- Email: [email protected]
RAPID DESENSITISATION FOR DESFERRIOXAMINE ANAPHYLACTOID REACTIONS
859
TWO LIGHTS FOR PHOTOTHERAPY and
have found that in infants
SIR,-Ennever Speck’ exposed phototherapy, photoreversible configurational isomers of bilirubin quickly reach a photostationary concentration, and their elimination proceeds only slowly. On the other hand, the structural, non-reversible bilirubin isomers ("lumirubin") attain much lower serum concentrations, but are more rapidly excreted. Thus configurational isomerisation may not be the most important process in jaundiced infants under phototherapy, and lumirubin is now thought to be the water-soluble product responsible for the rapid clearance of bilirubin during clinical phototherapy. If lumirubin originates from bilirubin molecules, only the rapid formation of configurational isomers is counterproductive since it considerably reduces the number of bilirubin molecules from which lumirubin can be produced, at a much smaller rate. In the bilirubin/configurational isomer reaction, which is reversible, the isomers revert to bilirubin to maintain the photoequilibrium as bilirubin concentration falls during lumirubin formation, and slowing down of the latter process may result. Moreover, photoreversible configurational isomers may diffuse to sites less accessible to light. The ideal light source for phototherapy should keep configurational bilirubin isomer concentrations as low as possible at sites of formation while still ensuring the substantial absorption by
to
be difficult to achieve with a bilirubin molecules. This source, single light although phototherapy could be more efficient by exploitation of the differences between the quantum yields and absorption coefficients of bilirubin and its photoreversible isomers. Another possibility would be to use two light sources of different wavelengths and intensities-a short-wavelength source to excite bilirubin to lumirubin and long-wavelength light to reverse to native bilirubin the molecules of isomers produced by the shortwavelength light. Narrow-spectrum blue and green2lights could be used to this end. Preliminary calculations show that the 21% photoreversible isomer concentration that is obtained by irradiating with laser-like light to steady-state a bilirubin solution at 450 nm can be lowered, with green light at 510 nm, to 10% or 7% if the greenlight intensity is 10 or 100 times the blue-light intensity, respectively. Quenching of bilirubin photoisomerisation has been confirmed by simultaneous irradiation of a bilirubin/human serum albumin solution with the 457 nm blue and the 514 nm green lines of an argon laser. A blue: green intensity ratio of 1:30 produces one order of magnitude reduction of photoequilibrium concentration of photoreversible configurational isomers. This result may account for the clinical success surprisingly obtained with green fluorescent seems to
lamps.2-4 If this reasoning is correct an immediate improvement in phototherapy should be produced by replacing some Westinghouse special blue lamps (West.F20T12/BB) with green lamps (Sylv.F20F12/G). Philips blue lamps (TL20W03/T) or equivalent should be avoided on grounds of both safety and efficiency: the light emitted (peak wavelength 421 nm, half-intensity full-width 33 nm) may be hazardous,skin optical losses may be high,2,5 and high concentrations of photoreversible bilirubin isomers will be produced. I thank Dr T. R. C.
helpful
McDonagh, and Dr J. F. Ennever for supported in part by the CNR special project
Sisson,
discussions. Work
Dr A. F.
