenge in an inhalation chamber. Pulmonary function and histamine challenge tests were consistently normal. At the time of the initial tests, nasal resistance was elevated, and nocturnal polysomnography revealed obstructive sleep apnea. After absence from work, obstructive sleep apnea resolved, and the nasal resistance returned to normal. After challenge with guar gum dust, the patient developed increased resistance to nasal air flow, and obstructive sleep apnea reappeared. This case demonstrates that allergy can cause reversible obstructive sleep apnea and that occupational exposure should be considered in the assessment of patients with this disease.
The standardized records of 144 asthmatic patients have been analyzed to determine whether the severity of their condition was correlated with the presence or absence of positive intradermal skin test reactions to a panel of seven allergen extracts (dust, feathers, Alternaria, Hormodendrum, mixed tree pollen, mixed grass pollen, and ragweed pollen). The skin tests were totally negative in 71 of the subjects, whereas in 73 subjects there was a strongly positive response to two or more allergens. The skin test-negative patients were older than the skin test-positive ones and had a shorter duration as well as a later onset of asthma. Also, they had lower serum-IgE levels and a lower frequency of a family history of atopic disease. Moreover, the skin test-negative group lost more time from their normal activities, required more visits to their doctor as a result of asthma, and were more frequently treated with oral corticosteroids. They additionally had greater air trapping on pulmonary function tests. However, when the groups were adjusted for the discordance in their age and duration of asthma, they tended to converge in the level of the variables that described the severity of their asthma. Thus the severity of asthma was found to be relatively similar in skin test-negative and skin test-positive patients.
Changes in the respiratory symptoms and pulmonary function of 441 grain elevator workers and a control group of 180 civic workers during a three-year period were compared. The grain handlers who left their jobs during the interval between the first and second surveys were found to have shown a significantly higher prevalence of cough and shortness of breath at the beginning of the study period than those who remained employed; this difference was not observed among the civic workers. The grain and civic workers who were examined on both occasions showed similar longitudinal changes in their symptoms and pulmonary function. Nevertheless, the results of this study are biased by the healthy worker effect among the grain handlers.
The health effects of employment as a grain handler were studied by examining workers on two occasions, firstly, immediately before or soon after they were hired and again about two and a half months after they were employed. Over this time there was a substantial increase in the prevalence of cough, sputum, and eye irritation, accompanied by small pulmonary function changes suggestive of a restrictive ventilatory defect. No comparable changes in symptoms were observed over a similar number of months in grain handlers employed for an average of nine years or in control workers consisting of newly hired or long term civic outside labourers. The long term grain handlers, however, developed a similar change in their pulmonary function. These findings indicate the occurrence of a change in the health of grain elevator workers after a relatively brief duration of employment.
The purpose of this study was to examine possible mechanisms of the obstructive and restrictive ventilatory defects of grain elevator workers. We found that grain handlers whose skin tests were positive to grain or fungal antigens had no excess of respiratory symptoms or pulmonary function abnormalities. Also, those having a possible work-related respiratory problem showed no response to inhalation challenge tests with grain dust extract. In addition, grain handlers exhibited neither an increase in positive serum precipitin tests with fungal antigens nor abnormal serum levels of C3 and C4, C-reactive protein, rheumatoid factor or antinuclear factor. However, their serum a1-antitrypsin level was elevated. The latter finding may be indicative of a pulmonary inflammatory process, but we have found no clear indication of a type 1 or 3 allergic state in grain elevator workers.
Seventeen patients, constituting 12.1% of 140 consecutively seen cases of chronic urticaria, demonstrated thyroid autoimmunity with thyroid microsomal antibodies (TMAs) in serum titers greater than or equal to 1:1,600. Eight of these 17 patients had goiter or thyroid dysfunction. In a control group of 477 consecutively seen patients, only 27 (5.6%) had similar TMA titers. Routine and special immunologic test results in this group of 17 patients did not differ from those found in other patients with chronic urticaria and angioedema (CUA), and the only notable clinical feature was that all 17 had angioedema. The age and sex distribution and thyroid features of these 17 patients were similar to those described in autoimmune thyroiditis. Patients (especially women) with CUA should be tested for the presence of TMAs. In this subgroup, CUA may have an autoimmune basis.