4 American Medical Association. Drug evaluations. 6th ed. Philadelphia: Saunders, 1986:975-87. Deficiencies in the relationships between pharmacists and 5 Mordeo JP, Swartz R, Arky RA. Extreme hypermagnesemia as a cause of refractory hypertension. doctors may be a principal reason for inadequate implementa- Ann Intern Med 1975;83:657-8. 6 Nanji AA, Lavener RW. Lactulose-induced hvpernatremia. Drug Intell Clin Pharm 1984;18:70-1. tion of formulary policies, and recent recommendations on 7 Florent C, Flourie B, Rautureau M, Bernicr JJ, Rambaud J. Influence of chronic lactulose developing clinical pharmacy services in hospitals point the ingestion on the colonic metabolism of lactulose in man. 7 Clin Invest 1985;75:608-13. 8 Ridlev H. Drugs ofchoice: a report on drug formularies used in NHS hospitals. London: Social Audit,

way forward."I 1986. BMJ: first published as 10.1136/bmj.297.6661.1421 on 3 December 1988. Downloaded from D N BATEMAN 9 Collier J, Foster J. Management of a restricted drugs policy in hospital: the first five years' Senior Lecturer in Clinical Pharmacology experience. Lancet 1985;i:331-3. 10 Petrie JC, Scott AK. Drug formularies in hospitals. BrMedJ 1987;294:919-20. J M SMITH 11 Tugwell AC, Thurston DR, Barrett CW. Design and preparation of a formulary-guide to the Lecturer in Clinical Pharmacy prescribing of medicines. Journal ofClinical and Hospital Pharmacy 1984;9:311-9. 12 Baker JA, Lant AF, Sutters CA. Seventeen years' experience of a voluntarily based drug Wolfson Unit of Clinical Pharmacology, rationalisation programme in hospital. BrMedj 1988;297:465-9. University of Newcastle upon Tyne, 13 Swallow RD, Remington HStC, Standing VF. Ward pharmacy: a positive contribution to cost Newcastle upon Tyne NEI 7RU control. Pharnaceuticallournal 1985;235:722-3. 14 Karki SD, Chandra P, Holden JMC, Shehata H. Impact of team approach on reducing drug costs. International/ournal of Geriatric Psychiatry 1988;3:89-93. I Anonvmous. Laxatives: replacilng danthron. Drug T'her Bull 1988;26:53-6. 15 Nuffield Foundation. Pharmacy. The report of a commtttee of enquiry appointed by the Nuffield 2 Tedesco FJ. Laxative use in constipation. Amj Gastroenterol 1985;80:303-9. I-oundarion. London: Nuffield Foundation, 1986:57-67. 3 Brunton LL. Laxatives. In: Gilman GA, Goodman LS, Rall rw, Murad F, eds. T'he 16 Department of Health. Health services management-the way forzward for hospital pharmaceutical pharmnacological basis oftherapeutics. 7th ed. New York: Macmillan, 1985:994-1003. servtces. London: DoH, 1988. (HC(88)54.)

