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Biomedical subjects

G L Rosenberg

Publications and source records attributed to G L Rosenberg.

18 recordsLinked to original sources
PubMed1996

Pain and dermal reaction caused by injected glycerin in immunotherapy solutions.

BACKGROUND: Fifty percent glycerin preserves immunotherapy solution potency for at least 3 years but must be diluted before injection to reduce glycerin-induced pain and inflammation. We studied pain, erythema, induration, and bruises caused by glycerin (0% to 30%). METHODS: In 15 healthy subjects we compared, in double-blind fashion, pain scores, injection site erythema, induration, and bruising caused by subcutaneous injections in randomized order of 0.1, 0.5, and 1 ml of glycerin 0%, 10%, 20%, and 30%. RESULTS: Injection volume did not significantly influence pain scores from diluent alone (0% glycerin) (p greater than 0.1). Pain scores of subjects given glycerin (0.1 to 1 ml, 10% to 30%) increased significantly as both injection volume (p less than 0.001) and glycerin concentration (p less than 0.001) increased. Pain scores correlated with total glycerin dose administered (volume x concentration) (rs = 0.67, p less than 0.0005) but varied widely, from minimal to severe, in those given the same dose. Injection site erythema, induration, and bruising occurred in some subjects with significant positive correlations between total glycerin dose and both frequency and diameters of erythema and induration. However, these dermal reactions were of trivial clinical importance. CONCLUSION: Injected glycerin produces pain that is proportional to total injected dose of glycerin, but individual variation in perceived discomfort is substantial. Total glycerin doses of less than 0.05 ml rarely produce clinically important pain.

Contusions↗
PubMed1989

Immunotherapy decreases skin sensitivity to cat extract.

In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients matched by intradermal skin test titration, leukocyte histamine release, and the doses of both cat extract and methacholine required for 20% fall in FEV1 were randomly assigned to one of the two treatment groups. Immunotherapy doses were increased to a maintenance dose of 4.56 Food and Drug Administration (FDA) units of Fel d I or if maintenance dose was less, to the highest tolerated dose. Before and during immunotherapy, we measured by intradermal titration the dose of cat extract, in FDA units of Fel d I equivalents, required for (1) 2+ end point (wheal diameter, greater than or equal to 10 mm; erythema diameter, 20 to 30 mm) and (2) 20 mm end point (erythema diameter, 20 mm). By prick skin test, we measured (1) the dose of cat extract that produced a wheal equal in area to that produced by histamine, 1 mg/ml, (2) the doses of cat extract that produced a wheal 22 mm2 in area, and (3) the sum of the wheal areas produced by five prick tests to 23.8, 7.1, 2.4, 0.7, and 0.2 FDA units per milliliter of Fel d I, respectively. After 1 year of treatment, in comparison to control patients, treated patients had significant increases in the ratio 1 year value/pretreatment value for the doses of cat extract required for intradermal test end points 1 and 2 (p less than 0.01), for prick test end point 1 (p less than 0.01), for end point 2 (p = 0.015), and significant decreases in this ratio for prick test end point 3 (p = 0.015). Treated patients also had significant increases in cat extract required for a 20% fall in FEV1 (p less than 0.01), in IgG antibodies toward whole cat extract, Fel d I and cat albumin (p less than 0.001), and in IgE antibodies toward whole cat extract, (p less than 0.01). Thus, a decrease in skin sensitivity to cat extract demonstrated by both intradermal and prick methods occurred in patients after 1 year of immunotherapy with cat extract at a time when bronchial sensitivity to cat extract was decreased and IgG and IgE antibodies toward cat extract were increased.

Allergens↗
PubMed1988

Immunotherapy for cat asthma.

In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients were matched by the dose of the cat extract expressed in Food and Drug Administration (FDA) units of Fel d I (previously called cat allergen 1) required for end point reaction in intradermal skin test end point titration (STEPT), for in vitro leukocyte histamine release (LHR), and for the dose of cat extract producing a 20% fall in FEV1 (cat-extract PD20) in bronchoprovocation test. Patients were matched also for bronchoprovocation dose of methacholine producing a 20% fall in FEV1 (methacholine PD20). Patients were randomly assigned to one of two treatment groups. During immunotherapy, doses were increased to maintenance dose of 4.56 FDA units of Fel d I, or, if this were less, to the highest tolerated dose. Systemic reactions to cat-extract immunotherapy were mild and infrequent. Before and during immunotherapy, we measured (in FDA units of Fel d I) cat-extract PD20, cat-extract intradermal STEPT, cat-extract in vitro LHR, serum levels of cat IgG and cat IgE, and methacholine PD20. After they had received 1 year of immunotherapy, patients receiving cat extract, in comparison to patients receiving placebo, had decreased cat-extract PD20 (p less than 0.01), diminished responses to cat-extract intradermal STEPT (p less than 0.025), increased IgE antibodies toward cat extract (p less than 0.01), increased IgG antibodies toward cat extract, Fel d I, and cat albumin (p less than 0.001), but no significant change in cat-extract in vitro LHR or in methacholine PD20. We conclude that cat-extract immunotherapy was well tolerated, significantly decreased skin and bronchial responses to cat extract, and significantly increased IgE antibodies to cat extract and IgG antibodies to cat extract, Fel d I, and cat albumin.

