- Email: [email protected]
Occupational asthma induced by ethylene oxide
in those without the mutation, although food intake and exercise were similar in these groups. This mutation may cause a low resting metabolic rate (as shown here), and defects in (33-adrenergic-receptor binding, signal transduction, or regulation may result in low lipolytic response in adipose tissue. The Trp64Arg allele of the 03-adrenergic-receptor gene may be a predictor of difficulty in losing weight in obese women.
*Toshihide Yoshida, Naoki Sakane, Tunekazu Umekawa, Mayumi Sakai, Toshihiro Takahashi, Motoharu Kondo *First Department of Internal Medicine,
Kyoto Prefectural University of Medicine, 465-Kajucho, Hirokoji-Kawaramachi, Kamikyo-ku, Kyoto 602, Japan; and Department of Bio Industry, Bio College Kyoto, Kyoto
generation of superoxide anion by monocytes and macrophages from Gaucher’s patients are severely impaired.5 This deficiency may be one of the factors responsible for the considerable morbidity in such patients caused by common bacterial pathogens. The higher the frequency of infusions the larger seems the threat of contracting bacterial infections. Taken together, I believe that efforts to establish a less costly regimen to treat patients with Gaucher’s disease should be aimed at decreasing the dose but maintaining a reasonable and tolerable frequency of infusion. László Maródi Department of Paediatrics, Debrecen University School of Medicine, PO Box 32, H-4012 Debrecen, Hungary
Beutler E, Kay AC, Saven A, et al. Enzyme replacement therapy for Gaucher disease. Blood 1991; 78: 1183-89. 2 Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency—macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 1991; 324: 1464-70. 3 Barton NW, Brady RO, Dambrosia JM, et al. Dose-dependent responses to macrophage-targeted glucocerebrosidase in a child with Gaucher disease. J Pediatr 1992; 120: 277-80. 4 Parker RI, Barton NW, Read EJ, et al. Hematologic improvement in a patient with Gaucher disease on a long-term enzyme replacement therapy: evidence for decreased splenic sequestration and improved red blood cell survival. Am J Hematol 1991; 38: 130-37. 5 Maródi L, Káposzta R, Judit Tóth, Aranka László. Impaired microbiocidal capacity of mononuclear phagocytes from patients with type I Gaucher disease: partial correction by enzyme replacement therapy. Blood (in press). 1
Walston J, Silver K, Bogardus C, et al. Time of onset of non-insulindependent diabetes mellitus and genetic variation in the &bgr;3-adrenergic receptor gene. N Engl J Med 1995; 333: 343-47. 2 Widen E, Lehto M, Kanninen T, et al. Association of a polymorphism in the &bgr;3-adrenergic receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 1995; 333: 348-51. 3 Clement K, Vaisse C, Manning BSJ, et al. Genetic variation in the &bgr;3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 1995; 333: 352-54. 4 Yoshida T, Sakane N, Umekawa T, et al. Relationship between basal metabolic rate, thermogenic response to caffeine, and body weight loss following combined low calorie and exercise treatment. Int J Obes 1
1994; 18: 345-50.
Low-dose versus high-frequency Gaucher’s disease
regimens in
SiR-To reduce the cost of enzyme replacement therapy of patients with Gaucher’s disease a low-dose high-frequency regimen’ (30 IU/kg monthly, three infusions per week), as opposed to the high-dose low-frequency protocol (120 IU/kg monthly, infusions every 2 weeks), has been proposed. Hollak and colleagues (June 10, p 1474) report their experience with a very-low-dose high-frequency regimen (15 IU/kg monthly, three infusions per week) in 25 patients with type I Gaucher’s disease. This study raises several controversial issues. First, Hollak and co-workers conclude that their results are similar to those obtained by others with high-dose regimens, and that they are better than a low-dose regimen of 10 IU/kg every 2 weeks. Although the endeavour to establish the lowest effective dose regimen for the treatment of Gaucher’s patients is shared by all, previous reports suggest that the rate and extent of response to treatment with glucocerebrosidase are dose dependent, and the clinical response to replacement therapy is far more dependent on the amount of enzyme infused than on frequency of administration.2-5 It should be pointed out that in Hollak’s study (their table 3) a third of patients who were treated for at least a year (six of 19) did require an increase of the dose after 6 months of treatment because of the absence of an appropriate response. This finding is clearly different from those in reports with doses of 30-60 U/kg every 2 weeks.z°3 How can treating a third of patients with ineffective doses be cost efficient? Should patients need to wait for months before receiving effective treatment? Second, a thrice weekly infusion schedule on a long-term basis is very difficult for patients. The inconvenience and the effect of such frequent infusion on quality of life should be taken seriously. Third, the cost of infusion itself is important. 156 compared with 26 infusions per year will prove more costly over the lifetime of the patient and adds substantial cost to that of the drug. Finally, frequent infusions might predispose patients to infection. We have shown that the bactericidal capacity and 1434
