Figure: Serum SI results collected for baseline Al, Si, and a full blood count. After dialysis and before the next dialysis (48 h later), blood samples were collected for Al and Si analysis. 15 patients had a positive DFO test (group 1) and 18 had a negative DFO test (group 2). There was no clinical evidence of Al related toxicity in all patients, and there was no significant difference in the mean cell volume index between patients from group 1 and group 2 (mean [SE] 87-1[1 -9] vs 88-1[1’8], p 0-1). Serum Si concentrations were high in patients (571 [3-8] mol/L) compared with healthy controls (5  mol/L). As shown in the figure, the serum Si concentrations before DFO were significantly higher in patients from group 1 than in group 2 (70-2 [6’4] vs 46-2 [2’5] µmol/L, p < 0-001). Serum Si after haemodialysis fell significantly in all patients, but in group 1 serum Si after haemodialysis was significantly higher than in group 2 (39-2 [5’67] vs 25.6 [2’1]] [tmol/L, p < 0 -002). Our data indicate that serum Si was significantly higher before and immediately after dialysis in the Al overload group. The observations suggest that Si and Al show some evidence of association in serum. Does this association have a protective role in limiting the bioavailability of Al? =
Ibrahim H Fahal, Muhammad Yaqoob, Peter S Williams, Rasheed Ahmad, Norman B Roberts, Gordon M Bell Departments of Nephrology and Clinical Chemistry, Royal Liverpool University Hospital, Liverpool L7 8XP, UK
be started before conception and continued until the twelfth week of pregnancy.’ But in the UK folic acid 5 mg is only available on prescription at an annual cost to the patient of k 17 if the prescription is quarterly, or L50 on a monthly basis. For women on the smaller dose of 04 mg daily, over-the-counter preparations of folic acid will cost between L8 and C45 a year. (The period of medication will be longer if they fail to become pregnant.) Folic acid is very cheap and the basic cost of a year’s supply of 5 mg tablets is less than £2. We support the suggestion of the advisory group that folic acid should be made available free to both groups. A further difficulty arises when anticonvulsant drugs are prescribed to women of childbearing age. The Committee on Safety of Medicines has received a total of 60 reports of babies with spina bifida born to mothers taking valproate (48) or carbamazepine (12) (CSM, personal communication). 6 reports were received in 1991, a year in which the number of births born with spina bifida had fallen to 104 (1-5 per 10 000 babies).2 This finding suggests that about 6% of babies with spina bifida born in 1991 were associated with maternal anticonvulsant therapy. Prescribers of valproate and carbamazepine should be reminded of the recommendations in the British National Formulary and warn their female patients (including teenagers) about the risk of spina bifida.3 They should also advise specialist preconceptional counselling, folic acid supplements,’ and screening specifically for spina bifida during pregnancy. The cost of these recommendations should be set against the potential cost of life-long care for a patient with spina bifida.
Pippa Oakeshott Department of General Practice and Primary Care, St George’s Hospital Medical School, London SW17 ORE, UK
Gillian Hunt 65 Grantchester Street,
1 Birchall JD. The role of silicon in biology. Chem Brit 1990; 26 (2): 141-44. 2 Peaslee DE, Frink CR. Influence of silicic acid on uptake of Mn, Al, Zn and Cu by tomatoes. Soil Sci Soc Am Proc 1969; 33: 569-71. 3 Carlisle EM, Curran MJ. Effect of dietary silicon and aluminium on silicon and aluminium levels in rat brain. Alzheimer Dis Assoc Disord
1987; 1: 83-89. 4 Birchall JD, Exley C, Chappell JS. Acute toxicity of aluminium to fish eliminated in silicon rich waters. Nature 1989; 338: 146-48. 5 Edwardson JA, Moore PB, Ferrier IN, et al. Effect of silicon on gastrointestinal absorption of aluminium. Lancet 1993; 342: 211-12.