Benefits from oily

May help in coronary artery disease and several inflammatory conditions

Greenland Eskimos and the Japanese have a higher intake of whether and fish and a lower incidence of than modify inflammatory and immune responses. Eicosapen- Western populations.' Within Japan the lowest death rates taenoic acid, it seems, competes with arachidonic acid not from coronary artery disease are seen in Okinawa, where fish only for metabolism by the cyclo-oxygenase pathway but consumption is about twice as high as on the mainland.2 also for metabolism by the lipoxygenase pathway to the Meanwhile, a study from The Netherlands has shown an leukotrienes.'2 Leukotrienes are a family of molecules that inverse dose-response relation between fish consumption in have potent proinflammatory properties.'3 Leukotriene B4 1960 and death from coronary artery disease during the next elicits chemotaxis of neutrophils, whereas leukotrienes C4, 20 years.' These and other4 limited epidemiological studies D4, and E4 (which comprise what was previously recognised have led to great interest in the possible beneficial effects of as the slow reacting substance of anaphylaxis) enhance vas- oily fish-benefits that seem to extend to conditions other cular permeability and contract smooth muscle. Eicosapen- than coronary artery disease. taenoic acid is metabolised by the lipoxygenase pathway to The fat in fish is rich in the long chain polyunsaturated fatty leukotrienes B5, C5, D5, and E5.'2 Leukotriene B5 has only http://www.bmj.com/ acids eicosapentaenoic acid and docosahexaenoic acid. Oily 1-10% ofthe activities of leukotriene B4, whereas leukotrienes cold water fish - such as and from the C5, D5, and E5 are as effective in contracting smooth muscle Atlantic-contain the largest amounts of these fatty acids. as leukotrienes C4, D4, and E4.'2 Dietary supplementation The acids may be beneficial in coronary artery disease, partly with 3 g eicosapentaenoic acid and 2 g docosahexaenoic acid because of their hypolipidaemic effects. In two studies daily for six weeks reduces the capacity of neutrophils and 20-30 g of the acids daily over four weeks reduced serum monocytes to produce the inflammatory mediators leukotriene concentrations of cholesterol, low density lipoproteins, and B4 and platelet activating factor and inhibits both the cells' on 25 September 2021 by guest. Protected copyright. triglycerides.96 may also prevent coronary artery response in chemotaxis and endothelial cell adherence.4 '" disease by inhibiting the activity of the cyclo-oxygenase Dietary supplementation with fish oil lipids may thus have pathway,7 which metabolises arachidonic acid to prosta- anti-inflammatory effects. glandins and thromboxane A2. Eicosapentaenoic acid is Double blind and placebo controlled trials have now been both a substrate and an inhibitor of the pathway,7 whereas completed of increasing the eicosapentaenoic acid in the docosahexaenoic acid is simply an inhibitor.8 Thromboxane diet to treat rheumatoid arthritis,'6 '7 psoriasis," 19 atopic A3 derived from eicosapentaenoic acid is less active in dermatitis 20 and bronchial asthma.2'-23 Eicosapentaenoic acid aggregating platelets than conventional thromboxane A2.9 In provides subjective improvement in patients with active contrast, prostaglandin 13 derived from eicosapentaenoic acid rheumatoid arthritis and psoriasis. Significantly fewer tender and prostacyclin are equally active in their anticoagulant joints were found in patients with arthritis after 14 weeks of a properties and potency in relaxing vascular smooth muscle.'0 combination of 2 7 g eicosapentaenoic acid and 1 8 g docosa- Thus anticoagulant activities are preserved while platelet hexaenoic acid, and the time to the first experience of fatigue aggregating properties are reduced by eicosapentaenoic after arising in the morning was also improved. Patients acid, which should inhibit platelet deposition on vascular reduced their consumption ofnon-steroidal anti-inflammatory endothelium. This might explain the prolonged bleeding time drugs. Eicosapentaenoic acid t' i; produced mild to moderate and reduced platelet aggregation seen in Greenland Eskimos improvement in patients wit i psoriasis. In patients with compared with Danish volunteers." atopic dermatitis fish oils led to a mild improvement in Not only coronary artery disease but also certain chronic cutaneous scaling, itch, and overall subjective assessment of inflammatory and immunological diseases-such as rheuma- severity. toid arthritis, psoriasis, and asthma-are less common in In patients with asthma fish oil lipids may inhibit the late Greenland Eskimos than in other Western populations. These phase asthmatic response (the inflammatory component ofthe observations have led to clinical and laboratory studies of asthmatic reaction) after inhalation of an allergen.2' A diet

