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EFFECT OF ANTICONVULSANT DRUGS ON INSECTICIDE RESIDUES
520 INTERMITTENT COMPLETE HEART-BLOCK SIR,-In patients with complete heart-block causing Stokes-Adams attacks the diagnosis is easy if the characteristic clinical and electrocardiographic features are present between the attacks. Even if the complete heart-block is intermittent the electrocardiogram between such episodes almost always shows some disorder of conduction such as a prolonged P-R interval or bundle-branch block. Harris et al.,! in 19 patients with intermittent complete heart-block, noted no exception to this rule but later found 3 such exceptions.2 Johanson3 reviewed 35 cases of Stokes-Adams disease, of whom 19 had intermittent heart-block, some with prolongation of the Q-T interval between the attacks. Cookson’s 3 cases4 of paroxysmal ventricular standstill were said to have normal electrocardiograms between the attacks, but in fact one showed right-bundle-branch block (often considered non-pathological) and one showed a P-R interval of 0-3 seconds. Likewise, a minor abnormality of conductionprolongation of the QRS to 0-16 seconds-was noted in the report by Schwartz and Hauswirth.6 Out of over 1700 patients with organic heart-disease seen in the cardiac clinic of Mulago Hospital since 1963, 11 cases
in 1943 (and quoted by Renpenning et al.?). Although sex-linkage was not proved, there is insufficient
published
evidence to assert that the disease was different from that described by Renpenning and his colleagues nineteen years later. It is also possible that the families of Allan et al.and Losowsky9 are clinical variants of the same condition. It would be wiser to use descriptive language for the time
being. St. Lawrence’s
Hospital, Caterham, Surrey.
B. W. RICHARDS.
EFFECT OF ANTICONVULSANT DRUGS ON INSECTICIDE RESIDUES
SiR,—Last of pesticide
year, Davies et al.1o reported that serum levels reduced in patients taking phenytoin
were
and phenobarbitone (phenobarbital). They indicated that these drugs might offer a means of lowering body pesticide levels. In support of this, we wish to report the case of a farmer with epilepsy who had been treated with phenobarbitone for 20 years and with a combination of phenobarbitone (21 mg. five times daily) and phenytoin (90 mg. four times daily) for the past 4 years. We suspect that this case is unique, since the farmer comes from an area where pesticide usage has been heavy throughout the period of his treatment. The pesticide levels in his serum were compared with those in 391 farmers from the same area
(’Dilantin’)
(see accompanying table). All values reported are for serum extracted by the method of Dale et al.ll The Microtek Model MT-220 gas chromatograph was used for identifying and quantitating the pestiElectrocardiograms illustrating transient heart-block
of complete heart-block have been recorded. Only 1 had unequivocal Stokes-Adams attacks, the others presenting with congestive heart-failure, giddiness, or non-cardiac symptoms. The accompanying electrocardiograms show that in one of our patients the heart-block was transient. This 50-year-old woman gave a 2-year history of giddiness and palpitation, but denied ever having lost consciousness. Her previous medical history was unremarkable. On examination her pulse-rate was 32 per minute and bloodpressure 160/180 nun. Hg. Occasional cannon waves were seen in the jugular venous pulse. The left ventricle felt hypertrophied. The first heart-sound varied in intensity, and an atrial sound and soft apical systolic murmur were heard. The rest of the clinical examination and chest X-ray were normal. She was treated with ephedrine, and at her second visit to the clinic 13 weeks later she felt much better, and had no clinical or electrocardiographic evidence of heart-block despite stopping treatment one week previously. Furthermore, there was no electrocardiographic evidence of impaired conduction. Department of Medicine, R. F. GUNSTONE Mulago Hospital, K. SOMERS Kampala, Uganda, A. I. PATEL. East Africa.
"RENPENNING" SYNDROME
SiR.—It does not seem justified to give the name " Renpenning syndrome " to sex-linked mental deficiency. There is a well-known article, entitled A Pedigree of Mental Defect showing Sex-linkage, by Purdon Martin and Julia Bell 6 Harris, A., Bluestone, R., Busby, E., Davies, G., Leatham, A., Siddons, H., Sowton, E. Br. Heart J. 1965, 27, 469. 2. Harris, A., Davies, M., Redwood, D., Leatham, A., Siddons, H. ibid. 1969, 31, 206. 3. Johanson, B. W. Am. J. Cardiol. 1961, 8, 76. 4. Cookson, H. Br. Heart J. 1952, 14, 350. 5. Schwartz, S. P., Hauswirth, L. Am. J. med. Sci. 1934, 187, 478. 6. Purdon Martin, J., Bell, J. J. Neurol. 1943, 6, 154. 1.
