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Chronic Camphor Ingestion Mimicking Reye's Syndrome
GASTROENTEROLOGY 1983;84:394-8
CASE REPORTS
Chronic Camphor Ingestion Mimicking Reye's Syndrome JORGE F. JIMENEZ, ALLEN L. BROWN, WATSON C. ARNOLD, and WILLIAM J. BYRNE Departments of Pathology, Pharmacy, and Pediatrics, Arkansas Children's Hospital and the University of Arkansas for Medical Sciences, Little Rock, Arkansas
Camphor is a potentially dangerous drug which nevertheless remains popular as a home remedy. Because of its hepatoneurotoxic effects, camphor toxicity may clinically mimic Reye's syndrome. The differentiation between the two requires histologic examination of liver tissue, further emphasizing the need for a liver biopsy to establish the diagnosis of Reye's syndrome. Home remedies are in common use among many segments of society. Although most ingredients are harmless, some may be toxic. One example of a commonly used and easily obtainable toxic substance is camphor. Classified as a class IV chemical, as little as 1 g, taken orally, may prove fatal in children (1,2). The following case is unique in that it illustrates the hepatoneurotoxic effects of this agent, which clinically may mimic Reye's syndrome. Further, it emphasizes the importance of histologic examination of liver tissue in the evaluation of all children suspected of having Reye's syndrome.
Case Report A 6-mo-old black male was seen initially because of a 2-day history of cough, coryza, and fever. A clinical diagnosis of pneumonia was made by his private physician, and ampicillin was prescribed. The following day the infant became lethargic but was arousable. Rales and wheezing were heard diffusely in both lungs. No hepatomegaly was appreciated. Chest roentgenogram showed hyperinflation with diffuse interstitial infiltrates. The diagnosis was changed to bronchiolitis, and supportive therapy was instituted. Six hours later the infant was not arousable, and the liver was palpable 3 cm below the right
Received April 5, 1982. Accepted July 20, 1982. Address requests for reprints to: William J. Byrne, M.D., Department of Pediatrics, Box 54, C6105 OPB, University of Michigan Medical Center, Ann Arbor, Michigan 48109. © 1983 by the American Gastroenterological Association 0016-5085/83/020394-05$03.00
costal margin. Because of the SuspICIOn of Reye's syndrome, he was transferred to our institution. On admission to Arkansas Children's Hospital, the infant was comatose but responsive to deep pain. Diffuse rales, wheezing, and hepatomegaly were again appreciated. Reflexes were hyperactive and doll's eyes were present. Initial laboratory data revealed a hemoglobin of 13.5 g%; white blood cells, 20,000/mm 3 with 52% polys, 2% bands, 17% monos, 28% lymphocytes, and adequate platelets. Serum electrolytes and creatinine were normal. Glucose was 40 mg/dl (normal 65-104). Liver function results are presented in Table 1. Supportive therapy for Reye's syndrome, which consisted of hypertonic dextrose and intracranial pressure monitoring with controi via intravenous mannitol and regulated respiratory alkalosis, was begun (3). Six hours after admission, an electroencephalogram (EEG) and percutaneous liver biopsy were performed. The EEG showed diffuse slowing with no seizure activity. The hepatic light microscopy (Figure 1), ultrastructural pathology (Figure 2), and histochemistry were not characteristic for Reye's syndrome. The family was questioned further about possible exposure to toxins. Although initially evasive, the mother admitted to having given the child, on a chronic basis, a home remedy containing camphor and alcohol. Although the infant's liver function studies improved (Table 1), his neurologic status continued to deteriorate. By the fifth hospital day, deep tendon, corneal, and ocularvestibulo-cephalic reflexes were absent. A repeat EEG showed an absence of electrical activity. The patient suffered a cardiac arrest later in the day and died. On postmortem examination, findings were limited to the brain and liver. The brain weighed 1250 g (normal mean weight 660 g), and on gross inspection was diffusely and symmetrically swollen with prominent flattening of the gyri and narrowing of the sulci. The leptomeninges appeared congested. Microscopically diffuse edema with patchy individual neuronal degeneration and frank necrosis, predominently in the sections from the Sommer's sector of the hippocampus and from the frontal cortex, were present (Figure 3). There was no evidence of any inflammatory reaction. The myelin fibers were histologically unremarkable by special histochemistry. Grossly, the
February 1983
CHRONIC CAMPHOR INGESTION
Table 1. Liver Function Tests
SGOT
Admission
Day 2
Day 3
Day 4
1050
1020
212
788
780
468
1120
336
(16-371 U/L)Q
SGPT (16-361 U/L)
Ammonia
84
28
(36-57 mmol/L)
Total bilirubin
1.04
(0.1 mg/dl)
Prothrombin time (10.7-13.9 s) a
20.5
14
Values in parentheses are normal values.
