intense inflammatory infiltration throughout the wall of the tube and multiple microabscesses. Postoperatively she received penicillin G and streptomycin parenterally. Her recovery was uneventful. Since tubal ligation is being performed with increasing frequency, one should be aware that inflammatory disease can develop in the tubal segments. S. SEMcHYSHYN, MD Department of obstetrics and gynecology St. Michael's Hospital Toronto, Ont.
A link between Reye's syndrome and aflatoxins? To the editor: We present a brief summary of evidence linking an acute disease of Thai children with aflatoxin poisoning and request autopsy specimens of Canadian children dying from a similar disease, referred to as Reye's syndrome. Reye's syndrome is an acute disease of children from a few months of age to adolescence. Onset of the disease is abrupt, starting with an illness similar to a mild respiratory tract infection. This stage is rapidly followed by disturbed consciousness, fever, vomiting, convulsions, coma and frequently death. Abnormal laboratory findings include hypoglycemia and elevated values of serum transaminases and unesterified fatty acids. Histopathologically the disease is characterized by cerebral edema and fatty degeneration of the viscera, particularly the liver.14 This syndrome has been recognized in Australia, New Zealand, Puerto Rico, the United States, the United Kingdom, South Africa and Czechoslovakia.2'4'5 In Canada an average of 5 to 10 cases are diagnosed each year6 but the actual incidence is likely higher. An examination of the records of The Hospital for Sick Children, Toronto revealed 21 cases in the period 195466.. The cause of this disease remains unknown but suggested factors include: (a) a virus infection; (b) a metabolic defect; (c) exogenous toxins such as medications, household chemicals and pesticides; and (d) an interaction between a virus infection and an intoxication. Possibly the syndrome is an expression of the body's reaction to a number of different insults.2'4 Becroft1 suggested that the aflatoxins, a group of toxic *and carcinogenic mould metabolites,8 may cause Reye's syndrome. This suggestion was based on: (a) pathological indications that the liver lesions were caused by a toxin; (b) the similarity of the lesions to those observed in experimental aflatoxicosis; (c) the high sensitivity of young animals to aflatoxins; and (d) indications from case histories that the disease is likely to result from in-
gestion of a toxin present in food.' A syndrome of encephalopathy and fatty degeneration of the viscera (EFDV), similar to Reye's syndrome, is particularly common in Thailand, where it may affect hundreds of children annually.10'11 The following facts indicate that the aflatoxins may be etiologic agents in this disease. 1. In Thailand many foods contain aflatoxins, and the incidence of EFDV geographically and seasonally parallels the extent of aflatoxin contamination of foods.'0 2. In autopsy specimens (brain, liver, kidney, stool, stomach and intestinal contents, bile and urine) from 23 Thai children who died with EFDV, aflatoxin B1 was detected in one or more specimens from 22 children. The highest concentrations were 93 .g/ kg of liver, 123 .g/kg of stool, 127 .g/kg of stomach and intestinal contents, and 8 .g/ ml of bile; traces were present in brain, kidney and urine. Only small amounts (1 to 4 .g/kg of tissue) were found in some autopsy specimens from 11 of 15 children who had died from unrelated causes.'2 3. The disease induced in Macaque monkeys by oral administration of aflatoxin B1 is clinically and pathologically similar to Reye's syndrome in children.'3 4. Liver extracts of two children who died of Reye's syndrome in New Zealand contained fluorescent materials with retardation factor (Rf) values on thin-layer chromatograms corresponding to those of aflatoxins B1 and G1;' likewise, liver extracts of two of three such children in Czechoslovakia contained a fluorescent compound similar in Rf to aflatoxin B1.14 At the end of January 1975 the health protection branch (HPB) of Health and Welfare Canada received a request from Dr. G. Fortin of Centre Hospitalier Universitaire de Laval to analyse a liver specimen of a child who had died of Reye's syndrome. No aflatoxins were detected in this autopsy specimen, which was taken at least 3 days after the child was admitted to the hospital. However, the HPB should analyse such specimens, particularly when it is known that the child had consumed nuts shortly before falling ill. Nuts that may be contaminated with aflatoxins include peanuts, Brazil nuts, pistachio nuts, almonds, pecans and walnuts.15 Samples of nuts and autopsy specimens should be as large as is practically feasible to facilitate analysis and chemical confirmation. Judging from the Thailand findings, autopsy specimens should preferably include samples of liver, stool, stomach and intestinal contents and bile. They should be collected as soon after death as possible and shipped by air on dry
ice. Small pieces of liver for histological examination should be shipped in 10% formalin or another routine fixative. At the time of shipment the HPB should be notified by telegram or telex and a case history should accompany the samples. Samples and telegrams may be addressed to: Mr. W. Przybylski, Health protection branch, Foods directorate, Tunney's Pasture, Ottawa, Ont. KlA 0L2; telephone (613) 9929959; telex 053-3679. J. HARWIG, PH D W. PRZYBYLSKI C.A. MOODIE, MD
Health protection branch Health and Welfare Canada Ottawa, Ont.