Occupational asthma induced by ethylene oxide SIR-In October, 1988, a surgeon in training developed dermatitis of his hands when he used sterile powdered latex gloves (Triflex R, Travenol, Belgium). After wearing these gloves turned inside-out, the contact dermatitis went without any other treatment. In March, 1989, he had an attack of wheezing and dyspnoea at work. His FEVj was 3-6 L (predicted 4-54 L) and returned to normal after 02-agonist inhalation. As occupational asthma was suggested, sensitivity testing was carried out. Serum IgE concentration (PRIST, Phadebas, Belgium) was 351 U/mL, and specific IgE (RAST, Pharmacia, Sweden) were 4-50 and 2-60 U/mL for aspergillus and ethylene oxide (k78, Pharmacia), respectively; tests for other airborne allergens
negative. Skin-prick tests (Bencard, UK) were negative except for neurospora (m4, Bencard). By use of nonpowdered (Triflex R, Baxter, Belgium) or powdered (Triflex R, Baxter, USA) latex gloves sterilised by gamma rays (25k Gy), the symptoms completely disappeared. Our patient was not allergic to the latex or to the glove powder, since gamma-ray-sterilised powdered or nonpowdered latex gloves from the same manufacturer did not induce any symptoms. IgE sensitisation to ethylene oxide gas (acting as a hapten) is likely since a positive RAST was considered specific for sensitisation to ethylene oxide in healthy donors of platelets with allergic reactions.’ Traces of ethylene oxide gas were probably absorbed by the powder of the gloves, inducing dermatitis on direct contact with the skin and asthma when the powder was airborne after the patient had turned the gloves inside-out, a mechanism reported in latex allergy.2 Occupational dermatitis and asthma to latex rubber gloves can be produced by an IgE sensitisation to ethylene oxide used to sterilise the gloves rather than to the latex itself. were
Sylvie Verraes,
*Olivier Michel
Clinic of Allergology and Respiratory Disease, Saint-Pierre University Hospital, 1000 Brussels, Belgium
Boltansky H, Alter HJ, et al Allergic reactions in healthy plateletpheresis donors caused by sensitisation to ethylene oxide gas. N Engl J Med 1986; 315: 1192-96. Beezhold DH, Beck WC Surgical glove powders bind latex antigens. Arch Surg 1992; 127: 1354-57.
1 Leitman SF,
2
Scanning laser tomography intracranial hypertension
in
benign
SiR-Scanning laser tomography (SLT) is a non-invasive technique which uses confocal optics to attain objective, of the fundus.’1 A reproducibility of less than 50 jjum has been found in the of optic disc topography. 2-4 SLT was measurement as an aid for the clinical management of developed glaucomatous optic neuropathy; however, it has wider potential application in the assessment of any fundus
three-dimensional
measurements
abnormality characterised by topographic change. An obese 26-year-old woman with papilloedema due to benign intracranial hypertension was assessed with SLT (figure, bottom). The margin of the optic disc exhibited pronounced elevation when compared with that of a normal eye (figure, top). The magnitude of elevation was greater at the nasal optic disc margin than at the temporal margin. After weight reduction, acetazolamide, repeated therapeutic
lumbar puncture, and optic nerve sheath fenestration over 11 months, SLT showed that treatment resulted in a significant reduction of retinal height over the entire optic disc and disc margin. SLT agreed with the qualitative impression of topographical change gained from clinical assessment over the follow-up period, and was able to detect subtle change which was not clinically obvious. *Chris Hudson, Sunil Shah, John G Flanagan, Arun Brahma, Alec Ansons *University Department of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WH, UK; and Department of Ophthalmology, University
1
2
3
4
of Toronto, Ontario, Canada
Zinser G, Wijnaendts-van-Resandt RW, Dreher AW, et al. Confocal laser tomographic scanning of the eye. SPIE Vol 1161. New methods in microscopy and low light imaging. San Diego, California, Aug 8-11, 1989: 337-44. Cioffi GA, Robin AL, Eastman RD, Perell HF, Sarfarazi FA, Kelman SE. Confocal laser scanning ophthalmoscope. Ophthalmology 1993; 100: 57-62. Lusky M, Bosem ME, Weinreb RN. Reproducibility of optic nerve head topography measurements in eyes with undilated pupils. J Glaucoma 1993; 2: 104-09. Rohrschneider K, Burk ROW, Kruse FE, Völcker HE. Reproducibility of the nerve head topography with a new laser tomographic scanning device. Ophthalmology 1994; 101: 1044-49.
