.o.
Investigation and treatment of allergic asthma To the editor: I have several comments on the article "New perspectives in allergic asthma", by Dr. Samuel 0. Freedman (Can Med Assoc J 114: 346, 1976). In the first place, Dr. Freedman gives the impression that the radioallergosorbent test (RAST) is as good as, and will probably replace, prick testing in the investigation of allergic disease. Our work suggests that this is not so. In a recent study, the results of which are to be published in the Annals of Allergy, we did 12 prick tests and RASTs (using inhalants, pollens and epidermal allergens) on 50 patients who were clinically allergic to many allergens, and found that the prick test was positive in 25.7% of tests and the RAST in only 11.7%. Clinically, we felt that the prick test gave much more reliable information about these patients than did the RAST. In addition, for only 10 tests was the prick test negative when the RAST was positive. In another study, to be reported in the Journal of Allergy and Clinical Immunology, in which we did prick tests and RASTs for 100 food allergens to which the patient had had a definite clinical reaction, the prick test was positive in 70% of tests and the RAST in only 52%, so that there was a much greater correlation between history and prick test results than between history and RAST results. In addition, particularly in these days of economic restraint, we must remember that prick tests command a fee of only 50. each (in Ontario), which includes performance, material and the professional component, and it contributions to the correspondence section are welcomed and if considered suitable will be published as space permits. They should be typewritten double spaced and should not exceed 11/2 pages in length.
... -....
can be done in a physician's private office; RASTs, however, cost $5.50 each for the material alone, and, in addition, there are the expenses of a technician, laboratory facilities and the professional component, bringing the cost of each to at least 15 times the cost of a prick test. This does not invalidate Dr. Freedman's statement that the RAST "appears to be the diagnostic procedure of choice in patients for whom the skin test either is not feasible or yields unreliable results". My point is, for the majority of patients who require allergy investigation the prick test is far superior to the RAST. My next comment applies to Dr. Freedman's reference to hyposensitization therapy. His experience with allergy patients has been confined largely to adults, in whom extrinsic asthma is not nearly as common as it is in children, and it may be that this is the reason he has come to different conclusions than I have. After 25 years of using hyposensitization therapy in children with extrinsic asthma I am still highly impressed with the value of this procedure. Over the last few years we have learned a great deal about the immunologic effects of hyposensitization therapy and these are beautifully summarized in the recent article by Irons, Pruzanski and Patterson.1 This article not only includes many references to the studies that have proved the efficacy of hyposensitization therapy but also lists the known immunologic changes that this therapy brings about: briefly, (a) development of blocking antibody, (b) decreased release of histamine from basophils and, therefore, presumably also from mast cells and (c) decreased formation of the specific IgE that is responsible for the patient being allergic to a specific allergen. In many cases these changes can be correlated with clinical improvement. The subject is discussed further
1086 CMA JOURNAL/JUNE 19, 1976/VOL. 114
HALOG CREAM Halcinonlde 0.1% Halog Cream (halcinonide, 0.1%) is intended for use as an anti-inflammatory agent for topical application. Halog Cream, 0.1%, provides 0.1% halcinonide, in a specially formulated water-washable base consisting of glycerylmonostearate, cetyl alcohol, myristyl stearate, isopropyl palmitate, polysorbate 60, and propylene glycol. ACTION: Haiog Cream, 0.1%, produces significant or complete therapeutic responses in patients with acute or chronic corticosteroid-responsive dermatoses. INDICATIONS: Haiog Cream, 0.1%, is indicated for topical application for relief of the many acute or chronic corticosteroid-responsive dermatoses. CONTRAINDICATIONS: Turberculous, fungal and most viral lesions of the skin (including herpes simplex, vaccinia and varicella). Halog Cream is not intended for use in the eye nor in the external auditory canal of patients with perforated eardrums. WARNINGS: Systemic side effects may occur and must be kept in mind particularly during use over large areas or for an extended period of time. Occasionally, symptoms of steroid withdrawal may deveiop when the medication is stopped after probnged use. Pregnancy: Safety has not been established. Potential benefit should be weighed against possible hazard. PRECAUTIONS: If local infection (other than those cited in CONTRAINDICATIONS) exists, suitable concomitant antimicrobial therapy should be administered. If a favourable response does not occur promptly, application of the corticosteroid should be discontinued until the infection is adequately controlled by apprornate measures. local irritation or sensitization deveiops, halcinonide cream should be discontinued.
