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205. The effect of fenoterol on passive cutaneous anaphylaxis and histamine skin reactions in rats
2
American
Academy
of
J. ALLERGY CLIN. ;MiVlUNOL. MARCH 1978
Allergy
which were mild and of short duration. Complications occurred only on daily tberapy and included menorrhagia (3 patients), depression (2 patients), and hirsutism (1 patient). In 2 instances, therapy was interrupted as a consequence of these complications. The mean daily therapy value of C4 function of 62,068 2 60,443 (~1 SD) (N, 95% confidence limit = 134,600 to 390,700 U/ml), C4 protein of 243 2 96 (N = 258832 pg/ml), and CiINH function of 10,450 ? 3,949 (N = 19,750 to 55,150 U/ml) were significantiy increased (p < 0.001) over the pretherapy values for C4 function (25,736 ? 31,244), C4 protein (125 ? 52), and C?INH function (3,078 ? 2,440). Control of IIAE symptoms can be accomplished without complete correction of the biochemical defect, thereby minimizing the adverse androgenic effects of oxymetholone and even permitting alternate-day therapy. Lower dosages in some patients may offer control while minimizing suppression of pituitary function.
pression of papain-induced pruritus taminas. Gerald Kivett, B.S., Robert B. Rhoades, M.D., Kent N. Leifer, M.D., Larry D Haugh, Ph.D., and Heinz J. Wittig, M.D., Gainesville, Fla. and Augusta, Ga. We have previously reported the effectiveness of antihistamines in suppressing histamine-induced pruritis (J. ALLERGY CLIN. IMMUNOL. 55:180, 1975) with the most effective being hydroxyzine (Atarax). Endopeptidases including papain are highly pruritogenic and simulate the probable mediators of most clinical pruritus (i.e., tissue cathepsins) rather than histamine. In 26 healthy volunteers, itch threshold to intradermal papain was determined after pretreatment with Benadryl, Atarax, Periactin, Temaril, and placebo in a randomized double-blind crossover study. The replicate variability was somewhat greater than with histamine thresholds and a reproducible desensitization was noted over time. Analysis of variance revealed the interpatient difference (p < 0.002) and time trend (p < 0.006) to be significant but interdrug differences were not statistically significant (p > 0.5). The differences between drugs and drug vs placebo were small (with placebo being in the middle) and did not exceed the replicate variability of the method. With the use of similar techniques, Atarax was l,OOO-fold superior to placebo in histamine pruritus. This lack of antipruritic activity in the study agrees with the clinical lack of antipruritic efficacy of antihistamines in many situations and a growing body of experimental data on mechanisms of pm&us.
effect of fenoterol on passive s anaphylaxis and histamine skin rea&oIIa Abdolah Townley,
~II rata. Kenji Mano, M.D., Akbarzadeh, M.D., and Robert M.D., Omaha, Nebr.
G.
This study was undertaken to evaluate and compare the effect of the beta-2 agonist, fenoterol, with diphenhy-
dramine hydrochloride and aminophylline on the inhibition of passive cutaneous anaphylaxis (PCA) and histamine skin reactions (HSR) in rats. Balb/c mice were immunized intraperitoneally with ovalbumin and pertussis vaccine. Rats were used for 4- and 72-hr passive cutaneous anapbylaxis (PCA) induced by mouse antiovalbumin antibody at 1:41 : 256 dilutions and HSR with histamine (1 pg to IO mg per site). Test drugs were injected intravenously immediately before antigen challenge. All three drugs shifted me PCA and HSR dose-response curves to the right3 suggesting protection in a dose-dependent manner. Diphenhydratnine and aminophylline were effective in doses from 10 mg/kg to 1 mg/kg, while fenoterol at only 1 pg/kg inhibited both reactions (p < 0.05). Fenoterol, 10 pg, was equipotent to 10 mg of aminophylline on the HSR. In the doses used, fenoterol alone was as effective as the combination of fenoterol plus aminophylline on PCA. The fenoterol IDS,, (i.e., dose required for 50% inhibition) for 4- and 72-m PCA (titers, 1: 128) was 0.7 pg and 0.4 pg/kg, respectively, and for HSR (histamine, 1 pg/site) was 3 .O pg/kg. The order of potency was fenoterol > diphenhydramine > aminophylline against PCA reaction, and fenoterol = diphenhydramine > aminophylline against IISR.