Prevention of neural tube defects SiR-Sutcliffe and colleagues (Nov 6, p 1174) emphasise the need for education of professionals and the general public about the benefit of periconceptional folic acid supplementation in the prevention of neural tube defects (NTD). However, lack of awareness is not the only difficulty. Cost may also prevent compliance. The Expert Advisory Group on Folic Acid and Neural Tube Defects recommends that women who have had a child with NTD and who are likely to become pregnant should take folic acid 5 mg daily. All other women planning a pregnancy should take a smaller (04 mg) dose. In both instances folic acid should
Department of Health. Folic acid and the prevention of neural tube defects: report from an expert advisory group. Heywood: DOH Health Publication Unit, 1992: 21. Office of Population and Census Surveys. Congenital malformations. (OPCS Monitor MB3 No 7). London: HM Stationery Office, 1991. Joint Formulary Committee. Antiepileptics: pregnancy and breastfeeding. In: British National formulary, no 26. London: British Medical Association, 1993: 180. O’Brien MD, Gilmour-White S. Epilepsy and pregnancy. BMJ 1993; 307: 492-95. Anon. Sodium valproate and 59-60.
spina bifida. Drug
Ther Bull 1990; 28:
SIR-Sutcliffe and colleagues’ findings that only 2-4% of had increased their folate intake before conception almost exactly matches our experience. We questioned all 507 women attending their first antenatal clinic at the University Hospital of Wales, Cardiff, in May and June, 1993. We asked whether the pregnancy was planned, if there was any family history of NTD, and if they had used the recommended periconceptional folate supplements.2 325 (64%) women said that the pregnancy was planned but only 11 (3%) of this group had taken folate supplements. 5 did so on the advice of their general practitioner whereas the other 6 had taken folate supplements on their own initiative. Among the 182 with unplanned pregnancies 3 (2%) had been taking folate supplements, a level not significantly different from those with planned pregnancies; thus, a total of 14 (3%) women took periconceptional folate supplements. Of the 7 women with a positive history of NTD (2 with spina bifida, 1 with a previously affected pregnancy, and 4 with first-degree relatives affected) only 1 was taking the higher level of folic acid recommended (5 mg daily) before conception. 49 (10%) women said they took proprietary multivitamin supplements before conception. It is ironic that if they could specify the
brand used, the supplements were more likely to contain vitamin A than 400 g folic acid. Wales has a higher incidence of pregnancies affected by NTD, as is indicated by the higher rate of births affected by spina bifida (31 per 10 000 births in Wales vs 1-6 per 10 000 births in England)3 and higher rates of termination of pregnancy for fetal central nervous system abnormalities. Our survey suggests that even within an area known for a high risk of NTD the use of folate supplements is low. Those with a history of NTD seem to be faring little better. Sutcliffe et al found that 97-6% of women were not taking the recommended level of periconceptional folate supplements. In our population, which is at higher risk of NTD, 97-2% were not using folate supplements. More attention should be paid to ensuring that the general public and their health care professionals are aware of the recommended folate supplements. Robert B Smith, Nigel Davies, Joy Davies University Hospital of Wales, Cardiff CF4 4XW, UK
Figure: Immunoadsorptlon In myasthenia gravis Reduction of anti-AChR (91 4 [10-8]%). IgG (74 1 (46-99 [10 5]%) and IgA (22 8 [8-1]%); expressed
Department of Health. Folic acid and the prevention of neural tube defects: report from an expert advisory group. Heywood: DOH Health Publication Unit, 1992: 21. 2 Office of Population Censuses and Surveys. Congenital malformation statistics notifications. (Series MB3 no 6; 12). HM Stationery Office
[13 7]%), IgM as means
SIR-Sutcliffe and colleagues draw attention to the fact that few women are aware of Department of Health advice to take folic acid before conception and during the early months of pregnancy. The main approach to educate doctors has been to send them a copy of a report! and by issuing recommendations. I think that this approach is flawed and it clearly has not had much impact on women. Women do not perceive conception as a medical problem and will rarely seek medical advice unless they are worried about their fertility. They will have stopped using contraceptive services. Are medical agencies therefore likely to reach most women at the relevant time wishing to conceive? Should the emphasis therefore not be on educating the public directly by advertising? This approach would reach the relevant group of women directly and could result in an increased demand for prescriptions (which in turn would jog the memories of any health professionals who at present fail to advise their patients, while, for example, giving contraceptive
advice). Wulf Franzen 2
Brymore Close, Bridgwater TA6 7PL, UK
Department of Health.