Occlusive Dressing Technique: The use of occlusive
dressings increases the percutaneous absorption of corticosteroids and the possibility of systemic effects. For patlents with extensive lesions it may be preferable to use a sequential approach. The patient should be kept under close observation during proionged occlusive therapy. Thermal homeostasis may be impaired if large areas of the body are occluded. Occasionally, a patlent may develop a sensitivity reaction to a particular occlusive dressing material or adhesive. If infection deveiops, discontinue the use of the occlusive dressings and institute appropriate antimicrobial therapy. ADVERSE REACTIONS: Significant local irritation is uncommon; a transient burning sensation may occur in some patients. The use of corticosteroids under ccclusive dressings is known to produce miliaria, folliculitis, pyoderma, or localized cutaneous atrophy; striae occasionally devebp. Erythema, dryness, itching and change in skin pigmentation have been reported with topical steroids.
SYMPTOMS AND TREATMENT OFOVERDOSAGE:
Mild, reversible suppression of adrenal function, ecchymoses of the skin, peptic ulceration, hypertension, aggravation of infection, hirsutism, acne, edema and muscle weakness due to protein depletion are all toxic symptoms of corticosteroids. Animal studies suggest that overdosage may result in swollen breasts or Lactation. Treatment is symptomatic; corticosteroid administration should be discontinued.
DOSAGE AND ADMINISTRATION: Usual adult dosage range: 2 to 3 applications daily.
Occlusive Dressing Technique: Gently rub a small
amount of the Halog Cream, 0.1%, into the lesion until the cream disappears. Then re-apply the cream, leaving athin coating on the lesion and cover with a pliable non-porous film. Good results have been obtained by applying Halog Cream, 0.1%, under occlusion in the evening and reapplying Halog Cream, 0.1%, without occlusion in the moming (i.e. - 12-hour occlusion). Reapplication of the preparation is essential at each dressing change. DOSAGE FORMS: Halog Cream is supplied as cream formulation contalning 0.1% halcinonide, in tubes of 15,30 and 60g. STORAGE: Store at room temperature. Avoid freezing. Avoid prolonged storage at temperatures exceeding3O"C.
Product monograph available to physicians and pharmacists on request. References: 1. Data on file, Squibb Institute of Medical Research. 2. Sudilovsky A, Clewe TH: J Clin Pharmacol 15:779-784, 1975.3. Clark RF, Clement ER:Arch Dermatol 111:731-733, 1975.
E R.SQUIBB& SONS LTD.
EEJ 2365 COTE DE LIESSE, MONTREAL, QUE. H4N 2M7
VELOSEF 250 CAPSULES VELOSEF 500 CAPSULES Cephradine Capsules VELOSEF 125 FOR ORAL SUSPENSION VELOSEF 250 FOR ORAL SUSPENSION Cephradlne for Oral Suspension VELOSEF FOR INJECTION, 500 mg and 1 g Cephradine for Injection ACTION: Cephradine is a semi-synthetic, cephalosporin antibiotic eshibiting bactericidal activity through inhibition at cell-wall synthesis. INDICATIONS: Infections in the respiratory and genitourinary tracts, and in the skin and soft tissues, due to susceptible organisms. Sensitivity tests should be performed: therapy may be instituted before receiving the results. CONTRAINDICATIONS: Hypersensitivity to the cephalosporin group of antibiotics. WARNINGS: There is evidence of partial cross-allergenicity between the penicillins and the cephalosporins. Therefore, cephradine should be used with caution in patients with known hypersensitivity to penicitlins. Antibiotics, including cephradine, should be used cautiously and only when absolutely necessary in patients with a history of allergies, particularly to drugs. Usage during pregnancy and lactation: Safety for use of this product during pregnancy has not been established. Cephradine is secreted in breast milk. PRECAUTIONS: Patients should be observed carefully during therapy. Allergic