987 bv
w-oxidation’ with the formation of adipic acid. The persist-
of the patient’s metabolic changes and the early neonatal death of her sister suggest a genetic origin. Hypoglycxmia may have been caused by an inhibition of gluconeogenesis by ethylmalonic acid.l.4 Similar unusual metabolites including ethylmalonic and adipic acids have been detected in two patients with Jamaican vomiting’,’ and in a baby with glutaricaciduria type n.8 Hexanoylglycine was also detected in Jamaican vomiting disease. 1,6 However, in contrast to the present case, these three patients invariably excreted large amounts of glutaric acid as well. They also excreted large amounts of isobutyric and isovaleric acids in addition to hexanoic acid. These findings indicated that several short-chain acyl CoA dehydrogenases, including butyryl, isovaleryl, and glutaryl CoA dehydrogenases, are inhibited in these two previously known diseases.l,8 In Jamaican vomiting sickness the inhibition is caused by a food toxin, hypoglycin A.9-11 In glutaricaciduria type n a genetic deficiency of a cofactor or protein component shared by these similar dehydrogenases, has been postulated.8 Our patient did not have glutaricaciduria type n:. glutaric acid was undetectable in many of her urines, and even when present the amount was small. (The urinary glutaric acid excreted by the patient with glutaricaciduria type n8 was over 11 mg/mg creatinine.) After a loading test with lysine, a precursor of glutaryl CoA, small amounts of glutaric acid (106 and 331 fLg/mg creatinine) were detected in two 12 h urines collected during the two days of loading but not in two 12 h urines collected the same night; the same loading test caused a profound enhancement of glutarate excretion in a patient with glutaricaciduria type i (glutaryl CoA dehydrogenase deficiency) the highest value being 10 mg/mg.12 Our patient is the first published case of a deficiency of butyryl CoA dehydrogenase. (In 1967, Sidbury et all reported four cases of "the odor-of-sweaty-feet syndrome" and suggested that these were due to a deficiency of butyryl CoA dehydrogenase; on gas chromatography of serum there were two peaks which behaved like butyric and hexanoic acids, but the retention-times differed from those of authentic standards, and gas-chromatography/mass-spectrometry on one patient demonstrated isovalericacidaemia.14) Skin fibroblast culture is now being done to confirm a specific deficiency of butyryl CoA ence
dehydrogenase. This investigation is supported by N.I.H. grants (AM 17453, RR 125, HD 00198) and a grant (1-378) from the National FoundationMarch of Dimes. KAY TANAKA STEPHANOS MANTAGOS MYRON GENEL Departments of Human Genetics MARGRETTA R. SEASHORE and Pediatrics BEATRICE A. BILLINGS Yale University School of Medicine, BRUCE H. BARETZ New Haven, Connecticut 06510, U.S.A.
BROMOCRIPTINE IN IMPOTENCE
Cooper (Sept. 10, p. 567) we have found be ineffective in the treatment of sexual impotence. An initial trial was promising, treatment with 7.5 mg bromocriptine daily for 3-6 weeks causing some improvement in 9 of 17 patients, but in a double-blind study of another 30 SIR,-Like
bromocriptine
Dr to
patients a placebo was equally effective and there was no correlation between the clinical results and changes in serum-prolactin and serum-testosterone. Bromocriptine altered serumprolactin but failed to influence testosterone, 17-oestradiol, luteinising hormone, or follicle-stimulating hormone in serum. Thorner and Besser2found that bromocriptine restored potency in most hyperprolactinaemic patients with pituitary tumours, but in our study impotence was unaffected in both mildly hyperprolactinaemic patients and those with normal ser-
um-prolactin.3 Since monoaminergic (dopaminergic-stimulatory and serotoninergic-inhibitory) substances have been found to control sexual activity in animals and a similar control has been suggested in manbromocriptine (7.5 mg daily) was administered in association with the serotonin antagonist methysergide (3 mg daily) to 4 impotent patients for 30 days. No improvement was observed. Parachlorophenylalanine, an inhibitor of 5-hydroxytryptamine synthesis, restores sexual potency when given with testosterone,5 but frequently induces severe side-effects. In a preliminary study, we administered a serotonin antagonist, methysergide (3 mg daily), with mesterolone (100 mg daily) to 4 impotent patients for 25-50 days. No improvement has yet been noted. We thus remain unconvinced that bromocriptine is useful in the treatment of impotence. Monoaminergic substances may turn out to
he
more
valnahle.
