990 CHRONIC RENAL DISEASE SIR,-Dr Bengtsson1 has raised questions about our. longitudinal epidemiological studywith its finding of a low frequency of impaired renal function in a group of Swiss women with proven high intake of analgesics containing phenacetin compared with a control group (each with 600 persons) observed in 1968-72. A low specific gravity after thirsting overnight was observed in 3-8% and a raised serum-creatinine in 2-9% in the study group,
08% and 0-4%, respectively, in the controlsresults which are statistically significant. No difference between the two groups was noted regarding the development of proteinuria, haematuria, or bacteriuria. As a cut-off point for a pathological result, a specific gravity of 1-010 or less was used in all persons initially negative for this condition in 1968. Dr Bengtsson objects to the low normal value of 1-010 and says that she would only accept a value below 1-020 as indicating decreased concentrating-capacity in kidney damage from analgesics containing phenacetin. We have reanalysed the specificgravity data after thirsting, defining an abnormal specific gravity as 1 019 or less and a normal one as 1-020 or more.2 We then reconstructed tables i and III of our paper. The results are similar to our previous results in that (a) the study group as a whole is significantly different from the ’control group on both the measure of two or more positives and the measure of consistent positivity; (b) the high and low N-acetyl-p-aminophenol (N.A.P.A.P.) subgroups are significantly different from each other on both these measures. The differences in (a) and (b) remain versus
significant. Furthermore, a surprisingly high proportion people had specific gravities of less than 1-019 in the study group (55%) and in the control group (34%). Thus there were many fewer people who were " initially normal " for specific gravity, compared with table i of our paper: 279 instead of 552 in the study group and 406 instead of
of
590 in the control group. It seems to us that the cut-off value of 1-020-1-022 suggested by Dr Bengtsson might not be particularly meaningful in a study conducted under field conditions rather than in a controlled hospital setting, since compliance with the thirsting procedure is difficult to guarantee. Under field conditions, the cut-off proposed by Dr Bengtsson may be non-specific as an indicator of concentrating
deficiency.
Medizinische
Universitäts-Poliklinik, Departement für Innere Medizin, Kantonsspital Basle, Switzerland.
U. C. DUBACH P. S. LEVY B. ROSNER H. R. BAUMELER A. MÜLLER A. PEIER T. EHRENSPERGER
BLOOD, PLASMA, OR SERUM SIR,-May I support Professor Dent (Nov. 1, p. 867)
in all his pleas? Sloppy nomenclature of the kind he deplores usually indicates sloppy thought, which at best results in the wro type of sample being sent to the laboratory, and at worst lead to misunderstanding of the significance of results. For instance, taking up his second point, the use of "lactic acid" for "lactate" implies that hydrogen ion is being produced by the same process as, and in equimolar amounts to, lactate, and leads to a misunderstanding of so-called "lactic acidosis". I fully confess to committing such sins myself in the past: in my ignorance I am probably still committing similar ones.
may
1. 2.
Bengtsson, U. Lancet, 1975, i, 1195. Dubach, U. C., Levy, P. S., Rosner, B., Baumeler, H. R., Müller, A., Peier, A., Ehrensperger, T. ibid. p. 539.
However, we should all stop to think what it is we really mean before
"saying (or writing)".
Department of Chemical Pathology, Westminster Medical School, 17 Page Street, London SW1P 2AR.
JOAN F. ZILVA
CARDIAC ARRHYTHMIA INDUCED BY PHENOTHIAZINE
StR,--The risk of dangerous arrhythmias following overdo-
sage of tricyclic antidepressive drugs is generally reaped. the electrocardiogram is commonly monitored in these patients. The management of phenothiazine poisoning is often more casual. We report episodic ventricular tachycardia and fibrillation occurring after ingestion of 2500 mg of thioridazine (’Melleril’, Sandoz), a phenothiazine.
Accordingly
A previously fit 30-year-old man was admitted 6 hours after the overdose and for 36 hours progressed uneventfully. He then suffered repeated episodes of cardiac arrest over the next 12 hours. Sinus rhythm was first interrupted by multifocal ventricular premature beats followed within seconds by ventricular tachycardia and then fibnllation. Later eptsodes were recorded in which the transition from smus rhythm to ventricular tachycardia was abrupt. Strikingly btfid.i waves were present during periods of sinus rhythm (this abnormality has been previously reported in patients taking therapeutic doses of phenothiazines’). The serum-potassium was normal throughout. The attacks lasted for periods of seconds to minutes when cardiac massage was applied. Neither intravenous lignocaine or practolol appeared completely effective in preventing the arrhythmias.
