928
diagnosis was a Mallory-Weiss tear of the gastric mucosa. Over the next few days, the patient’s mid-epigastric pain abated and there were no further signs of active gastrointestinal bleeding. This case emphasises that nausea and vomiting, a common toxicity with many chemotherapeutic agents, may have serious clinical sequelx. Fortunately for our patient, the MalloryWeiss tear was self-limiting and was managed without blood transfusions. Because giving 5-F.u. and methyl-c.c.N.u. on the same day may have potentiated the gastrointestinal toxicity, we now give them on separate days and encourage the early use of antiemetics. Our experience should alert others to this possible complication in the combined use of these drugs and other chemotherapeutic agents which evoke nausea and vomiting. Department
of Medicine,
Hematology/Oncology Service, William Beaumont Army Medical Center, El Paso, Texas 79920, U.S.A.
ROBERT E. ENCK
CIMETIDINE AND MENTAL CONFUSION
SIR,-The reports by Grimson’ and Dr Delaney and Dr Ravey (Sept. 3, p. 512) of confusion after treatment with cimetidine prompt me to describe a recent case. A 78-year-old man, with a long history of reflux oesophagitis, presented with hsematemesis and melaena. Endoscopy showed fresh bleeding from the lower third of his oesophagus secondary to peptic cesophagitis. He was treated with a normal dose of cimetidine and 48 h later became drowsy, confused, restless, and unmanageable. His renal function was normal. The cimetidine was stopped and within 24 h his mental state improved with a subsequent return to normal. This improvement suggests that the confusion was caused by the treatment. Central Middlesex London NW10
Hospital,
NEIL MENZIES-GOW
SIR,-Little is known about the acute toxic effects of the histamine H2-receptor blocking agent cimetidine. Smith, Kline & French Laboratories Ltd, the makers, have details of 3 cases of overdose, 1 of which has been published.2 I describe here a case with some unusual features. A 25-year-old man was admitted to hospital 4 h after allegedly taking about 60 tablets (12 g) of cimetidine recently prescribed for a proven duodenal ulcer. His speech was slurred, his pupils dilated with a sluggish light reflex, and his pulse-rate was 120/min. There was no evidence that alcohol or other drugs had been taken. Gastric lavage was done. 5 h later he was seen picking the bedclothes in an agitated, aimless fashion. He was disoriented in time and place and his conversation was staccato and nonsensical. His pulse-rate was 110/min, blood-pressure 100/70 mm Hg and his pupils were still dilated. The following day he was completely lucid mentally. The patient’s electrocardiograph, hepatic and renal function, and blood indices remained normal throughout his admission. His blood-sugar was 3.6 mmol/1 36 h after taking the drug, although it was normal (5.7 mmol/1) during his acute cerebral disturbance. Grimson3 reported mental confusion in 2 patients who had been taking twice the recommended therapeutic dose of cimetidine for a short time. This report and others4,5 adds weight to the growing suspicion that the drug may occasionally cause
cerebral toxicity.
FETAL WASTAGE AND CHROMOSOME ANOMALIES IN OFFSPRING OF PATIENTS WITH
TURNER SYNDROME
SIR,-We have investigated a 21-year-old White female with short stature, cubitus valgus, and multiple cutaneous naevi. Quinacrine banding of peripheral-blood lymphocytes, skin fibroblasts, and tissue from uterus and ovaries identified cells with a 45,X chromosome complement. The patient was delivered of a normal male. His karyotype is 46,XY. The patient has resumed normal menstruation, and hormonal studies are compatible with ovulatory cycles. Questions raised by this patient and the comments of Dr Otto and his colleagues (July 30, p. 257) prompted us to review the literature on fetal wastage and anomalies in the offspring of women with a 45,X or 45,X mosaic chromosome constitution. We identified forty-five such pregnancies. 2 pregnancies were terminated.. 15 ended in spontaneous abortion and 4 in stillbirth. 2 infants died during the neonatal period. 3 had trisomy 21. 5 cases of gonadal dysgenesis were identified. Thus 21 of the 43 non-terminated pregnancies (49%) ended in fetal loss or neonatal death. Congenital anomalies (trisomy 21,
gonadal dysgenesis, congenital heart-disease, or hydrocephalus) occurred in 26% (11 of 43) of these pregnancies. If only liveborn infants are considered 10 of 25 pregnancies (40%) had a congenital anomaly. Although data are available from only a limited number of patients, we feel that the following conclusions are warranted: (1) pregnancy in a woman with Turner syndrome carries an increased risk of fetal wastage; (2) the frequency of congenital malformations is increased in infants born to such women; and (3) such infants will have an increased frequency of chromosome anomalies. Most patients with the Turner syndrome are infertile but some patients will become pregnant and they should be advised of these risks. Because of the increased frequency of chromosome anomalies (especially trisomy 21) in their offspring these women should be told that amniocentesis is available for the midtrimester diagnosis of such anomalies. A complete list of references for these obtained from C. R. K.