reactions require discontinuation of VELOSEF and appropriate treatment. Prolonged use of VELOSEF may result in overgrowth of nonsusceptible organisms: appropriate measures should be instituted. During long-term therapy, hematological, renal and hepatic functions should be monitored periodically. Patients with known or suspected renal impairment should be observed carefully since cephradine may accumulate in the serum and tissues unless dosage is suitably reduced. See DOSAGE AND ADMINISTRATION section. Indicated surgical procedures should be performed in conjunction with antibiotic therapy; e.g., the incision and drainage of abscesses. After treatment with cephalosporins, a false-positive reaction for glucose in the urine may occur, but not with enzymebased tests. A false-positive Coombe test has also been reported. VELOSEF for Injection is not compatible with Lactated Ringer's Solution or other calcium-containing infusion fluids. ADVERSE REACTIONS: Usually limited to gastrointestinal disturbances and occasional hypersensitivity, but may include hematological and hepatobiliary disturbances, as well as elevated BUN, LDH or serum creatinine; superinfection; vaginitis and joint pains. Thrombophlebitis following IV. injection and sterile abscesses after IM. injection have occurred. Only occasionally severe enough to warrant cessation of therapy DOSAGE AND ADMINISTRATION: The presence of food in the gastrointestinal tract delays the absorption and reduces the peak level but does not aftect the total amount of cephradine absorbed. VELOSEF Capsules and VELOSEF for Oral Suspension Adults: Respiratory tract infections: 250 mg, q6h. Pneumococcal lobar pneumonia: 500 mg, q6H. Genitourinary tract infections: 500 mg, q6h. Prolonged therapy is advisable for the treatment of prostatitis and epididymitis. Children: 25 to 50 mg/kg/day, divided into four equally spaced doses, e.g.: VELOSEF for Oral Suspension Child's Weight 125 mg/S ml 250 mg/S ml 10kg (22 Ibs) /2 to 1 tsp. q6h 20 kg (44 Ibs) 1 to 2 tsp. q6h /2 to 1 tsp. q6h 4Okg(881bs) 2to4tsp.q6h 1 to2tsp.q6h Smaller doses than those indicated above should not be used. For otitis media due to H. influenzae, doses from 75 to 100 mg/kg/day are recommended. VELOSEF for Injection: For use in serious and life-threatening infections or where oral therapy is not possible. Average adult daily dose is 2 - 4 g, depending on the infection. In children, a daily dose of 50 - 100 mg/kg is recommended. All patients; all formulations: Larger doses (up to 1 g q6h in adults or up to 25 mg/kg q6h in children) may be given for severe or chronic infections: maximum daily dose should not esceed 4 g. Therapy should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. In infections caused by hemolytic streptococci, a minimum 10-daytreatment period is recommended. Stubborn infections may require treatment for several weeks with frequent bacteriological and clinical appraisal. A modified dosage schedule in patients with decreased renal function is necessary. Each patient should be considered individually: the following schedule is recommended as a guideline. Initial loading dose: 750 mg. Maintenance dose: 500 mg at the time intervals listed below: Creatinine Clearance Time Interval (ml /min/1.73m2) > 20m1/min 6-12 hours 15-19m1/min 12-24hours 10-14 mI/mm 24-40 hours 5-9 mI/mm 40-50 hours < SmI/min 50-l0hours DOSAGE FORMS: Capsules of 250 mg and 500 mg in bottles of 50, and bottles of VELOSEF 125 and 250 for Oral Suspension which, after reconstitution, provide 100 ml of pleasantly flavoured suspension containing 25 mg/mI and 50 mg/mI respectively. VELOSEF for Injection is provided as a sterile powder for reconstitution in vials containing 500 mg or 1 g. Consult Product Monograph for reconstitution procedure. Product Monograph available to physicians and pharmacists on request.
