FEVER IN ENDOCARDITIS

164 DRUG MARKETING IN THE THIRD WORLD

SiR,—Dr Greenhalgh (June 7,

p 1318) provides yet another clear of the unfortunate practices pursued by several major western based pharmaceutical companies in the developing world. I was interested in her observations in India on the promotion and availability of ’Encephabol’ (pyritinol). This drug is indeed claimed to have an impressive range of indications, only some of which Greenhalgh lists. It will surprise no-one to learn that there is no scientific evidence for this drug’s efficacy. I have seen this drug prescribed for children with various disabilities, including cerebral palsy, mental retardation, epilepsy, and learning and behavioural problems, in Syria, India, Sri Lanka, Malaysia, Singapore, and Indonesia. In almost all cases the drug had been prescribed by doctors, usually in private practice. Marketing is one issue, but why do doctors prescribe a drug when they have no evidence that it confers any benefit. It could be argued that many private practice doctors in developing countries are compelled always to "do something". Access to remedial services is poor or non-existent, contact with colleagues is tennous, and the pressure patients put upon them to prescribe something is intense. Many such doctors are isolated and they have to respond to pressure from families if they are to survive professionally or financially. I agree that the World Health Organisation should give "financial and scientific support for the continued education and updating of Third World doctors in the difficult and ever-changing subject of clinical pharmacology" and "that it is time the British Medical Association had the courage to use its professional power to demand that British-based drug companies be morally accountable for the deaths their drugs have caused in the Third World". But I feel also that we should try and understand more the circumstances under which many of our colleagues work in developing countries, particularly in private practice, and with this why they are so vulnerable to marketing practices. At the same time we should look at some of our own practices in the UK which do not always bear close scrutiny. account

Ryegate Centre, Children’s Hospital, Sheffield S10 5DD

GWILYM HOSKING

PSYCHOSOCIAL OUTCOME OF HEAD

that there is almost no coherent, organised head injury rehabilitation going on in the UK-indeed, thanks to the move and shrinking of the Joint Services Medical Rehabilitation Unit at Chessington, and the restrictions imposed on Rivermead Rehabilitation Centre by the Oxford Regional Health Authority, there is less than there was a year ago. In particular, Glasgow has never had any such facility.2 The Lancet should not be fostering a rose-tinted view of what is in fact a sadly barren area. Burden Neurological Hospital,

Stapleton,

PETER EAMES

Bristol BS16 1QT

1. Earnes P, Wood R. Rehabilitation after severe brain injury; a follow-up study of a behaviour modification approach. J Neurol Neurosurg Psychiatry 1985; 48: 613-19. 2. Brooks DN, Campsie LM, Beattie A, Bryden JS, Symington C. Head injury and the rehabilitation professions in the West of Scotland. Scott Home Health Dep Health Bull 1986; 44 (no 2): 110-17.

FEVER IN ENDOCARDITIS

SiR,—The survey on fever in patients being treated for infective endocarditis undertaken at St Thomas’ Hospital, London, over a ten-year period (June 14, p 1341) was enlightened. In 15% of febrile patients fever remained unexplained. We have experience of a similar patient with vegetations on the mitral valve caused by Haemophilus aphrophilus. He had had an aortic valve prosthesis implanted some years previously, and this remained unaffected throughout his illness. He was treated with adequate doses of penicillin and gentamicin, as judged by post-dose serum bactericidal activity of 1:16. He became afebrile 36 h after the start of antibiotic treatment, but intermittent fever returned 10 days later. A routine immunological screen was done when the cardiologist and cardiac surgeon could find no reason for his continued pyrexia. The Raji cell, Clq binding, and Clq solid phase assays, all tests for immune complexes, were strongly positive (see figure). The serum level of C3d, a breakdown product of C3, was very high. The failure of these tests to return to normal paralleled this patient’s poor

INJURY

S:R,—Iwelcome attention (June 14 editorial) to the fact that the "invisible" effects of head injury (behaviour, personality, cognition, and mood) are much greater determinants of outcome than are the more obvious physical disorders. However, daily experience, especially with medicolegal referrals, makes it clear that this message has as yet reached only a small audience; most surgeons and physicians who deal with the head injured in the UK still rely on physical features in their assessments. Moreover, we will not have a full picture of the human and economic impacts of head injury until we have studied the complete spectrum of outcome in the complete spectrum of injury severity. Since there is no coherent approach in the UK or elsewhere to the follow-up of all those who come to hospital with a head injury, such a study is but a dream. Your editorial uses "behaviour" and "personality" as though the terms were interchangeable. This common error has profound effects on expectations for treatment. To say that the victim of head injury has "suffered a personality change" is taken almost universally to mean that nothing can be done. Yet more often than not the patient’s personality (the pervasive characteristics of his temperament and methods of relating) is unchanged; what presents problems in everyday life, and in rehabilitation, is intermittently unacceptable behaviour. Whilst personality disorders may well be impervious to treatment, behaviour disorders are most often eminently treatable.1 You write that "Glasgow has been a leading centre for research on all aspects of head injury", and speak of the usefulness of the Glasgow assessment schedule for planning rehabilitation. No doubt this would be a legitimate and valuable use, and it is even probable that such instruments could be used to evaluate the efficacy of different rehabilitation approaches and techniques. The irony is

Changes in response to therapy. Measurement of immune complexes was by radiometric assays,’ of C3 and C4 by single radial diffusion,2 and of C3d by rocket immunoelectrophoresis after fractionation with polyethyleneglycol.3 .3 ---

