1223
1. Cornelis G, Laroche Y, Balligand G, Sory M-P, Wauters G Yersinia enterocolitica, a primary model for bacterial invasiveness. Rev Infect Dis 1987; 9: 64-87. 2. Jones BL, Saw MH, Hanson MF, Mackie MJ, Scott JG, Murphy WG. Yersinia enterocolitica septicaemia from blood transfusion. Transfusion Med 1992; 2 (suppl
1)· 86. I, Norlander L, Wolf-Watz H. Temperature-inducible outer-membrane protein of Yersinia pseudotuberculosis and Yersima enterocolitica is associated with the virulence plasmid. Infect Immun 1982; 37: 506-12. 4. CDC. Update: Yersinia enterocolitica bacteraemia and endotoxic shock associated with red blood cell transfusions: United States, 1991. MMWR 1991; 40: 176-78. 5. Scott J, Boulton FE, Govan JRW, Miles RS, McClelland DBL, Prowse CV. A fatal 3. Bolin
transfusion reaction associated with blood contaminated with Pseudomonas Vox Sang 1988; 54: 201-04.
fluorescens.
Lamotrigine for generalised epilepsies SIR,-4Controlled trials of new antiepileptic drugs are done initially in adults with chronic drug-resistant epilepsy. Such patients usually have partial seizures with or without secondary generalisation. Lamotrigine is now licensed in Ireland and the UK as add-on treatment in these seizure types. In reviewing their experience of 82 patients treated with lamotrigine on a namedpatient basis, Timmings and Richens1 excluded 22 patients with no response or unacceptable adverse events and found that, among the remaining 60, those with primary generalised epilepsy did at least as well as those with partial epilepsies. Our experience also suggests an important role for lamotrigine in primary generalised epilepsy. Since 1987 we have treated 72 chronic drug-resistant adult epileptic patients with lamotrigine, of whom 63 had partial seizures with or without secondary generalisation, 4 had primary generalised epilepsy, and 5 seizures of uncertain classification. Without excluding any, we found that of the patients with partial seizures with or without secondary generalisation, 30% had improved seizure control of 50% or greater. This finding is similar to that in controlled and uncontrolled studies.2 Only 1 of these patients (with frequent secondary generalised attacks) has become seizure-free. However, of the 4 with primary generalised epilepsy, 2 have been seizure-free for up to 3 years and 2 have improved by over 75%. Overall experience suggests that efficacy of lamotrigine in patients with chronic partial epilepsies is not quite as good as that with vigabatrin, although individual patients may do better on one drug than the other. The overall response rate (! 50% fall in seizure frequency) of around one-third with lamotrigine can be compared with a rate of approximately one-half with vigabatrin.3 However, lamotrigine may prove to be more effective than vigabatrin for primary generalised seizures. Furthermore, we have been impressed with 3 intractable patients who had failed to respond to temporal lobectomies and who subsequently considerably improved (> 80% reduction in seizure frequency) on lamotrigine plus vigabatrin, having shown modest or no response to either drug given individually.4 These patients had clinical and electroencephalographic evidence of frequent secondary generalisation (which may have accounted for their poor response to neurosurgery), which improved after the addition of lamotrigine to vigabatrin. The potential value of this combination of two new drugs has also been noted by Dr G. Schapel (Queen Elizabeth Hospital, Woodville, South Australia). Because vigabatrin, which increases inhibition by raising gamma-aminobutyric acid concentrations, seems more useful for partial seizures and lamotrigine, which reduces excitation (perhaps by inhibiting glutamate release), seems more useful for generalised seizures, studies of the combination in intractable patients with both seizure types are indicated. Department of Neurology, King’s College Hospital, London SE5 9RS, UK 1. Timmings PL, Richens A
J. STEWART E. HUGHES E. H. REYNOLDS
Lamotrigine in primary generalised epilepsy. Lancet 1992; 339: 1300-01. 2. Binnie C. An overview. efficacy of lamotrigine. In Richens A, ed. Clinical update on lamotrigine: a novel antiepileptic agent. Royal Tunbridge Wells: Wells Medical, International Clinical Practice Series, 1992: 31-41. 3. Ring HA, Reynolds EH. Vigabatrin. In: Pedley TA, Meldrum BS, eds. Recent advances in epilepsy, No 5. Edinburgh: Churchill Livingstone, 1992: 177-95. 4 Kirker A, Reynolds EH. Vigabatrin and lamotrigine in a patient with intractable epilepsy. Acta Neurol Scand 1990; 82 (suppl 133): S38-39. 5. Stewart J, Hughes E, Kirker S, Reynolds EH. Combined vigabatrin and lamotrigine for very intractable epilepsy. Seizure 1992; 1 (Suppl A): 13-39.
