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RECOMBINANT HUMAN ERYTHROPOIETIN IN ANAEMIC PATIENTS ON HAEMODIALYSIS
392 Stemby NH. Atherosclerosis m a defined population. Acta Pathol Microbiol 1968; suppl 194: 1-216. 8. McCully KS, Wilson RB. Homocysteine theory of arteriosclerosis. Atherosclerosis
7.
1975; 22: 215-27. 9.
Hughes W. Atherosclerosis, Down’s syndrome, and Alzheimer’s disease.
Br
Med J
1977; ii: 702. 10. Jamada M, Mehraein P. Uber die Haufigkeit der zerebralen Arteriosklerose bei Morbus Alzheimer und seniler Demenz. Arz Forsch 1968; 22: 113-20.
MESOTHELIOMA IN MANUFACTURERS OF ASBESTOS-CONTAINING CIGARETTE FILTERS
SIR,-We have observed mesothelioma in makers of cigarette filters that contained asbestos. Exposure of cigarette filter-makers to asbestos has not been reported to produce mesothelioma, but is associated with asbestosis.1,2 In the past year, peritoneal mesothelioma was diagnosed in three men, aged 51-56. All had worked for 2-24 months for a small company when it made cigarette filters containing asbestos (1951-58). According to the patent, the filter contained 5-30% blue asbestos (crocidolite).3 A state health report during that period and our patients said the workplaces were dusty. One patient became a plumber for the company, an occupation which is associated with exposure to asbestos. 160 employees of the company made cigarette filters during 1951-58. Compared with data for white men in the United States, the finding of mesothelioma in three workers exceeds the 011 cases expected by chance (160 workers x about 40 adult-years at risk x 15/ 1000 000 annual incidence of mesothelioma).’ The actual excess will be greater if further investigations confirm reports of additional cases of mesothelioma within this worker group.
JAMES TALCOTT Dana-Farber Cancer Institute, 44 Binney Street,
Boston, MA 02115, USA
WENDY THURBER EDWARD GAENSLER KAREN ANTMAN FREDERICK P. LI
AM, Gaensler EA. Asbestosis following brief exposure in cigarette filter manufacture. Respiration 1972; 29: 83-93. 2. Carrington CB, Gaensler EA. Clinical-pathologic approach to diffuse infiltrative lung disease. In: Thurlbeck WM, Abell MA, eds. The lung. Structure, function and disease. Baltimore: Williams and Wilkms, 1978: 58-87. 3. Knudson HW. Filter for tobacco smoke. Patent 2,761,798. United States Patent Office. Sept 4, 1956. 4. Spirtas R, Beebe GW, Connelly RR, et al. Recent trends in mesothelioma incidence in the United States. Am J Industr Med 1986; 9: 397-407. 1. Goff
RECOMBINANT HUMAN ERYTHROPOIETIN IN ANAEMIC PATIENTS ON HAEMODIALYSIS
SIR,—The availability of human erythropoietin derived from recombinant DNA (rHuEPO) opens the possibility of effective treatment of anaemia of renal failure.1-3 However, the optimum dose and the side-effect profile are unknown. In a current, open, dose-ranging trial, we have studied 13 dialysed patients who received, after each dialysis, a rHuEPO bolus of 24 U/kg. The dose was doubled every other week up to 96 or 192 U/kg. Median thrombocyte counts increased from 209 x 10/1 (range 154-292) to 239 x 109(1 (185-378). The increase was first seen in the second week and the effect was significant (p < 0-01) by the fifth week. This increase concurs with the stimulatory effect of rHuEPO on megakaryocytes in vitro.4 Winearls1 found no increase in thrombocytes after the administration of 3-192 U/kg in rising doses. The increase we saw means that considerable caution must be taken in deciding the optimum dose, because the combined rise of haematocrit (ie, viscosity) and thrombocytes may expose patients to the risk of thrombosis.2 6 out of 7 of our patients who had complained of Raynaud’s phenomenon’ before receiving rHuEPO reported amelioration 11 weeks after rHuEPO. Their median haematocrit had risen from 20% (15-24) to 29% (22-35). Their digital perfusion was studied objectively with the ’Medimatic’ method and confirmed the subjective improvement. The finding was unexpected and hard to explain in view of the rising haematocrit and presumed higher blood viscosity.
Of the 6 males of reproductive age in our study, 3 reported improvement of sexual function. This may reflect improved well-being and libido, but more specific mechanisms cannot be excluded. Finally, our patients reported increased appetite and food intake, and thus presumably gained weight. We took care not to increase postdialysis bodyweight. Despite this, median predialysis systolic blood pressure rose from 135 mm Hg (115-180) to 155 mm Hg (125-165), and diastolic blood pressure increased significantly (p < 0-01) from 75 mm Hg (60-90) to 80 mm Hg (70-100). Blood pressure rose despite greater use of antihypertensives in 5 patients. When rHuEPO doses were increased more rapidly to higher final levels,2blood pressure increased and hypertensive complications ensued. The quantitatively smaller rise in our trial shows the need for more cautious dose-finding. JÜRGEN BOMMER Department of Internal Medicine, University of Heidelberg, 6900 Heidelberg, West Germany
E. MÜLLER-BÜHL E. RITZ J. EIFERT
1. Winearls
CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986; ii: 1175-78. 2. Eschbach JW, Egne JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. N Engl J Med 1987; 316: 73-78. 3. Zins B, Drueke T, Zingraff J, et al. Erythropoietin treatment m anaemic patients on haemodialysis. Lancet 1986; ii: 1329. 4. Ishibashi T, Koziol JA, Burstein SA. Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro. J Clin Invest 1987; 79: 286-89.