165 17 CASES OF FETAL ANEUPLOIDY

to antibiotic therapy. Only when corticosteroids given did the patient improve; his fever settled and the immunological tests returned to normal. Circulating immune complexes have been demonstrated in infective endocarditis’ and are important in the pathogenesis of

clinical response were

many of the clinical features of the disease. It may well be that some of the 15% of patients with unexplained fever in the St Thomas’ survey had circulating immune complexes which remained high, in

spite of adequate antibiotic therapy. Some of these have benefited from a course of corticosteroids. Departments of Medical Microbiology and Immunology of Rheumatic Diseases, Charing Cross Hospital, London W6 8RF

patients might

LENA ROBINSON D. J. M. WRIGHT B. E. BOURKE

1. Mumford P, Horsfall AC, Maini RN. The circulating immune complexes in rheumatoid arthritis and systemic lupus erythematosis: a comparative study using, three immune complex assays. Rheumatol Int 1982; 1: 181-86. 2. Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion Int J Immunochem 1965; 2: 235-54. 3. Bourke BE, Moss IK, Maini RN. Measurement of the complement C3 breakdown product C3d by rocket electrophoresis. J Immunol Methods 1982; 48: 87-108. 4. Bacon PA, Davidson C, Smith B. Antibodies to candida and auto-antibodies in sub-acute bacterial endocarditis. Quart Med 1974; 43: 537-50. J *Fetus with normal karyotype.

ANAESTHESIA AND PROPHYLAXIS FOR INFECTIVE ENDOCARDITIS

SiR,—The letter from the Working Party of the British Society of Antimicrobial Chemotherapy (May 31, p 1276) amending their recommendations for prophylaxis of infective endocarditis for adults who are at risk of endocarditis and who are to have a general anaesthetic for a dental procedure does not take cognisance of the mode of anaesthesia. The frequency of bacteraemia after nasotracheal intubation, the most common route in patients having dental surgery, was 21 0, when a cuffed endotracheal tube was used. Staphylococcus epidermidis was the most frequently isolated microorganism from blood cultured within 5 min of nasal intubation.1 This organism has been reported to cause up to 24% of cases of late prosthetic valve endocarditis.2 We suggest that adults with prosthetic valves who are undergoing anaesthesia by nasotracheal intubation with a cuffed tube should receive the antibiotic prophylactic regimen recommended by the working party for penicillin allergic patients, which is also effective against staphylococci-ie, vancomycin 1 g by slow intravenous infusion over 60 mins, followed by gentamicin 120 mg intravenously immediately before induction of anaesthesia. Department of Anaesthesiology and Critical Care Medicine, Johns Hopkins Medical Institution, Baltimore, Maryland, USA

A. J. MC SHANE

maternal

AFP being measured before and after the AFP was measured by double antibody radioprocedure.6 immunoassay (Biodata, Milan) with a sensitivity of at least 5 ng/ml and intra-assay and inter-assay coefficients of variation of 5% and 10% over the range 10-20 ng/ml and 100’0 and 15%, respectively, below 10 ng/ml. Each maternal serum specimen was analysed in duplicate in the same assay run. In this assay data are handled by a logit/log program (Hewlett Packard). Total binding (BofT) is 640±295; binding at 5 ng/ml is 89-84+1-26; and binding at 10 ng/ml is 8096±208. Dose values are: ED=151-50±12-06, ED=39-59±376; and serum

ED so = 10-39 ±1-22.

patients reported natural menstrual cycles of 26-30 days gestational age was calculated from the time since the day of last menstrual period: it ranged from 8 to 11weeks. A All the so

normal range of maternal serum AFP level at 8-12 weeks was constructed using the results in 446 pregnancies where the fetal karyotype and the pregnancy outcome had been shown to be normal.6 17 cases of fetal aneuploidy were detected(table). In all but 1 (the trisomy 14) it had been possible to confirm, in fetal tissue obtained at pregnancy termination, the cytogenetic abnormality detected in the villous material. In 1 case the placental karyotype (trisomy 16) and fetal karyotype (normal)

discrepant.s

Department of Microbiology,

were

Mater Hospital, Dublin 7, Ireland

In all 8 cases of trisomy 21 and in 7 of the 9 other aneuploidies the maternal serum AFP was below the normal median (figure).

R. HONE

AJ, Hone R. Prevention of bacterial endocarditis: Does nasal intubation prophylaxis? Br Med J 1986; 292: 26-27. 2. Karchmer AW, Archer GL, Dismukes WE. Staphylococcus epidermdis causing prosthetic valve endocarditis: Microbiologic and clinical observations as guides to 1. Mc Shane

warrant

therapy. Ann Intern Med 1983.

98: 447-55.

FETAL CHROMOSOMAL ANEUPLOIDIES AND MATERNAL SERUM ALPHA-FETOPROTEIN LEVELS IN FIRST TRIMESTER

SIR,-The association of low maternal serum cx-fetoprotein (AFP) levels with fetal aneuploidy, first reported by Merkatz et all and later confirmed by others,2-5 prompted us to evaluate retrospectively the relation between fetal aneuploidy detected by chorionic villus sampling (CVS) in the first trimester of pregnancy and the maternal serum AFP level in 520 patients. Maternal blood samples had been drawn before CVS and stored at - 20°C as part of a research programme to investigate the possibility of fetomaternal transfusion after CVS, the

serum AFP levels for fetal trimester of pregnancy.

Maternal

aneuploidies (M)in first