E R, SQUIBB & SONS LTD, E.EJ 2365 COTE DE LIESSE, MONTREAL, QUE, H4N 2M7
in our review.2 The physician interested in hyposensitization therapy should read these articles in detail. Dr. Freedman continues that the use of pollen immunotherapy in hay fever may have been shown to have good results but its efficacy in any form of asthma is presently lacking. We know that the development of symptoms in the patient with hay fever depends on the allergen reaching the mucous membrane of the nose or eye, or both, combining with specific IgE attached to the mast cells, and causing release from these cells of mediators that produce the symptoms. We know that the mechanism is the same in pollen-produced asthma except that the mediators are released in the lung. We also have good evidence that the decreased production of specific IgE is caused by suppressor T-lymphocytes acting on the pollenantibody-producing B-lymphocytes to suppress formation of specific IgE, and that this should result in clinical improvement since the specific IgE is the cause of the patient's symptoms in the first place. If one cannot extrapolate the information from studies on hay fever to asthma caused by the same pollen, then one has to postulate that the suppressor T- and B-lymphocyte populations are different in hay fever and in asthma, and there is not a shred of evidence in the literature to suggest that the T- and B-lymphocytes that relate to a specific antigen differ from one disease to another or from one organ to another. Therefore, it seems logical that the results of studies that have been done on hay fever patients apply also to asthma patients if their asthma is precipitated by the same pollen. The reason the studies have been done on hay fever patients is that hay fever patients who have practically no other allergies are relatively easy to find, whereas asthma is a much more complex disease and it is virtually impossible to find a series of asthmatic patients whose asthma is precipitated by only one pollen; therefore, asthmatic patients are not as suitable for study. I do not mean to imply that hyposensitization is 100% perfect in the treatment of allergic patients, particularly asthmatic patients in whom there are a great many other factors besides extrinsic allergens. It is useful only for that part of the disease process caused by external allergens. In addition, hyposensitization is a very slow process for the patient and a tremendous amount of work for the physician, if he does it properly, over a period of years. Therefore, although I believe it is helpful to these patients, I would be one of the first to wish for something better to become available. However, until this happens, I think it would be most
unfortunate for patients with extrinsic allergy to be denied hyposensitization therapy, because there is no question in my mind that they benefit from it if it is properly performed. C. COLLINS-WILLIAMS, MD
Head, allergy division Hospital for Sick Children Professor of pediatrics University of Toronto Toronto, ON
References 1. IRoi.is JS, PRUZAN5KI JJ, PAi.-rassoN R: Immunotherapy: mechanisms of action suggested by measurements of immunologic and cellular parameters. I Allergy Clin Immunol 56: 64, 1975 2. NIZAMI RM, COLLINS-WILLIAMS C: Hyposensitization therapy in allergic disease. Ann Allergy 35: 296, 1975
To the editor: I am grateful to Dr. Collins-Williams for his thoughtful comments in response to my recent article in the Journal. The publication of the results of his studies on the lack of correlation between history and results of prick tests and RASTs is awaited with interest, since they appear to be at variance with much of the previously published data on this admittedly controversial topic. A recent investigation of grass-pollen allergy, for example, showed a 91 % correlation between positive history and positive RAST, compared with a 92% correlation between positive history and positive prick test.1 I agree that the prick test is currently less costly to perform than the RAST, although the eventual automation of the RAST procedure in centralized clinical immunology laboratories would probably reduce the expense to a comparable level. Furthermore, the use of the automated RAST for selected allergens may encourage the clinician to be more discriminating in the number of tests ordered - a desirable objective from both a medical and an economic viewpoint. In evaluating the results of hyposensitization therapy in allergic asthma the criteria of efficacy must be the same as for other treatment modalities, despite the immunologic considerations so clearly summarized by Dr. Collins-Williams. Controlled double-blind studies have proved the efficacy of the /32-adrenergic agents, disodium cromoglycate and beclomethasone dipropionate aerosol in the management of asthma; no similar clinical trials have ever been conducted for the immunotherapy of asthma. These new pharmacologic agents, which are relatively free of serious side effects, indeed may be the "something better" that Dr. CollinsWilliams wishes for. SAMUEL 0. FREEDMAN, MD, FRcP[c], FAcP, FRCS Director, division of clinical immunology and allergy Montreal General Hospital Professor of medicine
McGill University
Montreal, PQ
CMA JOURNAL/JUNE 19, 1976/VOL. 114 1089