Folic acid and prevention of neural tube defects: report from an expert advisory group. Heywood: DOH Health Publication Unit, 1992.
immunoadsorption in immunosuppression-resistant myasthenia gravis Protein-A
myasthenia gravis (MG), antibodies to nicotinic acetylcholine receptors (anti-AChR) interfere with neuromuscular transmission, leading to muscle weakness and fatiguability. Since anti-AChR is mostly IgG,l we treated 2 immunosuppression-resistant MG patients with staphylococcal protein A, a ligand able to remove immunoglobulins selectively, particularly IgG, from plasma.2 Patient 1, a 20-year-old woman who had had MG for 3 years, was not responding to prednisone (100 mg/day for 4 months), azathioprine (150 mg/day for two months), and repeated plasma exchanges. She had dysphagia and weakness of tongue, head, neck, and limb muscles. Her pre-treatment anti-AChR 124
15-5 pmol/mL. Patient 2, a 25-year-old woman with MG for 3 years, had relapsed with severe weakness of neck and trunk muscles, dysphagia necessitating nasogastric feeding, and partial respiratory compromise, while on prednisone (100 mg on alternate days) and cyclosporin (200 mg/day), for a year. Before that she had received prednisone (100 mg/day) for a year and plasma exchanges every 15 days which produced only transient clinical improvements. Pre-treatment anti-AChR was 89-7 pmol/mL. In courses of 3 sessions on alternate days, plasma was separated by centrifugation and passed in series through two protein A columns (Immunosorba, Excorim, Lund, Sweden). Patient 1 had three, and patient 2 had two courses at 4-week intervals. The volume of plasma processed at each session was 4906 (630) mL. Serum immunoglobulins were assayed by nephelometry and anti-AChR titres by an immunoprecipitation assay.3 Patient 1’s bulbar symptoms remitted during the first course, and over the 3-month treatment period she had only mild limb fatiguability. Patient 2 had an immediate benefit, being able to eat after the first session. She had a relapse 3 weeks after the first course and improved immediately during the second one, after which she had only mild weakness of facial and trunk muscles. The marked clinical improvements, closely related in time to the treatments, could be attributed to immunoadsorption. Reductions in serum immunoglobulins and anti-AChR titres after each session are given in the figure. Protein A had a high affinity for IgG, whereas IgM and IgA were removed less efficiently. Specific autoantibodies were markedly reduced by the procedure, confirming the report by Somnier et al in in-vitro experiments.4 Protein A immunoadsorption is a promising alternative to plasma exchange for selected treatment-resistant MG patients. was
Supported by a grant from Telethon Italia to
Carlo Antozzi, Emilia Berta, Paolo Confalonieri, Marta Ferdinando Cornelio, Renato Mantegazza Department of Neuromuscular Diseases, "C Besta" National Via Celoria 11, 20133 Milan, Italy
1 2 3 4
Lindstrom J, Shelton D, Fujii Y. Myasthenia gravis. Adv Immunol 1988; 42: 233-84. Gjorstrup P, Watt RM. Therapeutic protein immunoadsorption. A review. Transfus Sci 1990; 11: 281-302. Gotti C, Mantegazza R, Clementi F. New antigen for antibody detection in myasthenia gravis. Neurology 1984; 34: 374-77. Somnier FE, Langvad E. Plasma exchange with selective immunoadsorption of anti-acetylcholine receptor antibodies. J Neuroimmunol 1989; 22: 123-27.