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APLASTIC ANAEMIA AFTER METHOXYCHLOR EXPOSURE
1349 SPANISH TOXIC OIL AND CONGENITAL MALFORMATIONS
SIR,—To see if "Spanish toxic oil" might have caused congenital malformations in babies born to mothers who had used this oil when pregnant we analysed data from the Spanish collaborative study of congenital malformations (E.C.E.M.C.), a participant in the International Clearinghouse for Birth Defects Monitoring Systems. E.C.E.M.C. is a hospital-based case-control study of livebirths in almost all regions of Spain and now covers about 65 000 births a year. Major and minor defects are ascertained, within the first three days of life, by physicians who examine all live births in every hospital. For each malformed baby the next non-malformed baby of the same sex, born in the same hospital, is selected as a control. Mothers’of malformed children and controls are interviewed within three days of delivery by the use of a standard questionnaire via which information about toxic oil exposure during pregnancy is obtained. 502 babies (251 malformed, 251 controls), were ascertained from September, 1981, to March, 1982. Among the malformed children there were 5 exposures to toxic oil (2 · 0%) whereas among the controls there were 4 exposures (1 - 6%). The odds ratio was 1 ’22 (95% confidence intervals 0 -33-4 -7) for a chi-square of 0.11 (not significant). 1 of the 5 malformed children with exposure to toxic oil had a familial cleidocranial dysostosis, another had only a sacral fossette, 1 had an angioma, and 2 had multiple osseous malformations. Our data do not support an association between congenital malformations and use of toxic oil during pregnancy. Supported by a grant from Plan Nacional de Prevencion de la Subnormalidad (Ministry of Health, Spain). E.C.E.M.C.,
Faculty of Medicine, Universidad Autónoma de Madrid, Madrid - 34, Spain
MARÍA-LUISA MARTÍNES-FRÍAS
JOAQUÍN SALVADOR LUIS PRIETO
SPECIFIC CHROMOSOME CHANGE, TESTICULAR TUMOURS?
i(12p), IN
SIR,—Specific chromosome changes have been described in several forms of leukaemia and lymphoma but, with a few exceptions, not in solid tumours. We have found a possibly specific marker chromosome in direct preparations and 24 h cultures from all of ten seminomas, one malignant teratoma, and one combined seminoma and teratoma of the testis. This chromosome was a small metacentric, commonly present in duplicate, which, in four of the seminomas, was identified as an isochromosome for the short arm of chromosome 12. The marker in the other tumours had a similar appearance, but the preparations were poorer and its precise origin could not be determined. However, it seems feasible that an identical marker is present in all the tumours and that this represents a chromosomal change that is specific for malignant testicular tumours. We have only rarely seen similar marker chromosomes in tumours of the breast, bladder, colon and rectum, endometrium, ovary, and bronchus, but an abnormal small metacentric (tentatively identified in two tumours, however, as a 5p-) was seen in 12 out of 18 carcinomas of the cervix.’1 Chromosome changes in cancer cells, including those that are site specific, are believed to contribute to the malignant phenotype through gene loss, modification, or amplification. The study of the genetic changes that lead to cancer has accelerated as a result of the application of the new techniques of molecular biology, but vital information concerning the location of "cancer genes" may yet be forthcoming from light microscope studies of the chromosomal changes in cancer cells. Since these genes are apparently site specific their normal alleles may be important for tissue differentiation,2 and chromosome studies on cancer cells may throw light on problems of normal as well as abnormal differentiation. Most of the site specific chromosome changes so far described in cancer are translocations3 1. Atkin
NB, Baker MC, Nonrandom chromosome changes in carcinoma of the cervix uteri. Acta Cytol 1982; 26: 568-69. 2. Knudson AG Jr. Human cancer genes. In: Arrighi FE, Rao PN, Stubblefield E, eds. Genes, chromosomes and neoplasia. New York: Raven Press, 1981: 453-62. 3. Hecht F, Kaiser-McCaw B, Sandberg AA. Chromosome translocations in cancer. N Engl J Med 1981; 304: 1493.
in which the genes that are critically involved are presumed to be situated close to the breakpoints. That described here would be the
first example of an isochromosome, although isochromosomes for I q and 17q have each been described in several forms of cancer and, while of probable importance in tumour progression, are not site
specific. Besides the presumed isochromosomes for 12p, we have noted a relative excess of normal chromosomes 12 in four out of five of the seminomas that were analysed in detail. It would seem from our findings that the amplification of one or more genes on the short arm of chromosome 12 may be of importance in the development of malignant testicular tumours. Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN *Present address:
N. B. ATKIN MARION C. BAKER*
Department of Cytogenetics, Royal Marsden Hospital, Sutton, Surrey.