"laser". Institute of Quantum Electronics, Via Panciatichi 56/30,
50127 Firenze, Italy
R. PRATESI
RAPID DESENSITISATION FOR DESFERRIOXAMINE ANAPHYLACTOID REACTIONS
SIR,-Desferrioxamine mesylate (DF) has been reported to elicit untoward reactions. A patient with &bgr;-thalassaemia had presented anaphylactoid reactions and was successfully desensitised by a rapid (rush) procedure. Three other patients with similar symptoms were reported by Dr Davies and her colleagues (July 23, p 181) to have been desensitised but the procedure was not described. In both papers an allergic mechanism was suggested, but no investigations were done. We report a case of anaphylactoid reactions to DF in a young woman with successful desensitisation and disease mechanism for these reactions. A 28-year old woman of Italian origin with &bgr;-thalassaemia major began receiving transfusions at age 4. When DF became available she also received intermittent intramuscular injections of this agent. In 1981, at the age of 25, she had a severe anaphylactoid reaction described as hypotension (70/<40 mm Hg), generalised itching, and tachycardia (140/min) and quickly fell into a coma which lasted 20 min. DF was stopped but since the patient as having severe symptoms of haemochromatosis another injection of DF, by the intravenous route, was attempted. Within minutes the patient had similar symptoms and we decided to attempt rapid desensitisation. after Before treatment specific IgE against DF was coupling DF to RAST (radioallergosorbent test) discs2 and by using human serum albumin.3No serum IgE could be detected by either test in the serum of patient or in non-intolerant subjects treated for long periods with DF or in control sera. Specific IgG against DF (sought with the same RAST discs) was not found. Skin tests with DF were done first by prick tests and then intradermally. Intradermal tests with the full-strength DF were positive in the patient and also in all subjects tested whether or not they had received DF. The patient was admitted to an intensive care unit and desensitisation was started using Miller and colleagues’ methodl slightly modified in the light of our experience in rapid immunotherapy for venom and inhalant allergy.4The amounts of DF in bottles 1-11 were (in mg) 0-015, 0-15,1-5, 15, 50, 100, 200, 400, 600, 1000, and 1500, respectively. The content of each bottle was infused intravenously over 30 min. During the infusion of bottles 7 and 8 the patient had two minor reactions (mild urticaria, lingual paraesthesia, tachycardia 120/min, and hypotension 100/50 mm Hg). The rate of infusion was halved. No other symptoms occurred. The patient was subsequently started on a 24 h continuous subcutaneous infusion of 1500 mg DF for 4 days. Then the same DF dose was given over 12 h every day for 15 days, every 2 days for another fortnight, every 3 days for another fortnight, and then every 4 days. During the second injection of the 4-day regimen the patient had a mild erythematous reaction at the injection site. The third injection was immediately followed by a generalised
sought
erythematous rash, hypotension (80/<40 mm Hg), tachycardia (150/min), and faintness. The infusion was stopped and the patient recovered immediately after treatment with 0-55 mg adrenaline intramuscularly. The next injection was given the following morning under diphenhydramine cover (50 mg intravenously) and there was no reaction. After a week of daily injections, the patient received 1500 mg DF every 2 days. Another attempt at subcutaneous infusions with DF every 4 days was attempted, the patient receiving a placebo on the second day. A systemic reaction was observed after the infusion of 12 mg DF and resolved promptly when the infusion was stopped and the patient was given adrenaline. The patient has now been treated for 12 months without an
1 Ennever JF, Speck WT. Mechanism of action of phototherapy: New concepts. In. Rubaltelli F, Jori G, eds. New trends in phototherapy. New York: Plenum Press, 1983. 2 Donzelli GP, Migliorini MG, Sbrana G, Pratesi R, Vecchi C. Laser-oriented search of the optimum light for phototherapy. In: Rubaltelli F, Jori G, eds. New trends in phototherapy. New York: Plenum Press, 1983. 3 Vecchi C, Donzelli GP, Sbrana G, Migliorini MG, Pratesi R. New light in phototherapy Lancet 1982; ii: 390. 4 Vecchi C, DonzelliGP, Sbrana G, MiglioriniMG. Green light inphotherapy. Pediatr Res 1983; 17: 461. 5 Pratesi R, Ronchi L, Cecchi G, Sbrana G, Migliorini MG, Vecchi C, Donzelli GP. Skin optics and phototherapy of jaundice. Biol Med Envir 1983; 11: 461.
allergic reaction.
