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INDOMETHACIN IN FAMILIAL MEDITERRANEAN FEVER
1202 CARDIOTOXICITY OF AMITRIPTYLINE
SIR,-We have followed with interest the versy in The Lancet on this subject.
recent contro-
A 58-year-old man with no history of heart-disease was treated with the drug for the past two years in gradually increasing dosage. Three weeks before admission, when an electrocardiogram was normal, the dose was increased to 150 mg. daily. On admission he gave a two-day history of palpitations and profound weakness without chest pain. The blood-pressure was 80/60 mm. Hg with physical and E.C.G. findings of ventricular tachycardia at 180 per minute. He responded to D.c. cardioversion but continued to have T-wave inversions and many ventricular extrasystoles which gradually subsided over the next 8 days. There was no biochemical or E.c.G. evidence of myocardial infarction. The arrhythmia was attributed to amitriptyline toxicity, and the drug discontinued. Because of slowly deepening depression over the ensuing 4 months, he was readmitted so that amitriptyline could be resumed cautiously under constant telemetric cardiac monitoring. His E.C.G. at that time was normal except for rare ventricular extrasystoles, and amitriptyline was begun at 75 mg. daily without incident. The dose was then increased to 150 mg. daily and within 24 hours there was a striking increase in frequency of ventricular extrasystoles with sustained runs of ventricular trigeminy. The drug was again discontinued, with disappearance of the arrhythmias in about 24 hours.
The risk of amitriptyline in patients with known cardiac dysfunction has been debated.1,2 This case re-emphasises that the drug must be used cautiously even in patients without clinical evidence of heart-disease, and also illustrates clearly the associated risk of life-threatening arrhythmia. Palpitations related to this drug are usually attributed to its atropinic effect, and ventricular tachycardia has not been reported previously except in overdosage.3,4Although sudden deaths linked to amitriptyline have been attributed to hypotension and conduction disturbances, it is possible that acute ventricular arrhythmias are responsible for many. Clinical Pharmacology Unit, M. J. SCOLLINS University of Vermont S. ROBINSON D. College of Medicine, A. NIES. U.S.A. Vermont Burlington, 05401,
COLD WATER FOR SCALDS
SIR,—II am concerned at the number of children admitted to hospitals with scalds. The severity of the skin damage due to scalding may be reduced by rapid immersion in cold water. A
16 months was sitting in his high chair when he pulled at a pot of tea and spilled it over himself. The father wrapped up the child and brought him to casualty. Tea leaves were found in the child’s clothing. The child was admitted with an extensive area of scalded skin. The anterior abdominal skin and both legs had large areas which were weeping or vesiculated. He was treated with intravenous fluids and silver-nitrate paint. He subsequently required two skin-grafts to full thickness burns of the abdomen and right thigh. He was discharged well after 6 weeks in hospital. A girl aged 18 months walked up to the table, pulled down a pot of tea which had been made two minutes before, and drenched herself. The father carried the child to the kitchen, put her in the sink, and turned the cold water on to her. She was fighting and screaming. After soaking the clothing the father noticed that the right arm was still out of the water and cooled the arm as well. When the mother undressed the child she found tea leaves inside the vest and the rest of the clothing. Subsequently there was found to be a small area of vesiculation on the volar aspect of the right forearm. This healed in a week, leaving no
boy aged
1. Boston Collaborative
Drug Surveillance Program. Lancet, 1972, i, 529. 2. Moir, D. C., Crooks, J., Cornwell, W. B., O’Malley, K., DingwallFordyce, I., Turnbull, M. J., Weir, R. D. ibid. Sept. 16, 1972, p. 561. 3. Brackenridge, R. G., Peters, T. J., Watson, J. M. Scott. med. J. 1968, 13, 208. 4. Rasmussen, E. B., Kristjansen, P. Am. J. Psychiat. 1963, 119, 781.
scar.
There
was no
visible effect
on
the
rest
of the skin of the
child.
These two cases demonstrate that the contents of a pot of tea can cause serious damage to the skin but the damage may be prevented by rapidly cooling the skin. It is important not to remove the clothes. The time taken in undressing allows time for the skin to be damaged by the hot fluid. Cold water quickly cools the skin and clothes
together. for example) should be this first-aid treatment of scalds. Schools should given also instruct their pupils, and pregnant mothers should be informed in the clinics and in the maternity wards. Wide
publicity (on television,
to
Copthorne Hospital, Shrewsbury SY3 8XF.