206. Sinusitis in childre allergy. R Katz, M.D., G. Rachel M. Goldberg, M.D., G. Bori M.D., M. Shapiro, M.D., M. S. Finegold, M.D., and S. Siegel, Los Angeles, Calif.
M.D.!
Seventy consecutive atopic children between the ages of 3 to 16 yr were studied prospectively for sinus disease. History, physical examination, x-ray, and laboratory tests, including CBC, ESR, nasal smears, QI6s (A, G> M, E), as well as aerobic and anaerobic cultures, were obtained and correlated with each other for significant relationships. Abnormal sinus x-rays were found in 37 (53%). Of these, 15 (21%) had opacified sinuses. On the basis of x-ray changes, the children were divided into 5 groups: group i (normal); group 2 (less than 2 mm mucosal thickening of maxillary walls); group 3 (2 to 6 mm thickening); group 4 (greater than 6 mm thickening); and group 5 (opacification}. Fifteen patients comprised group 5; 14 in group 3; 4 each in groups 2 and 4. Besides x-rays, the only helpful Iaboratory test was the nasal smear evaluation for eosinophils and polymorphs. Clinically, PND, day and night coughing and nasal discharge correlate significantly (p < O.Q5) with sinus disease. All other parameters were of no diagnostic help”
207. Tartrazine-specific IgD an antibodies. Norman Weliky, Ph.D., Heiner, M.D., Ph.D., Hiroshi Tamura, Scott Anderson, 55, Torrance, Calif. Allergic symptoms following tartrazine (TZ) ingestion have been verified by several groups. The mechanisms
American
Academy
of
J. ALLERGY CLIN. ;MiVlUNOL. MARCH 1978
Allergy
which were mild and of short duration. Complications occurred only on daily tberapy and included menorrhagia (3 patients), depression (2 patients), and hirsutism (1 patient). In 2 instances, therapy was interrupted as a consequence of these complications. The mean daily therapy value of C4 function of 62,068 2 60,443 (~1 SD) (N, 95% confidence limit = 134,600 to 390,700 U/ml), C4 protein of 243 2 96 (N = 258832 pg/ml), and CiINH function of 10,450 ? 3,949 (N = 19,750 to 55,150 U/ml) were significantiy increased (p < 0.001) over the pretherapy values for C4 function (25,736 ? 31,244), C4 protein (125 ? 52), and C?INH function (3,078 ? 2,440). Control of IIAE symptoms can be accomplished without complete correction of the biochemical defect, thereby minimizing the adverse androgenic effects of oxymetholone and even permitting alternate-day therapy. Lower dosages in some patients may offer control while minimizing suppression of pituitary function.
pression of papain-induced pruritus taminas. Gerald Kivett, B.S., Robert B. Rhoades, M.D., Kent N. Leifer, M.D., Larry D Haugh, Ph.D., and Heinz J. Wittig, M.D., Gainesville, Fla. and Augusta, Ga. We have previously reported the effectiveness of antihistamines in suppressing histamine-induced pruritis (J. ALLERGY CLIN. IMMUNOL. 55:180, 1975) with the most effective being hydroxyzine (Atarax). Endopeptidases including papain are highly pruritogenic and simulate the probable mediators of most clinical pruritus (i.e., tissue cathepsins) rather than histamine. In 26 healthy volunteers, itch threshold to intradermal papain was determined after pretreatment with Benadryl, Atarax, Periactin, Temaril, and placebo in a randomized double-blind crossover study. The replicate variability was somewhat greater than with histamine thresholds and a reproducible desensitization was noted over time. Analysis of variance revealed the interpatient difference (p < 0.002) and time trend (p < 0.006) to be significant but interdrug differences were not statistically significant (p > 0.5). The differences between drugs and drug vs placebo were small (with placebo being in the middle) and did not exceed the replicate variability of the method. With the use of similar techniques, Atarax was l,OOO-fold superior to placebo in histamine pruritus. This lack of antipruritic activity in the study agrees with the clinical lack of antipruritic efficacy of antihistamines in many situations and a growing body of experimental data on mechanisms of pm&us.