liver was friable. exhibited a diffuse pale yellow discoloration, and weighed 354 g (normal mean weight 200 g). Histologically there was diffuse fatty metamorphosis with no cellular necrosis, inflammation, or bile stasis.
Discussion Several features in the clinical presentation of this case are consistent with the diagnosis of Reye's syndrome including the presence of a prodromal viral illness, the rapid neurologic deterioration, and
395
hepatomegaly. Distinctly unusual was the absence of a history of vomiting. Although vomiting is generally considered a consistent feature of Reye's syndrome, cases proven by liver biopsy have been reported in which vomiting was absent (5,6). Even the young age of the patient is not surprising because up to onethird of all cases occur in children <12 mo of age (7). Further, unlike the children >1 yr of age, in which the disease favors whites over blacks by a ratio of 9: 1, in children < 12 mo of age there is no difference in the distribution between those races (8). The initial biochemical results, including the markedly elevated serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and ammonia, prolonged prothrombin time, and low blood glucose were likewise consistent with Reye's syndrome. However, the necessary histologic and histochemical criteria on the liver biopsy specimen were not present (9,10). Histologically, the fat deposits within the hepatocytes were irregular in size and distribution rather than microvesicular and diffusely uniform. The majority of the hepatocyte nuclei were located peripherally and not centrally. Succinic dehydrogenase and cytochrome oxidase activity (11) were strong with excellent localization when compared with
Figure 1. Liver biopsy specimen exhibiting diffuse, irregular fatty metamorphosis, and mild proliferation of Kupffer cells. Notice the large irregular fat droplets (arrows) in the cytoplasm of the hepatocytes compressing the nuclei to the periphery. H & E, x 400.
396
JIMENEZ ET AL.
GASTROENTEROLOGY Vol. 84 , No. 2
Figure 2. Electron micrograph from injured hepatocytes. The nucleus (N) is uniformly round with rarification of the nucleoplasm. Fat droplets (F) of different sizes occupy most of the cytoplasm. The number of peroxisomes (P) appear increased. The endoplasmic reticulum (ER) and glycogen (*) granules appear prominent (x 5000). The mitochondria are minimally s w ollen with preserved cri stae and membranes (inset, x 2 5,000).