J. W. OGILVIE.
INDOMETHACIN IN FAMILIAL MEDITERRANEAN FEVER
SIR,—Dr. Alkalay (Sept. 16, p. 607) concludes: "II believe that the absence of any attacks during the time the patient has been on indomethacin is not due only to chance ". Today, when we rely on the results of controlled drug trials, if we use the word chance it has a statistical meaning; but the results of the treatment of one patient cannot be given any significance, however dramatic they might appear. Familial Mediterranean fever (F.M.F.) is unpredictable in its clinical manifestations: its very nature is periodicity. There is no constant time interval for the recurrence of symptoms or for their disappearance. Under such conditions even the best studies will fail to show reliable results. F.M.F. is a rare disease. Owing to a concentration of more cases have been reported from Sephardi immigrants Israel than from elsewhere, but the largest reported series1 does not exceed 253 cases. The only effective treatment so far is preventive-namely, genetic counselling. Joint manifestations are the less common ones in F.M.F. The main problem is to distinguish them from more common arthritic conditions.2 Dr. Alkalay will have a difficult time proving that the condition he treated was F.M.F. Usually, sedimentation-rates far above the ones he quotes are found in F.M.F. Reports of this kind may suggest more than they contain, and the uncritical reader might draw the wrong conclusions. Department of Preventive Medicine, Ohio State University, Columbus, Ohio 43210, U.S.A.
B. A. KATS.
TREATMENT OF SICKLE-CELL DISEASE SIR,—In the letter 3 you kindly published I referred to your editorial,4 underlining the possible toxic effect of any treatment with cyanates. In this connection I referred to our work on the effect of sodium cyanide causing degeneration of nerve tissue, including the neurones of the developing inner ear. I am indebted to Dr. D. M. Kirschenbaum, associate professor of biochemistry at the State University of New York, for the following notes: " Cyanates have been suggested for therapeutic purposes for sickle-cell anemias. They act by carbamylating the amino termini of the cx and&bgr; chains of globin. Cyanides have never been suggested for this purpose and under physiological conditions would not react with amino termini." 1. 2. 3. 4.
Kats, B. A. Manitoba med. Rev. 1964, 44, 154. Kats, B. A. Ned. Tijdshr. Geneesk. 1965, 109, 373. Lancet, 1972, i, 790. ibid. p. 671.
SIR,-We have followed with interest the versy in The Lancet on this subject.
recent contro-
A 58-year-old man with no history of heart-disease was treated with the drug for the past two years in gradually increasing dosage. Three weeks before admission, when an electrocardiogram was normal, the dose was increased to 150 mg. daily. On admission he gave a two-day history of palpitations and profound weakness without chest pain. The blood-pressure was 80/60 mm. Hg with physical and E.C.G. findings of ventricular tachycardia at 180 per minute. He responded to D.c. cardioversion but continued to have T-wave inversions and many ventricular extrasystoles which gradually subsided over the next 8 days. There was no biochemical or E.c.G. evidence of myocardial infarction. The arrhythmia was attributed to amitriptyline toxicity, and the drug discontinued. Because of slowly deepening depression over the ensuing 4 months, he was readmitted so that amitriptyline could be resumed cautiously under constant telemetric cardiac monitoring. His E.C.G. at that time was normal except for rare ventricular extrasystoles, and amitriptyline was begun at 75 mg. daily without incident. The dose was then increased to 150 mg. daily and within 24 hours there was a striking increase in frequency of ventricular extrasystoles with sustained runs of ventricular trigeminy. The drug was again discontinued, with disappearance of the arrhythmias in about 24 hours.