APLASTIC ANAEMIA AFTER METHOXYCHLOR EXPOSURE a
SIR,-I recently encountered a case of a 49-year-old man who used tomato pesticide dust containing methoxychlor (2,2-bis[p-
methoxyphenyl]-!, 1, 1-trichloroethane) and captan in his back yard. A strong gust of wind came up and blew the dust into his face, nose, and mouth. He could taste the dust for many hours despite thorough mouth washings. After several weeks symptoms of fatigue and bruising gradually developed and he sought medical care about 2 months after the pesticide exposure. Aplastic anaemia was diagnosed and he died within 6 months. Before the exposure he had been completely well and had not taken any drugs. He had had several light exposures to the same pesticide over the previous 2 years without symptoms. Careful evaluation by a haematologist did not reveal any other known predisposing factors for aplastic anaemia. Methoxychlor has some chemical structural similarities to DDT and lindane, agents for which there are published case-reports of aplastic anaemia following exposure. The metabolic pathways of these three pesticides have some similarities but are not identical. I was unable to locate, through extensive interviews and a literature search, a single reported case of methoxychlor-induced aplastic anaemia. Department of Health Services Administration, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, U.S.A.
GRACE ZIEM
ANATOLY KORYAGIN
SIR,—The sad situation of Dr Koryagin which you report (Nov.i. 27, p. 1232) has been confirmed from other
sources. Your readers may be heartened to know that Koryagin has been elected a fellow of the American Psychiatric Association and that a similar action is contemplated by the Royal College of Psychiatrists. Recently, Mr Kevin Klose, the Washington Post correspondent in Moscow, addressed our working group on the subject of his meetings with Koryagin. He believes that Koryagin, in attempting to protect Soviet victims of politically motivated psychiatric abuse, has acted in the finest traditions of the medical profession. Our working group intends to send the following telegram to the Secretary General of the Communist Party of the U.S.S.R., Mr Yuri Andropov:
"We urge you to take into consideration the eminent service to psychiatry and to medicine generally rendered by Dr Koryagin in raising, by his attitude, respect for the ethical principles of the medical profession. We ask you to free Dr Koryagin and to restore to him the means to pursue the practice of psychiatry. This measure would make a favourable impression on world medical opinion."
Any doctor willing to be associated with this appeal should send his name, medical qualifications, and present position to the Secretary of the Working Group (Christine Shaw) at this address. Working Group on the Internment of Dissenters in Mental 17 Norland
Square,
London W11
Hospitals,
ALAN WYNN, Chairman
SIR,—To see if "Spanish toxic oil" might have caused congenital malformations in babies born to mothers who had used this oil when pregnant we analysed data from the Spanish collaborative study of congenital malformations (E.C.E.M.C.), a participant in the International Clearinghouse for Birth Defects Monitoring Systems. E.C.E.M.C. is a hospital-based case-control study of livebirths in almost all regions of Spain and now covers about 65 000 births a year. Major and minor defects are ascertained, within the first three days of life, by physicians who examine all live births in every hospital. For each malformed baby the next non-malformed baby of the same sex, born in the same hospital, is selected as a control. Mothers’of malformed children and controls are interviewed within three days of delivery by the use of a standard questionnaire via which information about toxic oil exposure during pregnancy is obtained. 502 babies (251 malformed, 251 controls), were ascertained from September, 1981, to March, 1982. Among the malformed children there were 5 exposures to toxic oil (2 · 0%) whereas among the controls there were 4 exposures (1 - 6%). The odds ratio was 1 ’22 (95% confidence intervals 0 -33-4 -7) for a chi-square of 0.11 (not significant). 1 of the 5 malformed children with exposure to toxic oil had a familial cleidocranial dysostosis, another had only a sacral fossette, 1 had an angioma, and 2 had multiple osseous malformations. Our data do not support an association between congenital malformations and use of toxic oil during pregnancy. Supported by a grant from Plan Nacional de Prevencion de la Subnormalidad (Ministry of Health, Spain). E.C.E.M.C.,
Faculty of Medicine, Universidad Autónoma de Madrid, Madrid - 34, Spain
MARÍA-LUISA MARTÍNES-FRÍAS
JOAQUÍN SALVADOR LUIS PRIETO
SPECIFIC CHROMOSOME CHANGE, TESTICULAR TUMOURS?
