- Email: [email protected]
CEPHALOSPORIN NEPHROTOXICITY
1408 potency enzyme powder concentrates are diluted with a carrier powder while the laboratory does quality-control assays. The workplaces of the individuals are given in the table. The offices were immediately above the enzyme-handling plant. Individuals sensitised to both preparations said that, in respect both of causation and severity of symptoms, a-amylase was worse than papain. All those giving positive skin pricktests to sf-amylase had experienced symptoms, whereas two of those giving positive reactions to papain had had no symptoms, and of the four sensitised to both enzymes, only the two sensit-’ ised to x-amylase had experienced chest symptoms. An adjuvant effect from papain is unlikely because the two enzyme powders were handled infrequently and not at the same time. These findings have implications for a-amylase users, such as those in the flour milling and bakery industries, and they underline the importance of treating all enzyme preparations, proteolytic or not, as potentially allergenic and of taking precautions.8 Department of Occupational University of Manchester, Manchester M13 9PT
M. L. H. FLINDT
5 editorial you noted that cefuroxime be free of nephrotoxic side-effects, on animal and, drawing studies, you suggest that they may even have a protective effect. Previous studies have shown a similar protective effect by cephalothin against gentamicin
May
seem to
nephrotoxicity. 1.2 Accumulating data in patient trials, however, indicate that cephalothin plus an aminoglycoside, either gentamicin or tobramycin, is more nephrotoxic than the aminoglycoside alone. Klastersky et al. compared the combination of tobramycin and cephalothin with that of tobramycin and ticarcillin, and with ticarcillin and cephalothin, in a prospective randomised study in 186 patients with cancer. The incidence of nephrotoxicity was significantly increased (21%) in the cephalothin-tobramycin group. Two additional prospective studies4,5have compared gentamicin and/or tobramycin with cephalothin versus other aminoglycoside regimens and have also found significant increases in nephrotoxicity in cephalothin-containing groups. These studies point out the large unexplained discrepancy between animal and human data. To state that animal studies on the newer cephalosporins indicate that they are probably free of nephrotoxicity, and possibly protective, without at the same time indicating the discrepancy between human and animal data on cephalothin, is potentially misleading to the clinician prescribing these drugs. Division of Infectious Diseases, Washington University Medical Center, St. Louis, Missouri 63110, U.S.A.
SIR,-Dr Marks and Mr Power (Feb. 17, p. 371) have suggested that the risks of ocular toxicity related to chloroquine are acceptably low. However, our experience with 68 patients Flindt, M. L. H. Process Biochem. 1978, 13, no. 8 p. 3. Dellinger, P., Murphy, T., Pinn, V., Barza, M., Weinstein, L. Antimicrob.
Ag. Chemother. 1976, 9, 172. 2. Barza, M., Pinn, V., Tanguay, P., Murray, T. J. antimicrob. Chemother. 1978,4 suppl. A, p. 59. 3. Klastersky, J., Hensgens, C., Debusscher, L. Antimicrob. Ag. Chemother. 1975, 7, 640. 4. The E.O.R.T.C. International Antimicrobial Therapy Project Group. J. infect. Dis. 1978, 137, 14. 5.
Wade, J. C , and others. Lancet, 1978, ii, 604.
with chloroquine visual acuity. We conducted
retinopathy indicates
severe
deterioration of
questionnaire survey on 68 chloroquine retinopathy patients who had instituted a lawsuit against chloroquine manufacturers. The 68 patients, 39 men and 29 women, ranged in age from 20 to 73 years (mean 46). They had been treated with chloroquine for various diseases: 6 for discoid lupus erythematosus, 4 for rheumatoid arthritis, 1 for systemic lupus erythematosus, and 57 for chronic nephritis. Treatment of chronic nephritis with chloroquine has been practised only in Japan. The total dose of chloroquine base per patient ranged from 45 to 674 g (mean 274 g) and the duration of therapy ranged from 16 to 129 months (mean 51 months). The patients answered the questionnaire 41-156 months (mean 89 months) after the end of chloroquine therapy. All patients had visual-field defects and none showed improvement. Moreover, progression was noted in 10 patients after discontinuation of chloroquine therapy. Almost all patients showed seriously impaired visual acuity: 35 patients (51%) showed decreased visual acuity to below 6/60 and 14 of these showed impairment to below counting fingers. Information on serial change of visual acuity before, during, and after chloroquine therapy was available in 19 patients. Visual acuity decreased in 12 patients during chloroquine therapy (see figure). After cessation of therapy, visual acuity improved in only 1, and remained unchanged in 6 patients. The others showed progressive impairment, and in 5 of these the impairment became progressively worse for more than five years after discontinuation of chloroquine therapy. Other workers1,2 have previously reported irreversibility or progression of chloroquine retinopathy 2-3 years after discontinuation of therapy. Our study indicates not only that impaira
progresses more than five years after cessation of chlorobut also that the impairment of visual acuity after a mean of 89 months of discontinuation of chloroquine therapy is more serious than formerly reported.3 We, therefore, would like to emphasise the severity of ocular toxicity of chloroquine. ment
JAMES H. HINRICHS
PROGRESSION OF RETINOPATHY LONG AFTER CESSATION OF CHLOROQUINE THERAPY
8. 1.