Ondansetron and
hyperemesis gravidarum
SiR,—In a case of life-threatening hyperemesis gravidarum in which the expected benefit to the patient was thought to outweigh any possible risk to the fetus, we decided to administer ondansetron as an anti-emetic. A 21-year-old pregnant primigravida in her 6th gestational week was admitted on Feb 2,1992, with 8-16 vomits daily. The patient was treated for 1 month with intravenous metoclopramide 10 mg three times daily and dimenhydrinate suppository 100 mg twice daily without success. During the month, the patient could not take anything by mouth and she received continuous intravenous infusion of fluids. The patient’s condition began to deteriorate (dehydration, loss of weight, electrolyte imbalance) to the point of needing urgent and intensive care. Her condition was considered so life-threatening for her as well as the fetus that we decided to administer ondansetron after informing the patient and her immediate family about possible risks. Ondansetron 8 mg was administered in the 11 th gestational week intravenously three times a day. The patient vomited only once during the first day of treatment and stopped vomiting from the second day. Ondansetron had to be continued for 14 days, because every time we decided to stop treatment the patient started to vomit. Because of her significant improvement, the patient began to eat and drink normally from the second day onwards. We followed up this pregnancy until the patient gave birth to a full-term healthy girl of 3-2kg. The second stage of labour lasted 2 h
only. 3rd Department of Obstetrics and
Gynaecology,
Obstetric and Gynaecological Centre of Athens, "Helena E Venizelou", Athens 115 21, Greece
EVAN GUIKONTES ANASTASIOS SPANTIDEAS
JOHN DIAKAKIS
Hiccough relief with cisapride SIR,-Persistent hiccough is distressing, and management can 84-year-old man, who had had a previous mild cerebrovascular accident, presented with renal failure as a result of
prove difficult. An
obstructive uropathy. The obstruction was cleared and renal function returned to normal. However, hiccoughs, which were originally attributed to the above diagnoses, persisted. Treatment with
chlorpromazine, baclofen,
naproxen, and
metoclopramide
unsuccessful. The patient was subsequently found to have gastrooesophageal reflux and he was started on cisapride. The hiccoughs resolved. Withdrawal of cisapride was associated with hiccough recurrence, and rechallenge relieved the hiccough. was
Medicine for the Elderly, Stracathro Hospital,
Brechin,
Angus DD9 7QA, UK
M. C. DUFFY H. EDMOND K. CAMPBELL J. D. FULTON
Benzodiazepine sensitivity in Leber’s hereditary optic neuroretinopathy SIR,-In Leber’s hereditary optic neuropathy (LHON), 50-62% of patients have a mutation in the ND4 and 14% in the NDof the mitochondrially encoded subunits of complex I (NADH-ubiquinone oxidoreductase) of the respiratory chain.l,22 Patients with LHON have reduced complex I activity, which demonstrates that these mtDNA mutations cause functional disturbances.3-5 Affected and non-affected LHON family members may develop cardiac arrhythmia with fatal outcome.6 LHON patients may be exceptionally sensitive to ordinary doses of drugs that normally have little respiratory depressant activity.7 We describe a patient with LHON who developed severe respiratory
insufficiency after oxazepam. Our patient is a 33-year-old
man from a large Finnish family with LHON. His visual symptoms manifested in 1978 and led to
1. Cornelis G, Laroche Y, Balligand G, Sory M-P, Wauters G Yersinia enterocolitica, a primary model for bacterial invasiveness. Rev Infect Dis 1987; 9: 64-87. 2. Jones BL, Saw MH, Hanson MF, Mackie MJ, Scott JG, Murphy WG. Yersinia enterocolitica septicaemia from blood transfusion. Transfusion Med 1992; 2 (suppl
1)· 86. I, Norlander L, Wolf-Watz H. Temperature-inducible outer-membrane protein of Yersinia pseudotuberculosis and Yersima enterocolitica is associated with the virulence plasmid. Infect Immun 1982; 37: 506-12. 4. CDC. Update: Yersinia enterocolitica bacteraemia and endotoxic shock associated with red blood cell transfusions: United States, 1991. MMWR 1991; 40: 176-78. 5. Scott J, Boulton FE, Govan JRW, Miles RS, McClelland DBL, Prowse CV. A fatal 3. Bolin
transfusion reaction associated with blood contaminated with Pseudomonas Vox Sang 1988; 54: 201-04.
