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Biomedical subjects

A L Sheffer

Publications and source records attributed to A L Sheffer.

At least 55 records · Page 3Linked to original sources

A multicenter study on skin-test reactivity of human volunteers to venom as compared with whole body Hymenoptera antigens.

Twenty-four control and 104 stinging insect-allergic patients were tested in this multicenter study, which compared the utility of individual venom and whole body extract (WBE) preparations for diagnosis. This study indicates that venom skin testing is more specific and more reliable than is testing with WBE. There was a high rate of WBE skin-test reactivity among controls. False-positive skin testing with venom was not a problem at concentrations of 1 microgram/ml or less. Only one mild and easily treated adverse reaction occurred in this study.

Antigens↗

Clinical and biochemical effects of stanozolol therapy for hereditary angioedema.

Stanozolol, an inexpensive anabolic steroid with a 30:1 anabolic:androgenic ratio, was administered to 12 male and 15 female patients with biochemically proven hereditary angioedema over a 2-yr period to obtain a systematic assessment of the relationship between drug dosage and clinical response, incidence of side effects, and amelioration of complement abnormalities. All 27 patients attained the minimal effective dose, ranging from 0.5 to 2 mg daily, which controlled the frequency and intensity of symptoms with minimal side effects. At daily maintenance doses of 2, 1, and 0.5 mg the frequencies of attacks per weeks of therapy were 1/14.6, 1/7.2, and 1/8.2 wk, respectively. Side effects with maintenance therapy included menstrual abnormalities and virilization in four females and elevation of serum creatinine phosphokinase (CPK) in five males. In six patients on maintenance doses of stanozolol, serum levels of testosterone, free thyroxin (T4), and thyroxin binding globulin (TBG) (four males), and of estradiol, progesterone, T4, and TBG (two females) were normal. Slightly low serum levels of progesterone and TBG were found in two females who had normal menstrual cycles. Statistically significant elevations above pretherapy levels of serum inhibitor to the activated first component of complement function and C4 protein and function occurred when patients were on maintenance therapy, but these measurements remained below the lower limit of normal range. Higher doses of stanozolol (4 mg/day), which caused greater immunochemical responses, were unnecessary for control of clinical disease and were unjustified for chronic therapy because of more frequent side effects.

Adolescent↗

Generation of antigen-specific suppressor cells during allergy desensitization.

We used a suppressor-cell assay to study a possible mechanism of allergy desensitization. Before specific immunotherapy, blood mononuclear cells from 20 patients with ragweed hayfever failed to exhibit suppressor activity in vitro after stimulation by ragweed antigen E. However, when the 10 patients with allergic rhinitis had been desensitized by injections of ragweed extract, their mononuclear cells specifically suppressed a ragweed proliferative response six and 12 months after desensitization was begun (31 per cent and 48 per cent suppression, respectively). Suppressor mononuclear cells were not detected in 10 control subjects of in 10 patients with ragweed hayfever who were not desensitized. When mononuclear cells taken from treated patients were passed over columns containing insolubilized histamine, antigen-specific suppressor cells that could be activated by ragweed antigen were depleted. These results indicate that antigen-specific suppressor cells, probably bearing histamine receptors, are generated during desensitization to allergy and may be partly responsible for the efficacy of this therapy.

Adult↗

Exercise-induced anaphylaxis.

Sixteen patients were seen because of possibly life-threatening exercise-associated symptoms similar to anaphylactic reactions. Asthma attacks, cholinergic urticaria and angioedema, and cardiac arrythmias are recognized as exertion-related phenomena in predisposed patients but are distinct from the syndrome described here. A syndrome characterized by the exertion-related onset of cutaneous pruritus and warmth, the development of generalized urticaria, and the appearance of such additional manifestations as collapse in 12 patients, gastrointestinal tract symptoms in five patients, and upper respiratory distress in 10 patients has been designated exercise-induced anaphylaxis, because of the striking similarity of this symptom complex to the anaphylactic syndrome elicited by ingestion or injection of a foreign antigenic substance. There is a family history of atopic desease for 11 patients and cold urticaria for two others and a personal history of atopy in six. The size of the wheals, the failure to develop an attack with a warm bath or shower or a fever, and the prominence of syncope rule against the diagnosis of conventional cholinergic urticaria. There is no history or evidence of an encounter with an environmental source of antigen during the exercise period.