effect of fenoterol on passive s anaphylaxis and histamine skin rea&oIIa Abdolah Townley,
~II rata. Kenji Mano, M.D., Akbarzadeh, M.D., and Robert M.D., Omaha, Nebr.
G.
This study was undertaken to evaluate and compare the effect of the beta-2 agonist, fenoterol, with diphenhy-
dramine hydrochloride and aminophylline on the inhibition of passive cutaneous anaphylaxis (PCA) and histamine skin reactions (HSR) in rats. Balb/c mice were immunized intraperitoneally with ovalbumin and pertussis vaccine. Rats were used for 4- and 72-hr passive cutaneous anapbylaxis (PCA) induced by mouse antiovalbumin antibody at 1:41 : 256 dilutions and HSR with histamine (1 pg to IO mg per site). Test drugs were injected intravenously immediately before antigen challenge. All three drugs shifted me PCA and HSR dose-response curves to the right3 suggesting protection in a dose-dependent manner. Diphenhydratnine and aminophylline were effective in doses from 10 mg/kg to 1 mg/kg, while fenoterol at only 1 pg/kg inhibited both reactions (p < 0.05). Fenoterol, 10 pg, was equipotent to 10 mg of aminophylline on the HSR. In the doses used, fenoterol alone was as effective as the combination of fenoterol plus aminophylline on PCA. The fenoterol IDS,, (i.e., dose required for 50% inhibition) for 4- and 72-m PCA (titers, 1: 128) was 0.7 pg and 0.4 pg/kg, respectively, and for HSR (histamine, 1 pg/site) was 3 .O pg/kg. The order of potency was fenoterol > diphenhydramine > aminophylline against PCA reaction, and fenoterol = diphenhydramine > aminophylline against IISR.
206. Sinusitis in childre allergy. R Katz, M.D., G. Rachel M. Goldberg, M.D., G. Bori M.D., M. Shapiro, M.D., M. S. Finegold, M.D., and S. Siegel, Los Angeles, Calif.
M.D.!
Seventy consecutive atopic children between the ages of 3 to 16 yr were studied prospectively for sinus disease. History, physical examination, x-ray, and laboratory tests, including CBC, ESR, nasal smears, QI6s (A, G> M, E), as well as aerobic and anaerobic cultures, were obtained and correlated with each other for significant relationships. Abnormal sinus x-rays were found in 37 (53%). Of these, 15 (21%) had opacified sinuses. On the basis of x-ray changes, the children were divided into 5 groups: group i (normal); group 2 (less than 2 mm mucosal thickening of maxillary walls); group 3 (2 to 6 mm thickening); group 4 (greater than 6 mm thickening); and group 5 (opacification}. Fifteen patients comprised group 5; 14 in group 3; 4 each in groups 2 and 4. Besides x-rays, the only helpful Iaboratory test was the nasal smear evaluation for eosinophils and polymorphs. Clinically, PND, day and night coughing and nasal discharge correlate significantly (p < O.Q5) with sinus disease. All other parameters were of no diagnostic help”
207. Tartrazine-specific IgD an antibodies. Norman Weliky, Ph.D., Heiner, M.D., Ph.D., Hiroshi Tamura, Scott Anderson, 55, Torrance, Calif. Allergic symptoms following tartrazine (TZ) ingestion have been verified by several groups. The mechanisms