PESTICIDE LEVELS IN THE SERUM OF AN EPILEPTIC FARMER TREATED WITH PHENYTOIN AND PHENOBARBITONE AND EXPOSED CONTROLS
FROM THE SAME AREA
-_
-_
-_
_
-
_
-
p. p.b. = parts per loe--___ p,p’-D.D.T. 1,1,1-trichloro-2,2-bis(para-chlorophenyl) ethane p,p’ -D.D,E. 1,1-dichloro-2,2-bis(para-chlorophenyl) ethane &bgr;-B.H.C. =&bgr;-isomer of 1,2,3,4,5,6-hexachlorocyclohexane =
=
cides, using SE-30/QF-1 and OV-17/QF-1 columns 195°C and a tritium-type electron-capture detector
at at
205°C. The table shows that the serum-chlorinated-hydrocarbon levels in the treated epileptic farmer are only a fraction of those of the untreated farmers. Other investigators have demonstrated the effect of phenobarbitone on pesticide levels. Menzer and Best 12 showed a pronounced effect of sodium phenobarbitone on 7.
Renpenning, H., Gerrard, J. W., Zaleski, W. A., Tabata, T. Can. med. Ass. J. 1962, 87, 954. 8. Allan, W., Herndon, C. N., Dudley, F. C. Am. J. ment. Defic. 1944, 48, 325. 9. Losowsky, M. S. J. ment. Defic. Res. 1961, 5, 60. 10. Davies, J. E., Edmundson, W. F., Carter, C. H., Barquet, A. Lancet, 1969, ii, 7. 11. Dale, W. E., Curley, A., Cueto, C. Life Sci, 1966, 5, 47. 12. Menzer, R. E., Best, N. H. Toxic appl. Pharmac. 1968, 13, 37.
521 ’
,
Dimethoate ’, Phosphamidonand Bidrin ’metabolism in mice. Ikeda et all reported that phenobarbitone stimulated warfarin metabolism in the rat as shown by a decrease in the plasma-warfarin level. Alary et al.’4 showed a decrease
dicophane (D.D.T.) level in milk from dairy cows treated with phenobarbitone. This was thought to be due to in the
increased metabolic breakdown of D.D.T., since there was a substantial increase in urinary D.D.A. Cueto and Hayes 15 also showed a decrease in dieldrin storage in the fat of rats treated with phenobarbitone. There are two possible interpretations of these data. The first is that certain microsomal enzymes are induced by the drugs, and that these enzymes are involved in the breakdown of the pesticides. Davies et a1.1O support this hypothesis. The second is that the pesticides are bound by serumproteins, and are consequently relatively inert.’sThe action of the drugs on the pesticides depends on the competition of both for the same binding sites on the proteins. The more tightly bound drugs would displace the pesticides from the proteins, which would render them liable to catabolism and excretion. Our interpretation is supported by pharmacodynamic considerations, since the action of a number of drugs depends on their ability to become bound to serumproteins and thus release other substances. 17-20 Department of Pharmacology, Louisiana State Medical Center, New Orleans, Louisiana 70119.
WILHELM P. SCHOOR.
PHENOBARBITONE IN POSTHEPATITIC
UNCONTUGATED HYPERBILIRUBINÆMIA SIR,-We were interested in the report by Dr. Black and Professor Sherlock on the treatment of Gilbert’s syndrome with phenobarbitone.21 We have lately used phenobarbitone in a 21-year-old man with posthepatitic chronic unconjugated hyperbilirubinxmia .22 This patient had had a welldocumented acute hepatitis in June, 1969, and in the succeeding 8 months his plasma-unconjugated-bilirubin levels remained between 3 and 5 mg. per 100 ml.; he had no symptoms, and there was no other evidence of hepatic insufficiency. A liver-biopsy specimen showed only mild cicatrisation and quiescent inflammatory infiltrate. In March, 1970, he was started on 90 mg. phenobarbitone daily. The bilirubin level fell within a week to 0-5-0-8 mg. per 100 ml. The correction of jaundice removed the patient’s anxiety, and sedation was not excessive. J. C. DE OYA Department of Internal Medicine A. DEL RÍO University of M. NOYA Santiago de Compostela, A. VILLANUEVA. Spain.