control specimens from children with and without hepatocyte lipid accumulation. In florid Reye 's syndrome, such activity is usually mildly or severely depressed (10). Electron microscopic findings did not demonstrate the pleomorphic greatly swollen mitochondria with absent intramitochondrial dense bodies , expansion of the matrix space, and separation of the mitochondrial matrix substance into fine strands, usually seen in fatal cases of Reye's syndrome (9). Instead, in the biopsy specimen from our patient (Figure 2), the mitochondria were minimally swollen with well-preserved cristae and dense bodies. Another important organelle change seen in early biopsy samples from patients with Reye's syndrome is the absence of lipoprotein particles in the Golgi apparatus at a time when hepatic triglyceride is increasing (9). In our patient, the Golgi apparatus was filled with very low density lipoproteinlike particles. We agree with Gall et al. (12) that a liver biopsy is necessary to confirm the diagnosis of Reye's syndrome. When morphologic criteria are not met, other causes, including acute or chronic exposure to toxins, or both, must be sought. Most cases of acute camphor poisoning are secondary to accidental ingestion when it is mistaken
for another proprietary medication (13) . Intoxication has also been reported secondary to vapor inhalation (14), skin absorption (14,15), intranasal instillation (16), and transplacental transfer (17 ,18). Our patient received camphor daily, beginning at the age of 1 mo, in dropperful quantities, as part of a remedy for fretfulness and cold. The remedy was prepared from a l-oz block of camphor and 8 oz of whiskey diluted with water to a final volume of 16 oz. Over a 5-mo period the infant had been given ~ 28 oz of the solution, including 4 oz during the 3 days before hospitalization. Quantitative analysis of the solution showed it to have an alcohol content of 33.3% and a camphor content of 29.2 mg/m!. Therefore, the total dosage of camphor given was ~24.5 g or 3 g/kg. This is more than six times the amount (0.05-0.5 g/kg) known to be lethal following acute ingestion (1). Camphor is detoxified in the liver by hydroxylation and then conjugation with glucouronic acid with excretion of the inactivated compound in the urine (19). After acute ingestion, transient elevation of the SGOT and SGPT have been reported (16,17), and fatty changes in the liver similar to those found in our patient have been described (18). It seems doubtful that the alcohol content of the mixture
CHRONIC CAMPHOR INGESTION
February 1983
39 7
Figure 3. Section of the frontal cortex taken at postmortem. The brain exhibits diffuse edema manifested by an irregular empty halo around individual neurons and vessel (large arrow). Multiple neurons show vacuolar degeneration, eosinophilic cytoplasm, picnosis, and karyorrhexis (small arrows) (H & E, x 400) . The myelin structure was unremarkable by special histochemistry.
contributed directly to the liver injury seen in this infant. Although steatosis was present histologically, other changes suggestive of alcoholic hepatitis such as cellular necrosis, inflammation, bile stasis, or Mallory bodies were not. Even at the subcellular level, typical changes such as enlargement of the mitochondria and abnormal cristae were absent (20). Whether alcohol might potentiate the hepatotoxic effects of camphor is unknown. Although hepatocellular damage may be extensive, death due to camphor poisoning is more likely the result of extensive degenerative and necrotic changes in the central nervous system limited primarily to neurons. Pathologic findings in the central nervous system similar to those found in our patient have been reported (2) and experimentally produced in animals. Barbiturates may be of therapeutic benefit and are indicated in cases of known intoxication. This report further illustrates the danger of camphor and camphor-containing products. The American Academy of Pediatrics Committee on drugs concluded that camphor has no therapeutic role in medicine (8). However, it continues to be marketed. Physicians and other health care professionals
should warn parents of its potential danger. Because camphor is hepatotoxic and its use is popular as a home remedy, acute or chronic intoxication, or both, with this agent should be considered in the differential diagnosis of acute hepatic encephalopathy.
References 1. Gleason MN, Gosselin RE, Hodge NC, Smith RP. Clinical
2. 3. 4. 5.
6. 7. 8.
toxicology of commercial products . 4th ed. Baltimore: Williams and Wilkins, 1976:77-9 . Smith AG, Margolis G. Camphor poisoning. Am J Pathol 1954;30:857-68. DeVivo DC, Keating JP, Haymond NW. Reye's syndrome: results of intensive supportive care. JPediatr 1975;87:857-80. Huttenlocher PR. Reye's syndrome: relation of outcome to therapy. JPediatr 1972;80:845-50. Samaha FJ, Blaw E, Berardinelli J1. Reye's syndrome: clinical diagnosis and treatment with peritoneal dialysis. Pediatrics 1974;53:3 36-40. van CailIe M, Morin CL, Roy CC, et al. Reye's syndrome: relapses and neurologic sequelae. Pediatrics 1977;59:244-9. AlagilIe D, Odievu M. Liver and biliary tract disease in children . New York: John Wiley and Sons , Inc., 1979. Suilivan-Bolyai JZ, Nelson DB, Morens DM, et al. Reye syndrome in children less than 1 year old: some epidemiologic observations. Pediatrics 1980;65:627-9.
