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Unusual presentation of porphyria cutanea tarda
55 and 868 umol/L, respectively. Tremor and ataxia resolved when lamotrigine was lowered to 100 mg. The severe postural and action tremor predominantly affecting the upper limbs in these cases was unlike the mild, often intermittent, postural tremor that may occur when valproate is used alone at similar doses and plasma levels.2 The tremor was disabling, sometimes preventing patients from feeding themselves. Although the current target range for plasma lamotrigine (4-16 limol/L) is tentative and may be too low,3 it is likely that high levels were at least partly responsible for the tremor. Valproate inhibits lamotrigine metabolism,4 whereas phenytoin induces the hepatic enzymes responsible for the metabolism of valproate and lamotrigine.3 In the third case, severe tremor developed only when phenytoin was withdrawn, unmasking the effect of valproate on lamotrigine metabolism. In addition to this pharmacokinetic interaction, a pharmacodynamic interaction between valproate and lamotrigine and individual susceptibility may have played a part. We have measured similar or higher random plasma lamotrigine (mean=81 mol/L, range 53-118) without clinical toxicity in six patients. Valproate was also used in three of these patients at daily doses of 500-1000 mg, achieving plasma concentrations within the therapeutic range. Our report emphasises the clinical significance of interactions between lamotrigine and other antiepileptic agents. Whilst a combination of valproate and lamotrigine may have beneficial effects on seizure frequency, it may result in functionally disabling adverse effects, especially at higher doses.
tarda. She
were
DC
Reutens, J S Duncan, P N Patsalos
National Hospital for Neurology and London WC1N 3BG, UK
Neurosurgery, and Institute of Neurology,
Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 445. 2 Hyman NM, Dennis PD, Sinclair KGA. Tremor due to sodium valproate. Neurology 1979; 29: 1177-80. 3 Brodie MJ. Lamotrigine. Lancet 1992; 339: 1397-400. 4 Peck AW. Clinical pharmacology of lamotrigine. Epilepsia 1991; 32 (suppl 2): S9-S12. 1
Unusual tarda
presentation of porphyria cutanea
SIR-A 46-year-old premenopausal woman presented in May, 1989, with epigastric pain unrelieved by antacids or H2antagonists. Her alcohol intake was 5 units per week. There was no family history of liver disease or porphyria. Physical examination was normal, and she had no skin rash. Aspartate aminotransferase was repeatedly raised at 36-52 IU/L; liver function tests were normal. Auto-antibody tests, including anti-smooth muscle and anti-mitochondrial antibodies, were negative. Ferritin was raised at 294 ug/L, as was serum iron 38 -11 umol/L. Gamma glutamyl transaminase was normal. Her oral cholecystogram and barium meal were normal; gastroscopy showed a small hiatus hernia but no oesophagitis; abdominal ultrasound confirmed a normal biliary tree, but there was an uneven texture of the right lobe of the liver, which prompted computerised axial tomography of the abdomen. This showed a liver of below-average size with an abnormally dense texture. Liver biopsy showed siderosis, consistent with a differential diagnosis of early haemachromatosis, alcoholic liver disease,
pernicious anaemia, or porphyria. Urinary porphyrins were 3974 nmol/L per 24 h, with normal concentrations of 5-aminolaevulinate and porphobilinogen, suggestive of porphyria cutanea tarda. A second sample sent to the Porphyrias Service at the Western Infirmary, Glasgow, UK, confirmed the findings. 3 weeks later, the patient developed the photosensitive dermatosis of porphyria cutanea 186
was treated with serial venesection and use of and all her symptoms, including her abdominal
sunblocks, pain, are currently slight. This