Investigation and treatment of allergic asthma To the editor: I have several comments on the article "New perspectives in allergic asthma", by Dr. Samuel 0. Freedman (Can Med Assoc J 114: 346, 1976). In the first place, Dr. Freedman gives the impression that the radioallergosorbent test (RAST) is as good as, and will probably replace, prick testing in the investigation of allergic disease. Our work suggests that this is not so. In a recent study, the results of which are to be published in the Annals of Allergy, we did 12 prick tests and RASTs (using inhalants, pollens and epidermal allergens) on 50 patients who were clinically allergic to many allergens, and found that the prick test was positive in 25.7% of tests and the RAST in only 11.7%. Clinically, we felt that the prick test gave much more reliable information about these patients than did the RAST. In addition, for only 10 tests was the prick test negative when the RAST was positive. In another study, to be reported in the Journal of Allergy and Clinical Immunology, in which we did prick tests and RASTs for 100 food allergens to which the patient had had a definite clinical reaction, the prick test was positive in 70% of tests and the RAST in only 52%, so that there was a much greater correlation between history and prick test results than between history and RAST results. In addition, particularly in these days of economic restraint, we must remember that prick tests command a fee of only 50. each (in Ontario), which includes performance, material and the professional component, and it contributions to the correspondence section are welcomed and if considered suitable will be published as space permits. They should be typewritten double spaced and should not exceed 11/2 pages in length.
... -....
can be done in a physician's private office; RASTs, however, cost $5.50 each for the material alone, and, in addition, there are the expenses of a technician, laboratory facilities and the professional component, bringing the cost of each to at least 15 times the cost of a prick test. This does not invalidate Dr. Freedman's statement that the RAST "appears to be the diagnostic procedure of choice in patients for whom the skin test either is not feasible or yields unreliable results". My point is, for the majority of patients who require allergy investigation the prick test is far superior to the RAST. My next comment applies to Dr. Freedman's reference to hyposensitization therapy. His experience with allergy patients has been confined largely to adults, in whom extrinsic asthma is not nearly as common as it is in children, and it may be that this is the reason he has come to different conclusions than I have. After 25 years of using hyposensitization therapy in children with extrinsic asthma I am still highly impressed with the value of this procedure. Over the last few years we have learned a great deal about the immunologic effects of hyposensitization therapy and these are beautifully summarized in the recent article by Irons, Pruzanski and Patterson.1 This article not only includes many references to the studies that have proved the efficacy of hyposensitization therapy but also lists the known immunologic changes that this therapy brings about: briefly, (a) development of blocking antibody, (b) decreased release of histamine from basophils and, therefore, presumably also from mast cells and (c) decreased formation of the specific IgE that is responsible for the patient being allergic to a specific allergen. In many cases these changes can be correlated with clinical improvement. The subject is discussed further
1086 CMA JOURNAL/JUNE 19, 1976/VOL. 114
HALOG CREAM Halcinonlde 0.1% Halog Cream (halcinonide, 0.1%) is intended for use as an anti-inflammatory agent for topical application. Halog Cream, 0.1%, provides 0.1% halcinonide, in a specially formulated water-washable base consisting of glycerylmonostearate, cetyl alcohol, myristyl stearate, isopropyl palmitate, polysorbate 60, and propylene glycol. ACTION: Haiog Cream, 0.1%, produces significant or complete therapeutic responses in patients with acute or chronic corticosteroid-responsive dermatoses. INDICATIONS: Haiog Cream, 0.1%, is indicated for topical application for relief of the many acute or chronic corticosteroid-responsive dermatoses. CONTRAINDICATIONS: Turberculous, fungal and most viral lesions of the skin (including herpes simplex, vaccinia and varicella). Halog Cream is not intended for use in the eye nor in the external auditory canal of patients with perforated eardrums. WARNINGS: Systemic side effects may occur and must be kept in mind particularly during use over large areas or for an extended period of time. Occasionally, symptoms of steroid withdrawal may deveiop when the medication is stopped after probnged use. Pregnancy: Safety has not been established. Potential benefit should be weighed against possible hazard. PRECAUTIONS: If local infection (other than those cited in CONTRAINDICATIONS) exists, suitable concomitant antimicrobial therapy should be administered. If a favourable response does not occur promptly, application of the corticosteroid should be discontinued until the infection is adequately controlled by apprornate measures. local irritation or sensitization deveiops, halcinonide cream should be discontinued.