Endocrine Unit, Medical Clinic II, University of Milan, 35 Milan, Italy
B. AMBROSI R. BARA G. FAGLIA
REMISSION OF JUVENILE RHEUMATOID ARTHRITIS (STILL’S DISEASE) AFTER MEASLES seen a striking remission in a 28-month-old with juvenile rheumatoid arthritis (Still’s disease). Her girl arthritis began in September, 1976, progressing rapidly. Gold treatment was started in November. She has been an inpatient since March 1, 1977, continuously febrile, with typical polyarticular Still’s disease inadequately controlled by prednisone 40 mg every other day. She was apathetic, was not moving around spontaneously at all, and responded reluctantly to physiotherapy. Gold was discontinued in May and D-penicillamine was tried. Except for a low serum-IgA (4 mg/dl), laboratory data were unremarkable (for her disease) and her erythrocyte-sedimentation rate (E.S.R.) was 80 mm in the lst hour. On June 15measles was brought into the paediatric ward. Our patient had the typical rash 18 days later. The course of the infection was normal but as she recovered she became afebrile, for the first time in 4 months. She began to move about spontaneously as she woke up, and started to take an interest in her surroundings. Her E.S.R. fell to 31 mm/h. This remission lasted for 5 weeks. Six other patients with juvenile rheumatoid arthritis also got measles in the same ward epidemic, but none of them had the acute form of Still’s disease. Two of them, a 27-month-old boy and a 18-month-old girl, both with a subacute polyarticular type of the disease, showed a notable clinical improvement of arthritis, which lasted for several weeks. The other four, all older children with chronic juvenile rheumatoid arthritis, did
SIR,-We have
not
improve.
no previous case of an effect of measles on the course of juvenile rheumatoid arthritis. Although remission in our first patient might have been a late effect of penicil-
We have found
5 Barlett, K., Gompertz, D.Biochem. Med. 1974, 10, 15. 6
Baretz, B. H, Ramsell,
H.
S., Tanaka, K. Clin. chim. Acta, 1976, 73, 199.
7 Wakabayashi, K., Shimazono, N. Biochim. biophys. Acta, 1963, 70, 132. 8 Przyrembel, H., Wendel, U., Becker, K., Bremer, H. J., Bruinvis, L., Ketting, D., Wadman, S. K. Clin. chim. Acta, 1976, 66, 227. 9 Tanaka, K., Miller, E. M., Isselbacher, K. J. Proc. natn. Acad. U.S.A. 1971, 68, 20. 10 Tanaka, K. J. biol Chem. 1972, 247, 7465. 11 Kean, E A. Biochim, biophys. Acta, 1976, 422, 8. 12 Goodman, S. I., Markey, S. P., Moe, P. G., Miles, B. S., Teng, C. C. Biochem.Med. 1975, 12, 12 13 Sidbury, J. B., Smith, E K., Harlan, W. J. Pediat. 1967, 70, 8. 14 Ando, T, Nyhan, W. L, Bachmann, C., Rasmussen, K., Smith, E. ibid.
1973, 82, 243.
1. Ambrosi, B., Travaglini, P., Bara, R., Beck-Peccoz, P., Elli, R., Rondena, M., Faglia, G. Acta endocr. 1977, suppl. 212, 29. 2. Thorner, M. O., Besser, G. M. in Prolactin and Human Reproduction (edited by P. G. Crosignani and C. Robyn); p. 285. New York, 1976. 3. Ambrosi, B., Bara, R., Travaglini, P., Weber, G., Beck-Peccoz, P., Rondena, M., Elli, R., Faglia, G. Clin. Endocr. (in the press). 4. Gessa, G. L., Tagliamonte, A. Life Sci. 1974, 14, 425. 5. Sicuteri, F., Del Bene, E., Anselmi, B. in Sexual Behaviour—Pharmacology and Biochemistry (edited by M. Sandler and G. L. Gessa); p. 335. New York, 1975.
988 lamine
or
ease, it is
simply a quirk in the course of an unpredictable distempting to postulate a causal relationship with the
measles infection. Measles is a potent interferon inducer, so perhaps interferon in some way ameliorates juvenile rheumatoid arthritis. However, when our patient had mumps in April, 1977, her underlying disease was not affected. One feature of measles infection is the loss of tuberculin-type skin hypersensitivity and the diminished lymphocyte response to phytohoemagglutinin during convalescence. Perhaps the remission could be ascribed to the immunosuppressive effect of measles inftprttnn
T"-’
Rheumatism Foundation Hospital, 18120 Heinola 12, Finland
R. VON ESSEN H. ISOMÄKI
BLOOD IN THE ALCOHOL STREAM p. 806) would be and address of your spirit merchant. If he can cram 244+102 g of alcohol into 4-10 single measures of gin or whisky he is assured of our custom.
