INFORMED CONSENT

1221 adults? Redistribution of milk from high to low contamination areas ensures a spreading of risk but, if ICRP models have meaning, this affects neither the whole population dose commitment nor the estimate for excess cancers. I cannot accept that the handful of thyroid cancers arising from Chernobyl radioiodine can be regarded as negligible because they will not be visible when buried within annual cancer figures. ANTHONY TUCKER

**This letter has been shown to Dr Bowlt, whose reply follows.ED. L.

SiR,—Details

of the work

on

which my letter

was

based will be

published elsewhere. The age-structure of the sample group was perforce weighted to the older end, with most over 50 years of age. The sample group died from a variety of causes, including accidents and coronary artery thrombosis, for most of which there seems little to suppose an abnormal diet. The measurements also suggested no evidence of abnormal diets except in 3 cases of significantly low activity. Indeed the comparative uniformity of the initial specific activity of the z1 in British thyroids from Chernobyl fallout was a surprising fmding, as pointed out. in my letter. The very few children in the study group had specific activities within the range found in the adults, indicating thyroid doses of the same order. reason

Department of Radiation Biology, Medical College of St Bartholomew’s Hospital, London EC1M 6BQ

COLIN BOWLT

ILEAL PREDILECTION OF GRAFT-VERSUS-HOST DISEASE

SIR,-I read Dr Spencer and colleagues’ letter (Oct 25,

p

983)

with great interest. The fact that normal gut mucosal enterocytes above the Peyer’s patches express HLA-DR antigen on their surfaces may be the long-awaited explanation for the peculiar predilection of the lesions of graft-versus-host disease (GVHD) for the ileum and other areas containing Peyer’s patches,’ notably areas above Peyer’s patches.2 "Aberrant" expression of HLA-DR antigen in epidermal keratinocytes, bile ductules, and enterocytes occurs in GVHD. Epithelial DR expression also occurs in several other inflammatory conditions in which lymphocytic infiltrates participate.3 We and others4-6 have suggested that epithelial DR expression may act as an amplifying, trophic, or homing signal for the influx of lymphoid effector cells in such reactions. Since the mucosa directly above Peyer’s patches is normally positive for HLA-DR expression-perhaps (as suggested by Spencer et al) due to y-interferon secretion by the underlying lymphocytes-the stage is already set upon marrow transplant for the GVH reaction to begirl at these sites. Since the distribution of Peyer’s patches seems identical to that of the earliest or most severe GVHD lesions in the gut, the adjacent normal epithelial DR expression probably explains the peculiar regional distribution of these lesions.

Supported in part by grants CA 15704, HL 36444 (ibrmerly CA 30924 from the Heart, Lung, and Blood Institute, DHHS), and CA 18029. Marrow Transplant Team, Fred Hutchmson Cancer Research Center, Seattle, Washington 98104, USA 1. Slavin 2.

3.

4. 5.

6.

GEORGE E. SALE

RE, Woodruff JM. The pathology of bone marrow transplantation. Pathol Annu 1974; 9: 291-344. Sale GE, Shulman HM, McDonald GB, Thomas ED. Gastrointestinal graft-versushost disease in man: a clinico-pathologic study of the rectal biopsy. Am J Surg Pathol 1979; 3: 291-99 (see fig 4). Lampert IA. Expression of HLA-DR (Ia-like) antigen on epidermal keratinocytes in human dermatoses. Clin Exp Immunol 1984; 57: 93-100. Sale GE. Pathology and recent pathogeneuc studies in human graft-versus-host disease. Surv Synth Pathol Res 1984; 3: 235-53. Seemayer TA, Lapp WS. Graft-versus-host induced immunosuppression and tissue injury: Experimental and theoretical considerations. Surv Synth Pathol Res 1984; 3: 254-63. Sullivan KM, Parkman R. The pathophysiology and treatment of graft-versus-host disease. Clin Haematol 1983; 12: 775-89.