BMJ VOLUME 297 3 DECEMBER 1988 1421 3 Hirai A, Hamazaki T, 'I'erano F. et al. hicosapentaenoic acid and platelet function in Japanese. enriched with eicosapentaenoic acid given to patients with Lancet 1980;ii: 1132-3. asthma over 10-12 weeks did not, however, lead to any 4 Kromhout 1), Bosschieter ED, Coulander C de'L. The inverse relation between fish consumption and 20 year mortality from coronary heart disease. N Engli.Med 1985;312:1205-9. symptomatic improvement or to objective changes in lung 5 Harris WC, Connor WE. The effects of oil upon plasma lipids, lipoproteins and triglyceride function and non-specific bronchial hyperresponsiveness.2223 clearance. 7ransAssoc Am Phvsicians 1980;43:148-55. 6 Harris WC, Connor WE, McMurrv Ml. The comparative reduction of the plasma lipids and Although dietary fish oil lipids produced no change in most lipoproteins by dietarx polyunsaturated fats: salmon oil vs. vegetable oils. Metabolism 1983;32: BMJ: first published as 10.1136/bmj.297.6661.1421 on 3 December 1988. Downloaded from patients with asthma, eicosapentaenoic acid may modulate 179-84. 7 Needleman 1', Raz A, Minkes MS, Ferrendelli JA, et al. Triene prostaglandins: prostaglandin and the disease in a few people. Picado et al showed that a diet thromboxane biosynthesis and unique biological properties. Proc Nail Acad Sci USA 1979;76: of acid for six weeks 944-8. containing 3 g eicosapentaenoic daily 8 Corey EJ, Shih C, Cashman JR. Docosahexaenoic acid is a strong inhibitor of prostaglandin but not worsened airflow obstruction in 10 patients with asthma leukotriene boossnthesis. Proc NaloAcad Sci USA 1983;80:3581-4. 9 Whitaker MIO, Wvche A, Fitzpatrick F. Prostaglandin D3 and eicosapentaenoic acid as potential and aspirin intolerance.24 These effects were attributed to anti-thrombotic substances. Pros Natl Acad Sci USA 1979;76:5919-23. inhibition of the cyclo-oxygenase pathway. 10 Fischer S, Weber P. Prostaglandin II is formed in sivo in man after dietary eicosapentaenoic acid. Nature 1984;307:165-8. Thus adding eicosapentaenoic acid to the diet will lead to it 11 Dverberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. being incorporated into membranes and tissues, which may ILancet 1979;ii:433-5. 12 Lee TH, Austen KF. Arachidonit acid metabolism by the 5-lipoxygenase pathway, and the effects result in important changes in cellular biochemistry and of alternative dietary fatty acids. Adz Immunologv 1986;39:145-75. 13 Samuelsson B. Leukotrienes: mediators tof immediate hypersensitivity reactions and inflammation. function and may provide some benefit in selected diseases. Science 1983;220:568-75. Coronary artery disease is the condition that is most amenable 14 l ee TH, Hooser RL, Williams JD, et al. Effect of dietary enrichmeiot with eicosapentacnoic and docosahexaenoic acids on in nitro neutrophil and monocyte leukotriene generation and to this dietary manipulation, but whether the benefit is neutrophil function. N Eng1] Med 1985;312:1217-24. sufficient to replace or reduce drug treatment in any condition 15 Sperling RL, Robin J-L, Kylander KA, et al. The effects of N-3 polyunsaturated fatty acids on the generation of PAF-acether by human monocytes. ] Immunol 1987;12:4187-91. remains to be seen. 16 Kremer JM, Bigauoettc J, Mlichalek AV, et al. Effects of manipulation of dietary fatty acids on TAK H LEE clinical manifestations of' rheumatoid arthritis. Luancet 1985;i: 184-7. 17 Kremer JIM, Jubiz W, Michalek A, et al. Fish oil fatty acid supplementation in actise rheumatoid Professor of Allergy and arthritis. A4nn Intern Med 1987;106:497-503. Allied Respiratory Disorders 18 Bittiner SB, 'Tucker WFG, Cartwright 1, ei al. A double-blind, ramdomised placebo-controlled JONATHAN P ARM trial of fish oil in psoriasis. Lanutt 1988;i:378-83. Honorary Lecturer 19 Maurice PI)L, Allen BR, Barkley ASJ, et al. IFie effects of dietary supplementation with fish oil in patients with psoriasis. Br] IDermattol 1987;117:599-606. Department of Allergy and Allied Respiratory Disorders, 20 Bhorneboe A, Soyland E, Bltorneboo G-EA, 't al. Ef'fect of' dietary supplementation with United Medical and Dental Schools of Guy's and St Thomas's Hospitals, eicosapentacnoic acid in the treatment of atopic dcrmatitis. Br,7 Dirmnatol 1987;117:463-9. Guy's Hospital, London SE1 9RT 21 Arm JP, Horton CE, Eiser NM. tt a. 'rhe effetcts of dietary supplementation with fish oil on asthmatic responses to antigen. Allergv (liin Immunol 1988;81:183. 22 Arm Jl', Horton CE, Miencia-Huerta JM totl. Effect of dietary supplementation with fish oil lipids on mild bronchial asthma. i'horax 1988;43:84-92. I Dyerberg J, Bang HO. Dietary t:at and thrombosis. Lancet 1978;ii: 152. 23 Kirsch CM, Payan DG, Wong MYS et al. Effect of'eicosapentacnoic acid in asthma. ClIn Allergv 2 Kagawa Y, Nishizawa M, Suzuki M, et al. Eicosapolyenoic acid of serum lipids of Japanese 1988;18: 177-87. islanders with low incidence of cardiovascular discascs.7 Nrt Sci luminol 'I'ks 1982;28: 24 IPicado C, Castillo JA, Schiinca N, et al. Effects ol' a hish oil eniriched diet on aspirin intolerant 441-53. asthmatic patients: a pilot study. I'horax 1988;43:93-7.