Although one review2 dismisses myocardial lesions and sudden death in phenothiazine-treated patients it seems extremely likely that the arrhythmias observed in this case were a direct toxic effect of thioridazine. This potentially fatal complication occurred at a time when many patients would have been discharged from hospital. Cardiac monitoring should be employed in selected cases of phenothiazine overdosage for at least 48 hours. Royal Infirmary, Bristol BS2
D. F. LFVINF A. J. MARSHAILL
POTATO SCAB AND TERATOGENY
SIR,-We have previously reported teratogeny in mice fed an extract
obtained from "potato scab" found in this
region,’
Two male mice so fed developed eczematous lesions. The infected males were placed in contact with uninfected Charles River COBS mice (fifteen male, fifteen female). All males developed infected eczematous lesions; the females remained free of infection. No other animals in our colony have shown similar symptoms. Nine months after the initial infection, one male developed a subcutanous benign growth in the eczematous area. Histological examination four months later showed malignant tissue indicative of melanotic melanoma, or undifferentiated sarcoma or carcinoma ansing from skin adnexal structures. Since the time of the original infection, seven of the seventeen males have developed similar malignant tumours; females exposed to infected animals show no lesions. These results suggest that in these males carcinogenesis is associated with ingestion of potato scab or physical contact with lesions. Examination of Sabouraud broth extract of scab revealed two predominant organisms-a gram-negative rod and coccus. These organisms predominated also in cultures obtained from the eczematous lesions and the neoplasms. In addition, five male and five female COBS mice were fed extracts from these neoplasms. Eczema developed in all the males, and cultures from the lesions showed gram-negative rods and cocci to be dominant. The animals are under observation for possible tumour formation. Our results suggest that these organisms have some role in the carcinogenic process. The observation that the carcinogenesis is apparently sex-linked suggests a hormone-mediated mechanism. The possibility of prenatal immunisation against cancer is also suggested. We originally reported3 that animals born 35 days after potato1. Jeeva, R. M. V., 2 Wendkos, M. H.
Benson, R. Postgrad. med.J. 1975, 51, 65 J. Am Ger. Soc. 1967, 15, 20 3. Zimmerman, N., Gifford, W. H., Gray, B. Lancet, 1974, 1, 1111.
08% and 0-4%, respectively, in the controlsresults which are statistically significant. No difference between the two groups was noted regarding the development of proteinuria, haematuria, or bacteriuria. As a cut-off point for a pathological result, a specific gravity of 1-010 or less was used in all persons initially negative for this condition in 1968. Dr Bengtsson objects to the low normal value of 1-010 and says that she would only accept a value below 1-020 as indicating decreased concentrating-capacity in kidney damage from analgesics containing phenacetin. We have reanalysed the specificgravity data after thirsting, defining an abnormal specific gravity as 1 019 or less and a normal one as 1-020 or more.2 We then reconstructed tables i and III of our paper. The results are similar to our previous results in that (a) the study group as a whole is significantly different from the ’control group on both the measure of two or more positives and the measure of consistent positivity; (b) the high and low N-acetyl-p-aminophenol (N.A.P.A.P.) subgroups are significantly different from each other on both these measures. The differences in (a) and (b) remain versus
significant. Furthermore, a surprisingly high proportion people had specific gravities of less than 1-019 in the study group (55%) and in the control group (34%). Thus there were many fewer people who were " initially normal " for specific gravity, compared with table i of our paper: 279 instead of 552 in the study group and 406 instead of
of
590 in the control group. It seems to us that the cut-off value of 1-020-1-022 suggested by Dr Bengtsson might not be particularly meaningful in a study conducted under field conditions rather than in a controlled hospital setting, since compliance with the thirsting procedure is difficult to guarantee. Under field conditions, the cut-off proposed by Dr Bengtsson may be non-specific as an indicator of concentrating
deficiency.
Medizinische
Universitäts-Poliklinik, Departement für Innere Medizin, Kantonsspital Basle, Switzerland.