PROCOLLAGEN-III-PEPTIDE AND HYRERTHYROIDISM

SiR,—ProcolIagen-III-peptide, the precursor of collagen, is synthesised in fibroblasts and can be measured in blood radioimmunologically. Serum levels are significantly increased in liver disease1 and can also be used to monitor raised globulin states.2 Like Locher and Oberleitner3 we have investigated procollagen111-peptide in thyroid disease. We used a radioimmunoassay kit (’RIA-gnost’ procollagen III); Hoechst-Behringwerke AG, Marburg, West Germany). The sensitivity of the assay is 0’ng/ml; within-assay reproducibility varies between 68 and 9-4%, according to serum values, betweenassay reproducibility varies from 11 to 12-8 %. We studied 16 euthyroid individuals, euthyroidism being confirmed by a thyrotropin-releasing-hormone test. We used ’Amerlex M’ kits (Amersham International) to measure triiodothyronine (T3) and free thyroxine (FT4) (1-5 ±0-72 [2 SD] nmol/1 and 16-85 ±5-0, respectively) and an ultrasensitive immunoradiometric assay kit (’Magic mab TSH’; Ciba Corning Diagnostics) for thyrotropin (TSH), which was always above 0-45 mIU/1. We also studied 10 patients with hyperthyroidism (2 toxic adenoma; 7 Graves’ diseases, including 1 familial case and 1 with only one thyroid lobe; and 1 secondary toxic goitre). Their hormone levels were: T3 5-84±3 84 nmol/l, FT4 64-6±31 07 pmol/1, TSH below 0-3 mIU/1. Plasma concentrations were procollagen-111-peptide consistently below 17.1 ng/ml in the reference group (mean 11.79 ng/ml, SD 3-07). In hyperthyroidism there was no overlap (mean 34-78 ng/ml, SD 10-51; range 20-50). Procollagen-III-peptide may prove to be a useful peripheral blood marker for hyperthyroidism, especially when the diagnosis is in doubt, and it may also permit the detection of changes for the worse in patients being treated with thyroid hormones. Nuclear Medicine

Service, Hôpital de l’Antiquaille, 69321 Lyon, France; Biophysique UER Lyon Nord; and Endocrinology Clinic, Hôpital de l’Antiquaille, Lyon

A. M. CHARRIE M. C. FLEURY-GOYON P. DUTEY J. TOURNIAIRE

H, Vargas L, Hahn E, et al. Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest 1979; 9: 451-59. 2. Arrago JP, Poirier O, Najean Y. Evolution des polyglobulies primitives vers la myélofibrose: surveillance par le dosage de l’amino-propeptide du procollagène 1. Rohde

III. Nouv Press Méd 1984; 13: 40. 3. Locher JT, Oberleitner M. Procollagen-III-peptide in Med 1984; 9: A311.

thyroid disorders. Eur J Nucl

INFORMED CONSENT

SiR,—We support Professor Baum’s views (Oct 18, p 911) on the widening gap between ethics for controlled clinical trials and those applying in the conduct of "accepted" medical practice. He identifies the need for patient and public views on informed consent in the hope that these may counteract the imposition of double standards. There is already some information on patients’ attitudes to consent issues, and in general these indicate that patients want to be informed about details and risks of treatment and to play -an active part in medical decisions affecting them.1-5 However, several patients in some studies have indicated that they do not wish to be informed of additional risks or details.6,7 We too have sought patients’ attitudes on informed consent issues in a study (to be published) of candidates for randomised trials of cancer treatment. Of 55 patients most (84%) felt they should be involved in deciding how much they were told about their illness and its treatment, but (53%) also felt that the law should not have a say in how much information they were given. Although virtually all wished to be involved in decisions about their medical care, 85 % still preferred to leave the actual decisions to their doctors. Hence there is some information on patients’ attitudes to consent issues but we agree that public attitudes have not been adequately canvassed. More important than information on attitudes to consent, we feel, is the lack of information about the impact on patients of different