PORTABLE HEPARIN INJECTOR SIR,-Describing his ingenious device for continuous intravenous infusion of heparin (Aug. 8, p. 313), Dr. Handley states that the dose of heparin (he recommends 20,000 units) should be diluted in 5% dextrose solution. 13.
14. 15. 16. 17. 18. 19. 20. 21. 22.
Ikeda, M., Conney, A. H., Burns, J. J. J. Pharmac. exp. Ther. 1968, 162, 338. Alary, J. G., Brodeur, J., Cote, M. G., Panisset, J. C., Lamothe, P., Guay, P. Rev. can. Biol. 1968, 27, 269. Cueto, C., Hayes, W. J. Indust. Med. Surg. 1967, p. 546. Schoor, W. P. Unpublished. Sellers, E. M., Koch-Weser, J. New Engl. J. Med. 1969, 281, 1141. Meyer, M. C., Guttman, D. E. J. pharm. Sci. 1968, 57, 895. Dollery, C. T., Emslie-Smith, D., Muggleton, D. F. Br. J. Pharmac. 1961, 17, 488. Symposium on Clinical Effects of Interaction between Drugs. Proc. R. Soc. Med. 1965, 58, 943. Black, M., Sherlock, S. Lancet, 1970, i, 1359. de Oya, J. C., del Rio, A., Noya, M., Villanueva, A. Communication to Ninth Congress of Sociedad Española de Medicina Interna, Santiago de Compostela, June, 1970.
Perhaps he is not aware that the stability of heparin is greatly reduced at pH values below 6-0.1 5% dextrose solution has a pH of 46, and is therefore unsuitable. (We have tested someother solutions for intravenous infusion, and found the following pH values: 0-9% saline, 6-3; Ringer lactate solution, 57, Hartmann’s solution, 6-2; Rheomacrodex ’ in 5 % glucose, 4 1; and rheomacrodex in 0-9% saline, 4-9.) We have found heparin therapy very difficult to control using 5% dextrose as the diluent, and we recommend either physiological saline (0-9%) or Hartmann’s solution. Department of Surgery, Royal College of Surgeons in Ireland and St. Laurence’s Hospital, Dublin.
JOHN O’RIORDAN WILLIAM MACGOWAN.
&bgr;-HYDROXYISOVALERIC ACIDURIA AND &bgr;-METHYLCROTONYLGLYCINURIA: A NEW INBORN ERROR OF METABOLISM SIR,-We have found a new inborn error of metabolism in the leucine-degradation pathway, different from maplesyrup-urine disease and isovaleric acidxmia. The patient was a 41/2-month-old girl whose mother and father’s mother were first cousins. Two older siblings, both boys, are healthy. Pregnancy and delivery were normal as were the child’s birthweight and length. Right from the second week there were feeding difficulties. Gradually the signs of retarded motor development, muscular hyptonia, and muscular atrophy appeared. Growth was normal, but weight gain was rather slow. At that time the deep tendon reflexes could not be elicited, and fibrillation of the tongue was seen. Mental development, sensation, and sphincter function were normal. There were no signs of other diseases, and no acidotic episodes. The clinical picture resembled that of an infantile spinal muscular atrophy (Werdnig-Hoffmann’s disease). In addition, however, her urine had an unpleasant smell like that of a cat’s urine. She tended to sweat rather profusely, but her body and expired air did not smell. Chromatography of the aminoacids showed normal patterns in both serum and urine. The patient had raised lactic-acid-dehydrogenase levels, and excretion of creatine was increased. In the child’s urine large amounts of two abnormal metabolites were found. After acidification of the urine, extraction, and methylation, analysis by gas-liquid chromatography on columns containing butanediol succinate as stationary phase showed one compound with retention volume 1-47 relative to that of heptanoic acid methyl ester, and another compound with retention volume 2-45 relative to that of pentadecanoic acid methyl ester. Mass spectrometric analyses of the urinary metabolites revealed spectra compatible with p-hydroxy-isovaleric acid and (3-methylcrotonylglycine (&bgr;-M.C.G.). The nature of the substances was confirmed by gas-liquid chromatography and massspectrometry of synthetic compounds of the same composition. The smell of these synthesised compounds is, however, not identical to that of the patient’s urine. The daily amounts of metabolites excreted in the urine were about 400 mg. of p-hydroxyisovaleric acid and about 100 mg. of P-M.C.G. Our gas-liquid chromatography method did not detect either of the metabolites or any short-chain fatty acids (including isovaleric acid) in the blood. The concentration of these compounds in blood must therefore be below 0-5 mg. per 100 ml. In the urine of the mother, the father, and the two older brothers, significant amounts of &bgr;-M.C.G. could be detected. The daily excretion of the metabolites varied between 15 and 40 mg. In a large series of control urines these compounds could never be detected. 1.