References 1. BEcROFT DM0: Syndrome of encephalopathy and fatty degeneration of viscera in New Zealand children. Br Med J 2: 135, 1966 2. BRADFORD WD. PARKER JC: Reye's syndrome, possible causes and pathogenetic pathways. Clin Pediatr (Phila) 10: 148, 1971 3. Ram
RDK,
MORGAN
G,
BARAL
J:
Ence-
phalopathy and fatty degeneration of the viscera: a disease entity in childhood. Lancet 2: 749, 1963 4. RILEY HD: Reye's syndrome. J Infect Dis 125: 77. 1972 5. GLsc.c TH. LIKASKY WH, LEVITr LP, et al: Reye's syndrome: an epidemiologic approach. Pediatrics 46: 371. 1970 6. WHITRIDGE
7.
8.
9. 10. 11.
ME,
HANDZEL
5:
Reye.s
syn-
drome. Epidemiol Bull 18: 61, 1974 NORMAN MG: Encephalopathy and fatty degeneration of the viscera in childhood. 1. Reviews, of cases at The Hospital for Sick Children, Toronto (1954-1966). Can Med Assoc 1 99: 522, 1968 CAMPBELL TC. STOLOFF L: Implication of mycotoxins for human health. I Agric Food Chem 22: 1006, 1974 BECROFT DM0, WEBsTER DR: Aflatoxins and Reye's disease. Br Med 1 4: 117. 1972 BouRGEois C. OLsoN L, COMER D, et al: Encephalopathy and fatty degeneration of the viscera. Am I Clin Pathol 56: 558, 1971 OLsoN LC, BOURGEOIS CH COTTON RB. Ct al: Encephalopathy and fatty degeneration of the viscera in northeastern Thailand. Clinical syndrome and epidemiology. Pediatrics 47: 707, 1971
12. SHANK RC. BOURGEOIS CH, KESCHAMRAS N,
et al: Aflatoxins and autopsy specimens from Thai children with an acute disease of unknown aetiology. Food Cosmet Toxicol 9: 501. 1971
13. BouRGEOIS CH, SHANK RC, GROSSMAN RA,
et al: Acute aflatoxin Bi toxicity in the macaque and its similarities t. Reye's syndrome. Lab Invest 24: 206,1971
14. DvORACKOVA
I,
BRODSKY
F,
CERMAN
3:
Aflatoxin and encephalitic syndrome With fatty degeneration of viscera. Nuir Rep mt 10: 89. 1974 15. WESSEL JR. STOLOFF L: Regulatory surveillance for aflatoxin and other mycotoxins in feeds, meat, and milk. I Am Vet Med Assoc 163: 1284, 1973
PostgraduatQ Courses SYMPOSIUM LES ULCtRES GASTRODUOD.. NAUX. Universit6 Laval. Les 21.22 novembre 1975. Renseignements: Dr Robert Gourdeau, Facult6 de m6decine, Universlt6 Laval, Ou.bec, 0u6. KiK 7P4 CREATIVE SEXUALITY. Hotel Toronto. Nov. 26 to 28, 1975. SemInar with Dra. Noam and Beryl Cher. nIck. Information: Creative Sexuality, Ste. 400, 73 Richmond St., Toronto. Ont. M5H 2A1
CMA JOURNAL/AUGUST 23, 1975/VOL. 113 281
A link between Reye's syndrome and aflatoxins? To the editor: We present a brief summary of evidence linking an acute disease of Thai children with aflatoxin poisoning and request autopsy specimens of Canadian children dying from a similar disease, referred to as Reye's syndrome. Reye's syndrome is an acute disease of children from a few months of age to adolescence. Onset of the disease is abrupt, starting with an illness similar to a mild respiratory tract infection. This stage is rapidly followed by disturbed consciousness, fever, vomiting, convulsions, coma and frequently death. Abnormal laboratory findings include hypoglycemia and elevated values of serum transaminases and unesterified fatty acids. Histopathologically the disease is characterized by cerebral edema and fatty degeneration of the viscera, particularly the liver.14 This syndrome has been recognized in Australia, New Zealand, Puerto Rico, the United States, the United Kingdom, South Africa and Czechoslovakia.2'4'5 In Canada an average of 5 to 10 cases are diagnosed each year6 but the actual incidence is likely higher. An examination of the records of The Hospital for Sick Children, Toronto revealed 21 cases in the period 195466.. The cause of this disease remains unknown but suggested factors include: (a) a virus infection; (b) a metabolic defect; (c) exogenous toxins such as medications, household