1. Miller KB, Rosenwasser LJ, Bessette JM, Beer DJ, Rocklin RE. Rapid desensitisation
for desferrioxamine anaphylactic reaction. Lancet 1981; i: 1059. 2. Ceska M, Eriksson R, Varga JM. Radio-immunosorbent assay for allergens. J Allergy Clin Immunol 1972; 49: 1-9. 3. Zeiss CR, Patterson R, Pruzansky JJ, Miller MM, Rosenberg M, Levitz D. Trimellitic anhydride-inducedairway syndromes: clinicalandimmunological studies. J Allergy Clin Immunol 1977; 60: 96-105. 4. Bousquet J, Guérin B, Michel F-B. Rush immunotherapy with standardized allergen extracts. In: Proceedings of Third Paul Ehrlich Seminar, Berlin: Springer-Verlag
(in press).
,
860
Total eosinphil counts, total serum IgE (’PRIST’), C3 and C4 fractions of complement, and total plasma histamine (single step radioisotope techniques) were measured twice daily for the first 6 days, daily for 6 days, weekly for the first month, and at 2, 3, 6, and 12 months, and during the two reactions. All values were normal except for the plasma histamine on the days of the two systemic reactions (7 -and 6’ 5 ng/ml, respectively; normal 0’ 5 ng/ml). This is the fourth successful desensitisation in a patient intolerant to DF. There was no clear support for an allergic mechanism: the patient did not have DF-specific IgE or IgG in her serum and skin tests with DF were positive in all subject tested; furthermore there was a latency phase of 3 days during which DF could be given without untoward reactions and the reactions reappeared after 4 a mechanism similar to that of aspirin days, desensitisation.6, Taken together there findings suggest that systemic reactions to DF are not rare, that they can easily be desensitised, but that they are not immunologically mediated. They resemble idiosyncrasy or intolerance and should be called
suggesting
"anaphylactoid". JEAN BOUSQUET Diseases Clinic, Blood Diseases Clinic, and Anaesthetic/Intensive Care Service,
Respiratory
Centre Hospitalier Universitaire,
Montpellier 34000,
France
MAURICE NAVARRO GABRIEL ROBERT PAUL AYE FRANCOIS-BERNARD MICHEL
ARTHRITIS AND SEAT BELTS
SIR,-Dr Higgens and Dr Erhardt (Sept 10, p 32) have confirmed
of our observations on the problems faced by patients with rheumatoid arthritis who use seat belts. However, the issue is a wider one, affecting patients with all forms of arthritis. In a survey of 518 arthritic patients conducted in 1982 we found 86 had problems using and tolerating their seat belts due to their arthritis. The leaflet Higgens and Erhardt referred to (obtainable from this department, price 20p plus stamped, addressed envelope) was prepared as a result of a survey before seat belt wearing became compulsory. The leaflet shows how arthritic patients can overcome their difficulties with standard seat belt models. We had to deal with 24 requests for exemption from seat belt legislation in the last three months of 1982. With advice and adaptations (within the limits set by the British Standard and EEC regulations) only 4 exemptions had to be recommended. During the survey our attention was drawn to clip devices being marketed to relieve the discomfort of seat belt tension across the shoulder. These are not covered by any British Standard. We tested three of these devices—’Comficlip’ (Grayston Engineering, Sutton, Surrey), ’Cleverclip’ (K. C. Sales, Bournemouth), and ’Klunk-Klip’ (Tonken Auto Products, Daventry). We asked the manufacturers about safety testing but had no response for the comficlip and klunkclip. We received an account of "satisfactory" dummy crash testing by the British Standards Institution for th cleverclip, when applied to an inertia reel belt according to the manufacturer’s instructions. All the clips are applied in a manner designed to introduce some slack into the seat belt system. Instructions are not always precise but generally suggest that not more than 5 cm of extra belt should be withdrawn. We asked 18 healthy volunteers and 16 patients with rheumatoid arthritis to apply the devices as instructed in a dummy car seat fitted with a standard inertia reel belt. We measured the amount by which the seat belt was withdrawn from the fitted retracted position for three clip applications by each patient.
EVALUATION OF TENSION RELIEVING CLIPS FITTED TO STANDARD INERTIA REEL SEAT BELTS
I
Results
as
mean±SD for three attempts
by every volunteer or patient.