is unusual in two respects. Firstly, to our is the first documented instance in which the this knowledge, diagnosis of porphyria cutanea tarda was confirmed biochemically before the onset of a rash. Secondly, the presenting symptom was one of recurrent abdominal pain, normally associated with the acute porphyrias. It is difficult to be certain whether this patient’s abdominal pain was related to her porphyria, although it is interesting that the pain has subsided since her treatment started. case
Neil J Boyle Ciba Pharmaceuticals, Wimblehurst Road, Horsham, West Sussex RH12 4AB, UK
Donal P
Murray
Medical Department,
Sligo General Hospital, Sligo, Ireland
Stability of glutamine in parenteral feeding solutions SIR-van der Hulst et al (May 29, p 1363) provide further evidence that glutamine maintains the integrity of gut mucosa in postoperative patients. They state that glutamine must be provided as a synthetic dipeptide, because its free aminoacid form is unstable in solution during storage. We believe this to be a misconception. Several independent studes have shown that glutamine is stable if the correct pharmaceutical and sterilisation techniques are followed. Wilmore1 reported that the concentration of glutamine in a standard total parenteral nutrition (TPN) solution decreased by 0-1% per 24 h at room temperature and that an aqueous solution of glutamine can be stored for 7-10 days at 4°C without any appreciable accumulation of ammonia. Similarly, Khan et al2 showed only a 2% loss in a TPN solution stored at 4°C for 14 days. We have confirmed that aseptically prepared and filtersterilised solutions containing 25 g/L glutamine can be stored in oxygen-impermeable bags for up to 30 days at 4°C with glutamine losses of less than 0.05%.3 Conversion to glutamate was negligible, pyroglutamate formation was less than 0-02% per day, and ammonia formation less than 0-01 mmol/L per day. These solutions have been incorporated into TPN containing aminoacids, fats, and carbohydrate in a 3 L bag. Stability of the mixture was not adversely effected by the glutamine during storage at 4°C. Ammonia production was less than 01mmol/L per day and glutamine content remained at 98-2% of the original after 30 days.3 Our concern is that many clinicians may consider dipeptide glutamine supplementation too expensive to have a widespread application and we wish to emphasise that, where aseptic pharmacy facilities are available, the use of glutamine in parenteral nutrition is highly costeffective. G Hardy, S J Bevan Oxford Nutrition Ltd, PO Box 31E, Oxford OX4 3UH, UK
B
McElroy
Pharmacy Department, Royal Shrewsbury Hospital, Shrewsbury, UK
T E A
Palmer, R D Griffiths, C Braidwood
Whiston Hospital, Merseyside, UK
1
2 3
Wilmore DW. The safety and efficacy of glutamine in humans. Clin Nutr 1990; 9: 35. Khan K, Hardy G, McElroy B, Elia M. The stability of L-glutamine in total parenteral nutrition solution. Clin Nutr 1991; 10: 193-98. Hardy G, Wiggins D, McElroy B, Thompson GR. Formulation of a glutamine-containing total parenteral nutrition mixture for clinical use. Proc Nutr Soc 1992; 51: 136.
tarda. She
were
DC
Reutens, J S Duncan, P N Patsalos
National Hospital for Neurology and London WC1N 3BG, UK
Neurosurgery, and Institute of Neurology,
Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 445. 2 Hyman NM, Dennis PD, Sinclair KGA. Tremor due to sodium valproate. Neurology 1979; 29: 1177-80. 3 Brodie MJ. Lamotrigine. Lancet 1992; 339: 1397-400. 4 Peck AW. Clinical pharmacology of lamotrigine. Epilepsia 1991; 32 (suppl 2): S9-S12. 1
Unusual tarda
presentation of porphyria cutanea
SIR-A 46-year-old premenopausal woman presented in May, 1989, with epigastric pain unrelieved by antacids or H2antagonists. Her alcohol intake was 5 units per week. There was no family history of liver disease or porphyria. Physical examination was normal, and she had no skin rash. Aspartate aminotransferase was repeatedly raised at 36-52 IU/L; liver function tests were normal. Auto-antibody tests, including anti-smooth muscle and anti-mitochondrial antibodies, were negative. Ferritin was raised at 294 ug/L, as was serum iron 38 -11 umol/L. Gamma glutamyl transaminase was normal. Her oral cholecystogram and barium meal were normal; gastroscopy showed a small hiatus hernia but no oesophagitis; abdominal ultrasound confirmed a normal biliary tree, but there was an uneven texture of the right lobe of the liver, which prompted computerised axial tomography of the abdomen. This showed a liver of below-average size with an abnormally dense texture. Liver biopsy showed siderosis, consistent with a differential diagnosis of early haemachromatosis, alcoholic liver disease,
