664 different ways of using the hands in cooking and eating. Inaccuracies in measuring the solute ingredients, especially salt, could be exaggerated by inaccuracies in measuring the solvent, water. Consequently hand measurements cannot be recommended unless they have been carefully tested in the community in which they are to be used. to
London School of Hygiene and
Tropical Medicine,
WILLIAM A. M. CUTTING
London WC1
PERIPHERAL GANGRENE COMPLICATING BETA-BLOCKADE SIR,—In relation to the report by Dr Vale and his colleagues (Aug. 20 p. 412) I would like to point out that Udwadia and I measured the effect of beta-adrenoceptor blockade on noradrenergic vasoconstriction in hand veins. After systemic administration of propranolol on a double-blind basis, the sensitivity of the hand.vein to the vasoconstrictor activity of noradrenaline in a group of healthy individuals was increased more than seven-fold. This finding supports the notion that
alpha-adrenoceptor agonist potentiation by beta-adrenoceptor MISMANAGED FACIAL INFECTION p.
SIR,—The unfortunate case reported by Mr Webb (Sept. 3, 511) draws attention to the all-too-common treatment of
have been a dental infection by the antibiotic nostrum. Perhaps, with hindsight, surgical drainage might best have been achieved by the extraction of the carious teeth at the outset. The invidious position in which so many colleagues in hospital practice find themselves in these cases could easily be avoided by closer cooperation between general medical practitioners and their dental colleagues, particularly those with experience of treating children.
what appears
to
Department of Children’s Dentistry and Preventive Dentistry, Dental School, University of Wales,
P. J. M. CRAWFORD D. R. LLEWELYN D. M. H. SMITH
Cardiff CF4 4XY
LIMB-REDUCTION ANOMALIES IN INFANTS BORN TO DISULFIRAM-TREATED ALCOHOLIC MOTHERS
SIR,—Maternal alcoholism is a well-recognised cause of birth defects.’ Alcohol-induced maldevelopment may be prevented by abstinence, with or without the assistance of disulfiram. We would like to draw attention to the possibility that disulfiram may also produce significant malformations. In our teratogen surveillance programme we have seen 2 infants with severe limb-reduction anomalies whose mothers had been maintained on a disulfiram sobriety regimen during the first trimester of pregnancy. There was no exposure to alcohol or other established teratogenic agents during this trimester. 1 of these infants had multiple anomalies including radial aplasia, vertebral fusion, and tracheo-cesophageal fistula (VACTERL syndrome).2 This was the male twin of a completely normal female co-twin. The second patient, also a male, had phocomelia of the lower extremities. We reviewed a cohort of 1320 prospective teratogenic histories obtained during the same time frame in which these patients were born. There were no other exposures to disulfiram, which indicates that the use of this drug during pregnancy is not widespread. Previous experimental and clinical data are slight. In one study there was 88% absorption, but no gross malformations, in rats fed 100 mg daily.3 A prospective cohort of five human pregnancies in which there was maternal exposure to disulfiram revealed 1 spontaneous abortion, 2 infants with clubfeet, and 2 normal infants.4 This limited total experience of maldevelopment of limbs in 4 patients, suggests that care needs to be taken with the use of disulfiram to combat alcoholism in women of reproductive age. Department of Pediatrics, University of Colorado Medical Center
Denver, Colorado, 80262 U.S.A.
AUDREY H. NORA JAMES J. NORA
JANET BLU
1. Jones, K. L., Smith, D. W. Lancet, 1973, ii, 999. 2. Nora, A. H., Nora, J. J. Archs envir Hlth, 1975, 30, 17. 3. Salgo, M. P., Oster, G. J. Reprod. Fercil 1974, 39, 375. 4. Favre-Tissot, M., Broussole, P. 5th int Cong. Neuropsychopharmac.
p. 583.
blockade is the mechanism underlying complications of betablockade such as peripheral vasospasm. Practolol also increased the sensitivity of the hand vein to the vasoconstrictor activity of infused noradrenaline, though to a more limited extent.
Maudsley Hospital,
C.