A
Figure: Scanning
Mtt
laser tomography intensity images and corresponding horizontal retinal profiles of a papilloedematous (bottom) optic disc
normal
(top)
and
a
1435
*Toshihide Yoshida, Naoki Sakane, Tunekazu Umekawa, Mayumi Sakai, Toshihiro Takahashi, Motoharu Kondo *First Department of Internal Medicine,
Kyoto Prefectural University of Medicine, 465-Kajucho, Hirokoji-Kawaramachi, Kamikyo-ku, Kyoto 602, Japan; and Department of Bio Industry, Bio College Kyoto, Kyoto
generation of superoxide anion by monocytes and macrophages from Gaucher’s patients are severely impaired.5 This deficiency may be one of the factors responsible for the considerable morbidity in such patients caused by common bacterial pathogens. The higher the frequency of infusions the larger seems the threat of contracting bacterial infections. Taken together, I believe that efforts to establish a less costly regimen to treat patients with Gaucher’s disease should be aimed at decreasing the dose but maintaining a reasonable and tolerable frequency of infusion. László Maródi Department of Paediatrics, Debrecen University School of Medicine, PO Box 32, H-4012 Debrecen, Hungary
Beutler E, Kay AC, Saven A, et al. Enzyme replacement therapy for Gaucher disease. Blood 1991; 78: 1183-89. 2 Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency—macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 1991; 324: 1464-70. 3 Barton NW, Brady RO, Dambrosia JM, et al. Dose-dependent responses to macrophage-targeted glucocerebrosidase in a child with Gaucher disease. J Pediatr 1992; 120: 277-80. 4 Parker RI, Barton NW, Read EJ, et al. Hematologic improvement in a patient with Gaucher disease on a long-term enzyme replacement therapy: evidence for decreased splenic sequestration and improved red blood cell survival. Am J Hematol 1991; 38: 130-37. 5 Maródi L, Káposzta R, Judit Tóth, Aranka László. Impaired microbiocidal capacity of mononuclear phagocytes from patients with type I Gaucher disease: partial correction by enzyme replacement therapy. Blood (in press). 1
Walston J, Silver K, Bogardus C, et al. Time of onset of non-insulindependent diabetes mellitus and genetic variation in the &bgr;3-adrenergic receptor gene. N Engl J Med 1995; 333: 343-47. 2 Widen E, Lehto M, Kanninen T, et al. Association of a polymorphism in the &bgr;3-adrenergic receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 1995; 333: 348-51. 3 Clement K, Vaisse C, Manning BSJ, et al. Genetic variation in the &bgr;3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 1995; 333: 352-54. 4 Yoshida T, Sakane N, Umekawa T, et al. Relationship between basal metabolic rate, thermogenic response to caffeine, and body weight loss following combined low calorie and exercise treatment. Int J Obes 1
1994; 18: 345-50.
Low-dose versus high-frequency Gaucher’s disease
regimens in
SiR-To reduce the cost of enzyme replacement therapy of patients with Gaucher’s disease a low-dose high-frequency regimen’ (30 IU/kg monthly, three infusions per week), as opposed to the high-dose low-frequency protocol (120 IU/kg monthly, infusions every 2 weeks), has been proposed. Hollak and colleagues (June 10, p 1474) report their experience with a very-low-dose high-frequency regimen (15 IU/kg monthly, three infusions per week) in 25 patients with type I Gaucher’s disease. This study raises several controversial issues. First, Hollak and co-workers conclude that their results are similar to those obtained by others with high-dose regimens, and that they are better than a low-dose regimen of 10 IU/kg every 2 weeks. Although the endeavour to establish the lowest effective dose regimen for the treatment of Gaucher’s patients is shared by all, previous reports suggest that the rate and extent of response to treatment with glucocerebrosidase are dose dependent, and the clinical response to replacement therapy is far more dependent on the amount of enzyme infused than on frequency of administration.2-5 It should be pointed out that in Hollak’s study (their table 3) a third of patients who were treated for at least a year (six of 19) did require an increase of the dose after 6 months of treatment because of the absence of an appropriate response. This finding is clearly different from those in reports with doses of 30-60 U/kg every 2 weeks.z°3 How can treating a third of patients with ineffective doses be cost efficient? Should patients need to wait for months before receiving effective treatment? Second, a thrice weekly infusion schedule on a long-term basis is very difficult for patients. The inconvenience and the effect of such frequent infusion on quality of life should be taken seriously. Third, the cost of infusion itself is important. 156 compared with 26 infusions per year will prove more costly over the lifetime of the patient and adds substantial cost to that of the drug. Finally, frequent infusions might predispose patients to infection. We have shown that the bactericidal capacity and 1434