chemicals and pesticides; and (d) an interaction between a virus infection and an intoxication. Possibly the syndrome is an expression of the body's reaction to a number of different insults.2'4 Becroft1 suggested that the aflatoxins, a group of toxic *and carcinogenic mould metabolites,8 may cause Reye's syndrome. This suggestion was based on: (a) pathological indications that the liver lesions were caused by a toxin; (b) the similarity of the lesions to those observed in experimental aflatoxicosis; (c) the high sensitivity of young animals to aflatoxins; and (d) indications from case histories that the disease is likely to result from in-
gestion of a toxin present in food.' A syndrome of encephalopathy and fatty degeneration of the viscera (EFDV), similar to Reye's syndrome, is particularly common in Thailand, where it may affect hundreds of children annually.10'11 The following facts indicate that the aflatoxins may be etiologic agents in this disease. 1. In Thailand many foods contain aflatoxins, and the incidence of EFDV geographically and seasonally parallels the extent of aflatoxin contamination of foods.'0 2. In autopsy specimens (brain, liver, kidney, stool, stomach and intestinal contents, bile and urine) from 23 Thai children who died with EFDV, aflatoxin B1 was detected in one or more specimens from 22 children. The highest concentrations were 93 .g/ kg of liver, 123 .g/kg of stool, 127 .g/kg of stomach and intestinal contents, and 8 .g/ ml of bile; traces were present in brain, kidney and urine. Only small amounts (1 to 4 .g/kg of tissue) were found in some autopsy specimens from 11 of 15 children who had died from unrelated causes.'2 3. The disease induced in Macaque monkeys by oral administration of aflatoxin B1 is clinically and pathologically similar to Reye's syndrome in children.'3 4. Liver extracts of two children who died of Reye's syndrome in New Zealand contained fluorescent materials with retardation factor (Rf) values on thin-layer chromatograms corresponding to those of aflatoxins B1 and G1;' likewise, liver extracts of two of three such children in Czechoslovakia contained a fluorescent compound similar in Rf to aflatoxin B1.14 At the end of January 1975 the health protection branch (HPB) of Health and Welfare Canada received a request from Dr. G. Fortin of Centre Hospitalier Universitaire de Laval to analyse a liver specimen of a child who had died of Reye's syndrome. No aflatoxins were detected in this autopsy specimen, which was taken at least 3 days after the child was admitted to the hospital. However, the HPB should analyse such specimens, particularly when it is known that the child had consumed nuts shortly before falling ill. Nuts that may be contaminated with aflatoxins include peanuts, Brazil nuts, pistachio nuts, almonds, pecans and walnuts.15 Samples of nuts and autopsy specimens should be as large as is practically feasible to facilitate analysis and chemical confirmation. Judging from the Thailand findings, autopsy specimens should preferably include samples of liver, stool, stomach and intestinal contents and bile. They should be collected as soon after death as possible and shipped by air on dry
ice. Small pieces of liver for histological examination should be shipped in 10% formalin or another routine fixative. At the time of shipment the HPB should be notified by telegram or telex and a case history should accompany the samples. Samples and telegrams may be addressed to: Mr. W. Przybylski, Health protection branch, Foods directorate, Tunney's Pasture, Ottawa, Ont. KlA 0L2; telephone (613) 9929959; telex 053-3679. J. HARWIG, PH D W. PRZYBYLSKI C.A. MOODIE, MD
Health protection branch Health and Welfare Canada Ottawa, Ont.