Adult↗
PubMed1986

Dose of cat (Felis domesticus) allergen 1 (Fel d 1) that induces asthma.

In 10 patients with cat asthma and hay fever, we quantified the doses of cat allergen (expressed as cat allergen 1 [Cat-1] in log Food and Drug Administration [FDA] units) inspired from the ambient air of a room containing living cats required to induce a 20% drop in FEV1. These doses were compared with the doses required to cause the same change in FEV1 when the patients were subjected to bronchial challenge with aerosols of cat hair and dander extract in the conventional manner. Patients highly sensitive to cat extract by skin, leukocyte histamine release, and bronchoprovocation tests and with measurable levels of anticat IgE by RAST were exposed for up to 2 hours in a room occupied full-time by two cats. At the same time, room air was sampled by a Durham gravity sampler, by an Andersen sampler, and by lapel fiberglass filters. When hair and dander particles trapped on greased slides by gravity and Andersen samplers were stained, sized, and counted, squamous cell fragments in the less than 10 mm range were abundant. Assays of extracts from the lapel filters for Cat-1 content by radioimmunoassay and for allergenic activity by leukocyte histamine release demonstrated a significant correlation (p less than 0.05) between the results of the two assays. All patients developed rhinitis and asthma during exposure. At the time of a 20% drop in FEV1, when air sampling was stopped, the lapel filters had trapped a total of -1.86 to less than -3.04 (median -2.74) log FDA units Cat-1. These measurements of Cat-1 exposure in the room correlated (p less than 0.01) with the doses of cat extract (-1.18 to -3.15 [median -2.26] log FDA units Cat-1 equivalents) required to induce a 20% fall in FEV1 in the conventional bronchoprovocation tests.

Administration, Intranasal↗
PubMed1984

Dose response of IgE and IgG antibodies during ragweed immunotherapy.

We studied the detailed dose-response relationship for ragweed (RW) antibody responses in 51 patients who received maximal-dose immunotherapy with crude RW extract. Serum RW-IgG and RW-IgE levels were determined by solid-phase radioimmunoassay at frequent intervals during initiation and maintenance of immunotherapy. Pretreatment RW-IgE ranged from 0.94 to 974 ng/ml (median 105); 45/51 patients had insignificant levels (less than 250 ng/ml) of RW-IgG. The maximal doses given ranged from 0.19 to 93.5 micrograms of RW antigen E per injection. All patients produced a significant IgG response (median peak 3462 ng/ml, range 689 to 24,395), and 46/51 had significant increases in IgE antibody (median peak 231 ng/ml, range 12 to 1528). A threshold dose was defined for each patient's IgG and IgE response as that dose level which initiated a persistent increment in immunoglobulin to greater than or equal to 25% of pretreatment levels. The median threshold dose for IgE was 0.13 micrograms of antigen E, which was achieved in a median time of 42 days. The threshold dose for IgG was significantly higher (median 0.56 micrograms of antigen E; p = 0.001) and occurred significantly later (median 79 days; p = 0.003). Despite variability over 3 orders of magnitude, the thresholds for IgE and IgG responses were significantly correlated for individual patients (r = 0.487; p = 0.002). The maximum RW-IgE response occurred in a median of 107 days, after which IgE antibodies declined in 46 of 49 patients. The maximal IgG response occurred significantly later (median 245 days; p less than 0.001) and then plateaued or declined modestly. The doses required to achieve maximal IgE and IgG responses were significantly correlated (r = 0.638; p less than 0.001). The maximum IgG response was positively correlated with the maximal dose of RW antigen E received (r = 0592; p less than 0.001). In 28 of the 51 patients, the incremental rise in total serum IgE was more than twice that observed for RW-IgE at the time of the maximum response, suggesting a nonspecific effect of RW immunotherapy on total serum IgE levels. This discrepancy could not be accounted for by environmental stimulation from other known allergens, as assessed by skin testing, or by pretreatment levels of RW-IgE or total IgE. These observations indicate that the human IgE antibody response during high-dose RW immunotherapy is more sensitive to both stimulation and suppression by continuous allergen administration than is the IgG response.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1983

Inhalation challenge with ragweed pollen in ragweed-sensitive asthmatics.