ALLERGY IN CYSTIC FIBROSIS NURSES TO PANCREATIC EXTRACT
SiR;-Allergy to pancreatic extract has been described in the parents of children with cystic fibrosis (CF).1 We have recently become aware of this problem in nurses who care for children with CF. All children admitted for in-patient treatment in the Leeds Regional Cystic Fibrosis Unit are cared for on one ward. Of 11 permanent nurses, 6 reported symptoms of allergy whilst
administering powdered pancreatic extract (’Cotazym’, Organon). Administration involves opening the capsule and mixing the powder with rice or milk. 3 nurses reported nasal irritation, 2 reported coughing, and 1 experienced two episodes of bronchospasm (one episode required treatment with nebulised salbutamol). 1 of the nurses who reported coughing had peak flow recorded before and after feeding an infant-a13% decrease was seen. None of these nurses have a history of atopic disease. We are not aware that this problem has been reported before although it is not unexpected that allergic symptoms may develop in nurses who have repeated and prolonged exposure to pancreatic in the same way that allergy can develop in parents of children with CF. The introduction of micro-encapsulated preparations of pancreatic enzymes has led to a reduction in the use of powdered extract. Although we understand that some centres use the micro-encapsulated forms in small infants, it is our policy to use powdered extract until weaning, as is generally recommended,2 because we have found that some infants cough and choke on extract
microspheres. - Medical and nursing staff should be aware of the possibility of sensitivity to pancreatic extract developing if they care for children with CF. If it is necessary to use powdered extract with small babies, who administer this medication should be advised to take Someone who does not have symptoms of allergy should open the capsule and prepare the contents. Ideally this person should wear a mask to prevent inhalation of the powder, especially if he/she does suffer allergic symptoms.
nurses
precautions.
St James’s University Leeds LS9 7TF
Hospital,
1. Sakula A. Bronchial asthma due
G. W. LIPKIN D. W. VICKERS
to allergy to pancreatic extract: a hazard in the of cystic fibrosis. Br J Dis Chest 1977; 71: 295-99. 2. Goodchild MC. Practical management of nutrition and gastrointestinal tract in cystic fibrosis. J Roy Soc Med 1986; 79 (suppl 12). 32-35.
treatment
7.
1975; 22: 215-27. 9.
Hughes W. Atherosclerosis, Down’s syndrome, and Alzheimer’s disease.
Br
Med J
1977; ii: 702. 10. Jamada M, Mehraein P. Uber die Haufigkeit der zerebralen Arteriosklerose bei Morbus Alzheimer und seniler Demenz. Arz Forsch 1968; 22: 113-20.
MESOTHELIOMA IN MANUFACTURERS OF ASBESTOS-CONTAINING CIGARETTE FILTERS
SIR,-We have observed mesothelioma in makers of cigarette filters that contained asbestos. Exposure of cigarette filter-makers to asbestos has not been reported to produce mesothelioma, but is associated with asbestosis.1,2 In the past year, peritoneal mesothelioma was diagnosed in three men, aged 51-56. All had worked for 2-24 months for a small company when it made cigarette filters containing asbestos (1951-58). According to the patent, the filter contained 5-30% blue asbestos (crocidolite).3 A state health report during that period and our patients said the workplaces were dusty. One patient became a plumber for the company, an occupation which is associated with exposure to asbestos. 160 employees of the company made cigarette filters during 1951-58. Compared with data for white men in the United States, the finding of mesothelioma in three workers exceeds the 011 cases expected by chance (160 workers x about 40 adult-years at risk x 15/ 1000 000 annual incidence of mesothelioma).’ The actual excess will be greater if further investigations confirm reports of additional cases of mesothelioma within this worker group.