Only the volunteer group using the cleverclip approached the recommended limit of 5 cm of belt withdrawal (see table). In all other cases the mean amount of slack was greater than the manufacturers’ recommended maximum; in 93 of 273 clip applications the amount of slack achieved was more than twice the recommended limit. The patients with arthritis tended to introduce the greater amount of slack, though this difference was not significant. We found no evidence of a learning effect between first and third applications, despite repetition of the instructions. We suggest that these comfort clips are unlikely to be applied in a safe manner by members of the public, able-bodied or not. They are likely, if misapplied, seriously to impair the protective action of the inertia reel belt during sudden deceleration. We cannot recommend them. Department of Rheumatology, City Hospital, Nottingham NG5 1PB
E. ARIE F. BOOTHROYD
some
5. Guilloux
L, Hartmann D, Ville G. Enzymatic isotopic assay for human plasma histamine. Clin Cham Acta 1981; 116: 269-75. 6. Stevenson DD, Simon RA, Mathison DA. Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges. J Allergy Clin Immunol 1980; 66: 82-91. 7. Zeiss CR, Lockay RF Refractory period to aspirin in a patient with aspirin inducedasthma. J Allergy Clin Immunol 1976; 57: 440-49. 1. Arie ME. Seat belt legislation: Do patients with arthritis need exemption? Ann Rheum Dis 1982; 41: 634
OESTROGENS AND CORONARY ARTERY DISEASE IN MEN
SIR,-There have now been a number of reports of raised levels of
circulating
oestrogensl-5
in
men
with coronary artery disease
(CAD). The most recent of these is from the Framingham Heart Study in Massachusetts.5 The investigators conclude that in men "hyperestrogenemia is an important correlate of coronary heart disease". They were not able to determine if the raised oestrogen levels had preceded the onset of the disease, but they quote a number of observations which point to that possibility. In this connection, we should like to report the mortality, studied prospectively, in a group of men believed to have above-average circulating levels of oestrogens from an early age. They are men with a female pattern of nuclear chromatin in non-dividing cells (chromatin-positive males) whose sex-chromosome constitution includes at least one supernumerary X. They comprise about O. 1% of the male population. With rare exceptions they have
hypergonadotropic hypogonadism (Klinefelter’s syndrome), a disorder that causes primary infertility and is recognisable from the age of puberty by the small size of the testes. Their plasma oestrogen levels are raised, 6, and we find that they are at least as high as those described in men with coronary artery disease. Since 1959 men with this disorder have been notified to the Medical Research
how
GB. Evidence for hyperoestrogenaemia as a risk factor for myocardial infarction in men. Lancet 1976; ii: 14-18. 2. Entrican JH, Beach C, Carroll D, Kenmure ACF, Klopper A, Mackie M, Douglas AS Raised plasma oestradiol and oestrone levels in young survivors of myocardial infarction. Lancet 1978; ii: 487-90. 3. Luria MH, Johnson MW, Pego R, Seuc CA, Manubens SJ, Wieland MR, Wieland RG. Relationship between sex hormones, myocardial infarction, and occlusive coronary disease. Arch Intern Med 1982; 142: 42-44. 4. Klaiber EL, Broverman DM, Haffajee CI, Hochman JS, Sacks GM, Dalen JE. Serum estrogen levels in men with acute myocardial infarction. Am J Med 1982; 73: 872-81. 5. Phillips GB, Castelli WP, Abbott AD, McNamara PM. Association of hyperestrogenemia and coronary heart disease in men in the Framingham Cohort. Am J Med 1983; 74: 863-69. 6 Wang C, Baker HWG, Burger HG, De Kretser DM, Hudson B. Hormonal studiesin Klinfelter’s syndrome. Clin Endocrinol 1975, 4: 399-411. 7. Forti G, Giusti G, Borghi A, et al. Klinefelter’s syndrome: a study of its hormonal plasma pattern J Endocrinol Invest 1978; 2: 149-54 1.