fluorescens.
Lamotrigine for generalised epilepsies SIR,-4Controlled trials of new antiepileptic drugs are done initially in adults with chronic drug-resistant epilepsy. Such patients usually have partial seizures with or without secondary generalisation. Lamotrigine is now licensed in Ireland and the UK as add-on treatment in these seizure types. In reviewing their experience of 82 patients treated with lamotrigine on a namedpatient basis, Timmings and Richens1 excluded 22 patients with no response or unacceptable adverse events and found that, among the remaining 60, those with primary generalised epilepsy did at least as well as those with partial epilepsies. Our experience also suggests an important role for lamotrigine in primary generalised epilepsy. Since 1987 we have treated 72 chronic drug-resistant adult epileptic patients with lamotrigine, of whom 63 had partial seizures with or without secondary generalisation, 4 had primary generalised epilepsy, and 5 seizures of uncertain classification. Without excluding any, we found that of the patients with partial seizures with or without secondary generalisation, 30% had improved seizure control of 50% or greater. This finding is similar to that in controlled and uncontrolled studies.2 Only 1 of these patients (with frequent secondary generalised attacks) has become seizure-free. However, of the 4 with primary generalised epilepsy, 2 have been seizure-free for up to 3 years and 2 have improved by over 75%. Overall experience suggests that efficacy of lamotrigine in patients with chronic partial epilepsies is not quite as good as that with vigabatrin, although individual patients may do better on one drug than the other. The overall response rate (! 50% fall in seizure frequency) of around one-third with lamotrigine can be compared with a rate of approximately one-half with vigabatrin.3 However, lamotrigine may prove to be more effective than vigabatrin for primary generalised seizures. Furthermore, we have been impressed with 3 intractable patients who had failed to respond to temporal lobectomies and who subsequently considerably improved (> 80% reduction in seizure frequency) on lamotrigine plus vigabatrin, having shown modest or no response to either drug given individually.4 These patients had clinical and electroencephalographic evidence of frequent secondary generalisation (which may have accounted for their poor response to neurosurgery), which improved after the addition of lamotrigine to vigabatrin. The potential value of this combination of two new drugs has also been noted by Dr G. Schapel (Queen Elizabeth Hospital, Woodville, South Australia). Because vigabatrin, which increases inhibition by raising gamma-aminobutyric acid concentrations, seems more useful for partial seizures and lamotrigine, which reduces excitation (perhaps by inhibiting glutamate release), seems more useful for generalised seizures, studies of the combination in intractable patients with both seizure types are indicated. Department of Neurology, King’s College Hospital, London SE5 9RS, UK 1. Timmings PL, Richens A
J. STEWART E. HUGHES E. H. REYNOLDS
Lamotrigine in primary generalised epilepsy. Lancet 1992; 339: 1300-01. 2. Binnie C. An overview. efficacy of lamotrigine. In Richens A, ed. Clinical update on lamotrigine: a novel antiepileptic agent. Royal Tunbridge Wells: Wells Medical, International Clinical Practice Series, 1992: 31-41. 3. Ring HA, Reynolds EH. Vigabatrin. In: Pedley TA, Meldrum BS, eds. Recent advances in epilepsy, No 5. Edinburgh: Churchill Livingstone, 1992: 177-95. 4 Kirker A, Reynolds EH. Vigabatrin and lamotrigine in a patient with intractable epilepsy. Acta Neurol Scand 1990; 82 (suppl 133): S38-39. 5. Stewart J, Hughes E, Kirker S, Reynolds EH. Combined vigabatrin and lamotrigine for very intractable epilepsy. Seizure 1992; 1 (Suppl A): 13-39.