London SE5 8AZ
DE
B. WHITE
DEATHS AFTER OVERDOSES OF ORPHENADRINE
SIR,—Professor Millar (Sept. 10, p. 561) seems to assume that, because a drug may cause death when taken in an overdose, that drug is potentially lethal at the recommended therapeutic dosage. He states that, in two reports submitted to the Mental Welfare Commission for Scotland, "... the drug had been made available to the patient without precautions as to its possible lethal effect-i.e., when taken together with phenothiazines". This suggests that a potentially lethal interaction can occur between orphenadrine and the phenothiazines. We have never received any report which suggests that orphenadrine, given in the recommended dosage, can produce a potentially lethal reaction in combination with phenothiazines. Professor Millar states that Dr A. T. Proudfoot believes that orphenadrine may be prescribed by psychiatrists who are not fully aware of the drug’s dangers "when given in large therapeutic dosage". What constitutes "large therapeutic dosage?" The maximum recommended dosage for the treatment of parkinsonism is 400 mg/day in divided doses,,while the dose required to control the extrapyramidal side-effects of the phenothiazines is 50-100 mg three times a day. Professor Millar does not mention the quantity of orphenadrine taken by any of the patients whose cases he cites. Did any of them take 400 mg/day or less? I agree with Professor Millar that all drugs should be given with caution, especially to patients whose illness may exhibit episodes of suicidal depression, but would not advocate denying a large number of patients the benefits of orphenadrine simply because a minority misuse it. Medical Department, Brocades (Great Britain) Ltd, West Byfleet, Surrey KT14 6RA
IVOR I. DAINOW
HAZARD TO STAFF FROM PERITONEAL-DIALYSIS MACHINE
SIR,—LKB peritoneal dialysis machines have given us excellent service over four years. We were surprised therefore to find that the design contained an inherent hazard. The PD700 peritoneal-dialysis machine (LKB Instruments) brings the dialysate to 37°C by passage through an electrically heated stainless-steel tube before it enters the abdomen. This tube is in a prominent position on top of the machine, and, since there are no warning markings, one might expect that it can be touched without risk of electrical or thermal burn. Normally the tube will not be dangerous because if flow to
1967, 1.
White, C. de B., Udwadia,
B. P.
Br. J.
clin. Pharmac
1975, 2, 99.
London School of Hygiene and
Tropical Medicine,
WILLIAM A. M. CUTTING
London WC1
PERIPHERAL GANGRENE COMPLICATING BETA-BLOCKADE SIR,—In relation to the report by Dr Vale and his colleagues (Aug. 20 p. 412) I would like to point out that Udwadia and I measured the effect of beta-adrenoceptor blockade on noradrenergic vasoconstriction in hand veins. After systemic administration of propranolol on a double-blind basis, the sensitivity of the hand.vein to the vasoconstrictor activity of noradrenaline in a group of healthy individuals was increased more than seven-fold. This finding supports the notion that
alpha-adrenoceptor agonist potentiation by beta-adrenoceptor MISMANAGED FACIAL INFECTION p.
SIR,—The unfortunate case reported by Mr Webb (Sept. 3, 511) draws attention to the all-too-common treatment of
have been a dental infection by the antibiotic nostrum. Perhaps, with hindsight, surgical drainage might best have been achieved by the extraction of the carious teeth at the outset. The invidious position in which so many colleagues in hospital practice find themselves in these cases could easily be avoided by closer cooperation between general medical practitioners and their dental colleagues, particularly those with experience of treating children.