Pritchard, J. J. Pharm. Pharmac. 1964, 16, 487.
in 1943 (and quoted by Renpenning et al.?). Although sex-linkage was not proved, there is insufficient
published
evidence to assert that the disease was different from that described by Renpenning and his colleagues nineteen years later. It is also possible that the families of Allan et al.and Losowsky9 are clinical variants of the same condition. It would be wiser to use descriptive language for the time
being. St. Lawrence’s
Hospital, Caterham, Surrey.
B. W. RICHARDS.
EFFECT OF ANTICONVULSANT DRUGS ON INSECTICIDE RESIDUES
SiR,—Last of pesticide
year, Davies et al.1o reported that serum levels reduced in patients taking phenytoin
were
and phenobarbitone (phenobarbital). They indicated that these drugs might offer a means of lowering body pesticide levels. In support of this, we wish to report the case of a farmer with epilepsy who had been treated with phenobarbitone for 20 years and with a combination of phenobarbitone (21 mg. five times daily) and phenytoin (90 mg. four times daily) for the past 4 years. We suspect that this case is unique, since the farmer comes from an area where pesticide usage has been heavy throughout the period of his treatment. The pesticide levels in his serum were compared with those in 391 farmers from the same area
(’Dilantin’)
(see accompanying table). All values reported are for serum extracted by the method of Dale et al.ll The Microtek Model MT-220 gas chromatograph was used for identifying and quantitating the pestiElectrocardiograms illustrating transient heart-block
of complete heart-block have been recorded. Only 1 had unequivocal Stokes-Adams attacks, the others presenting with congestive heart-failure, giddiness, or non-cardiac symptoms. The accompanying electrocardiograms show that in one of our patients the heart-block was transient. This 50-year-old woman gave a 2-year history of giddiness and palpitation, but denied ever having lost consciousness. Her previous medical history was unremarkable. On examination her pulse-rate was 32 per minute and bloodpressure 160/180 nun. Hg. Occasional cannon waves were seen in the jugular venous pulse. The left ventricle felt hypertrophied. The first heart-sound varied in intensity, and an atrial sound and soft apical systolic murmur were heard. The rest of the clinical examination and chest X-ray were normal. She was treated with ephedrine, and at her second visit to the clinic 13 weeks later she felt much better, and had no clinical or electrocardiographic evidence of heart-block despite stopping treatment one week previously. Furthermore, there was no electrocardiographic evidence of impaired conduction. Department of Medicine, R. F. GUNSTONE Mulago Hospital, K. SOMERS Kampala, Uganda, A. I. PATEL. East Africa.
"RENPENNING" SYNDROME
SiR.—It does not seem justified to give the name " Renpenning syndrome " to sex-linked mental deficiency. There is a well-known article, entitled A Pedigree of Mental Defect showing Sex-linkage, by Purdon Martin and Julia Bell 6 Harris, A., Bluestone, R., Busby, E., Davies, G., Leatham, A., Siddons, H., Sowton, E. Br. Heart J. 1965, 27, 469. 2. Harris, A., Davies, M., Redwood, D., Leatham, A., Siddons, H. ibid. 1969, 31, 206. 3. Johanson, B. W. Am. J. Cardiol. 1961, 8, 76. 4. Cookson, H. Br. Heart J. 1952, 14, 350. 5. Schwartz, S. P., Hauswirth, L. Am. J. med. Sci. 1934, 187, 478. 6. Purdon Martin, J., Bell, J. J. Neurol. 1943, 6, 154. 1.