398
JIMENEZ ET AL.
9. Partin JC, Schubert WK, Partin JS. Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N Engl J Med 1971;285:1339-43. 10. Hove KE, McAdams AJ, Partin JC, et al. The hepatic lesion in Reye's syndrome. Gastroenterology 1975;69:585-697. 11. Humason GL. Animal tissue techniques. San Francisco: W.H. Freeman and Co., 1972. 12. Gall DG, Cuty E, McClung HJ, et al. Acute liver disease and encephalopathy mimicking Reye's syndrome. J Pediatr 1975;87:869-74. 13. Anon A. Camphor: who needs it? Pediatrics 1978;62:404-6. 14. Skoglund RR, Ware L, Schkanberger JE. Prolonged seizures due to contact and inhalation exposure to camphor. Clin Pediatr 1977;16:901-2.
GASTROENTEROLOGY Vol. 84, No.2
15. Summers GD. Case of camphor poisoning. Br Med J 1947; 2:1009-10. 16. Seite M, Leon JL. Camphor poisoning following ingestion of nose drops. JAMA 1954;155:1059-60. 17. Riggs J, Hamilton R, Homel S, et a!. Camphorated oil intoxication in pregnancy. Obstet GynecoI1965;25:255-9. 18. Weiss J, Catalano P. Camphorated oil intoxication during pregnancy. Pediatrics 1973;52:713-6. 19. Robertson JS, Mussain M. Metabolism of camphors and related compounds. J Biochem 1969;113:57-64. 20. Lieber CS. Pathogenesis and early diagnosis of alcoholic liver injury. N Engl J Med 1978;298:888-93.
CASE REPORTS
Chronic Camphor Ingestion Mimicking Reye's Syndrome JORGE F. JIMENEZ, ALLEN L. BROWN, WATSON C. ARNOLD, and WILLIAM J. BYRNE Departments of Pathology, Pharmacy, and Pediatrics, Arkansas Children's Hospital and the University of Arkansas for Medical Sciences, Little Rock, Arkansas
Camphor is a potentially dangerous drug which nevertheless remains popular as a home remedy. Because of its hepatoneurotoxic effects, camphor toxicity may clinically mimic Reye's syndrome. The differentiation between the two requires histologic examination of liver tissue, further emphasizing the need for a liver biopsy to establish the diagnosis of Reye's syndrome. Home remedies are in common use among many segments of society. Although most ingredients are harmless, some may be toxic. One example of a commonly used and easily obtainable toxic substance is camphor. Classified as a class IV chemical, as little as 1 g, taken orally, may prove fatal in children (1,2). The following case is unique in that it illustrates the hepatoneurotoxic effects of this agent, which clinically may mimic Reye's syndrome. Further, it emphasizes the importance of histologic examination of liver tissue in the evaluation of all children suspected of having Reye's syndrome.