Ondansetron and
hyperemesis gravidarum
SiR,—In a case of life-threatening hyperemesis gravidarum in which the expected benefit to the patient was thought to outweigh any possible risk to the fetus, we decided to administer ondansetron as an anti-emetic. A 21-year-old pregnant primigravida in her 6th gestational week was admitted on Feb 2,1992, with 8-16 vomits daily. The patient was treated for 1 month with intravenous metoclopramide 10 mg three times daily and dimenhydrinate suppository 100 mg twice daily without success. During the month, the patient could not take anything by mouth and she received continuous intravenous infusion of fluids. The patient’s condition began to deteriorate (dehydration, loss of weight, electrolyte imbalance) to the point of needing urgent and intensive care. Her condition was considered so life-threatening for her as well as the fetus that we decided to administer ondansetron after informing the patient and her immediate family about possible risks. Ondansetron 8 mg was administered in the 11 th gestational week intravenously three times a day. The patient vomited only once during the first day of treatment and stopped vomiting from the second day. Ondansetron had to be continued for 14 days, because every time we decided to stop treatment the patient started to vomit. Because of her significant improvement, the patient began to eat and drink normally from the second day onwards. We followed up this pregnancy until the patient gave birth to a full-term healthy girl of 3-2kg. The second stage of labour lasted 2 h
only. 3rd Department of Obstetrics and
Gynaecology,
Obstetric and Gynaecological Centre of Athens, "Helena E Venizelou", Athens 115 21, Greece
EVAN GUIKONTES ANASTASIOS SPANTIDEAS
JOHN DIAKAKIS
Hiccough relief with cisapride SIR,-Persistent hiccough is distressing, and management can 84-year-old man, who had had a previous mild cerebrovascular accident, presented with renal failure as a result of
prove difficult. An
obstructive uropathy. The obstruction was cleared and renal function returned to normal. However, hiccoughs, which were originally attributed to the above diagnoses, persisted. Treatment with
chlorpromazine, baclofen,
naproxen, and
metoclopramide
unsuccessful. The patient was subsequently found to have gastrooesophageal reflux and he was started on cisapride. The hiccoughs resolved. Withdrawal of cisapride was associated with hiccough recurrence, and rechallenge relieved the hiccough. was
Medicine for the Elderly, Stracathro Hospital,
Brechin,
Angus DD9 7QA, UK
M. C. DUFFY H. EDMOND K. CAMPBELL J. D. FULTON
Benzodiazepine sensitivity in Leber’s hereditary optic neuroretinopathy SIR,-In Leber’s hereditary optic neuropathy (LHON), 50-62% of patients have a mutation in the ND4 and 14% in the NDof the mitochondrially encoded subunits of complex I (NADH-ubiquinone oxidoreductase) of the respiratory chain.l,22 Patients with LHON have reduced complex I activity, which demonstrates that these mtDNA mutations cause functional disturbances.3-5 Affected and non-affected LHON family members may develop cardiac arrhythmia with fatal outcome.6 LHON patients may be exceptionally sensitive to ordinary doses of drugs that normally have little respiratory depressant activity.7 We describe a patient with LHON who developed severe respiratory
insufficiency after oxazepam. Our patient is a 33-year-old
man from a large Finnish family with LHON. His visual symptoms manifested in 1978 and led to
