893
(R chalepensis) growing near Malaga airport. Other cases involving this species have been reported.4 Other suspect species such as pitch trefoil (Psoralea bituminosa)3 also grow near popular Mediterranean resorts.
Several plants suspected of causing PPD in North America are also found in Britain. Yarrow (Achillea millefolium) and stinking chamomile (Anthemis cotula) are examples. Neither contains furocoumarins and it is disputable whether they cause PPD.1,3 The use ofstrimmers to clear vegetation on roadside verges and in gardens usually results in abundant airborne plant particles and sap-containing aerosols so it is a very efficient way of bringing phytotoxins into contact with skin. The plants involved in PPD incidents in Britain will often not be identified correctly and there is little awareness of the spectrum of species that contain furocoumarins. Increased consultation between doctors and botanists should help. School of Biological Sciences, University of Wales, Swansea, SA2 8PP, UK
C. R. HIPKIN
1 Mitchell J, Rook A. Botanical dermatology: plants and plant products injurious to the skin. Vancouver: Greengrass, 1979. 2. Camm E, Buck HWL, Mitchell JC. Phytophotodermatitis from Heracleum mantegazzianum. Contact Dermatitis 1989; 21: 300-03. 3. Benezra C, Ducombs G, Sell Y, Foussereau J. Plant contact dermatitis. Toronto: B C Decker, 1985. 4. Brener S, Friedman J. Phytophotodermatitis induced by Ruta chalepensis. Contact Dermatitis 1985; 12: 230-02.
Laparoscopic appendicectomy SIR,-Mr Mc Anena and colleagues (Sept 14, p 693) report a thoughtful analysis of the efficacy of appendicectomy done laparoscopically. However, their study raises some important
intake
were: carbamazepine 74 )ig/ml, sodium valproate 54 )ig/ml (both within therapeutic range), and vigabatrin 152 )g/ml. Electroencephalography (EEG) showed diffuse and multifocal abnormalities as before, without any signs of deterioration. When vigibatrin was reduced to 2000 mg daily the abnormal movement pattern disappeared within 3 days and did not return. Vigabatrin at
this dose was continued for another two months but was ineffective. Patient 2-A 2-year-old boy had severe symptomatic generalised epilepsy following Ohtahara syndrome (early infantile epileptic encephalopathy with suppression bursts). Severe hyperkinesia with bouts of inappropriate laughing developed following the gradual introduction of vigabatrin up to 1000 mg daily. He was also receiving carbamazepine and sodium valproate, with serum concentrations of both drugs well within the therapeutic range (carbamazepine 4-8 g/ml, sodium valproate 75 )g/ml). EEG at this time showed a deterioration of background activity compared with previous recordings; the epileptiform discharges were unchanged. Withdrawal of vigabatrin resulted in the disappearance of the abnormal motor behaviour and EEG findings returned to previous values. Akathisia, severe hyperkinesia, and possibly forced laughing have so far as we are aware not been reported as side-effects of vigabatrin, although comparable motor disturbances have occasionally been associated notably with the use of phenytoin, but also with other antiepileptic drugs, especially in brain-damaged patients.l-4 The pathophysiology underlying these reactions to vigabatrin remains unclear, as does the association of this drug with carbamazepine and sodium valproate co-medication. We therefore emphasise the need to be alert for further instances of effects of vigabatrin on motor behaviour and would welcome reports of
comparable cases. M. J. JONGSMA
issues. of normal histology at about 24% is quite high. This would clearly increase the chances of a successful operation, and therefore the proportion of failed laparoscopies would be artificially low. Secondly, the inpatient stay of open appendicectomy was rather long at an average of about 5 days. Many units have a typical stay of 3 days, which is much closer to the 2-2 days reported by Mc Anena et al for laparoscopic appendicectomy. Finally, what are the possible consequences for the provision of surgical services, particularly in district general hospitals? As in the study, the laparoscopic procedure can be done only by senior staff, of whom there are few in many hospitals. Most appendicectomies are done competently by junior staff (senior house officer and registrar grade); widespread adoption of this newer method with only possible marginal benefits would necessitate appendicectomies being done by consultants.
Firstly,
a rate
Department of Surgery, Sandwell District General Hospital, West Bromwich B71 4HJ, UK
ANJAN K. BANERJEE
Reversible motor disturbances induced by
vigabatrin SIR,-We report two patients with unusual disturbances of behaviour, associated with the introduction of vigabatrin as
motor
additional therapy for intractable seizures. Patient 1-A 15-year-old girl with tuberous sclerosis and refractory epilepsy was insufficiently controlled with carbamazepine 1400 mg daily and sodium valproate 1650 mg daily. Serum concentrations of both drugs were within the therapeutic range. Because of intolerable seizure frequency and the efficacy of vigabatrin in tuberous sclerosis we decided to add this drug to the existing regimen, starting at 500 mg daily and slowly increasing the dose by 500 mg per week. At 1500 mg daily vigabatrin did not have any effect on the seizures. A further increase of the dose to 3000 mg daily resulted in an increase in seizure frequency and induced excessive stereotyped involuntary movements. When relaxed she almost continuously rubbed her feet over the floor and her right or left arm with the other hand, while humming. These akathisia-like movements improved by attention and disappeared during sleep. Laboratory tests were normal. Drug serum concentrations 1 h after
Instituut voor Epilepsiebestrijding, "Meer en Bosch"/"De Cruquiushoeve", 2103 SW Heemstede, Netherlands
L. A. E. M. LAAN W. VAN EMDE BOAS H. MEINARDI
1. Wiznitzer M, Younkin D. Phenobarbital-induced dyskinesia in a neurologicallyimpaired child. Neurology 1984; 34: 1600-01. 2. Krishnamoorthy KS, Zalneraites EL, Young RSK, Bernard PG. Phenytoin-induced choreoathetosis in infancy. Pediatrics 1983; 72: 831-34. 3. Ehyai A, Kilroy A, Fenichel G. Dyskinesia and akathisia induced by ethosuximide. 4.