We reexamined the ability of inhaled ragweed pollen to induce bronchoconstriction in ragweed-sensitive asthmatic patients using a turbo-inhaler to administer pollen quantitatively. Adult subjects were selected for study on the basis of fall season asthmatic attacks, positive skin test, histamine release, RAST, and bronchial challenge responses to ragweed extract. Not one of 12 such subjects had any bronchial response to oral inhalation of whole pollen grains even when the dose was increased to 7640 pollen grains (more than the estimated maximum daily exposure in season), whereas nasal challenge by the same method produced brisk hay fever responses without bronchospasm. On the other hand, when the pollen was ground to fragments with a size range of 1 to 8 micrometers, oral inhalation produced a 35% fall in airways conductance in six of seven subjects in doses ranging from 59 to 20,000 pollen grain equivalents. Atropine pretreatment did not modify the response to pollen fragments, making an irritant response unlikely. These data, coupled with earlier observations that no more than a few pollen grains penetrate further than the larynx, raise further questions about the role of whole ragweed pollen in fall asthma in allergic patients. In addition, ragweed-allergic asthmatics appear not to have their symptoms at the time of maximum pollen load in the air. We believe that small-particle allergens other than ragweed pollen should be considered in most cases of fall seasonal asthma.

Antigens↗
PubMed1982

A comparison of immunotherapy schedules for injection treatment of ragweed pollen hay fever.

In 44 patients highly sensitive to ragweed, we compared weekly injections of single doses of ragweed extract (RW-Wk, 15 patients) with clustered doses of ragweed extract at 3-wk intervals (RW-Cl, 18 patients) for effects on ragweed hay fever symptom-medication scores and immunologic variates. Patients were matched and randomly assigned to treatment groups. Ragweed doses were advanced to the highest tolerated dose. Doses and number of visits were lower in the RW-Cl group than in the RW-Wk group. Despite lower doses, systemic reactions were not reduced and antiragweed IgE levels increased significantly more in the RW-Cl group than those in the RW-Wk group. Both the RW-Cl and RW-Wk groups had significant increases in antiragweed IgG levels, decreases in seasonal rise in antiragweed IgE levels, and lower symptom-medication scores (p less than 0.01) in comparison with the placebo group. We conclude that the RW-Cl regimen offered no important advantage over RW-Wk. Seventeen patients had previously received Rinkel-method immunotherapy with 0.5 ml of end-point dilution of ragweed extract for 1 to 2 yr without significant clinical improvement or immunologic changes. After adequate treatment with either RW-Wk or RW-Cl, these patients had significantly lower symptom-medication scores than those of the placebo groups and immunologic changes similar to those of the entire active-treatment group. Therefore, treatment failures on Rinkel immunotherapy respond well to adequate dose immunotherapy by either schedule.

Adolescent↗
PubMed1980

A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever.

In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2 + skin test to ragweed AgE at 0.1 microgram /ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance ("optimal dose") for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 micrograms of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 3f the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method.

Adolescent↗
PubMed1974

Production of chemotactic factor and lymphotoxin by human leukocytes stimulated with Herpes simplex virus.

Peripheral blood leukocytes (PBL) of 41 subjects were tested for their ability to be stimulated by herpes simplex virus antigens as measured by [(3)H]thymidine incorporation and lymphokine production (i.e., lymphocyte-derived chemotactic factor and lymphotoxin). The PBL of seronegative subjects failed to respond to viral antigens as measured by stimulation or lymphokine production. In contrast, PBL from seropositive subjects without clinical lesions of herpes labialis were stimulated by herpes simplex virus antigens and produced lymphokines. PBL from seropositive patients with clinical lesions of herpes labialis also produced lymphokines, but [(3)H]thymidine incorporation was slightly depressed. These findings suggest that lymphocytes from patients with a recent herpes simplex virus infection may respond less vigorously to in vitro stimulation by herpes antigens, but our study fails to show any basic defect in the responsiveness of the lymphocytes to account for recurrent herpetic episodes.

Animals↗
PubMed1972

In vitro stimulation of sensitized lymphocytes by herpes simplex virus and vaccinia virus.

Splenic lymphocytes from rabbits immunized with herpes simplex virus (HSV) were incubated in vitro with ultraviolet light-inactivated HSV, and the degree of lymphocyte transformation was determined by measurement of the incorporation of [(3)H]thymidine into acid-insoluble material. Lymphocytes from immunized rabbits were stimulated as much as 30-fold, whereas lymphocytes from control rabbits were unaffected. Lymphocyte sensitization occurred within 3 days after immunization; sensitized lymphocytes could still be detected 120 days after immunization. The antigenicity of the ultraviolet light-inactivated crude virus pool was found to reside primarily in the virion. Infectious virus, in comparison with inactivated virus, produced less lymphocyte stimulation. Studies on the interaction of the humoral and cellular immune responses showed that incubation of anti-HSV antibody with HSV antigens did not reduce the capacity of the viral antigens to stimulate sensitized lymphocytes. Other experiments revealed that lymphocytes from both the spleen and peripheral blood of animals immunized with vaccinia virus could be stimulated by vaccinia, but not by HSV. Conversely, lymphocytes from animals immunized with HSV could not be stimulated by vaccinia. The transformation of sensitized lymphocytes by viral antigens appears to be a simple, highly specific, and quantitative in vitro technique for the study of the cellular immune response to viral infections.

Animals↗