SIR,-Readers of your editorial (Oct. 15,
greatly obliged
to
you for the
name
Department of Pathology, North Lonsdale Hospital, Barrow-in-Furness, Cumbria LA14 2JD
J. E. HORROCKS
w-oxidation’ with the formation of adipic acid. The persist-
of the patient’s metabolic changes and the early neonatal death of her sister suggest a genetic origin. Hypoglycxmia may have been caused by an inhibition of gluconeogenesis by ethylmalonic acid.l.4 Similar unusual metabolites including ethylmalonic and adipic acids have been detected in two patients with Jamaican vomiting’,’ and in a baby with glutaricaciduria type n.8 Hexanoylglycine was also detected in Jamaican vomiting disease. 1,6 However, in contrast to the present case, these three patients invariably excreted large amounts of glutaric acid as well. They also excreted large amounts of isobutyric and isovaleric acids in addition to hexanoic acid. These findings indicated that several short-chain acyl CoA dehydrogenases, including butyryl, isovaleryl, and glutaryl CoA dehydrogenases, are inhibited in these two previously known diseases.l,8 In Jamaican vomiting sickness the inhibition is caused by a food toxin, hypoglycin A.9-11 In glutaricaciduria type n a genetic deficiency of a cofactor or protein component shared by these similar dehydrogenases, has been postulated.8 Our patient did not have glutaricaciduria type n:. glutaric acid was undetectable in many of her urines, and even when present the amount was small. (The urinary glutaric acid excreted by the patient with glutaricaciduria type n8 was over 11 mg/mg creatinine.) After a loading test with lysine, a precursor of glutaryl CoA, small amounts of glutaric acid (106 and 331 fLg/mg creatinine) were detected in two 12 h urines collected during the two days of loading but not in two 12 h urines collected the same night; the same loading test caused a profound enhancement of glutarate excretion in a patient with glutaricaciduria type i (glutaryl CoA dehydrogenase deficiency) the highest value being 10 mg/mg.12 Our patient is the first published case of a deficiency of butyryl CoA dehydrogenase. (In 1967, Sidbury et all reported four cases of "the odor-of-sweaty-feet syndrome" and suggested that these were due to a deficiency of butyryl CoA dehydrogenase; on gas chromatography of serum there were two peaks which behaved like butyric and hexanoic acids, but the retention-times differed from those of authentic standards, and gas-chromatography/mass-spectrometry on one patient demonstrated isovalericacidaemia.14) Skin fibroblast culture is now being done to confirm a specific deficiency of butyryl CoA ence
dehydrogenase. This investigation is supported by N.I.H. grants (AM 17453, RR 125, HD 00198) and a grant (1-378) from the National FoundationMarch of Dimes. KAY TANAKA STEPHANOS MANTAGOS MYRON GENEL Departments of Human Genetics MARGRETTA R. SEASHORE and Pediatrics BEATRICE A. BILLINGS Yale University School of Medicine, BRUCE H. BARETZ New Haven, Connecticut 06510, U.S.A.
BROMOCRIPTINE IN IMPOTENCE
Cooper (Sept. 10, p. 567) we have found be ineffective in the treatment of sexual impotence. An initial trial was promising, treatment with 7.5 mg bromocriptine daily for 3-6 weeks causing some improvement in 9 of 17 patients, but in a double-blind study of another 30 SIR,-Like
bromocriptine
Dr to
patients a placebo was equally effective and there was no correlation between the clinical results and changes in serum-prolactin and serum-testosterone. Bromocriptine altered serumprolactin but failed to influence testosterone, 17-oestradiol, luteinising hormone, or follicle-stimulating hormone in serum. Thorner and Besser2found that bromocriptine restored potency in most hyperprolactinaemic patients with pituitary tumours, but in our study impotence was unaffected in both mildly hyperprolactinaemic patients and those with normal ser-
um-prolactin.3 Since monoaminergic (dopaminergic-stimulatory and serotoninergic-inhibitory) substances have been found to control sexual activity in animals and a similar control has been suggested in manbromocriptine (7.5 mg daily) was administered in association with the serotonin antagonist methysergide (3 mg daily) to 4 impotent patients for 30 days. No improvement was observed. Parachlorophenylalanine, an inhibitor of 5-hydroxytryptamine synthesis, restores sexual potency when given with testosterone,5 but frequently induces severe side-effects. In a preliminary study, we administered a serotonin antagonist, methysergide (3 mg daily), with mesterolone (100 mg daily) to 4 impotent patients for 25-50 days. No improvement has yet been noted. We thus remain unconvinced that bromocriptine is useful in the treatment of impotence. Monoaminergic substances may turn out to
he
more
valnahle.