Phillips
TWO LIGHTS FOR PHOTOTHERAPY and
have found that in infants
SIR,-Ennever Speck’ exposed phototherapy, photoreversible configurational isomers of bilirubin quickly reach a photostationary concentration, and their elimination proceeds only slowly. On the other hand, the structural, non-reversible bilirubin isomers ("lumirubin") attain much lower serum concentrations, but are more rapidly excreted. Thus configurational isomerisation may not be the most important process in jaundiced infants under phototherapy, and lumirubin is now thought to be the water-soluble product responsible for the rapid clearance of bilirubin during clinical phototherapy. If lumirubin originates from bilirubin molecules, only the rapid formation of configurational isomers is counterproductive since it considerably reduces the number of bilirubin molecules from which lumirubin can be produced, at a much smaller rate. In the bilirubin/configurational isomer reaction, which is reversible, the isomers revert to bilirubin to maintain the photoequilibrium as bilirubin concentration falls during lumirubin formation, and slowing down of the latter process may result. Moreover, photoreversible configurational isomers may diffuse to sites less accessible to light. The ideal light source for phototherapy should keep configurational bilirubin isomer concentrations as low as possible at sites of formation while still ensuring the substantial absorption by
to
be difficult to achieve with a bilirubin molecules. This source, single light although phototherapy could be more efficient by exploitation of the differences between the quantum yields and absorption coefficients of bilirubin and its photoreversible isomers. Another possibility would be to use two light sources of different wavelengths and intensities-a short-wavelength source to excite bilirubin to lumirubin and long-wavelength light to reverse to native bilirubin the molecules of isomers produced by the shortwavelength light. Narrow-spectrum blue and green2lights could be used to this end. Preliminary calculations show that the 21% photoreversible isomer concentration that is obtained by irradiating with laser-like light to steady-state a bilirubin solution at 450 nm can be lowered, with green light at 510 nm, to 10% or 7% if the greenlight intensity is 10 or 100 times the blue-light intensity, respectively. Quenching of bilirubin photoisomerisation has been confirmed by simultaneous irradiation of a bilirubin/human serum albumin solution with the 457 nm blue and the 514 nm green lines of an argon laser. A blue: green intensity ratio of 1:30 produces one order of magnitude reduction of photoequilibrium concentration of photoreversible configurational isomers. This result may account for the clinical success surprisingly obtained with green fluorescent seems to
lamps.2-4 If this reasoning is correct an immediate improvement in phototherapy should be produced by replacing some Westinghouse special blue lamps (West.F20T12/BB) with green lamps (Sylv.F20F12/G). Philips blue lamps (TL20W03/T) or equivalent should be avoided on grounds of both safety and efficiency: the light emitted (peak wavelength 421 nm, half-intensity full-width 33 nm) may be hazardous,skin optical losses may be high,2,5 and high concentrations of photoreversible bilirubin isomers will be produced. I thank Dr T. R. C.
helpful
McDonagh, and Dr J. F. Ennever for supported in part by the CNR special project
Sisson,
discussions. Work
Dr A. F.