PESTICIDE LEVELS IN THE SERUM OF AN EPILEPTIC FARMER TREATED WITH PHENYTOIN AND PHENOBARBITONE AND EXPOSED CONTROLS
FROM THE SAME AREA
-_
-_
-_
_
-
_
-
p. p.b. = parts per loe--___ p,p’-D.D.T. 1,1,1-trichloro-2,2-bis(para-chlorophenyl) ethane p,p’ -D.D,E. 1,1-dichloro-2,2-bis(para-chlorophenyl) ethane &bgr;-B.H.C. =&bgr;-isomer of 1,2,3,4,5,6-hexachlorocyclohexane =
=
cides, using SE-30/QF-1 and OV-17/QF-1 columns 195°C and a tritium-type electron-capture detector
at at
205°C. The table shows that the serum-chlorinated-hydrocarbon levels in the treated epileptic farmer are only a fraction of those of the untreated farmers. Other investigators have demonstrated the effect of phenobarbitone on pesticide levels. Menzer and Best 12 showed a pronounced effect of sodium phenobarbitone on 7.
Renpenning, H., Gerrard, J. W., Zaleski, W. A., Tabata, T. Can. med. Ass. J. 1962, 87, 954. 8. Allan, W., Herndon, C. N., Dudley, F. C. Am. J. ment. Defic. 1944, 48, 325. 9. Losowsky, M. S. J. ment. Defic. Res. 1961, 5, 60. 10. Davies, J. E., Edmundson, W. F., Carter, C. H., Barquet, A. Lancet, 1969, ii, 7. 11. Dale, W. E., Curley, A., Cueto, C. Life Sci, 1966, 5, 47. 12. Menzer, R. E., Best, N. H. Toxic appl. Pharmac. 1968, 13, 37.
521 ’
,
Dimethoate ’, Phosphamidonand Bidrin ’metabolism in mice. Ikeda et all reported that phenobarbitone stimulated warfarin metabolism in the rat as shown by a decrease in the plasma-warfarin level. Alary et al.’4 showed a decrease
dicophane (D.D.T.) level in milk from dairy cows treated with phenobarbitone. This was thought to be due to in the
increased metabolic breakdown of D.D.T., since there was a substantial increase in urinary D.D.A. Cueto and Hayes 15 also showed a decrease in dieldrin storage in the fat of rats treated with phenobarbitone. There are two possible interpretations of these data. The first is that certain microsomal enzymes are induced by the drugs, and that these enzymes are involved in the breakdown of the pesticides. Davies et a1.1O support this hypothesis. The second is that the pesticides are bound by serumproteins, and are consequently relatively inert.’sThe action of the drugs on the pesticides depends on the competition of both for the same binding sites on the proteins. The more tightly bound drugs would displace the pesticides from the proteins, which would render them liable to catabolism and excretion. Our interpretation is supported by pharmacodynamic considerations, since the action of a number of drugs depends on their ability to become bound to serumproteins and thus release other substances. 17-20 Department of Pharmacology, Louisiana State Medical Center, New Orleans, Louisiana 70119.
WILHELM P. SCHOOR.
PHENOBARBITONE IN POSTHEPATITIC
UNCONTUGATED HYPERBILIRUBINÆMIA SIR,-We were interested in the report by Dr. Black and Professor Sherlock on the treatment of Gilbert’s syndrome with phenobarbitone.21 We have lately used phenobarbitone in a 21-year-old man with posthepatitic chronic unconjugated hyperbilirubinxmia .22 This patient had had a welldocumented acute hepatitis in June, 1969, and in the succeeding 8 months his plasma-unconjugated-bilirubin levels remained between 3 and 5 mg. per 100 ml.; he had no symptoms, and there was no other evidence of hepatic insufficiency. A liver-biopsy specimen showed only mild cicatrisation and quiescent inflammatory infiltrate. In March, 1970, he was started on 90 mg. phenobarbitone daily. The bilirubin level fell within a week to 0-5-0-8 mg. per 100 ml. The correction of jaundice removed the patient’s anxiety, and sedation was not excessive. J. C. DE OYA Department of Internal Medicine A. DEL RÍO University of M. NOYA Santiago de Compostela, A. VILLANUEVA. Spain.
PORTABLE HEPARIN INJECTOR SIR,-Describing his ingenious device for continuous intravenous infusion of heparin (Aug. 8, p. 313), Dr. Handley states that the dose of heparin (he recommends 20,000 units) should be diluted in 5% dextrose solution. 13.
14. 15. 16. 17. 18. 19. 20. 21. 22.