forty-five pregnancies may be ’
Department of Obstetrics and Gynecology and Division of Medical Genetics, Crippled Children’s Division, University of Oregon Health Sciences Center, Portland, Oregon 97207, U.S.A
CHARLES R. KING ELLEN MAGENIS
LIGNOCAINE AND DEEP-VEIN THROMBOSIS
SIR,-Dr Cooke and his colleagues (Oct. 15, p. 797) report that lignocaine lowers the frequency of deep-vein thrombosis after hip surgery. Discussing the mechanism involved they say that lignocaine has no effect on platelets. In 1949 Feissley and Ludinl used cocaine in high concentration to prevent platelet aggregation and advocated its use in a platelet-counting fluid. Cocaine, procaine, xylocaine, and cinchocaine (’Nupercaine’) have all been reported to inhibit platelet aggregation when added in vitro. These local anaesthetics, some antimalarial and some antihistamine drugs,2 and many anti-inflammatory drugs3 share the property of being membrane active. In vitro all alter platelet function. In vivo lignocaine may have other relevant effects but by extension from the above reports its reported effect in deepvenous thrombosis may be due to in-vivo alterations of the ntatftft mf’mhrl’lnf’
Accident & Emergency Department, Royal Victoria Hospital, Belfast BT12 6BA 1. 2.
Grimson, T. A. Lancet, 1977, i, 858. Curtes, J. P., Develay, P. Bull. med. leg.
PETER G. NELSON
urg. Med. Cent.
20, 137. 3. Grimson, T. A. Lancet, 1977, i, 858. 4. Delaney, J. C., Ravey, M. ibid. 1977, ii, 512. 5. Robinson, T. J., Mulligan, T. O. ibid. p. 719.
Anti-Poisons, 1977,
Portsmouth & South East Hampshire District Pathology Service, Central Laboratory, St. Mary’s Hospital, Portsmouth PO3 6AG 1. 2.
Feissley, R., Ludin, H. Rev. Hœmat. 1949, 4, 481. O’Brien, J. R. J. clin. Path. 1962, 15, 446.
3. O’Brien, J. R. Lancet, 1968, i, 894.
J. R. O’BRIEN
diagnosis was a Mallory-Weiss tear of the gastric mucosa. Over the next few days, the patient’s mid-epigastric pain abated and there were no further signs of active gastrointestinal bleeding. This case emphasises that nausea and vomiting, a common toxicity with many chemotherapeutic agents, may have serious clinical sequelx. Fortunately for our patient, the MalloryWeiss tear was self-limiting and was managed without blood transfusions. Because giving 5-F.u. and methyl-c.c.N.u. on the same day may have potentiated the gastrointestinal toxicity, we now give them on separate days and encourage the early use of antiemetics. Our experience should alert others to this possible complication in the combined use of these drugs and other chemotherapeutic agents which evoke nausea and vomiting. Department
of Medicine,
Hematology/Oncology Service, William Beaumont Army Medical Center, El Paso, Texas 79920, U.S.A.
ROBERT E. ENCK
CIMETIDINE AND MENTAL CONFUSION
SIR,-The reports by Grimson’ and Dr Delaney and Dr Ravey (Sept. 3, p. 512) of confusion after treatment with cimetidine prompt me to describe a recent case. A 78-year-old man, with a long history of reflux oesophagitis, presented with hsematemesis and melaena. Endoscopy showed fresh bleeding from the lower third of his oesophagus secondary to peptic cesophagitis. He was treated with a normal dose of cimetidine and 48 h later became drowsy, confused, restless, and unmanageable. His renal function was normal. The cimetidine was stopped and within 24 h his mental state improved with a subsequent return to normal. This improvement suggests that the confusion was caused by the treatment. Central Middlesex London NW10
Hospital,
NEIL MENZIES-GOW
SIR,-Little is known about the acute toxic effects of the histamine H2-receptor blocking agent cimetidine. Smith, Kline & French Laboratories Ltd, the makers, have details of 3 cases of overdose, 1 of which has been published.2 I describe here a case with some unusual features. A 25-year-old man was admitted to hospital 4 h after allegedly taking about 60 tablets (12 g) of cimetidine recently prescribed for a proven duodenal ulcer. His speech was slurred, his pupils dilated with a sluggish light reflex, and his pulse-rate was 120/min. There was no evidence that alcohol or other drugs had been taken. Gastric lavage was done. 5 h later he was seen picking the bedclothes in an agitated, aimless fashion. He was disoriented in time and place and his conversation was staccato and nonsensical. His pulse-rate was 110/min, blood-pressure 100/70 mm Hg and his pupils were still dilated. The following day he was completely lucid mentally. The patient’s electrocardiograph, hepatic and renal function, and blood indices remained normal throughout his admission. His blood-sugar was 3.6 mmol/1 36 h after taking the drug, although it was normal (5.7 mmol/1) during his acute cerebral disturbance. Grimson3 reported mental confusion in 2 patients who had been taking twice the recommended therapeutic dose of cimetidine for a short time. This report and others4,5 adds weight to the growing suspicion that the drug may occasionally cause
cerebral toxicity.