Case Report A 6-mo-old black male was seen initially because of a 2-day history of cough, coryza, and fever. A clinical diagnosis of pneumonia was made by his private physician, and ampicillin was prescribed. The following day the infant became lethargic but was arousable. Rales and wheezing were heard diffusely in both lungs. No hepatomegaly was appreciated. Chest roentgenogram showed hyperinflation with diffuse interstitial infiltrates. The diagnosis was changed to bronchiolitis, and supportive therapy was instituted. Six hours later the infant was not arousable, and the liver was palpable 3 cm below the right
Received April 5, 1982. Accepted July 20, 1982. Address requests for reprints to: William J. Byrne, M.D., Department of Pediatrics, Box 54, C6105 OPB, University of Michigan Medical Center, Ann Arbor, Michigan 48109. © 1983 by the American Gastroenterological Association 0016-5085/83/020394-05$03.00
costal margin. Because of the SuspICIOn of Reye's syndrome, he was transferred to our institution. On admission to Arkansas Children's Hospital, the infant was comatose but responsive to deep pain. Diffuse rales, wheezing, and hepatomegaly were again appreciated. Reflexes were hyperactive and doll's eyes were present. Initial laboratory data revealed a hemoglobin of 13.5 g%; white blood cells, 20,000/mm 3 with 52% polys, 2% bands, 17% monos, 28% lymphocytes, and adequate platelets. Serum electrolytes and creatinine were normal. Glucose was 40 mg/dl (normal 65-104). Liver function results are presented in Table 1. Supportive therapy for Reye's syndrome, which consisted of hypertonic dextrose and intracranial pressure monitoring with controi via intravenous mannitol and regulated respiratory alkalosis, was begun (3). Six hours after admission, an electroencephalogram (EEG) and percutaneous liver biopsy were performed. The EEG showed diffuse slowing with no seizure activity. The hepatic light microscopy (Figure 1), ultrastructural pathology (Figure 2), and histochemistry were not characteristic for Reye's syndrome. The family was questioned further about possible exposure to toxins. Although initially evasive, the mother admitted to having given the child, on a chronic basis, a home remedy containing camphor and alcohol. Although the infant's liver function studies improved (Table 1), his neurologic status continued to deteriorate. By the fifth hospital day, deep tendon, corneal, and ocularvestibulo-cephalic reflexes were absent. A repeat EEG showed an absence of electrical activity. The patient suffered a cardiac arrest later in the day and died. On postmortem examination, findings were limited to the brain and liver. The brain weighed 1250 g (normal mean weight 660 g), and on gross inspection was diffusely and symmetrically swollen with prominent flattening of the gyri and narrowing of the sulci. The leptomeninges appeared congested. Microscopically diffuse edema with patchy individual neuronal degeneration and frank necrosis, predominently in the sections from the Sommer's sector of the hippocampus and from the frontal cortex, were present (Figure 3). There was no evidence of any inflammatory reaction. The myelin fibers were histologically unremarkable by special histochemistry. Grossly, the
February 1983
CHRONIC CAMPHOR INGESTION
Table 1. Liver Function Tests
SGOT
Admission
Day 2
Day 3
Day 4
1050
1020
212
788
780
468
1120
336
(16-371 U/L)Q
SGPT (16-361 U/L)
Ammonia
84
28
(36-57 mmol/L)
Total bilirubin
1.04
(0.1 mg/dl)
Prothrombin time (10.7-13.9 s) a
20.5
14
Values in parentheses are normal values.
liver was friable. exhibited a diffuse pale yellow discoloration, and weighed 354 g (normal mean weight 200 g). Histologically there was diffuse fatty metamorphosis with no cellular necrosis, inflammation, or bile stasis.
Discussion Several features in the clinical presentation of this case are consistent with the diagnosis of Reye's syndrome including the presence of a prodromal viral illness, the rapid neurologic deterioration, and
395
hepatomegaly. Distinctly unusual was the absence of a history of vomiting. Although vomiting is generally considered a consistent feature of Reye's syndrome, cases proven by liver biopsy have been reported in which vomiting was absent (5,6). Even the young age of the patient is not surprising because up to onethird of all cases occur in children <12 mo of age (7). Further, unlike the children >1 yr of age, in which the disease favors whites over blacks by a ratio of 9: 1, in children < 12 mo of age there is no difference in the distribution between those races (8). The initial biochemical results, including the markedly elevated serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and ammonia, prolonged prothrombin time, and low blood glucose were likewise consistent with Reye's syndrome. However, the necessary histologic and histochemical criteria on the liver biopsy specimen were not present (9,10). Histologically, the fat deposits within the hepatocytes were irregular in size and distribution rather than microvesicular and diffusely uniform. The majority of the hepatocyte nuclei were located peripherally and not centrally. Succinic dehydrogenase and cytochrome oxidase activity (11) were strong with excellent localization when compared with
Figure 1. Liver biopsy specimen exhibiting diffuse, irregular fatty metamorphosis, and mild proliferation of Kupffer cells. Notice the large irregular fat droplets (arrows) in the cytoplasm of the hepatocytes compressing the nuclei to the periphery. H & E, x 400.