JAMES TALCOTT Dana-Farber Cancer Institute, 44 Binney Street,
Boston, MA 02115, USA
WENDY THURBER EDWARD GAENSLER KAREN ANTMAN FREDERICK P. LI
AM, Gaensler EA. Asbestosis following brief exposure in cigarette filter manufacture. Respiration 1972; 29: 83-93. 2. Carrington CB, Gaensler EA. Clinical-pathologic approach to diffuse infiltrative lung disease. In: Thurlbeck WM, Abell MA, eds. The lung. Structure, function and disease. Baltimore: Williams and Wilkms, 1978: 58-87. 3. Knudson HW. Filter for tobacco smoke. Patent 2,761,798. United States Patent Office. Sept 4, 1956. 4. Spirtas R, Beebe GW, Connelly RR, et al. Recent trends in mesothelioma incidence in the United States. Am J Industr Med 1986; 9: 397-407. 1. Goff
RECOMBINANT HUMAN ERYTHROPOIETIN IN ANAEMIC PATIENTS ON HAEMODIALYSIS
SIR,—The availability of human erythropoietin derived from recombinant DNA (rHuEPO) opens the possibility of effective treatment of anaemia of renal failure.1-3 However, the optimum dose and the side-effect profile are unknown. In a current, open, dose-ranging trial, we have studied 13 dialysed patients who received, after each dialysis, a rHuEPO bolus of 24 U/kg. The dose was doubled every other week up to 96 or 192 U/kg. Median thrombocyte counts increased from 209 x 10/1 (range 154-292) to 239 x 109(1 (185-378). The increase was first seen in the second week and the effect was significant (p < 0-01) by the fifth week. This increase concurs with the stimulatory effect of rHuEPO on megakaryocytes in vitro.4 Winearls1 found no increase in thrombocytes after the administration of 3-192 U/kg in rising doses. The increase we saw means that considerable caution must be taken in deciding the optimum dose, because the combined rise of haematocrit (ie, viscosity) and thrombocytes may expose patients to the risk of thrombosis.2 6 out of 7 of our patients who had complained of Raynaud’s phenomenon’ before receiving rHuEPO reported amelioration 11 weeks after rHuEPO. Their median haematocrit had risen from 20% (15-24) to 29% (22-35). Their digital perfusion was studied objectively with the ’Medimatic’ method and confirmed the subjective improvement. The finding was unexpected and hard to explain in view of the rising haematocrit and presumed higher blood viscosity.
Of the 6 males of reproductive age in our study, 3 reported improvement of sexual function. This may reflect improved well-being and libido, but more specific mechanisms cannot be excluded. Finally, our patients reported increased appetite and food intake, and thus presumably gained weight. We took care not to increase postdialysis bodyweight. Despite this, median predialysis systolic blood pressure rose from 135 mm Hg (115-180) to 155 mm Hg (125-165), and diastolic blood pressure increased significantly (p < 0-01) from 75 mm Hg (60-90) to 80 mm Hg (70-100). Blood pressure rose despite greater use of antihypertensives in 5 patients. When rHuEPO doses were increased more rapidly to higher final levels,2blood pressure increased and hypertensive complications ensued. The quantitatively smaller rise in our trial shows the need for more cautious dose-finding. JÜRGEN BOMMER Department of Internal Medicine, University of Heidelberg, 6900 Heidelberg, West Germany
E. MÜLLER-BÜHL E. RITZ J. EIFERT
1. Winearls
CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986; ii: 1175-78. 2. Eschbach JW, Egne JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. N Engl J Med 1987; 316: 73-78. 3. Zins B, Drueke T, Zingraff J, et al. Erythropoietin treatment m anaemic patients on haemodialysis. Lancet 1986; ii: 1329. 4. Ishibashi T, Koziol JA, Burstein SA. Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro. J Clin Invest 1987; 79: 286-89.
ALLERGY IN CYSTIC FIBROSIS NURSES TO PANCREATIC EXTRACT
SiR;-Allergy to pancreatic extract has been described in the parents of children with cystic fibrosis (CF).1 We have recently become aware of this problem in nurses who care for children with CF. All children admitted for in-patient treatment in the Leeds Regional Cystic Fibrosis Unit are cared for on one ward. Of 11 permanent nurses, 6 reported symptoms of allergy whilst
administering powdered pancreatic extract (’Cotazym’, Organon). Administration involves opening the capsule and mixing the powder with rice or milk. 3 nurses reported nasal irritation, 2 reported coughing, and 1 experienced two episodes of bronchospasm (one episode required treatment with nebulised salbutamol). 1 of the nurses who reported coughing had peak flow recorded before and after feeding an infant-a13% decrease was seen. None of these nurses have a history of atopic disease. We are not aware that this problem has been reported before although it is not unexpected that allergic symptoms may develop in nurses who have repeated and prolonged exposure to pancreatic in the same way that allergy can develop in parents of children with CF. The introduction of micro-encapsulated preparations of pancreatic enzymes has led to a reduction in the use of powdered extract. Although we understand that some centres use the micro-encapsulated forms in small infants, it is our policy to use powdered extract until weaning, as is generally recommended,2 because we have found that some infants cough and choke on extract
microspheres. - Medical and nursing staff should be aware of the possibility of sensitivity to pancreatic extract developing if they care for children with CF. If it is necessary to use powdered extract with small babies, who administer this medication should be advised to take Someone who does not have symptoms of allergy should open the capsule and prepare the contents. Ideally this person should wear a mask to prevent inhalation of the powder, especially if he/she does suffer allergic symptoms.
nurses
precautions.
St James’s University Leeds LS9 7TF
Hospital,
1. Sakula A. Bronchial asthma due
G. W. LIPKIN D. W. VICKERS
to allergy to pancreatic extract: a hazard in the of cystic fibrosis. Br J Dis Chest 1977; 71: 295-99. 2. Goodchild MC. Practical management of nutrition and gastrointestinal tract in cystic fibrosis. J Roy Soc Med 1986; 79 (suppl 12). 32-35.
treatment