"laser". Institute of Quantum Electronics, Via Panciatichi 56/30,
50127 Firenze, Italy
R. PRATESI
RAPID DESENSITISATION FOR DESFERRIOXAMINE ANAPHYLACTOID REACTIONS
SIR,-Desferrioxamine mesylate (DF) has been reported to elicit untoward reactions. A patient with &bgr;-thalassaemia had presented anaphylactoid reactions and was successfully desensitised by a rapid (rush) procedure. Three other patients with similar symptoms were reported by Dr Davies and her colleagues (July 23, p 181) to have been desensitised but the procedure was not described. In both papers an allergic mechanism was suggested, but no investigations were done. We report a case of anaphylactoid reactions to DF in a young woman with successful desensitisation and disease mechanism for these reactions. A 28-year old woman of Italian origin with &bgr;-thalassaemia major began receiving transfusions at age 4. When DF became available she also received intermittent intramuscular injections of this agent. In 1981, at the age of 25, she had a severe anaphylactoid reaction described as hypotension (70/<40 mm Hg), generalised itching, and tachycardia (140/min) and quickly fell into a coma which lasted 20 min. DF was stopped but since the patient as having severe symptoms of haemochromatosis another injection of DF, by the intravenous route, was attempted. Within minutes the patient had similar symptoms and we decided to attempt rapid desensitisation. after Before treatment specific IgE against DF was coupling DF to RAST (radioallergosorbent test) discs2 and by using human serum albumin.3No serum IgE could be detected by either test in the serum of patient or in non-intolerant subjects treated for long periods with DF or in control sera. Specific IgG against DF (sought with the same RAST discs) was not found. Skin tests with DF were done first by prick tests and then intradermally. Intradermal tests with the full-strength DF were positive in the patient and also in all subjects tested whether or not they had received DF. The patient was admitted to an intensive care unit and desensitisation was started using Miller and colleagues’ methodl slightly modified in the light of our experience in rapid immunotherapy for venom and inhalant allergy.4The amounts of DF in bottles 1-11 were (in mg) 0-015, 0-15,1-5, 15, 50, 100, 200, 400, 600, 1000, and 1500, respectively. The content of each bottle was infused intravenously over 30 min. During the infusion of bottles 7 and 8 the patient had two minor reactions (mild urticaria, lingual paraesthesia, tachycardia 120/min, and hypotension 100/50 mm Hg). The rate of infusion was halved. No other symptoms occurred. The patient was subsequently started on a 24 h continuous subcutaneous infusion of 1500 mg DF for 4 days. Then the same DF dose was given over 12 h every day for 15 days, every 2 days for another fortnight, every 3 days for another fortnight, and then every 4 days. During the second injection of the 4-day regimen the patient had a mild erythematous reaction at the injection site. The third injection was immediately followed by a generalised
sought
erythematous rash, hypotension (80/<40 mm Hg), tachycardia (150/min), and faintness. The infusion was stopped and the patient recovered immediately after treatment with 0-55 mg adrenaline intramuscularly. The next injection was given the following morning under diphenhydramine cover (50 mg intravenously) and there was no reaction. After a week of daily injections, the patient received 1500 mg DF every 2 days. Another attempt at subcutaneous infusions with DF every 4 days was attempted, the patient receiving a placebo on the second day. A systemic reaction was observed after the infusion of 12 mg DF and resolved promptly when the infusion was stopped and the patient was given adrenaline. The patient has now been treated for 12 months without an
1 Ennever JF, Speck WT. Mechanism of action of phototherapy: New concepts. In. Rubaltelli F, Jori G, eds. New trends in phototherapy. New York: Plenum Press, 1983. 2 Donzelli GP, Migliorini MG, Sbrana G, Pratesi R, Vecchi C. Laser-oriented search of the optimum light for phototherapy. In: Rubaltelli F, Jori G, eds. New trends in phototherapy. New York: Plenum Press, 1983. 3 Vecchi C, Donzelli GP, Sbrana G, Migliorini MG, Pratesi R. New light in phototherapy Lancet 1982; ii: 390. 4 Vecchi C, DonzelliGP, Sbrana G, MiglioriniMG. Green light inphotherapy. Pediatr Res 1983; 17: 461. 5 Pratesi R, Ronchi L, Cecchi G, Sbrana G, Migliorini MG, Vecchi C, Donzelli GP. Skin optics and phototherapy of jaundice. Biol Med Envir 1983; 11: 461.
allergic reaction.