FETAL WASTAGE AND CHROMOSOME ANOMALIES IN OFFSPRING OF PATIENTS WITH
TURNER SYNDROME
SIR,-We have investigated a 21-year-old White female with short stature, cubitus valgus, and multiple cutaneous naevi. Quinacrine banding of peripheral-blood lymphocytes, skin fibroblasts, and tissue from uterus and ovaries identified cells with a 45,X chromosome complement. The patient was delivered of a normal male. His karyotype is 46,XY. The patient has resumed normal menstruation, and hormonal studies are compatible with ovulatory cycles. Questions raised by this patient and the comments of Dr Otto and his colleagues (July 30, p. 257) prompted us to review the literature on fetal wastage and anomalies in the offspring of women with a 45,X or 45,X mosaic chromosome constitution. We identified forty-five such pregnancies. 2 pregnancies were terminated.. 15 ended in spontaneous abortion and 4 in stillbirth. 2 infants died during the neonatal period. 3 had trisomy 21. 5 cases of gonadal dysgenesis were identified. Thus 21 of the 43 non-terminated pregnancies (49%) ended in fetal loss or neonatal death. Congenital anomalies (trisomy 21,
gonadal dysgenesis, congenital heart-disease, or hydrocephalus) occurred in 26% (11 of 43) of these pregnancies. If only liveborn infants are considered 10 of 25 pregnancies (40%) had a congenital anomaly. Although data are available from only a limited number of patients, we feel that the following conclusions are warranted: (1) pregnancy in a woman with Turner syndrome carries an increased risk of fetal wastage; (2) the frequency of congenital malformations is increased in infants born to such women; and (3) such infants will have an increased frequency of chromosome anomalies. Most patients with the Turner syndrome are infertile but some patients will become pregnant and they should be advised of these risks. Because of the increased frequency of chromosome anomalies (especially trisomy 21) in their offspring these women should be told that amniocentesis is available for the midtrimester diagnosis of such anomalies. A complete list of references for these obtained from C. R. K.
forty-five pregnancies may be ’
Department of Obstetrics and Gynecology and Division of Medical Genetics, Crippled Children’s Division, University of Oregon Health Sciences Center, Portland, Oregon 97207, U.S.A
CHARLES R. KING ELLEN MAGENIS
LIGNOCAINE AND DEEP-VEIN THROMBOSIS
SIR,-Dr Cooke and his colleagues (Oct. 15, p. 797) report that lignocaine lowers the frequency of deep-vein thrombosis after hip surgery. Discussing the mechanism involved they say that lignocaine has no effect on platelets. In 1949 Feissley and Ludinl used cocaine in high concentration to prevent platelet aggregation and advocated its use in a platelet-counting fluid. Cocaine, procaine, xylocaine, and cinchocaine (’Nupercaine’) have all been reported to inhibit platelet aggregation when added in vitro. These local anaesthetics, some antimalarial and some antihistamine drugs,2 and many anti-inflammatory drugs3 share the property of being membrane active. In vitro all alter platelet function. In vivo lignocaine may have other relevant effects but by extension from the above reports its reported effect in deepvenous thrombosis may be due to in-vivo alterations of the ntatftft mf’mhrl’lnf’
Accident & Emergency Department, Royal Victoria Hospital, Belfast BT12 6BA 1. 2.
Grimson, T. A. Lancet, 1977, i, 858. Curtes, J. P., Develay, P. Bull. med. leg.
PETER G. NELSON
urg. Med. Cent.
20, 137. 3. Grimson, T. A. Lancet, 1977, i, 858. 4. Delaney, J. C., Ravey, M. ibid. 1977, ii, 512. 5. Robinson, T. J., Mulligan, T. O. ibid. p. 719.
Anti-Poisons, 1977,
Portsmouth & South East Hampshire District Pathology Service, Central Laboratory, St. Mary’s Hospital, Portsmouth PO3 6AG 1. 2.
Feissley, R., Ludin, H. Rev. Hœmat. 1949, 4, 481. O’Brien, J. R. J. clin. Path. 1962, 15, 446.
3. O’Brien, J. R. Lancet, 1968, i, 894.
J. R. O’BRIEN