Am J Dis Child 1978; 132: 527-28. Bimpong-Buta K, Froescher W. Carbamazepine-induced choreoathetoid dyskinesias. J Neurol Neurosurg Psychiatry 1982; 45: 560.
Immunoglobulin therapy SIR,-Your July 20 editorial on jmmunogiobutin therapy presents a lot of useful information but we wish to correct a misleading impression that may have been left among readers, especially those in North America. Although the use of intramuscular immune globulin (IMIG) in primary immunodeficiency was reported nearly 40 years ago,’ the product had already been used for years in the prophylaxis of hepatitis A2 and measles.3 Throughout this time, IMIG manufactured by the Cohn-Oncley cold alcohol process (or a streamlined variant) had a superb record with respect to transmission of hepatitis B, despite the fact that no test for HBsAg existed. Indeed, when a pool of known icterogenic plasma was fractionated by this procedure and the resulting IMIG was injected into human volunteers, no hepatitis B resulted,4-6 In the United States testing for HBsAg began more than 20 years ago, and testing with kits of third-generation sensitivity has been in place for more than 15 years. Although this testing may have had some beneficial effect on the safety of IMIG prepared by other methods (eg, ammonium sulphate or ether precipitation), it had no detectable impact on the risk of hepatitis B transmission by IMIG made by the Cohn-Oncley procedure because there was no direct evidence of risk posed by this product, even before testing was instituted. We agree that both IMIG and, with the notable exceptions cited, IVIG have had long and impressive safety records with respect to non-A, non-B hepatitis and that the reasons for this safety are unclear. However, for reasons discussed earlier,’ it cannot be
(R chalepensis) growing near Malaga airport. Other cases involving this species have been reported.4 Other suspect species such as pitch trefoil (Psoralea bituminosa)3 also grow near popular Mediterranean resorts.
Several plants suspected of causing PPD in North America are also found in Britain. Yarrow (Achillea millefolium) and stinking chamomile (Anthemis cotula) are examples. Neither contains furocoumarins and it is disputable whether they cause PPD.1,3 The use ofstrimmers to clear vegetation on roadside verges and in gardens usually results in abundant airborne plant particles and sap-containing aerosols so it is a very efficient way of bringing phytotoxins into contact with skin. The plants involved in PPD incidents in Britain will often not be identified correctly and there is little awareness of the spectrum of species that contain furocoumarins. Increased consultation between doctors and botanists should help. School of Biological Sciences, University of Wales, Swansea, SA2 8PP, UK
C. R. HIPKIN
1 Mitchell J, Rook A. Botanical dermatology: plants and plant products injurious to the skin. Vancouver: Greengrass, 1979. 2. Camm E, Buck HWL, Mitchell JC. Phytophotodermatitis from Heracleum mantegazzianum. Contact Dermatitis 1989; 21: 300-03. 3. Benezra C, Ducombs G, Sell Y, Foussereau J. Plant contact dermatitis. Toronto: B C Decker, 1985. 4. Brener S, Friedman J. Phytophotodermatitis induced by Ruta chalepensis. Contact Dermatitis 1985; 12: 230-02.