Occlusive Dressing Technique: The use of occlusive
dressings increases the percutaneous absorption of corticosteroids and the possibility of systemic effects. For patlents with extensive lesions it may be preferable to use a sequential approach. The patient should be kept under close observation during proionged occlusive therapy. Thermal homeostasis may be impaired if large areas of the body are occluded. Occasionally, a patlent may develop a sensitivity reaction to a particular occlusive dressing material or adhesive. If infection deveiops, discontinue the use of the occlusive dressings and institute appropriate antimicrobial therapy. ADVERSE REACTIONS: Significant local irritation is uncommon; a transient burning sensation may occur in some patients. The use of corticosteroids under ccclusive dressings is known to produce miliaria, folliculitis, pyoderma, or localized cutaneous atrophy; striae occasionally devebp. Erythema, dryness, itching and change in skin pigmentation have been reported with topical steroids.
SYMPTOMS AND TREATMENT OFOVERDOSAGE:
Mild, reversible suppression of adrenal function, ecchymoses of the skin, peptic ulceration, hypertension, aggravation of infection, hirsutism, acne, edema and muscle weakness due to protein depletion are all toxic symptoms of corticosteroids. Animal studies suggest that overdosage may result in swollen breasts or Lactation. Treatment is symptomatic; corticosteroid administration should be discontinued.
DOSAGE AND ADMINISTRATION: Usual adult dosage range: 2 to 3 applications daily.
Occlusive Dressing Technique: Gently rub a small
amount of the Halog Cream, 0.1%, into the lesion until the cream disappears. Then re-apply the cream, leaving athin coating on the lesion and cover with a pliable non-porous film. Good results have been obtained by applying Halog Cream, 0.1%, under occlusion in the evening and reapplying Halog Cream, 0.1%, without occlusion in the moming (i.e. - 12-hour occlusion). Reapplication of the preparation is essential at each dressing change. DOSAGE FORMS: Halog Cream is supplied as cream formulation contalning 0.1% halcinonide, in tubes of 15,30 and 60g. STORAGE: Store at room temperature. Avoid freezing. Avoid prolonged storage at temperatures exceeding3O"C.
Product monograph available to physicians and pharmacists on request. References: 1. Data on file, Squibb Institute of Medical Research. 2. Sudilovsky A, Clewe TH: J Clin Pharmacol 15:779-784, 1975.3. Clark RF, Clement ER:Arch Dermatol 111:731-733, 1975.
E R.SQUIBB& SONS LTD.
EEJ 2365 COTE DE LIESSE, MONTREAL, QUE. H4N 2M7
VELOSEF 250 CAPSULES VELOSEF 500 CAPSULES Cephradine Capsules VELOSEF 125 FOR ORAL SUSPENSION VELOSEF 250 FOR ORAL SUSPENSION Cephradlne for Oral Suspension VELOSEF FOR INJECTION, 500 mg and 1 g Cephradine for Injection ACTION: Cephradine is a semi-synthetic, cephalosporin antibiotic eshibiting bactericidal activity through inhibition at cell-wall synthesis. INDICATIONS: Infections in the respiratory and genitourinary tracts, and in the skin and soft tissues, due to susceptible organisms. Sensitivity tests should be performed: therapy may be instituted before receiving the results. CONTRAINDICATIONS: Hypersensitivity to the cephalosporin group of antibiotics. WARNINGS: There is evidence of partial cross-allergenicity between the penicillins and the cephalosporins. Therefore, cephradine should be used with caution in patients with known hypersensitivity to penicitlins. Antibiotics, including cephradine, should be used cautiously and only when absolutely necessary in patients with a history of allergies, particularly to drugs. Usage during pregnancy and lactation: Safety for use of this product during pregnancy has not been established. Cephradine is secreted in breast milk. PRECAUTIONS: Patients should be observed carefully during therapy. Allergic