1. Miller KB, Rosenwasser LJ, Bessette JM, Beer DJ, Rocklin RE. Rapid desensitisation
for desferrioxamine anaphylactic reaction. Lancet 1981; i: 1059. 2. Ceska M, Eriksson R, Varga JM. Radio-immunosorbent assay for allergens. J Allergy Clin Immunol 1972; 49: 1-9. 3. Zeiss CR, Patterson R, Pruzansky JJ, Miller MM, Rosenberg M, Levitz D. Trimellitic anhydride-inducedairway syndromes: clinicalandimmunological studies. J Allergy Clin Immunol 1977; 60: 96-105. 4. Bousquet J, Guérin B, Michel F-B. Rush immunotherapy with standardized allergen extracts. In: Proceedings of Third Paul Ehrlich Seminar, Berlin: Springer-Verlag
(in press).
,
860
Total eosinphil counts, total serum IgE (’PRIST’), C3 and C4 fractions of complement, and total plasma histamine (single step radioisotope techniques) were measured twice daily for the first 6 days, daily for 6 days, weekly for the first month, and at 2, 3, 6, and 12 months, and during the two reactions. All values were normal except for the plasma histamine on the days of the two systemic reactions (7 -and 6’ 5 ng/ml, respectively; normal 0’ 5 ng/ml). This is the fourth successful desensitisation in a patient intolerant to DF. There was no clear support for an allergic mechanism: the patient did not have DF-specific IgE or IgG in her serum and skin tests with DF were positive in all subject tested; furthermore there was a latency phase of 3 days during which DF could be given without untoward reactions and the reactions reappeared after 4 a mechanism similar to that of aspirin days, desensitisation.6, Taken together there findings suggest that systemic reactions to DF are not rare, that they can easily be desensitised, but that they are not immunologically mediated. They resemble idiosyncrasy or intolerance and should be called
suggesting
"anaphylactoid". JEAN BOUSQUET Diseases Clinic, Blood Diseases Clinic, and Anaesthetic/Intensive Care Service,
Respiratory
Centre Hospitalier Universitaire,
Montpellier 34000,
France
MAURICE NAVARRO GABRIEL ROBERT PAUL AYE FRANCOIS-BERNARD MICHEL
ARTHRITIS AND SEAT BELTS
SIR,-Dr Higgens and Dr Erhardt (Sept 10, p 32) have confirmed
of our observations on the problems faced by patients with rheumatoid arthritis who use seat belts. However, the issue is a wider one, affecting patients with all forms of arthritis. In a survey of 518 arthritic patients conducted in 1982 we found 86 had problems using and tolerating their seat belts due to their arthritis. The leaflet Higgens and Erhardt referred to (obtainable from this department, price 20p plus stamped, addressed envelope) was prepared as a result of a survey before seat belt wearing became compulsory. The leaflet shows how arthritic patients can overcome their difficulties with standard seat belt models. We had to deal with 24 requests for exemption from seat belt legislation in the last three months of 1982. With advice and adaptations (within the limits set by the British Standard and EEC regulations) only 4 exemptions had to be recommended. During the survey our attention was drawn to clip devices being marketed to relieve the discomfort of seat belt tension across the shoulder. These are not covered by any British Standard. We tested three of these devices—’Comficlip’ (Grayston Engineering, Sutton, Surrey), ’Cleverclip’ (K. C. Sales, Bournemouth), and ’Klunk-Klip’ (Tonken Auto Products, Daventry). We asked the manufacturers about safety testing but had no response for the comficlip and klunkclip. We received an account of "satisfactory" dummy crash testing by the British Standards Institution for th cleverclip, when applied to an inertia reel belt according to the manufacturer’s instructions. All the clips are applied in a manner designed to introduce some slack into the seat belt system. Instructions are not always precise but generally suggest that not more than 5 cm of extra belt should be withdrawn. We asked 18 healthy volunteers and 16 patients with rheumatoid arthritis to apply the devices as instructed in a dummy car seat fitted with a standard inertia reel belt. We measured the amount by which the seat belt was withdrawn from the fitted retracted position for three clip applications by each patient.
EVALUATION OF TENSION RELIEVING CLIPS FITTED TO STANDARD INERTIA REEL SEAT BELTS
I
Results
as
mean±SD for three attempts
by every volunteer or patient.