396
JIMENEZ ET AL.
GASTROENTEROLOGY Vol. 84 , No. 2
Figure 2. Electron micrograph from injured hepatocytes. The nucleus (N) is uniformly round with rarification of the nucleoplasm. Fat droplets (F) of different sizes occupy most of the cytoplasm. The number of peroxisomes (P) appear increased. The endoplasmic reticulum (ER) and glycogen (*) granules appear prominent (x 5000). The mitochondria are minimally s w ollen with preserved cri stae and membranes (inset, x 2 5,000).
control specimens from children with and without hepatocyte lipid accumulation. In florid Reye 's syndrome, such activity is usually mildly or severely depressed (10). Electron microscopic findings did not demonstrate the pleomorphic greatly swollen mitochondria with absent intramitochondrial dense bodies , expansion of the matrix space, and separation of the mitochondrial matrix substance into fine strands, usually seen in fatal cases of Reye's syndrome (9). Instead, in the biopsy specimen from our patient (Figure 2), the mitochondria were minimally swollen with well-preserved cristae and dense bodies. Another important organelle change seen in early biopsy samples from patients with Reye's syndrome is the absence of lipoprotein particles in the Golgi apparatus at a time when hepatic triglyceride is increasing (9). In our patient, the Golgi apparatus was filled with very low density lipoproteinlike particles. We agree with Gall et al. (12) that a liver biopsy is necessary to confirm the diagnosis of Reye's syndrome. When morphologic criteria are not met, other causes, including acute or chronic exposure to toxins, or both, must be sought. Most cases of acute camphor poisoning are secondary to accidental ingestion when it is mistaken
for another proprietary medication (13) . Intoxication has also been reported secondary to vapor inhalation (14), skin absorption (14,15), intranasal instillation (16), and transplacental transfer (17 ,18). Our patient received camphor daily, beginning at the age of 1 mo, in dropperful quantities, as part of a remedy for fretfulness and cold. The remedy was prepared from a l-oz block of camphor and 8 oz of whiskey diluted with water to a final volume of 16 oz. Over a 5-mo period the infant had been given ~ 28 oz of the solution, including 4 oz during the 3 days before hospitalization. Quantitative analysis of the solution showed it to have an alcohol content of 33.3% and a camphor content of 29.2 mg/m!. Therefore, the total dosage of camphor given was ~24.5 g or 3 g/kg. This is more than six times the amount (0.05-0.5 g/kg) known to be lethal following acute ingestion (1). Camphor is detoxified in the liver by hydroxylation and then conjugation with glucouronic acid with excretion of the inactivated compound in the urine (19). After acute ingestion, transient elevation of the SGOT and SGPT have been reported (16,17), and fatty changes in the liver similar to those found in our patient have been described (18). It seems doubtful that the alcohol content of the mixture
CHRONIC CAMPHOR INGESTION
February 1983
39 7
Figure 3. Section of the frontal cortex taken at postmortem. The brain exhibits diffuse edema manifested by an irregular empty halo around individual neurons and vessel (large arrow). Multiple neurons show vacuolar degeneration, eosinophilic cytoplasm, picnosis, and karyorrhexis (small arrows) (H & E, x 400) . The myelin structure was unremarkable by special histochemistry.