what appears
to
Department of Children’s Dentistry and Preventive Dentistry, Dental School, University of Wales,
P. J. M. CRAWFORD D. R. LLEWELYN D. M. H. SMITH
Cardiff CF4 4XY
LIMB-REDUCTION ANOMALIES IN INFANTS BORN TO DISULFIRAM-TREATED ALCOHOLIC MOTHERS
SIR,—Maternal alcoholism is a well-recognised cause of birth defects.’ Alcohol-induced maldevelopment may be prevented by abstinence, with or without the assistance of disulfiram. We would like to draw attention to the possibility that disulfiram may also produce significant malformations. In our teratogen surveillance programme we have seen 2 infants with severe limb-reduction anomalies whose mothers had been maintained on a disulfiram sobriety regimen during the first trimester of pregnancy. There was no exposure to alcohol or other established teratogenic agents during this trimester. 1 of these infants had multiple anomalies including radial aplasia, vertebral fusion, and tracheo-cesophageal fistula (VACTERL syndrome).2 This was the male twin of a completely normal female co-twin. The second patient, also a male, had phocomelia of the lower extremities. We reviewed a cohort of 1320 prospective teratogenic histories obtained during the same time frame in which these patients were born. There were no other exposures to disulfiram, which indicates that the use of this drug during pregnancy is not widespread. Previous experimental and clinical data are slight. In one study there was 88% absorption, but no gross malformations, in rats fed 100 mg daily.3 A prospective cohort of five human pregnancies in which there was maternal exposure to disulfiram revealed 1 spontaneous abortion, 2 infants with clubfeet, and 2 normal infants.4 This limited total experience of maldevelopment of limbs in 4 patients, suggests that care needs to be taken with the use of disulfiram to combat alcoholism in women of reproductive age. Department of Pediatrics, University of Colorado Medical Center
Denver, Colorado, 80262 U.S.A.
AUDREY H. NORA JAMES J. NORA
JANET BLU
1. Jones, K. L., Smith, D. W. Lancet, 1973, ii, 999. 2. Nora, A. H., Nora, J. J. Archs envir Hlth, 1975, 30, 17. 3. Salgo, M. P., Oster, G. J. Reprod. Fercil 1974, 39, 375. 4. Favre-Tissot, M., Broussole, P. 5th int Cong. Neuropsychopharmac.
p. 583.
blockade is the mechanism underlying complications of betablockade such as peripheral vasospasm. Practolol also increased the sensitivity of the hand vein to the vasoconstrictor activity of infused noradrenaline, though to a more limited extent.
Maudsley Hospital,
C.
London SE5 8AZ
DE
B. WHITE
DEATHS AFTER OVERDOSES OF ORPHENADRINE
SIR,—Professor Millar (Sept. 10, p. 561) seems to assume that, because a drug may cause death when taken in an overdose, that drug is potentially lethal at the recommended therapeutic dosage. He states that, in two reports submitted to the Mental Welfare Commission for Scotland, "... the drug had been made available to the patient without precautions as to its possible lethal effect-i.e., when taken together with phenothiazines". This suggests that a potentially lethal interaction can occur between orphenadrine and the phenothiazines. We have never received any report which suggests that orphenadrine, given in the recommended dosage, can produce a potentially lethal reaction in combination with phenothiazines. Professor Millar states that Dr A. T. Proudfoot believes that orphenadrine may be prescribed by psychiatrists who are not fully aware of the drug’s dangers "when given in large therapeutic dosage". What constitutes "large therapeutic dosage?" The maximum recommended dosage for the treatment of parkinsonism is 400 mg/day in divided doses,,while the dose required to control the extrapyramidal side-effects of the phenothiazines is 50-100 mg three times a day. Professor Millar does not mention the quantity of orphenadrine taken by any of the patients whose cases he cites. Did any of them take 400 mg/day or less? I agree with Professor Millar that all drugs should be given with caution, especially to patients whose illness may exhibit episodes of suicidal depression, but would not advocate denying a large number of patients the benefits of orphenadrine simply because a minority misuse it. Medical Department, Brocades (Great Britain) Ltd, West Byfleet, Surrey KT14 6RA
IVOR I. DAINOW
HAZARD TO STAFF FROM PERITONEAL-DIALYSIS MACHINE
SIR,—LKB peritoneal dialysis machines have given us excellent service over four years. We were surprised therefore to find that the design contained an inherent hazard. The PD700 peritoneal-dialysis machine (LKB Instruments) brings the dialysate to 37°C by passage through an electrically heated stainless-steel tube before it enters the abdomen. This tube is in a prominent position on top of the machine, and, since there are no warning markings, one might expect that it can be touched without risk of electrical or thermal burn. Normally the tube will not be dangerous because if flow to
1967, 1.
White, C. de B., Udwadia,
B. P.
Br. J.
clin. Pharmac
1975, 2, 99.
