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A hemodynamic model for anaphylactic shock
Abstracts 17
VOLUME 71 WJMBER 5
Pharmacology, physiology, and pathology A hemodynamic shock
model for anaphylactic
Barsan WG, Hedges JR, Syverud SA, Dalsey WC: Ann Emerg Med 14:834, 1985. These authors have developed a small animal model that evaluates the hemodynamic alterations occurring during anaphylactic shock. This permits more precise hemodynamic determinations than those made previously. Eight white New Zealand rabbits were sensitizedto horse serum. On the day of challenge, the animals were sedated with xylam and administered general anesthesiawith methoxyflurane. Femoral arterial pressureswere monitored via intrarterial catheter and strain gauge; and intra-aortic arch temperature probe was passed,as was a right atria1catheter. Subsequent to these procedures, the anesthesiawas withdrawn, and sedation was maintained during the experiment with intravenous diazepam. Continuous monitorings of arterial pressure, single lead ECG, and intravasculartemperature were recorded, and measurementswere made of cardiac output (CO). After baseline studies, the animals were challenged intravenously with horse serum, and CO was determined at 3, 5, 10, 15, 35, 45, and 60 minutes, unless death occurred sooner.Animals were killed at the 60-minute mark in order to verify the accuracyof catheter placement. The authors noted a significant decline of 50% in CO, cardiac index (CO/animal weight), and blood pressureby the third posthorse serum-challengeminute. Two animals died of anaphylactic shock, but in six animals the baseline hemodynamic values that recovered by 60 minutes included mean arterial blood pressure,stroke volume, the stroke volume index, peripheral vascular resistance,and its change during the experiment. D. S.
Effect of keLotifen treatment cold-induced utiicaria
on
St-Pierre JP, Kobric M, Rackham A: Ann Allergy 55:840,
1985.
Prior treatment regimens for primary acquired cold urticaria (PAW) have included cold avoidance, cold desensitization, and. most successfully, cyproheptadine (for its antihistamine, antiserotonin, and antimediator activity). This study was designed to evaluate the safety and efficacy of ketotifen in the therapy of PAW. The study group was comprised of 11 PACU patients (6 to 58 years) (generalized whealing after exposure to cold and a positive ice test) and excluded all subjects with the secondary (underlying disease) form of the disorder. The patients were ra.ndomlyassignedto two groups, and the 21day, placebo-controlled, double-blind crossoverstudy was divided into thmefollowing trial periods: (1) days 1 to 7,
treatment with 1 mg of ketotifen, twice daily (group 1) or placebo (group 2), (2) days 7 to 14, washout, and (3) days 14 to 21, treatment with placebo (group 1) or ketotifen, 1 mg, twice daily (group 2). All subjectshad a conventional “ice cube test,” and the minimum time (Tmin) of cold exposure required to produce a wheal was recorded before and on days 7, 14, and 21 after drug administration. The mean Tmin for groups 1 and 2 increased6.0 and 5.7 minutes, respectively, and the group mean for both was significantly higher than baseline. The mean Tmin for all ketotifen-treated patients was 11.7 minutes (83% increase from baseline). The authors suggest that the observed beneficial effect of ketotifen in PACU may result from the inhibition of mediator release from mast cells and basophils or the antagonism of specific receptors. Although the drug has both antianaphylacticand antihistamine activity, the mechanism for suppressionof the urticarial reactionsis uncertain. It is concluded that ketotifen may be useful in the treatment of PACU, especiallyin patients resistant to treatment with the standard antihistamines. S. B.
lmmunogenicity semisynthetic
of bovine, porcine, human insulins
and
Venekamp WJRR, Van der Hooft JC, Jacobsen L, van Schaik CL: Neth J Med l(suppl 28):57, 1985. The authors compared the immunogenicity of semisynthetic human insulin with that of (1) highly purified porcine insulin and (2) monocompetent bovine insulin in 65 previously untreated diabetic patients. These subjectswere divided into three groups: (1) received either monocompetent bovine insulin or a 75/25% (bovine/porcine) insulin mixture, (2) received highly purified porcine insulin, and (3) was injected with semisynthetichuman insulin. Serum insulin antibodies were determined %, 1, 3, and 6 months after onset of treatment, whereas insulin dosage needed to control hyperglycemia was recorded at 1, 3, and 6 months. A semiquantitative assayfor insulin binding IgG was used that used ‘*?-A 1Cmonoiodoporcine, “‘I-A 14-monoiodohuman, and “‘I-iodobovine insulin as tracers. In almost all the treated patients, there was increasedbinding of added porcine tracer with the greatestbinding found in the bovine insulin-treated group. The insulin antibody levels against human and porcine insulins at 0, %, 1, 3, and 6 months were comparable, but the antibovine insulin antibody levels were greater than the antibodies against the other two insulinsat 3 and 6 months from commencementof treatment. Bovine insulin-treated patients needed more insulin, with time, for control of diabetes than did the patients from the other groups. It is concluded that bovine insulin is the most immunogenic, whereas semisynthetic and highly purified porcine insulins do not differ in immunogenicity. The main rise in anti-insulin IgG occurs during the first 3 months of therapy. D. S.