Occupational asthma induced by ethylene oxide SIR-In October, 1988, a surgeon in training developed dermatitis of his hands when he used sterile powdered latex gloves (Triflex R, Travenol, Belgium). After wearing these gloves turned inside-out, the contact dermatitis went without any other treatment. In March, 1989, he had an attack of wheezing and dyspnoea at work. His FEVj was 3-6 L (predicted 4-54 L) and returned to normal after 02-agonist inhalation. As occupational asthma was suggested, sensitivity testing was carried out. Serum IgE concentration (PRIST, Phadebas, Belgium) was 351 U/mL, and specific IgE (RAST, Pharmacia, Sweden) were 4-50 and 2-60 U/mL for aspergillus and ethylene oxide (k78, Pharmacia), respectively; tests for other airborne allergens
negative. Skin-prick tests (Bencard, UK) were negative except for neurospora (m4, Bencard). By use of nonpowdered (Triflex R, Baxter, Belgium) or powdered (Triflex R, Baxter, USA) latex gloves sterilised by gamma rays (25k Gy), the symptoms completely disappeared. Our patient was not allergic to the latex or to the glove powder, since gamma-ray-sterilised powdered or nonpowdered latex gloves from the same manufacturer did not induce any symptoms. IgE sensitisation to ethylene oxide gas (acting as a hapten) is likely since a positive RAST was considered specific for sensitisation to ethylene oxide in healthy donors of platelets with allergic reactions.’ Traces of ethylene oxide gas were probably absorbed by the powder of the gloves, inducing dermatitis on direct contact with the skin and asthma when the powder was airborne after the patient had turned the gloves inside-out, a mechanism reported in latex allergy.2 Occupational dermatitis and asthma to latex rubber gloves can be produced by an IgE sensitisation to ethylene oxide used to sterilise the gloves rather than to the latex itself. were
Sylvie Verraes,
*Olivier Michel
Clinic of Allergology and Respiratory Disease, Saint-Pierre University Hospital, 1000 Brussels, Belgium
Boltansky H, Alter HJ, et al Allergic reactions in healthy plateletpheresis donors caused by sensitisation to ethylene oxide gas. N Engl J Med 1986; 315: 1192-96. Beezhold DH, Beck WC Surgical glove powders bind latex antigens. Arch Surg 1992; 127: 1354-57.
1 Leitman SF,
2
Scanning laser tomography intracranial hypertension
in
benign
SiR-Scanning laser tomography (SLT) is a non-invasive technique which uses confocal optics to attain objective, of the fundus.’1 A reproducibility of less than 50 jjum has been found in the of optic disc topography. 2-4 SLT was measurement as an aid for the clinical management of developed glaucomatous optic neuropathy; however, it has wider potential application in the assessment of any fundus
three-dimensional
measurements
abnormality characterised by topographic change. An obese 26-year-old woman with papilloedema due to benign intracranial hypertension was assessed with SLT (figure, bottom). The margin of the optic disc exhibited pronounced elevation when compared with that of a normal eye (figure, top). The magnitude of elevation was greater at the nasal optic disc margin than at the temporal margin. After weight reduction, acetazolamide, repeated therapeutic
lumbar puncture, and optic nerve sheath fenestration over 11 months, SLT showed that treatment resulted in a significant reduction of retinal height over the entire optic disc and disc margin. SLT agreed with the qualitative impression of topographical change gained from clinical assessment over the follow-up period, and was able to detect subtle change which was not clinically obvious. *Chris Hudson, Sunil Shah, John G Flanagan, Arun Brahma, Alec Ansons *University Department of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WH, UK; and Department of Ophthalmology, University
1
2
3
4
of Toronto, Ontario, Canada
Zinser G, Wijnaendts-van-Resandt RW, Dreher AW, et al. Confocal laser tomographic scanning of the eye. SPIE Vol 1161. New methods in microscopy and low light imaging. San Diego, California, Aug 8-11, 1989: 337-44. Cioffi GA, Robin AL, Eastman RD, Perell HF, Sarfarazi FA, Kelman SE. Confocal laser scanning ophthalmoscope. Ophthalmology 1993; 100: 57-62. Lusky M, Bosem ME, Weinreb RN. Reproducibility of optic nerve head topography measurements in eyes with undilated pupils. J Glaucoma 1993; 2: 104-09. Rohrschneider K, Burk ROW, Kruse FE, Völcker HE. Reproducibility of the nerve head topography with a new laser tomographic scanning device. Ophthalmology 1994; 101: 1044-49.
A
Figure: Scanning
Mtt
laser tomography intensity images and corresponding horizontal retinal profiles of a papilloedematous (bottom) optic disc
normal
(top)
and
a
1435