Ikeda, M., Conney, A. H., Burns, J. J. J. Pharmac. exp. Ther. 1968, 162, 338. Alary, J. G., Brodeur, J., Cote, M. G., Panisset, J. C., Lamothe, P., Guay, P. Rev. can. Biol. 1968, 27, 269. Cueto, C., Hayes, W. J. Indust. Med. Surg. 1967, p. 546. Schoor, W. P. Unpublished. Sellers, E. M., Koch-Weser, J. New Engl. J. Med. 1969, 281, 1141. Meyer, M. C., Guttman, D. E. J. pharm. Sci. 1968, 57, 895. Dollery, C. T., Emslie-Smith, D., Muggleton, D. F. Br. J. Pharmac. 1961, 17, 488. Symposium on Clinical Effects of Interaction between Drugs. Proc. R. Soc. Med. 1965, 58, 943. Black, M., Sherlock, S. Lancet, 1970, i, 1359. de Oya, J. C., del Rio, A., Noya, M., Villanueva, A. Communication to Ninth Congress of Sociedad Española de Medicina Interna, Santiago de Compostela, June, 1970.
Perhaps he is not aware that the stability of heparin is greatly reduced at pH values below 6-0.1 5% dextrose solution has a pH of 46, and is therefore unsuitable. (We have tested someother solutions for intravenous infusion, and found the following pH values: 0-9% saline, 6-3; Ringer lactate solution, 57, Hartmann’s solution, 6-2; Rheomacrodex ’ in 5 % glucose, 4 1; and rheomacrodex in 0-9% saline, 4-9.) We have found heparin therapy very difficult to control using 5% dextrose as the diluent, and we recommend either physiological saline (0-9%) or Hartmann’s solution. Department of Surgery, Royal College of Surgeons in Ireland and St. Laurence’s Hospital, Dublin.
JOHN O’RIORDAN WILLIAM MACGOWAN.
&bgr;-HYDROXYISOVALERIC ACIDURIA AND &bgr;-METHYLCROTONYLGLYCINURIA: A NEW INBORN ERROR OF METABOLISM SIR,-We have found a new inborn error of metabolism in the leucine-degradation pathway, different from maplesyrup-urine disease and isovaleric acidxmia. The patient was a 41/2-month-old girl whose mother and father’s mother were first cousins. Two older siblings, both boys, are healthy. Pregnancy and delivery were normal as were the child’s birthweight and length. Right from the second week there were feeding difficulties. Gradually the signs of retarded motor development, muscular hyptonia, and muscular atrophy appeared. Growth was normal, but weight gain was rather slow. At that time the deep tendon reflexes could not be elicited, and fibrillation of the tongue was seen. Mental development, sensation, and sphincter function were normal. There were no signs of other diseases, and no acidotic episodes. The clinical picture resembled that of an infantile spinal muscular atrophy (Werdnig-Hoffmann’s disease). In addition, however, her urine had an unpleasant smell like that of a cat’s urine. She tended to sweat rather profusely, but her body and expired air did not smell. Chromatography of the aminoacids showed normal patterns in both serum and urine. The patient had raised lactic-acid-dehydrogenase levels, and excretion of creatine was increased. In the child’s urine large amounts of two abnormal metabolites were found. After acidification of the urine, extraction, and methylation, analysis by gas-liquid chromatography on columns containing butanediol succinate as stationary phase showed one compound with retention volume 1-47 relative to that of heptanoic acid methyl ester, and another compound with retention volume 2-45 relative to that of pentadecanoic acid methyl ester. Mass spectrometric analyses of the urinary metabolites revealed spectra compatible with p-hydroxy-isovaleric acid and (3-methylcrotonylglycine (&bgr;-M.C.G.). The nature of the substances was confirmed by gas-liquid chromatography and massspectrometry of synthetic compounds of the same composition. The smell of these synthesised compounds is, however, not identical to that of the patient’s urine. The daily amounts of metabolites excreted in the urine were about 400 mg. of p-hydroxyisovaleric acid and about 100 mg. of P-M.C.G. Our gas-liquid chromatography method did not detect either of the metabolites or any short-chain fatty acids (including isovaleric acid) in the blood. The concentration of these compounds in blood must therefore be below 0-5 mg. per 100 ml. In the urine of the mother, the father, and the two older brothers, significant amounts of &bgr;-M.C.G. could be detected. The daily excretion of the metabolites varied between 15 and 40 mg. In a large series of control urines these compounds could never be detected. 1.
Pritchard, J. J. Pharm. Pharmac. 1964, 16, 487.