CAUSES OF CHRONIC LEG ULCER

615 NEURAL TUBE DEFECTS AND TRACHEO-OESOPHAGEAL DYSRAPHISM

SIR,-Professor Fraser and his colleagues (July 17, p. 144) draw attention to the possibility that the frequency of neural tube defects (NTD) may be higher in sibs of children with tracheo-oesophageal dysraphism (TOD) and suggest further studies would be desirable. Data from the Health Surveillance Registry of British Columbia were analysed for evidence of increased risk of NTD in siblings of individuals with TOD.l Since 1952 this registry has maintained statistics and other information on congenital malformations and chronic handicapping conditions in British Columbia. Each affected individual may be ascertained by the registry from a variety of sources; the most important for us were hospital discharge diagnoses for infants, physicians’ notices of birth, and vital registrations of death. Discharge diagnoses for children under 7 years of age are submitted to the registry by all public hospitals in the province. Of all congenital malformations NTD are among those most readily recognised at or shortly after birth. Virtually all cases of anencephaly and almost all those of spina bifida are ascertained in the first year oflife.Thus few cases ofNTD bornin this population ought to be missed. In British Columbia the prevalence of NTD is about 1’ 5 per 1000 births. Tne prevalence of TOD in this province for the period 1952-79 was 1 per 6075 live births; from 1966 on, when important ascertainment sources were added, the rate was 1 per 3824 live birth, comparable with published rates.3,4 Of the 167 infants with TOD born in 1952-79, 89 were male and 78 were female; 2 (1of each sex) were stillborn. Additional anomalies were found in 98, but none of these was an NTD. There were 10 siblings of the index cases registered; 3 had strabismus, 2 clubfoot, and 1 each syndactyly, microphthalmia, branchial cleft fistula, coeliac disease, and cerebral gigantism. None had an NTD or TOD. These data have limitations in that, although it is unlikely that any siblings born in the province with an NTD would be missed, siblings born subsequent to a family moving out of the province would not be ascertained. However, this is unlikely to represent a large error as out-migrants from the British Columbia population during the period the data was collected represented approximately 5% of the total population.b Other limitations are that the total number of siblings born to the index patients is not known, and that the sample size is small. However, in looking at the data available we found no evidence of an increased risk of NTD in the siblings of 167 patients with TOD. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia,

P. A. BAIRD

Canada V6T 1W5

CAROTENE, CARROTS, AND WHITE BLOOD CELLS SIR,-We read with interest the letter from Dr Schoenfeld and colleagues (May 29, p. 1245) reporting neutropenia induced by hypercarotenaemia. It is likely that this effect was an uncommon idiosyncratic response or that it was induced by a constituent of carrot juice other than beta-carotene. This view is supported by the fact that prolonged high doses of beta-carotene have been used to treat protoporphyria without the

EIGHT WEEK RESULTS OF BETA CAROTENE STUDY: MEAN±SD

of leukopenia. Furthermore, as part of a study of the effect of vitamins on serum vitamin and lipid levels, we measured baseline white blood cell (WBC) count and plasma carotene in 23 healthy volunteers. We then randomly assigned them to betacarotene (30 mg/day ’Solatene’, kindly provided by Roche Pharmaceuticals) or placebo for 8 weeks. The results are shown in the table. Despite very substantial increases of plasma carotene in the carotene group, there is no suggestion ofleukopenia. occurrence

Department of Medicine, Harvard Medical School, Brookline, Massachusetts 02146, U.S.A.; and Harvard School of Public Health

MEIR J. STAMPFER

WALTER WILLETT CHARLES H. HENNEKENS

CAUSES OF CHRONIC LEG ULCER

SIR,-Professor Browse, Mr Burnand, and their colleagues (July 31, p. 243) have enhanced our understanding of the pathogenesisof skin complications in chronic venous disease with their first-class series of studies, and your editorial in the sameissue is an excellent summary of the management of venous ulceration. However, what these and most other writings fail to emphasise is the multifactoral aetiology of most chronic leg ulcers and theinappropriateness, even danger, of treating all ulcers in the "gaiter area" as though they were venous.

Most published series are based on hospital experience, often gathered in units with a special interest in varicose veins, venous thrombosis, or both. Hence the emphasis. The picture that emerges from a more broadly based study may have a slightly different perspective. We have completed a population study of chronic leg ulcers in the Lothians and Forth Valley areas, including a detailed assessment of 600 patients. There were 827 ulcerated legs; of these, 76% had ulcers solelyin the gaiter areas. While venous disease was important (68% had varicose veins and 25% had a history of venous thrombosis), 24% of ulcerated legs had no history of venous disease whatsoever and no evidence of superficial or perforator incompetence on examination. The great majority of patients were

examined in their homes and hence assessment of the competence of the deep veins was not practicable. It was clear, however, that many other disorders appeared to have played an important part in the

aetiology.