reactions require discontinuation of VELOSEF and appropriate treatment. Prolonged use of VELOSEF may result in overgrowth of nonsusceptible organisms: appropriate measures should be instituted. During long-term therapy, hematological, renal and hepatic functions should be monitored periodically. Patients with known or suspected renal impairment should be observed carefully since cephradine may accumulate in the serum and tissues unless dosage is suitably reduced. See DOSAGE AND ADMINISTRATION section. Indicated surgical procedures should be performed in conjunction with antibiotic therapy; e.g., the incision and drainage of abscesses. After treatment with cephalosporins, a false-positive reaction for glucose in the urine may occur, but not with enzymebased tests. A false-positive Coombe test has also been reported. VELOSEF for Injection is not compatible with Lactated Ringer's Solution or other calcium-containing infusion fluids. ADVERSE REACTIONS: Usually limited to gastrointestinal disturbances and occasional hypersensitivity, but may include hematological and hepatobiliary disturbances, as well as elevated BUN, LDH or serum creatinine; superinfection; vaginitis and joint pains. Thrombophlebitis following IV. injection and sterile abscesses after IM. injection have occurred. Only occasionally severe enough to warrant cessation of therapy DOSAGE AND ADMINISTRATION: The presence of food in the gastrointestinal tract delays the absorption and reduces the peak level but does not aftect the total amount of cephradine absorbed. VELOSEF Capsules and VELOSEF for Oral Suspension Adults: Respiratory tract infections: 250 mg, q6h. Pneumococcal lobar pneumonia: 500 mg, q6H. Genitourinary tract infections: 500 mg, q6h. Prolonged therapy is advisable for the treatment of prostatitis and epididymitis. Children: 25 to 50 mg/kg/day, divided into four equally spaced doses, e.g.: VELOSEF for Oral Suspension Child's Weight 125 mg/S ml 250 mg/S ml 10kg (22 Ibs) /2 to 1 tsp. q6h 20 kg (44 Ibs) 1 to 2 tsp. q6h /2 to 1 tsp. q6h 4Okg(881bs) 2to4tsp.q6h 1 to2tsp.q6h Smaller doses than those indicated above should not be used. For otitis media due to H. influenzae, doses from 75 to 100 mg/kg/day are recommended. VELOSEF for Injection: For use in serious and life-threatening infections or where oral therapy is not possible. Average adult daily dose is 2 - 4 g, depending on the infection. In children, a daily dose of 50 - 100 mg/kg is recommended. All patients; all formulations: Larger doses (up to 1 g q6h in adults or up to 25 mg/kg q6h in children) may be given for severe or chronic infections: maximum daily dose should not esceed 4 g. Therapy should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. In infections caused by hemolytic streptococci, a minimum 10-daytreatment period is recommended. Stubborn infections may require treatment for several weeks with frequent bacteriological and clinical appraisal. A modified dosage schedule in patients with decreased renal function is necessary. Each patient should be considered individually: the following schedule is recommended as a guideline. Initial loading dose: 750 mg. Maintenance dose: 500 mg at the time intervals listed below: Creatinine Clearance Time Interval (ml /min/1.73m2) > 20m1/min 6-12 hours 15-19m1/min 12-24hours 10-14 mI/mm 24-40 hours 5-9 mI/mm 40-50 hours < SmI/min 50-l0hours DOSAGE FORMS: Capsules of 250 mg and 500 mg in bottles of 50, and bottles of VELOSEF 125 and 250 for Oral Suspension which, after reconstitution, provide 100 ml of pleasantly flavoured suspension containing 25 mg/mI and 50 mg/mI respectively. VELOSEF for Injection is provided as a sterile powder for reconstitution in vials containing 500 mg or 1 g. Consult Product Monograph for reconstitution procedure. Product Monograph available to physicians and pharmacists on request.