1222

approaches to seeking consent. In our study8 of different procedures for obtaining consent to randomised treatment in cancer clinical trials we found that total disclosure of all information compared with an individual approach to seeking consent resulted in a better understanding of treatment, side-effects, and research aspects of the treatment, but less willingness to agree to randomised treatment, and increased anxiety. No significant differences were found in patient perception of the doctor-patient relationship. We hope that these results will stimulate similar controlled trials of practices at other hospitals. Ludwig Institute for Cancer Research, Sydney Cancer Therapy Branch, University of Sydney, Sydney, NSW 2006, Australia 1. White

DR, Muss HB, Michielutte R,

consent

R. J. SIMES M. H. N. TATTERSALL et

al. Informed consent: Patient information

chemotherapy trials. Am J Clin Oncol 1984; 7: 183-90. 2. Reynolds PM, Sanson-Fisher RW, Poole AD, Harker J, Byme MJ. Cancer and communication. Information-giving in an oncology clinic. Br Med J 1981, 282: forms m

1449-51.

3.

Saurbrey N, Jensen J, Rasmussen PE, Gjorup T, Guldager H, Riis P. Danish patients’ attitudes to scientific-ethical questions. An interview study focussing therapeutic

trials. Acta Med Scand 1984; 215: 99-104. 4. Elian M, Dean G. To tell or not to tell the diagnosis of multiple sclerosis. Lancet 1985; ii 27-28. 5. Cassileth BR, Zupkis RV, Sutton-Smith K, March V. Information and participation preferences among cancer patients. Ann Intern Med 1980; 92: 832-36. 6. Fraser AG. Do patients want to be informed? A study of consent for cardiac catheterisation Br Heart J 1984; 52: 468-70. 7. Alfidi RJ Controversy, alternatives and decisions in complying with the legal doctrine of information consent. Radiology 1975; 114: 231-34. 8. Simes RJ, Tattersall MHN, Coates AS, et al. Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer. Br Med J 1986; 293: 1065-68.

PAIN AND THE MOTHER-CHILD INTERACTION

SIR,-According to current theories of mother-child interaction, child between the ages of about three and six months is in symbiotic relation with its mother. In this relation, it is said, unpleasant stimuli are projected outside the shared milieu and do not upset the fragile relationship.1 One might therefore expect childen of this age to react more lengthily to pain experienced when not in direct contact with their mothers. In Sweden, children between three and six months of age are given three shots of vaccine against tetanus and diphtheria (Duplex-vaccin pH 5,8-6). It is locally irritating and painful. Reactions to vaccination, measured as duration of crying, have been compared in two groups allocated at random, one sitting in the arms of the mother (n = 17), the other lying on a couch without contact with the mother (n 21) while being injected. In the second group the child was given to the mother immediately after vaccination. Either way she was encouraged to comfort the child. The children who were vaccinated while in the mother’s arms cried for significantly longer than those vaccinated without maternal contact (table). This could mean that the child in the arms a

=

DURATION OF CRYING AFTER VACCINATION

Numbers in

parenthesis are SDs.

of mother, when experiencing external pain, perceives it as coming from the mother herself. Thus the relationship is disturbed and comforting is made more difficult, which is contrary to current theories of mother-child interaction. It is noteworthy that as the children approached the age of six months the differences become smaller, so the relation between child and mother may be less easily "poisoned" with increasing age. These observations provide an argument for vaccinating such infants with the mother apart, though standing by ready to give comfort, unless she particularly wants to hold the child. Hallunda Health Clinic, Box 104, S-14501 Norsborg, Sweden 1 Mahler

GÖSTA ALFVÉN

M, Pine F, Bergman A. The psychological birth of the human infant. New York: Basic Books, 1975.