References 1. BEcROFT DM0: Syndrome of encephalopathy and fatty degeneration of viscera in New Zealand children. Br Med J 2: 135, 1966 2. BRADFORD WD. PARKER JC: Reye's syndrome, possible causes and pathogenetic pathways. Clin Pediatr (Phila) 10: 148, 1971 3. Ram
RDK,
MORGAN
G,
BARAL
J:
Ence-
phalopathy and fatty degeneration of the viscera: a disease entity in childhood. Lancet 2: 749, 1963 4. RILEY HD: Reye's syndrome. J Infect Dis 125: 77. 1972 5. GLsc.c TH. LIKASKY WH, LEVITr LP, et al: Reye's syndrome: an epidemiologic approach. Pediatrics 46: 371. 1970 6. WHITRIDGE
7.
8.
9. 10. 11.
ME,
HANDZEL
5:
Reye.s
syn-
drome. Epidemiol Bull 18: 61, 1974 NORMAN MG: Encephalopathy and fatty degeneration of the viscera in childhood. 1. Reviews, of cases at The Hospital for Sick Children, Toronto (1954-1966). Can Med Assoc 1 99: 522, 1968 CAMPBELL TC. STOLOFF L: Implication of mycotoxins for human health. I Agric Food Chem 22: 1006, 1974 BECROFT DM0, WEBsTER DR: Aflatoxins and Reye's disease. Br Med 1 4: 117. 1972 BouRGEois C. OLsoN L, COMER D, et al: Encephalopathy and fatty degeneration of the viscera. Am I Clin Pathol 56: 558, 1971 OLsoN LC, BOURGEOIS CH COTTON RB. Ct al: Encephalopathy and fatty degeneration of the viscera in northeastern Thailand. Clinical syndrome and epidemiology. Pediatrics 47: 707, 1971
12. SHANK RC. BOURGEOIS CH, KESCHAMRAS N,
et al: Aflatoxins and autopsy specimens from Thai children with an acute disease of unknown aetiology. Food Cosmet Toxicol 9: 501. 1971
13. BouRGEOIS CH, SHANK RC, GROSSMAN RA,
et al: Acute aflatoxin Bi toxicity in the macaque and its similarities t. Reye's syndrome. Lab Invest 24: 206,1971
14. DvORACKOVA
I,
BRODSKY
F,
CERMAN
3:
Aflatoxin and encephalitic syndrome With fatty degeneration of viscera. Nuir Rep mt 10: 89. 1974 15. WESSEL JR. STOLOFF L: Regulatory surveillance for aflatoxin and other mycotoxins in feeds, meat, and milk. I Am Vet Med Assoc 163: 1284, 1973
PostgraduatQ Courses SYMPOSIUM LES ULCtRES GASTRODUOD.. NAUX. Universit6 Laval. Les 21.22 novembre 1975. Renseignements: Dr Robert Gourdeau, Facult6 de m6decine, Universlt6 Laval, Ou.bec, 0u6. KiK 7P4 CREATIVE SEXUALITY. Hotel Toronto. Nov. 26 to 28, 1975. SemInar with Dra. Noam and Beryl Cher. nIck. Information: Creative Sexuality, Ste. 400, 73 Richmond St., Toronto. Ont. M5H 2A1
CMA JOURNAL/AUGUST 23, 1975/VOL. 113 281