=
Health,
CEPHALOSPORIN NEPHROTOXICITY
SIR,-In your and cefamandole
Sequential change of visual acuity after cessation of chloroquine therapy. CF counting fingers.
quine
Department of Public Health, Osaka University Medical School, 3-57, 4 Chome, Nakanoshima, Kita-ku, Osaka, Japan
SADAO OGAWA
Department of Public Health, Nara Medical University
NORIO KURUMATANI
Department of Public Health, Osaka University Medical School
NOBUAKI SHIBAIKE
Department of Education, Shiga University
SHIRO YAMAZOE
Hobbs, H. E., Sorsby, A., Freedman, A. Lancet, 1959, ii, 478. Mayer, W. Am. J. Ophthal. 1962, 53, 769. 3. Nylander, U. Acta ophthal. 1967, suppl. 92, p. 5.
1. 2.
M. L. H. FLINDT
5 editorial you noted that cefuroxime be free of nephrotoxic side-effects, on animal and, drawing studies, you suggest that they may even have a protective effect. Previous studies have shown a similar protective effect by cephalothin against gentamicin
May
seem to
nephrotoxicity. 1.2 Accumulating data in patient trials, however, indicate that cephalothin plus an aminoglycoside, either gentamicin or tobramycin, is more nephrotoxic than the aminoglycoside alone. Klastersky et al. compared the combination of tobramycin and cephalothin with that of tobramycin and ticarcillin, and with ticarcillin and cephalothin, in a prospective randomised study in 186 patients with cancer. The incidence of nephrotoxicity was significantly increased (21%) in the cephalothin-tobramycin group. Two additional prospective studies4,5have compared gentamicin and/or tobramycin with cephalothin versus other aminoglycoside regimens and have also found significant increases in nephrotoxicity in cephalothin-containing groups. These studies point out the large unexplained discrepancy between animal and human data. To state that animal studies on the newer cephalosporins indicate that they are probably free of nephrotoxicity, and possibly protective, without at the same time indicating the discrepancy between human and animal data on cephalothin, is potentially misleading to the clinician prescribing these drugs. Division of Infectious Diseases, Washington University Medical Center, St. Louis, Missouri 63110, U.S.A.
SIR,-Dr Marks and Mr Power (Feb. 17, p. 371) have suggested that the risks of ocular toxicity related to chloroquine are acceptably low. However, our experience with 68 patients Flindt, M. L. H. Process Biochem. 1978, 13, no. 8 p. 3. Dellinger, P., Murphy, T., Pinn, V., Barza, M., Weinstein, L. Antimicrob.
Ag. Chemother. 1976, 9, 172. 2. Barza, M., Pinn, V., Tanguay, P., Murray, T. J. antimicrob. Chemother. 1978,4 suppl. A, p. 59. 3. Klastersky, J., Hensgens, C., Debusscher, L. Antimicrob. Ag. Chemother. 1975, 7, 640. 4. The E.O.R.T.C. International Antimicrobial Therapy Project Group. J. infect. Dis. 1978, 137, 14. 5.
Wade, J. C , and others. Lancet, 1978, ii, 604.
with chloroquine visual acuity. We conducted
retinopathy indicates
severe
deterioration of
questionnaire survey on 68 chloroquine retinopathy patients who had instituted a lawsuit against chloroquine manufacturers. The 68 patients, 39 men and 29 women, ranged in age from 20 to 73 years (mean 46). They had been treated with chloroquine for various diseases: 6 for discoid lupus erythematosus, 4 for rheumatoid arthritis, 1 for systemic lupus erythematosus, and 57 for chronic nephritis. Treatment of chronic nephritis with chloroquine has been practised only in Japan. The total dose of chloroquine base per patient ranged from 45 to 674 g (mean 274 g) and the duration of therapy ranged from 16 to 129 months (mean 51 months). The patients answered the questionnaire 41-156 months (mean 89 months) after the end of chloroquine therapy. All patients had visual-field defects and none showed improvement. Moreover, progression was noted in 10 patients after discontinuation of chloroquine therapy. Almost all patients showed seriously impaired visual acuity: 35 patients (51%) showed decreased visual acuity to below 6/60 and 14 of these showed impairment to below counting fingers. Information on serial change of visual acuity before, during, and after chloroquine therapy was available in 19 patients. Visual acuity decreased in 12 patients during chloroquine therapy (see figure). After cessation of therapy, visual acuity improved in only 1, and remained unchanged in 6 patients. The others showed progressive impairment, and in 5 of these the impairment became progressively worse for more than five years after discontinuation of chloroquine therapy. Other workers1,2 have previously reported irreversibility or progression of chloroquine retinopathy 2-3 years after discontinuation of therapy. Our study indicates not only that impaira
progresses more than five years after cessation of chlorobut also that the impairment of visual acuity after a mean of 89 months of discontinuation of chloroquine therapy is more serious than formerly reported.3 We, therefore, would like to emphasise the severity of ocular toxicity of chloroquine. ment
JAMES H. HINRICHS
PROGRESSION OF RETINOPATHY LONG AFTER CESSATION OF CHLOROQUINE THERAPY
8. 1.
=
Health,
CEPHALOSPORIN NEPHROTOXICITY
SIR,-In your and cefamandole
Sequential change of visual acuity after cessation of chloroquine therapy. CF counting fingers.
quine
Department of Public Health, Osaka University Medical School, 3-57, 4 Chome, Nakanoshima, Kita-ku, Osaka, Japan
SADAO OGAWA
Department of Public Health, Nara Medical University
NORIO KURUMATANI
Department of Public Health, Osaka University Medical School
NOBUAKI SHIBAIKE
Department of Education, Shiga University
SHIRO YAMAZOE
Hobbs, H. E., Sorsby, A., Freedman, A. Lancet, 1959, ii, 478. Mayer, W. Am. J. Ophthal. 1962, 53, 769. 3. Nylander, U. Acta ophthal. 1967, suppl. 92, p. 5.
1. 2.