FETAL ALCOHOL SYNDROME IS NOW LEADING CAUSE OF MENTAL RETARDATION

SIR,--Fetal alcohol syndrome (FAS) is a pattern of birth defects in children born to alcoholic women, consisting of prenatal and postnatal growth retardation, facial anomalies, organ pathology, and central nervous system dysfunction, including mental retardation. We have reviewed nineteen epidemiological studies in which 164 FAS cases were reported from populations totalling 88 236 live births-a frequency of 1per 1000.’I In a study of the frequency of chromosomal anomalies done at six hospitals in the United States on every live bom infant (56 952 consecutive live births) the rate for Down syndrome was 1 25 per 1000.2 In a thorough study in Canada, as part of the British Columbia Health Surveillance Registry, Baird and Sadovnick33 found that the rate of spina bifida was 1 per 1000 and that about 50% of those identified had mental retardation. At the time the population of British Columbia was 2 7 million. Shortly after they identified FAS as a clinical entity, Smith and his colleagues4 stated that "in our experience, the fetal alcohol syndrome has become the third ranking recognised disorder in which mental deficiency is a feature. Only Down’s syndrome and neural tube defects, such as meningomyelocele are more common causes". Since that statement was made ten years ago much more information, such’ as the findings we have presented, has become available. Smith and colleagues’ conclusion needs to be amended. Mental retardation is a cardinal feature of FAS, and the syndrome, has emerged as the number one recognised disorder in which mental deficiency is a feature. Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA

ERNEST L. ABEL ROBERT J. SOKOL

1. Abel EL, Sokol RJ. Incidence of fetal alcohol syndrome and economic impact of FAS related anomalies. Drug Alcohol Dependence (in press). 2. Russell D. Mental handicap New York: Churchill Livingstone, 1985. 3. Baird PA, Sadovnick AD Mental retardation in over half-a-million consecutive live births an epidemiological study. Am J Ment Deficiency (in press). 4. Smith DW, Jones KL, Hanson W Perspectives on the cause and frequency of the fetal alcohol syndrome Ann NY Acad Sci 1976; 243: 138-39.

ACUTE TRANSVERSE MYELITIS AS PRESENTING NEUROLOGICAL FEATURE OF LYME DISEASE

SIR,-With up-to-date, specific serological tests a pathogenic burgdorferi has been demonstrated in some neurological disorders lacking the characteristic triad of Lyme role for Borrelia

disease.We describe here a case in Which acute transverse myelitis (ATM) was the prominent neurological manifestation. In August, 1986, a 19-year-old woman living in the Belgian Ardennes, an endemic area for B burgdorferi infection, complained of a pruritic swelling on her left ankle. Her general practitioner noted a 3 cm skin lesion resembling erythema chronicum migrans-a red ring surrounding a clear central part with the mark of a bite in the middle. She could not recall having been bitten by an insect. The only treatment prescribed was a topical antiinflammatory preparation. 2 days later, she noted numbness on the right side of her chest, extending to affect the whole of her right leg in about 2 days. Thereafter, paraesthesias were noted in both legs. On day 15, when she complained of gait disturbance and weakness in her legs, she was referred to our hospital. Neurological examination revealed severe spasmodic paraparesis with hyperreflexia and bilateral extensor plantar responses. There was a T4 level for pin, temperature, touch and vibration. The small muscles of her left hand and dorsal muscles of the left forearm were weak. Motor reflexes were normal except for a reduced right triceps response. She had difficulty urinating and was constipated. ATM was diagnosed. The CSF contained 10 white blood cells (90% lymphocytes, 10% monocytes) and protein 39 mg/dl, with a striking increase in gammaglobulins and more than twenty oligoclonal bands. IgG intrathecal synthesis was 28 mg per day (normal below 33 mg). Bacterial, fungal, and cryptococcal tests were negative. 1 week later the CSF contained 40 white cells (95% lymphocytes) and protein 60 mg/dl. Electrophoresis and isofocusing confirmed the same abnormalities. IgG intrathecal