1. Baird PA, MacDonald EC 2. 3. 4.

Siblings of childen with trachea-oesophageal dysraphism. Can Med Assoc J 1981; 125: 1083-84. Trimble BK, Baird PA. Congenital anomalies of the central nervous system. Incidence in British Columbia, 1952-72. Teratology 1978; 17: 43-49. Leck I, Record RG, McKeown T, Edwards JH. The incidence of malformations in Birmingham, England, 1950-1959. Teratology 1968, 1: 263-80. Cudmore RE. Esophageal atresia and tracheo-oesophageal distula. In: Rickham PP, Lister J, Irving IM, eds. Neonatal surgery, 5th ed. London: Butterworths, 1978:

percentages of 827 legs; other percentages are

of 600

patients

Some of these conditions could have been prevented or ameliorated by medical care, others were unavoidable but, as your

189-208

5. Farley AL Atlas of British Columbia. Press,

1979

Vancouver:

University of British Columbia

1. Roth MM and others.

&bgr;-carotene as an oral photoprotective protoporphyria. JAMA 1974; 288: 1004-08.

agent

in

erythropoietic

616 editorial notes: "lack of self-care amounting to self-neglect is a potent factor in ulcer recurrence". Our main concern, in pointing out the multiple aetiology in so many of these patients, is to discourage treatment which fails to take account of associated disease or, at worst, is positively dangerous.

.

For example, we have seen several patients in whom amputation has been precipitated by the application ofavenous type of compression dressing in the presence of arterial insufficiency. While most patients with leg ulcers can be cared for at home by the district nurse, they shriuld first be assessed at a hospital clinic. Such assessment should ideally include Doppler ankle pressure measurements.

it is to stress the importance of prevention of In our series the average ulcer history was 15 years with a range of 1-78 years. Many of our patients had occupied the attentions of district nurses, general practitioners, dermatologists, physiotherapists, general surgeons, and plastic surgeons intermittently for several decades. The cost to the Health Service is very great. The dismal catalogue of recurrent disability reveals how ineffective preventive medicine has been. It may be that the development of area clinics with special skill in the assessment and treatment ofleg ulcers, similar to that ofDr Stanley Allen in London (Nursing Times Jan. 18, 1973), with particular emphasis on encouraging self-care and prevention, should be recommended. An important part of the work of such a clinic would be liaison with dermatologists and physiotherapists and the provision of training for district nurses who provide such a large share of the care of these

How

right

recurrence.

patients. Department of Surgery, Royal Infirmary, Edinburgh EH3 9YW

C. V. RUCKLEY

South Lothian District

J. J. DALE

Royal Infirmary, Edinburgh Infirmary

Falkirk Royal

M.D. R.J. HARPER CALLAM

RANITIDINE AND THE HEART

SIR,-I have been interested in the correspondence on the cardiovascular effects of ranitidine. As you pointed out in your editorial of Aug. 21, the presence ofH2-receptors in the heart is now well documented, yet Dr Jack and his colleagues (July 31, p. 264), when discussing possible cardiovascular effects of ranitidine, omit all reference to such receptors. The functions mediated by cardiac H2-receptors have been 2 investigated by use of the specific H-agonist drug impromidine2 Kline & This increases the heart and rate agent French).1 (Smith lowers diastolic blood pressure, and these effects can be antagonised by the Hrantagonist cimetidine.2Bolus doses of cimetidine can increase the heart rate, suggesting either that cimetidine has a partial agonist activity or that it increases the rate by a pathway not related to the H2-receptors.3In their review of ranitidine, Brittain, Jack, and Priceshow a diagram in which the response of guineapig atria to histamine (H-receptor) is antagonised by ranitidine. If, as one might expect, H2-receptors in the heart have a physiological role, then it seems curious that an agent as specific and potent as we are told ranitidine is should have no effect on cardiovascular function. I think it is very important that further work be done on cimetidine and ranitidine and why they apparently differ in their reported effects on the heart. Such research should provide further insights into the role of histamine in cardiovascular function. M.R.C. Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, Oxford OX13RE