contributed directly to the liver injury seen in this infant. Although steatosis was present histologically, other changes suggestive of alcoholic hepatitis such as cellular necrosis, inflammation, bile stasis, or Mallory bodies were not. Even at the subcellular level, typical changes such as enlargement of the mitochondria and abnormal cristae were absent (20). Whether alcohol might potentiate the hepatotoxic effects of camphor is unknown. Although hepatocellular damage may be extensive, death due to camphor poisoning is more likely the result of extensive degenerative and necrotic changes in the central nervous system limited primarily to neurons. Pathologic findings in the central nervous system similar to those found in our patient have been reported (2) and experimentally produced in animals. Barbiturates may be of therapeutic benefit and are indicated in cases of known intoxication. This report further illustrates the danger of camphor and camphor-containing products. The American Academy of Pediatrics Committee on drugs concluded that camphor has no therapeutic role in medicine (8). However, it continues to be marketed. Physicians and other health care professionals
should warn parents of its potential danger. Because camphor is hepatotoxic and its use is popular as a home remedy, acute or chronic intoxication, or both, with this agent should be considered in the differential diagnosis of acute hepatic encephalopathy.
References 1. Gleason MN, Gosselin RE, Hodge NC, Smith RP. Clinical
2. 3. 4. 5.
6. 7. 8.
toxicology of commercial products . 4th ed. Baltimore: Williams and Wilkins, 1976:77-9 . Smith AG, Margolis G. Camphor poisoning. Am J Pathol 1954;30:857-68. DeVivo DC, Keating JP, Haymond NW. Reye's syndrome: results of intensive supportive care. JPediatr 1975;87:857-80. Huttenlocher PR. Reye's syndrome: relation of outcome to therapy. JPediatr 1972;80:845-50. Samaha FJ, Blaw E, Berardinelli J1. Reye's syndrome: clinical diagnosis and treatment with peritoneal dialysis. Pediatrics 1974;53:3 36-40. van CailIe M, Morin CL, Roy CC, et al. Reye's syndrome: relapses and neurologic sequelae. Pediatrics 1977;59:244-9. AlagilIe D, Odievu M. Liver and biliary tract disease in children . New York: John Wiley and Sons , Inc., 1979. Suilivan-Bolyai JZ, Nelson DB, Morens DM, et al. Reye syndrome in children less than 1 year old: some epidemiologic observations. Pediatrics 1980;65:627-9.
398
JIMENEZ ET AL.
9. Partin JC, Schubert WK, Partin JS. Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N Engl J Med 1971;285:1339-43. 10. Hove KE, McAdams AJ, Partin JC, et al. The hepatic lesion in Reye's syndrome. Gastroenterology 1975;69:585-697. 11. Humason GL. Animal tissue techniques. San Francisco: W.H. Freeman and Co., 1972. 12. Gall DG, Cuty E, McClung HJ, et al. Acute liver disease and encephalopathy mimicking Reye's syndrome. J Pediatr 1975;87:869-74. 13. Anon A. Camphor: who needs it? Pediatrics 1978;62:404-6. 14. Skoglund RR, Ware L, Schkanberger JE. Prolonged seizures due to contact and inhalation exposure to camphor. Clin Pediatr 1977;16:901-2.
GASTROENTEROLOGY Vol. 84, No.2
15. Summers GD. Case of camphor poisoning. Br Med J 1947; 2:1009-10. 16. Seite M, Leon JL. Camphor poisoning following ingestion of nose drops. JAMA 1954;155:1059-60. 17. Riggs J, Hamilton R, Homel S, et a!. Camphorated oil intoxication in pregnancy. Obstet GynecoI1965;25:255-9. 18. Weiss J, Catalano P. Camphorated oil intoxication during pregnancy. Pediatrics 1973;52:713-6. 19. Robertson JS, Mussain M. Metabolism of camphors and related compounds. J Biochem 1969;113:57-64. 20. Lieber CS. Pathogenesis and early diagnosis of alcoholic liver injury. N Engl J Med 1978;298:888-93.