Endocrine Unit, Medical Clinic II, University of Milan, 35 Milan, Italy
B. AMBROSI R. BARA G. FAGLIA
REMISSION OF JUVENILE RHEUMATOID ARTHRITIS (STILL’S DISEASE) AFTER MEASLES seen a striking remission in a 28-month-old with juvenile rheumatoid arthritis (Still’s disease). Her girl arthritis began in September, 1976, progressing rapidly. Gold treatment was started in November. She has been an inpatient since March 1, 1977, continuously febrile, with typical polyarticular Still’s disease inadequately controlled by prednisone 40 mg every other day. She was apathetic, was not moving around spontaneously at all, and responded reluctantly to physiotherapy. Gold was discontinued in May and D-penicillamine was tried. Except for a low serum-IgA (4 mg/dl), laboratory data were unremarkable (for her disease) and her erythrocyte-sedimentation rate (E.S.R.) was 80 mm in the lst hour. On June 15measles was brought into the paediatric ward. Our patient had the typical rash 18 days later. The course of the infection was normal but as she recovered she became afebrile, for the first time in 4 months. She began to move about spontaneously as she woke up, and started to take an interest in her surroundings. Her E.S.R. fell to 31 mm/h. This remission lasted for 5 weeks. Six other patients with juvenile rheumatoid arthritis also got measles in the same ward epidemic, but none of them had the acute form of Still’s disease. Two of them, a 27-month-old boy and a 18-month-old girl, both with a subacute polyarticular type of the disease, showed a notable clinical improvement of arthritis, which lasted for several weeks. The other four, all older children with chronic juvenile rheumatoid arthritis, did
SIR,-We have
not
improve.
no previous case of an effect of measles on the course of juvenile rheumatoid arthritis. Although remission in our first patient might have been a late effect of penicil-
We have found
5 Barlett, K., Gompertz, D.Biochem. Med. 1974, 10, 15. 6
Baretz, B. H, Ramsell,
H.
S., Tanaka, K. Clin. chim. Acta, 1976, 73, 199.
7 Wakabayashi, K., Shimazono, N. Biochim. biophys. Acta, 1963, 70, 132. 8 Przyrembel, H., Wendel, U., Becker, K., Bremer, H. J., Bruinvis, L., Ketting, D., Wadman, S. K. Clin. chim. Acta, 1976, 66, 227. 9 Tanaka, K., Miller, E. M., Isselbacher, K. J. Proc. natn. Acad. U.S.A. 1971, 68, 20. 10 Tanaka, K. J. biol Chem. 1972, 247, 7465. 11 Kean, E A. Biochim, biophys. Acta, 1976, 422, 8. 12 Goodman, S. I., Markey, S. P., Moe, P. G., Miles, B. S., Teng, C. C. Biochem.Med. 1975, 12, 12 13 Sidbury, J. B., Smith, E K., Harlan, W. J. Pediat. 1967, 70, 8. 14 Ando, T, Nyhan, W. L, Bachmann, C., Rasmussen, K., Smith, E. ibid.
1973, 82, 243.
1. Ambrosi, B., Travaglini, P., Bara, R., Beck-Peccoz, P., Elli, R., Rondena, M., Faglia, G. Acta endocr. 1977, suppl. 212, 29. 2. Thorner, M. O., Besser, G. M. in Prolactin and Human Reproduction (edited by P. G. Crosignani and C. Robyn); p. 285. New York, 1976. 3. Ambrosi, B., Bara, R., Travaglini, P., Weber, G., Beck-Peccoz, P., Rondena, M., Elli, R., Faglia, G. Clin. Endocr. (in the press). 4. Gessa, G. L., Tagliamonte, A. Life Sci. 1974, 14, 425. 5. Sicuteri, F., Del Bene, E., Anselmi, B. in Sexual Behaviour—Pharmacology and Biochemistry (edited by M. Sandler and G. L. Gessa); p. 335. New York, 1975.
988 lamine
or
ease, it is
simply a quirk in the course of an unpredictable distempting to postulate a causal relationship with the
measles infection. Measles is a potent interferon inducer, so perhaps interferon in some way ameliorates juvenile rheumatoid arthritis. However, when our patient had mumps in April, 1977, her underlying disease was not affected. One feature of measles infection is the loss of tuberculin-type skin hypersensitivity and the diminished lymphocyte response to phytohoemagglutinin during convalescence. Perhaps the remission could be ascribed to the immunosuppressive effect of measles inftprttnn
T"-’
Rheumatism Foundation Hospital, 18120 Heinola 12, Finland
R. VON ESSEN H. ISOMÄKI
BLOOD IN THE ALCOHOL STREAM p. 806) would be and address of your spirit merchant. If he can cram 244+102 g of alcohol into 4-10 single measures of gin or whisky he is assured of our custom.
SIR,-Readers of your editorial (Oct. 15,
greatly obliged
to
you for the
name
Department of Pathology, North Lonsdale Hospital, Barrow-in-Furness, Cumbria LA14 2JD
J. E. HORROCKS