A single seizure

Likely to recur http://www.bmj.com/

In 1881 Gowers concluded that when one seizure has occurred between 27% and 71% after three years of follow up.29 10 Two others usually follow,' but this view has recently come under recent studies based on children referred to electroencephalo- scrutiny, with some ensuing controversy.25 General practi- graphy departments found rates ofrelapse of 59%"1 and 52%.2 tioners, casualty officers, neurologists, and paediatricians In a retrospective community study based on the records commonly see patients who have had a single seizure. linkage system of the Mayo Clinic Annegers et al reported on 25 September 2021 by guest. Protected copyright. Sometimes it has occurred because of alcohol or drug abuse, recurrence of seizures in 56% of patients after five years.'3 All acute metabolic disturbance, acute cerebral disease or injury, the studies agree that relapse occurs most often within the first or (especially in children) fever. More often, however, none of year of follow up. In 408 adults over 16 the risk of recurrence these factors are present and the seizure is regarded as was greater if the seizure occurred between midnight and unprovoked, although various reflex mechanisms, changes in 9 am; older patients with a family history of seizures also sleep pattern, and emotional stress may be overlooked. seemed more likely to have a recurrence, but electro- Recent reports on the prognosis ofa single unprovoked attack encephalography was of no predictive value.7 Computed have seemed to conflict and management remains uncertain. tomography showed tumours in only 3%, and these subjects In Britain most patients are not treated after a single seizure have a higher rate of relapse. on the principle that a single seizure is not epilepsy, though in Some ofthe variation in the reported rates ofrelapse may be the United States two thirds of patients are treated, perhaps attributable to differences in the ages of the populations for medicolegal reasons. Both the British6 and the American2 studied, differences in the types and causes of the single practice have recently been questioned. seizures, whether the studies were prospective (most were In a multicentre study of patients presenting to neuro- retrospective), and whether some of the patients were treated logical departments in Britain Hopkins et al confirmed that with antiepileptic drugs. The most important factor, how- most single seizures (94%) are tonic-clonic attacks. Partial ever, is the interval between the seizure and the time of attacks are usually more frequent, may occur in clusters, and presentation and entry into the study. In patients with initially are often not recognised as seizures; they thus present established epilepsy the second attack follows the first within to doctors as a single event much more rarely. A substantial one month in one third of patients.' 4 Therefore if one month minority of patients with tonic-clonic attacks also seek advice elapses before a patient with a seizure is seen in a neurological only after two or more seizures.8 In patients presenting with a clinic those with early recurrence will be selected out because single seizure the rate of recurrence has been reported to vary they have already developed epilepsy. In the study of patients

1422 BMJ VOLUME 297 3 DECEMBER 1988