i(12p), IN
SIR,—Specific chromosome changes have been described in several forms of leukaemia and lymphoma but, with a few exceptions, not in solid tumours. We have found a possibly specific marker chromosome in direct preparations and 24 h cultures from all of ten seminomas, one malignant teratoma, and one combined seminoma and teratoma of the testis. This chromosome was a small metacentric, commonly present in duplicate, which, in four of the seminomas, was identified as an isochromosome for the short arm of chromosome 12. The marker in the other tumours had a similar appearance, but the preparations were poorer and its precise origin could not be determined. However, it seems feasible that an identical marker is present in all the tumours and that this represents a chromosomal change that is specific for malignant testicular tumours. We have only rarely seen similar marker chromosomes in tumours of the breast, bladder, colon and rectum, endometrium, ovary, and bronchus, but an abnormal small metacentric (tentatively identified in two tumours, however, as a 5p-) was seen in 12 out of 18 carcinomas of the cervix.’1 Chromosome changes in cancer cells, including those that are site specific, are believed to contribute to the malignant phenotype through gene loss, modification, or amplification. The study of the genetic changes that lead to cancer has accelerated as a result of the application of the new techniques of molecular biology, but vital information concerning the location of "cancer genes" may yet be forthcoming from light microscope studies of the chromosomal changes in cancer cells. Since these genes are apparently site specific their normal alleles may be important for tissue differentiation,2 and chromosome studies on cancer cells may throw light on problems of normal as well as abnormal differentiation. Most of the site specific chromosome changes so far described in cancer are translocations3 1. Atkin
NB, Baker MC, Nonrandom chromosome changes in carcinoma of the cervix uteri. Acta Cytol 1982; 26: 568-69. 2. Knudson AG Jr. Human cancer genes. In: Arrighi FE, Rao PN, Stubblefield E, eds. Genes, chromosomes and neoplasia. New York: Raven Press, 1981: 453-62. 3. Hecht F, Kaiser-McCaw B, Sandberg AA. Chromosome translocations in cancer. N Engl J Med 1981; 304: 1493.
in which the genes that are critically involved are presumed to be situated close to the breakpoints. That described here would be the
first example of an isochromosome, although isochromosomes for I q and 17q have each been described in several forms of cancer and, while of probable importance in tumour progression, are not site
specific. Besides the presumed isochromosomes for 12p, we have noted a relative excess of normal chromosomes 12 in four out of five of the seminomas that were analysed in detail. It would seem from our findings that the amplification of one or more genes on the short arm of chromosome 12 may be of importance in the development of malignant testicular tumours. Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN *Present address:
N. B. ATKIN MARION C. BAKER*
Department of Cytogenetics, Royal Marsden Hospital, Sutton, Surrey.
APLASTIC ANAEMIA AFTER METHOXYCHLOR EXPOSURE a
SIR,-I recently encountered a case of a 49-year-old man who used tomato pesticide dust containing methoxychlor (2,2-bis[p-
methoxyphenyl]-!, 1, 1-trichloroethane) and captan in his back yard. A strong gust of wind came up and blew the dust into his face, nose, and mouth. He could taste the dust for many hours despite thorough mouth washings. After several weeks symptoms of fatigue and bruising gradually developed and he sought medical care about 2 months after the pesticide exposure. Aplastic anaemia was diagnosed and he died within 6 months. Before the exposure he had been completely well and had not taken any drugs. He had had several light exposures to the same pesticide over the previous 2 years without symptoms. Careful evaluation by a haematologist did not reveal any other known predisposing factors for aplastic anaemia. Methoxychlor has some chemical structural similarities to DDT and lindane, agents for which there are published case-reports of aplastic anaemia following exposure. The metabolic pathways of these three pesticides have some similarities but are not identical. I was unable to locate, through extensive interviews and a literature search, a single reported case of methoxychlor-induced aplastic anaemia. Department of Health Services Administration, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, U.S.A.
GRACE ZIEM
ANATOLY KORYAGIN
SIR,—The sad situation of Dr Koryagin which you report (Nov.i. 27, p. 1232) has been confirmed from other
sources. Your readers may be heartened to know that Koryagin has been elected a fellow of the American Psychiatric Association and that a similar action is contemplated by the Royal College of Psychiatrists. Recently, Mr Kevin Klose, the Washington Post correspondent in Moscow, addressed our working group on the subject of his meetings with Koryagin. He believes that Koryagin, in attempting to protect Soviet victims of politically motivated psychiatric abuse, has acted in the finest traditions of the medical profession. Our working group intends to send the following telegram to the Secretary General of the Communist Party of the U.S.S.R., Mr Yuri Andropov:
"We urge you to take into consideration the eminent service to psychiatry and to medicine generally rendered by Dr Koryagin in raising, by his attitude, respect for the ethical principles of the medical profession. We ask you to free Dr Koryagin and to restore to him the means to pursue the practice of psychiatry. This measure would make a favourable impression on world medical opinion."
Any doctor willing to be associated with this appeal should send his name, medical qualifications, and present position to the Secretary of the Working Group (Christine Shaw) at this address. Working Group on the Internment of Dissenters in Mental 17 Norland
Square,
London W11
Hospitals,
ALAN WYNN, Chairman