Laparoscopic appendicectomy SIR,-Mr Mc Anena and colleagues (Sept 14, p 693) report a thoughtful analysis of the efficacy of appendicectomy done laparoscopically. However, their study raises some important
intake
were: carbamazepine 74 )ig/ml, sodium valproate 54 )ig/ml (both within therapeutic range), and vigabatrin 152 )g/ml. Electroencephalography (EEG) showed diffuse and multifocal abnormalities as before, without any signs of deterioration. When vigibatrin was reduced to 2000 mg daily the abnormal movement pattern disappeared within 3 days and did not return. Vigabatrin at
this dose was continued for another two months but was ineffective. Patient 2-A 2-year-old boy had severe symptomatic generalised epilepsy following Ohtahara syndrome (early infantile epileptic encephalopathy with suppression bursts). Severe hyperkinesia with bouts of inappropriate laughing developed following the gradual introduction of vigabatrin up to 1000 mg daily. He was also receiving carbamazepine and sodium valproate, with serum concentrations of both drugs well within the therapeutic range (carbamazepine 4-8 g/ml, sodium valproate 75 )g/ml). EEG at this time showed a deterioration of background activity compared with previous recordings; the epileptiform discharges were unchanged. Withdrawal of vigabatrin resulted in the disappearance of the abnormal motor behaviour and EEG findings returned to previous values. Akathisia, severe hyperkinesia, and possibly forced laughing have so far as we are aware not been reported as side-effects of vigabatrin, although comparable motor disturbances have occasionally been associated notably with the use of phenytoin, but also with other antiepileptic drugs, especially in brain-damaged patients.l-4 The pathophysiology underlying these reactions to vigabatrin remains unclear, as does the association of this drug with carbamazepine and sodium valproate co-medication. We therefore emphasise the need to be alert for further instances of effects of vigabatrin on motor behaviour and would welcome reports of
comparable cases. M. J. JONGSMA
issues. of normal histology at about 24% is quite high. This would clearly increase the chances of a successful operation, and therefore the proportion of failed laparoscopies would be artificially low. Secondly, the inpatient stay of open appendicectomy was rather long at an average of about 5 days. Many units have a typical stay of 3 days, which is much closer to the 2-2 days reported by Mc Anena et al for laparoscopic appendicectomy. Finally, what are the possible consequences for the provision of surgical services, particularly in district general hospitals? As in the study, the laparoscopic procedure can be done only by senior staff, of whom there are few in many hospitals. Most appendicectomies are done competently by junior staff (senior house officer and registrar grade); widespread adoption of this newer method with only possible marginal benefits would necessitate appendicectomies being done by consultants.
Firstly,
a rate
Department of Surgery, Sandwell District General Hospital, West Bromwich B71 4HJ, UK
ANJAN K. BANERJEE
Reversible motor disturbances induced by
vigabatrin SIR,-We report two patients with unusual disturbances of behaviour, associated with the introduction of vigabatrin as
motor
additional therapy for intractable seizures. Patient 1-A 15-year-old girl with tuberous sclerosis and refractory epilepsy was insufficiently controlled with carbamazepine 1400 mg daily and sodium valproate 1650 mg daily. Serum concentrations of both drugs were within the therapeutic range. Because of intolerable seizure frequency and the efficacy of vigabatrin in tuberous sclerosis we decided to add this drug to the existing regimen, starting at 500 mg daily and slowly increasing the dose by 500 mg per week. At 1500 mg daily vigabatrin did not have any effect on the seizures. A further increase of the dose to 3000 mg daily resulted in an increase in seizure frequency and induced excessive stereotyped involuntary movements. When relaxed she almost continuously rubbed her feet over the floor and her right or left arm with the other hand, while humming. These akathisia-like movements improved by attention and disappeared during sleep. Laboratory tests were normal. Drug serum concentrations 1 h after
Instituut voor Epilepsiebestrijding, "Meer en Bosch"/"De Cruquiushoeve", 2103 SW Heemstede, Netherlands
L. A. E. M. LAAN W. VAN EMDE BOAS H. MEINARDI
1. Wiznitzer M, Younkin D. Phenobarbital-induced dyskinesia in a neurologicallyimpaired child. Neurology 1984; 34: 1600-01. 2. Krishnamoorthy KS, Zalneraites EL, Young RSK, Bernard PG. Phenytoin-induced choreoathetosis in infancy. Pediatrics 1983; 72: 831-34. 3. Ehyai A, Kilroy A, Fenichel G. Dyskinesia and akathisia induced by ethosuximide. 4.
Am J Dis Child 1978; 132: 527-28. Bimpong-Buta K, Froescher W. Carbamazepine-induced choreoathetoid dyskinesias. J Neurol Neurosurg Psychiatry 1982; 45: 560.
Immunoglobulin therapy SIR,-Your July 20 editorial on jmmunogiobutin therapy presents a lot of useful information but we wish to correct a misleading impression that may have been left among readers, especially those in North America. Although the use of intramuscular immune globulin (IMIG) in primary immunodeficiency was reported nearly 40 years ago,’ the product had already been used for years in the prophylaxis of hepatitis A2 and measles.3 Throughout this time, IMIG manufactured by the Cohn-Oncley cold alcohol process (or a streamlined variant) had a superb record with respect to transmission of hepatitis B, despite the fact that no test for HBsAg existed. Indeed, when a pool of known icterogenic plasma was fractionated by this procedure and the resulting IMIG was injected into human volunteers, no hepatitis B resulted,4-6 In the United States testing for HBsAg began more than 20 years ago, and testing with kits of third-generation sensitivity has been in place for more than 15 years. Although this testing may have had some beneficial effect on the safety of IMIG prepared by other methods (eg, ammonium sulphate or ether precipitation), it had no detectable impact on the risk of hepatitis B transmission by IMIG made by the Cohn-Oncley procedure because there was no direct evidence of risk posed by this product, even before testing was instituted. We agree that both IMIG and, with the notable exceptions cited, IVIG have had long and impressive safety records with respect to non-A, non-B hepatitis and that the reasons for this safety are unclear. However, for reasons discussed earlier,’ it cannot be