Only the volunteer group using the cleverclip approached the recommended limit of 5 cm of belt withdrawal (see table). In all other cases the mean amount of slack was greater than the manufacturers’ recommended maximum; in 93 of 273 clip applications the amount of slack achieved was more than twice the recommended limit. The patients with arthritis tended to introduce the greater amount of slack, though this difference was not significant. We found no evidence of a learning effect between first and third applications, despite repetition of the instructions. We suggest that these comfort clips are unlikely to be applied in a safe manner by members of the public, able-bodied or not. They are likely, if misapplied, seriously to impair the protective action of the inertia reel belt during sudden deceleration. We cannot recommend them. Department of Rheumatology, City Hospital, Nottingham NG5 1PB
E. ARIE F. BOOTHROYD
some
5. Guilloux
L, Hartmann D, Ville G. Enzymatic isotopic assay for human plasma histamine. Clin Cham Acta 1981; 116: 269-75. 6. Stevenson DD, Simon RA, Mathison DA. Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges. J Allergy Clin Immunol 1980; 66: 82-91. 7. Zeiss CR, Lockay RF Refractory period to aspirin in a patient with aspirin inducedasthma. J Allergy Clin Immunol 1976; 57: 440-49. 1. Arie ME. Seat belt legislation: Do patients with arthritis need exemption? Ann Rheum Dis 1982; 41: 634
OESTROGENS AND CORONARY ARTERY DISEASE IN MEN
SIR,-There have now been a number of reports of raised levels of
circulating
oestrogensl-5
in
men
with coronary artery disease
(CAD). The most recent of these is from the Framingham Heart Study in Massachusetts.5 The investigators conclude that in men "hyperestrogenemia is an important correlate of coronary heart disease". They were not able to determine if the raised oestrogen levels had preceded the onset of the disease, but they quote a number of observations which point to that possibility. In this connection, we should like to report the mortality, studied prospectively, in a group of men believed to have above-average circulating levels of oestrogens from an early age. They are men with a female pattern of nuclear chromatin in non-dividing cells (chromatin-positive males) whose sex-chromosome constitution includes at least one supernumerary X. They comprise about O. 1% of the male population. With rare exceptions they have
hypergonadotropic hypogonadism (Klinefelter’s syndrome), a disorder that causes primary infertility and is recognisable from the age of puberty by the small size of the testes. Their plasma oestrogen levels are raised, 6, and we find that they are at least as high as those described in men with coronary artery disease. Since 1959 men with this disorder have been notified to the Medical Research
how
GB. Evidence for hyperoestrogenaemia as a risk factor for myocardial infarction in men. Lancet 1976; ii: 14-18. 2. Entrican JH, Beach C, Carroll D, Kenmure ACF, Klopper A, Mackie M, Douglas AS Raised plasma oestradiol and oestrone levels in young survivors of myocardial infarction. Lancet 1978; ii: 487-90. 3. Luria MH, Johnson MW, Pego R, Seuc CA, Manubens SJ, Wieland MR, Wieland RG. Relationship between sex hormones, myocardial infarction, and occlusive coronary disease. Arch Intern Med 1982; 142: 42-44. 4. Klaiber EL, Broverman DM, Haffajee CI, Hochman JS, Sacks GM, Dalen JE. Serum estrogen levels in men with acute myocardial infarction. Am J Med 1982; 73: 872-81. 5. Phillips GB, Castelli WP, Abbott AD, McNamara PM. Association of hyperestrogenemia and coronary heart disease in men in the Framingham Cohort. Am J Med 1983; 74: 863-69. 6 Wang C, Baker HWG, Burger HG, De Kretser DM, Hudson B. Hormonal studiesin Klinfelter’s syndrome. Clin Endocrinol 1975, 4: 399-411. 7. Forti G, Giusti G, Borghi A, et al. Klinefelter’s syndrome: a study of its hormonal plasma pattern J Endocrinol Invest 1978; 2: 149-54 1.
Phillips