Adolescent↗

Clinical and biochemical effects of impeded androgen (oxymetholone) therapy of hereditary angioedema.

Daily therapy and alternate-day therapy with the attenuated androgen oxymetholone were compared in patients with hereditary angioedema (HAE). Fifteen of 16 patients who experienced at least monthly attacks of HAE without treatment were asymptomatic on administration of 5 mg oxymetholene daily. When 13 of the patients who had been maintained asymptomatically on 5 mg oxymetholone daily were advanced to a treatment schedule of 5 mg every other day, seven attacks occurred during a cummulative 50 mo of therapy. The adverse effects that occurred with daily oxymetholone therapy largely subsided when the patients received alternate-day therapy, while a significant mean rise in C4 protein and function occurred only on daily therapy. Statistically significant mean increases in serum levels of C1INH occurred with daily therapy and were maintained with alternate-day therapy. Clinical benefit can be obtained with a treatment program that does not produce a statistically significant rise in C4 protein or function and does not raise C1INH to the lower limit of normal. The finding that alternate-day therapy diminished the side effects of the drug while affording a substantial reduction in the incidence and severity of attacks indicates the feasibility of this therapeutic approach.

Adult↗

Methyltestosterone therapy in hereditary angioedema.

In a double-blind study of four patients with hereditary angioedema, the efficacy of methyltestosterone (taken daily in 10-mg linguet form) in preventing attacks was shown. There were 19 episodes during 11.8 months of placebo administration, compared with only four attacks during the 46 months of cumulative methyltestosterone treatment (P less than 0.001). The mean serum C4 protein level was twice as high in all patients when they were taking the drug (176 +/- 36 mug/ml) as compared with the placebo (84 +/- 21 mug/ml), and rose to normal range in three of four patients.

Adolescent↗

Immune function in sarcoidosis. Studies on delayed hypersensitivity, B and T lymphocytes, serum immunoglobulins and serum complement components.

An assessment of immune function was performed in twenty-four patients with recently diagnosed active sarcoidosis. Four patients manifested skin anergy to four antigens. All subjects except one were capable of generating a positive skin response to a croton oil patch test. The incorporation of [3H]thymidine by lymphocytes in vitro in response to the nonspecific mitogens--phytohaemagglutinin, pokeweed mitogen and Con A did not differ between anergic and non-anergic thymidine incorporation in vitro when stimulated by the specific antigens, streptokinase/streptodornase or Candida albicans. Lymphocytes obtained from nine of eleven patients having positive delayed hypersensitivity skin reactions demonstrated MIF production in vitro upon specific antigen challenge. Quantities of circulating B and T lymphocytes did not differ between anergic and absolute numbers of circulating B and T lymphocytes, as well as hypercomplementaemia and hypergammaglobulinaemia when compared to the control group.

B-Lymphocytes↗

Immunologic components of hypersensitivity reactions to cromolyn sodium.

Manifestations of cellular and humoral hypersensitivity to cromolyn sodium were sought in six asthmatic patients suspected of having acute (three cases) or subacute (three cases) adverse reactions to cromolyn inhalation. Lymphocytes from all patients produced migration inhibition factor (MIF), and those from four patients incorporated increased amounts of 3H-thymidine in response to cromolyn in vitro. Lymphocytes from four of nine cromolyn-tolerant asthmatics demonstrated increased 3H-thymidine incorporation but none showed MIF production, whereas lymphocytes from normal subjects failed to react to cromolyn in either assay. Two of three patients with subacute reactions had increased serum binding of 3H-cromoglycate which was attributable to the IgG fraction. Thus although patients tolerating cromolyn therapy may demonstrate lymphocyte transformation in vitro, only those with clinically apparent adverse reactions produce lymphocyte MIF or possess serum-binding activity for the drug.

Acute Disease↗

Diagnosis of sarcoidosis by lip biopsy of minor salivary glands.

In two patients with bilateral parotid gland swelling of unknown etiology the diagnosis of sarcoidosis was established by lip biopsy of the minor salivary glands. This simple, innocuous biopsy procedure may prove useful in tissue documentation of sarcoidosis.

Adult↗