POLIOMYELITIS PRESENTING WITH SYMMETRICAL PARALYSIS OF UPPER LIMBS

SIR,-A previously healthy 2-year-old boy was admitted with a temperature of40°C, irritability, drowsiness, and weakness of the left arm. 1 month before admission he had fallen from about 1 metre, without loss of consciousness. 2 weeks before admission he had had a transient cough and a fever. He had received a single diphtheriapertussis-tetanus immunisation at the age of 3 months. When first seen by us, he showed nearly constant conjugate deviation to the right. There was mild head lag when he was pulled up from the supine posture. The left arm showed dense flaccid paralysis but the right limb could not be adequately tested because it was splinted. The deep tendon jerks in the left arm were absent. No atrophy or fasciculation was noted. The abdominal reflexes were symmetrical at 2 +. The knee and ankle jerks were symmetrically increased at 3 +. On the left side there were two beats of clonus and a weak extensor response. Power in the legs was normal and the child could be persuaded to take a few steps. Sensory examination was normal. There were no meningeal signs. The initial diagnosis was right cerebral dysfunction, in view of the previous head injury and the few lateralising signs. The CSF protein was 59 mg/dl, sugar 76 mg/dl, white cells 50 (66% lymphocytes) with 20 red cells, a chloride of 120 mmol/1, with negative Gram film and culture. An EEG contained diffuse symmetrical high and medium voltage delta and theta slowing. Skull X-rays and right carotid angiogram were normal. On the third day the patient was neither worse nor better. So we re-examined him, after removal of the splint. We noted complete flaccid paralysis of the right arm. The conjugate eye deviation had gone but the lower limb findings were unchanged. Poliomyelitis was considered, and this was confirmed by a rising titre against poliovirus type 3 in the serum, reaching 1:128. The patient subsequently showed a slow steady improvement. In this case the history of trauma was a red herring, and the first neurological examination was incomplete because of a splint on the right arm. The weakness may have started on the left side and progressed to the right; we cannot tell, but the fact remains that the weakness was symmetrical when the child was examined after removal of the splint. Furthermore, there were a few pyramidal lateralising signs; in fact such signs are occasionally seen in poliomyelitis, 1,2 and they are compatible with the cortical3 dysfunction suggested by the EEG and with pathological findings. Even when the symmetrical weakness was uncovered it was felt to be most unusual for poliomyelitis. The standard texts speak of asymmetrical weakness, usually in the legs, in poliomyelitis,4-8 and further evidence for asymmetry is provided by pathological

findings.3

In this area poliomyelitis is endemic because of a poor immunisation programme or poor compliance. Several hundred cases have been seen at this hospital in the past ten years, but this was the first with such unusual features. Neuroscience Department, Rashid Hospital, Dubai, United Arab Emirates

QAIS GHANEM MUHAMMAD A.

ABDUL RAZAK

1. Ford FR. Infections and parasitic invasions of the nervous systems In: Diseases of the nervous system in infancy, childhood and adolescence, 6th ed. Springfield, Charles Thomas, 1973: 443. 2. Lagos JC. Flaccid weakness of sudden onset. In- Differential diagnosis in pediatric

neurology. Boston: Little, Brown, 1971: 4. 3. Adams JH. Viral diseases of the

G. P. SPICKETT 4.

1. Durant GJ, et al. Impromidine (SK&F 92676) is a very potent and specific agonist for histamine H2-receptors. Nature 1978; 276: 403-04. 2. Boyce MJ Cimetidine and the cardiovascular system. In: Bacon JH, ed. Cimetidine in the 80’s. Edinburgh: Churchill Livingstone, 1982. 227-37. 3. Boyce MJ. Cardiovascular effects of intravenous cimetidine in healthy man. Br J Clin Pharmacol 1981; 12: 268P 4. Brittain RT, Jack D, Price BJ. Recent developments in histamine H2-antagonists. In: Lamble JW, ed. More about receptors: Current reviews in biomedicine 2. Amsterdam: Elsevier Biomedical Press, 1982: 134-39.

5. 6. 7. 8.

nervous system. In: Blackwood W, Corsellis JAN eds. Greenfield’s neuropathology, 3rd ed. Chicago: Year Book Medical Publishers, 1976: 307. Manson-Bahr P. Diseases of the central nervous system. In: Manson’s tropical diseases, 15th ed. London: Cassell, 1960: 619 Chun R. Viral diseases of the central nervous system. In: Swaiman KE, Wright FS.eds. The practice of pediatric neurology. St Louis: CV Mosby, 1973 587. Menkes J. Infections of the nervous system. In: Textbook of child neurology. Philadelphia: Lea and Fabiger, 1974: 245. Bray PF. Infections. In: Neurology in pediatrics. Chicago Year Book Medical Publishers, 1969: 285. Miller JR, Harter DH. Acute viral infections. In: Goldensohn ES, Appel SH, eds

Scientific approaches to clinical neurology. Philadelphia: Lea & Febiger, 1977: 392