VOLUME 71 WJMBER 5
Pharmacology, physiology, and pathology A hemodynamic shock
model for anaphylactic
Barsan WG, Hedges JR, Syverud SA, Dalsey WC: Ann Emerg Med 14:834, 1985. These authors have developed a small animal model that evaluates the hemodynamic alterations occurring during anaphylactic shock. This permits more precise hemodynamic determinations than those made previously. Eight white New Zealand rabbits were sensitizedto horse serum. On the day of challenge, the animals were sedated with xylam and administered general anesthesiawith methoxyflurane. Femoral arterial pressureswere monitored via intrarterial catheter and strain gauge; and intra-aortic arch temperature probe was passed,as was a right atria1catheter. Subsequent to these procedures, the anesthesiawas withdrawn, and sedation was maintained during the experiment with intravenous diazepam. Continuous monitorings of arterial pressure, single lead ECG, and intravasculartemperature were recorded, and measurementswere made of cardiac output (CO). After baseline studies, the animals were challenged intravenously with horse serum, and CO was determined at 3, 5, 10, 15, 35, 45, and 60 minutes, unless death occurred sooner.Animals were killed at the 60-minute mark in order to verify the accuracyof catheter placement. The authors noted a significant decline of 50% in CO, cardiac index (CO/animal weight), and blood pressureby the third posthorse serum-challengeminute. Two animals died of anaphylactic shock, but in six animals the baseline hemodynamic values that recovered by 60 minutes included mean arterial blood pressure,stroke volume, the stroke volume index, peripheral vascular resistance,and its change during the experiment. D. S.
Effect of keLotifen treatment cold-induced utiicaria
on
St-Pierre JP, Kobric M, Rackham A: Ann Allergy 55:840,
1985.
Prior treatment regimens for primary acquired cold urticaria (PAW) have included cold avoidance, cold desensitization, and. most successfully, cyproheptadine (for its antihistamine, antiserotonin, and antimediator activity). This study was designed to evaluate the safety and efficacy of ketotifen in the therapy of PAW. The study group was comprised of 11 PACU patients (6 to 58 years) (generalized whealing after exposure to cold and a positive ice test) and excluded all subjects with the secondary (underlying disease) form of the disorder. The patients were ra.ndomlyassignedto two groups, and the 21day, placebo-controlled, double-blind crossoverstudy was divided into thmefollowing trial periods: (1) days 1 to 7,
treatment with 1 mg of ketotifen, twice daily (group 1) or placebo (group 2), (2) days 7 to 14, washout, and (3) days 14 to 21, treatment with placebo (group 1) or ketotifen, 1 mg, twice daily (group 2). All subjectshad a conventional “ice cube test,” and the minimum time (Tmin) of cold exposure required to produce a wheal was recorded before and on days 7, 14, and 21 after drug administration. The mean Tmin for groups 1 and 2 increased6.0 and 5.7 minutes, respectively, and the group mean for both was significantly higher than baseline. The mean Tmin for all ketotifen-treated patients was 11.7 minutes (83% increase from baseline). The authors suggest that the observed beneficial effect of ketotifen in PACU may result from the inhibition of mediator release from mast cells and basophils or the antagonism of specific receptors. Although the drug has both antianaphylacticand antihistamine activity, the mechanism for suppressionof the urticarial reactionsis uncertain. It is concluded that ketotifen may be useful in the treatment of PACU, especiallyin patients resistant to treatment with the standard antihistamines. S. B.
lmmunogenicity semisynthetic
of bovine, porcine, human insulins
and
Venekamp WJRR, Van der Hooft JC, Jacobsen L, van Schaik CL: Neth J Med l(suppl 28):57, 1985. The authors compared the immunogenicity of semisynthetic human insulin with that of (1) highly purified porcine insulin and (2) monocompetent bovine insulin in 65 previously untreated diabetic patients. These subjectswere divided into three groups: (1) received either monocompetent bovine insulin or a 75/25% (bovine/porcine) insulin mixture, (2) received highly purified porcine insulin, and (3) was injected with semisynthetichuman insulin. Serum insulin antibodies were determined %, 1, 3, and 6 months after onset of treatment, whereas insulin dosage needed to control hyperglycemia was recorded at 1, 3, and 6 months. A semiquantitative assayfor insulin binding IgG was used that used ‘*?-A 1Cmonoiodoporcine, “‘I-A 14-monoiodohuman, and “‘I-iodobovine insulin as tracers. In almost all the treated patients, there was increasedbinding of added porcine tracer with the greatestbinding found in the bovine insulin-treated group. The insulin antibody levels against human and porcine insulins at 0, %, 1, 3, and 6 months were comparable, but the antibovine insulin antibody levels were greater than the antibodies against the other two insulinsat 3 and 6 months from commencementof treatment. Bovine insulin-treated patients needed more insulin, with time, for control of diabetes than did the patients from the other groups. It is concluded that bovine insulin is the most immunogenic, whereas semisynthetic and highly purified porcine insulins do not differ in immunogenicity. The main rise in anti-insulin IgG occurs during the first 3 months of therapy. D. S.