The risk of amitriptyline in patients with known cardiac dysfunction has been debated.1,2 This case re-emphasises that the drug must be used cautiously even in patients without clinical evidence of heart-disease, and also illustrates clearly the associated risk of life-threatening arrhythmia. Palpitations related to this drug are usually attributed to its atropinic effect, and ventricular tachycardia has not been reported previously except in overdosage.3,4Although sudden deaths linked to amitriptyline have been attributed to hypotension and conduction disturbances, it is possible that acute ventricular arrhythmias are responsible for many. Clinical Pharmacology Unit, M. J. SCOLLINS University of Vermont S. ROBINSON D. College of Medicine, A. NIES. U.S.A. Vermont Burlington, 05401,
COLD WATER FOR SCALDS
SIR,—II am concerned at the number of children admitted to hospitals with scalds. The severity of the skin damage due to scalding may be reduced by rapid immersion in cold water. A
16 months was sitting in his high chair when he pulled at a pot of tea and spilled it over himself. The father wrapped up the child and brought him to casualty. Tea leaves were found in the child’s clothing. The child was admitted with an extensive area of scalded skin. The anterior abdominal skin and both legs had large areas which were weeping or vesiculated. He was treated with intravenous fluids and silver-nitrate paint. He subsequently required two skin-grafts to full thickness burns of the abdomen and right thigh. He was discharged well after 6 weeks in hospital. A girl aged 18 months walked up to the table, pulled down a pot of tea which had been made two minutes before, and drenched herself. The father carried the child to the kitchen, put her in the sink, and turned the cold water on to her. She was fighting and screaming. After soaking the clothing the father noticed that the right arm was still out of the water and cooled the arm as well. When the mother undressed the child she found tea leaves inside the vest and the rest of the clothing. Subsequently there was found to be a small area of vesiculation on the volar aspect of the right forearm. This healed in a week, leaving no
boy aged
1. Boston Collaborative
Drug Surveillance Program. Lancet, 1972, i, 529. 2. Moir, D. C., Crooks, J., Cornwell, W. B., O’Malley, K., DingwallFordyce, I., Turnbull, M. J., Weir, R. D. ibid. Sept. 16, 1972, p. 561. 3. Brackenridge, R. G., Peters, T. J., Watson, J. M. Scott. med. J. 1968, 13, 208. 4. Rasmussen, E. B., Kristjansen, P. Am. J. Psychiat. 1963, 119, 781.
scar.
There
was no
visible effect
on
the
rest
of the skin of the
child.
These two cases demonstrate that the contents of a pot of tea can cause serious damage to the skin but the damage may be prevented by rapidly cooling the skin. It is important not to remove the clothes. The time taken in undressing allows time for the skin to be damaged by the hot fluid. Cold water quickly cools the skin and clothes
together. for example) should be this first-aid treatment of scalds. Schools should given also instruct their pupils, and pregnant mothers should be informed in the clinics and in the maternity wards. Wide
publicity (on television,
to
Copthorne Hospital, Shrewsbury SY3 8XF.
J. W. OGILVIE.
INDOMETHACIN IN FAMILIAL MEDITERRANEAN FEVER
SIR,—Dr. Alkalay (Sept. 16, p. 607) concludes: "II believe that the absence of any attacks during the time the patient has been on indomethacin is not due only to chance ". Today, when we rely on the results of controlled drug trials, if we use the word chance it has a statistical meaning; but the results of the treatment of one patient cannot be given any significance, however dramatic they might appear. Familial Mediterranean fever (F.M.F.) is unpredictable in its clinical manifestations: its very nature is periodicity. There is no constant time interval for the recurrence of symptoms or for their disappearance. Under such conditions even the best studies will fail to show reliable results. F.M.F. is a rare disease. Owing to a concentration of more cases have been reported from Sephardi immigrants Israel than from elsewhere, but the largest reported series1 does not exceed 253 cases. The only effective treatment so far is preventive-namely, genetic counselling. Joint manifestations are the less common ones in F.M.F. The main problem is to distinguish them from more common arthritic conditions.2 Dr. Alkalay will have a difficult time proving that the condition he treated was F.M.F. Usually, sedimentation-rates far above the ones he quotes are found in F.M.F. Reports of this kind may suggest more than they contain, and the uncritical reader might draw the wrong conclusions. Department of Preventive Medicine, Ohio State University, Columbus, Ohio 43210, U.S.A.
B. A. KATS.
TREATMENT OF SICKLE-CELL DISEASE SIR,—In the letter 3 you kindly published I referred to your editorial,4 underlining the possible toxic effect of any treatment with cyanates. In this connection I referred to our work on the effect of sodium cyanide causing degeneration of nerve tissue, including the neurones of the developing inner ear. I am indebted to Dr. D. M. Kirschenbaum, associate professor of biochemistry at the State University of New York, for the following notes: " Cyanates have been suggested for therapeutic purposes for sickle-cell anemias. They act by carbamylating the amino termini of the cx and&bgr; chains of globin. Cyanides have never been suggested for this purpose and under physiological conditions would not react with amino termini." 1. 2. 3. 4.
Kats, B. A. Manitoba med. Rev. 1964, 44, 154. Kats, B. A. Ned. Tijdshr. Geneesk. 1965, 109, 373. Lancet, 1972, i, 790. ibid. p. 671.