U. C. DUBACH P. S. LEVY B. ROSNER H. R. BAUMELER A. MÜLLER A. PEIER T. EHRENSPERGER
BLOOD, PLASMA, OR SERUM SIR,-May I support Professor Dent (Nov. 1, p. 867)
in all his pleas? Sloppy nomenclature of the kind he deplores usually indicates sloppy thought, which at best results in the wro type of sample being sent to the laboratory, and at worst lead to misunderstanding of the significance of results. For instance, taking up his second point, the use of "lactic acid" for "lactate" implies that hydrogen ion is being produced by the same process as, and in equimolar amounts to, lactate, and leads to a misunderstanding of so-called "lactic acidosis". I fully confess to committing such sins myself in the past: in my ignorance I am probably still committing similar ones.
may
1. 2.
Bengtsson, U. Lancet, 1975, i, 1195. Dubach, U. C., Levy, P. S., Rosner, B., Baumeler, H. R., Müller, A., Peier, A., Ehrensperger, T. ibid. p. 539.
However, we should all stop to think what it is we really mean before
"saying (or writing)".
Department of Chemical Pathology, Westminster Medical School, 17 Page Street, London SW1P 2AR.
JOAN F. ZILVA
CARDIAC ARRHYTHMIA INDUCED BY PHENOTHIAZINE
StR,--The risk of dangerous arrhythmias following overdo-
sage of tricyclic antidepressive drugs is generally reaped. the electrocardiogram is commonly monitored in these patients. The management of phenothiazine poisoning is often more casual. We report episodic ventricular tachycardia and fibrillation occurring after ingestion of 2500 mg of thioridazine (’Melleril’, Sandoz), a phenothiazine.
Accordingly
A previously fit 30-year-old man was admitted 6 hours after the overdose and for 36 hours progressed uneventfully. He then suffered repeated episodes of cardiac arrest over the next 12 hours. Sinus rhythm was first interrupted by multifocal ventricular premature beats followed within seconds by ventricular tachycardia and then fibnllation. Later eptsodes were recorded in which the transition from smus rhythm to ventricular tachycardia was abrupt. Strikingly btfid.i waves were present during periods of sinus rhythm (this abnormality has been previously reported in patients taking therapeutic doses of phenothiazines’). The serum-potassium was normal throughout. The attacks lasted for periods of seconds to minutes when cardiac massage was applied. Neither intravenous lignocaine or practolol appeared completely effective in preventing the arrhythmias.
Although one review2 dismisses myocardial lesions and sudden death in phenothiazine-treated patients it seems extremely likely that the arrhythmias observed in this case were a direct toxic effect of thioridazine. This potentially fatal complication occurred at a time when many patients would have been discharged from hospital. Cardiac monitoring should be employed in selected cases of phenothiazine overdosage for at least 48 hours. Royal Infirmary, Bristol BS2
D. F. LFVINF A. J. MARSHAILL
POTATO SCAB AND TERATOGENY
SIR,-We have previously reported teratogeny in mice fed an extract
obtained from "potato scab" found in this
region,’
Two male mice so fed developed eczematous lesions. The infected males were placed in contact with uninfected Charles River COBS mice (fifteen male, fifteen female). All males developed infected eczematous lesions; the females remained free of infection. No other animals in our colony have shown similar symptoms. Nine months after the initial infection, one male developed a subcutanous benign growth in the eczematous area. Histological examination four months later showed malignant tissue indicative of melanotic melanoma, or undifferentiated sarcoma or carcinoma ansing from skin adnexal structures. Since the time of the original infection, seven of the seventeen males have developed similar malignant tumours; females exposed to infected animals show no lesions. These results suggest that in these males carcinogenesis is associated with ingestion of potato scab or physical contact with lesions. Examination of Sabouraud broth extract of scab revealed two predominant organisms-a gram-negative rod and coccus. These organisms predominated also in cultures obtained from the eczematous lesions and the neoplasms. In addition, five male and five female COBS mice were fed extracts from these neoplasms. Eczema developed in all the males, and cultures from the lesions showed gram-negative rods and cocci to be dominant. The animals are under observation for possible tumour formation. Our results suggest that these organisms have some role in the carcinogenic process. The observation that the carcinogenesis is apparently sex-linked suggests a hormone-mediated mechanism. The possibility of prenatal immunisation against cancer is also suggested. We originally reported3 that animals born 35 days after potato1. Jeeva, R. M. V., 2 Wendkos, M. H.
Benson, R. Postgrad. med.J. 1975, 51, 65 J. Am Ger. Soc. 1967, 15, 20 3. Zimmerman, N., Gifford, W. H., Gray, B. Lancet, 1974, 1, 1111.