pernicious anaemia, or porphyria. Urinary porphyrins were 3974 nmol/L per 24 h, with normal concentrations of 5-aminolaevulinate and porphobilinogen, suggestive of porphyria cutanea tarda. A second sample sent to the Porphyrias Service at the Western Infirmary, Glasgow, UK, confirmed the findings. 3 weeks later, the patient developed the photosensitive dermatosis of porphyria cutanea 186
was treated with serial venesection and use of and all her symptoms, including her abdominal
sunblocks, pain, are currently slight. This
is unusual in two respects. Firstly, to our is the first documented instance in which the this knowledge, diagnosis of porphyria cutanea tarda was confirmed biochemically before the onset of a rash. Secondly, the presenting symptom was one of recurrent abdominal pain, normally associated with the acute porphyrias. It is difficult to be certain whether this patient’s abdominal pain was related to her porphyria, although it is interesting that the pain has subsided since her treatment started. case
Neil J Boyle Ciba Pharmaceuticals, Wimblehurst Road, Horsham, West Sussex RH12 4AB, UK
Donal P
Murray
Medical Department,
Sligo General Hospital, Sligo, Ireland
Stability of glutamine in parenteral feeding solutions SIR-van der Hulst et al (May 29, p 1363) provide further evidence that glutamine maintains the integrity of gut mucosa in postoperative patients. They state that glutamine must be provided as a synthetic dipeptide, because its free aminoacid form is unstable in solution during storage. We believe this to be a misconception. Several independent studes have shown that glutamine is stable if the correct pharmaceutical and sterilisation techniques are followed. Wilmore1 reported that the concentration of glutamine in a standard total parenteral nutrition (TPN) solution decreased by 0-1% per 24 h at room temperature and that an aqueous solution of glutamine can be stored for 7-10 days at 4°C without any appreciable accumulation of ammonia. Similarly, Khan et al2 showed only a 2% loss in a TPN solution stored at 4°C for 14 days. We have confirmed that aseptically prepared and filtersterilised solutions containing 25 g/L glutamine can be stored in oxygen-impermeable bags for up to 30 days at 4°C with glutamine losses of less than 0.05%.3 Conversion to glutamate was negligible, pyroglutamate formation was less than 0-02% per day, and ammonia formation less than 0-01 mmol/L per day. These solutions have been incorporated into TPN containing aminoacids, fats, and carbohydrate in a 3 L bag. Stability of the mixture was not adversely effected by the glutamine during storage at 4°C. Ammonia production was less than 01mmol/L per day and glutamine content remained at 98-2% of the original after 30 days.3 Our concern is that many clinicians may consider dipeptide glutamine supplementation too expensive to have a widespread application and we wish to emphasise that, where aseptic pharmacy facilities are available, the use of glutamine in parenteral nutrition is highly costeffective. G Hardy, S J Bevan Oxford Nutrition Ltd, PO Box 31E, Oxford OX4 3UH, UK
B
McElroy
Pharmacy Department, Royal Shrewsbury Hospital, Shrewsbury, UK
T E A
Palmer, R D Griffiths, C Braidwood
Whiston Hospital, Merseyside, UK
1
2 3
Wilmore DW. The safety and efficacy of glutamine in humans. Clin Nutr 1990; 9: 35. Khan K, Hardy G, McElroy B, Elia M. The stability of L-glutamine in total parenteral nutrition solution. Clin Nutr 1991; 10: 193-98. Hardy G, Wiggins D, McElroy B, Thompson GR. Formulation of a glutamine-containing total parenteral nutrition mixture for clinical use. Proc Nutr Soc 1992; 51: 136.