E R, SQUIBB & SONS LTD, E.EJ 2365 COTE DE LIESSE, MONTREAL, QUE, H4N 2M7
in our review.2 The physician interested in hyposensitization therapy should read these articles in detail. Dr. Freedman continues that the use of pollen immunotherapy in hay fever may have been shown to have good results but its efficacy in any form of asthma is presently lacking. We know that the development of symptoms in the patient with hay fever depends on the allergen reaching the mucous membrane of the nose or eye, or both, combining with specific IgE attached to the mast cells, and causing release from these cells of mediators that produce the symptoms. We know that the mechanism is the same in pollen-produced asthma except that the mediators are released in the lung. We also have good evidence that the decreased production of specific IgE is caused by suppressor T-lymphocytes acting on the pollenantibody-producing B-lymphocytes to suppress formation of specific IgE, and that this should result in clinical improvement since the specific IgE is the cause of the patient's symptoms in the first place. If one cannot extrapolate the information from studies on hay fever to asthma caused by the same pollen, then one has to postulate that the suppressor T- and B-lymphocyte populations are different in hay fever and in asthma, and there is not a shred of evidence in the literature to suggest that the T- and B-lymphocytes that relate to a specific antigen differ from one disease to another or from one organ to another. Therefore, it seems logical that the results of studies that have been done on hay fever patients apply also to asthma patients if their asthma is precipitated by the same pollen. The reason the studies have been done on hay fever patients is that hay fever patients who have practically no other allergies are relatively easy to find, whereas asthma is a much more complex disease and it is virtually impossible to find a series of asthmatic patients whose asthma is precipitated by only one pollen; therefore, asthmatic patients are not as suitable for study. I do not mean to imply that hyposensitization is 100% perfect in the treatment of allergic patients, particularly asthmatic patients in whom there are a great many other factors besides extrinsic allergens. It is useful only for that part of the disease process caused by external allergens. In addition, hyposensitization is a very slow process for the patient and a tremendous amount of work for the physician, if he does it properly, over a period of years. Therefore, although I believe it is helpful to these patients, I would be one of the first to wish for something better to become available. However, until this happens, I think it would be most
unfortunate for patients with extrinsic allergy to be denied hyposensitization therapy, because there is no question in my mind that they benefit from it if it is properly performed. C. COLLINS-WILLIAMS, MD
Head, allergy division Hospital for Sick Children Professor of pediatrics University of Toronto Toronto, ON
References 1. IRoi.is JS, PRUZAN5KI JJ, PAi.-rassoN R: Immunotherapy: mechanisms of action suggested by measurements of immunologic and cellular parameters. I Allergy Clin Immunol 56: 64, 1975 2. NIZAMI RM, COLLINS-WILLIAMS C: Hyposensitization therapy in allergic disease. Ann Allergy 35: 296, 1975
To the editor: I am grateful to Dr. Collins-Williams for his thoughtful comments in response to my recent article in the Journal. The publication of the results of his studies on the lack of correlation between history and results of prick tests and RASTs is awaited with interest, since they appear to be at variance with much of the previously published data on this admittedly controversial topic. A recent investigation of grass-pollen allergy, for example, showed a 91 % correlation between positive history and positive RAST, compared with a 92% correlation between positive history and positive prick test.1 I agree that the prick test is currently less costly to perform than the RAST, although the eventual automation of the RAST procedure in centralized clinical immunology laboratories would probably reduce the expense to a comparable level. Furthermore, the use of the automated RAST for selected allergens may encourage the clinician to be more discriminating in the number of tests ordered - a desirable objective from both a medical and an economic viewpoint. In evaluating the results of hyposensitization therapy in allergic asthma the criteria of efficacy must be the same as for other treatment modalities, despite the immunologic considerations so clearly summarized by Dr. Collins-Williams. Controlled double-blind studies have proved the efficacy of the /32-adrenergic agents, disodium cromoglycate and beclomethasone dipropionate aerosol in the management of asthma; no similar clinical trials have ever been conducted for the immunotherapy of asthma. These new pharmacologic agents, which are relatively free of serious side effects, indeed may be the "something better" that Dr. CollinsWilliams wishes for. SAMUEL 0. FREEDMAN, MD, FRcP[c], FAcP, FRCS Director, division of clinical immunology and allergy Montreal General Hospital Professor of medicine
McGill University
Montreal, PQ
CMA JOURNAL/JUNE 19, 1976/VOL. 114 1089
