CLINICAL VIRAL INFECTIONS AND MULTIPLE SCLEROSIS

165

hydrogen producer, as in our case. Failure to produce hydrogen may

COEFFICIENTS AND Z-VALUES DERIVED FROM COX ANALYSES

The other subjects many was her normal this of patient’s presentation interesting aspect nutritional status. It is easy to see how patients such as this, who thrive in the face of severe diarrhoea, could be labelled as having chronic non-specific diarrhoea of infancy, or toddler’s diarrhoea. be present in

as

as

21% of

Division of Gastroenterology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 1. 2.

tested.

DAVID MOORE STEVEN LICHTMAN PETER DURIE PHILIP SHERMAN

Kerry KR, Anderson CM. A ward test for sugar in faeces. Lancet 1964; i: 981-82. Ford RPK, Barnes GL. Breath-hydrogen test in sucrase-isomaltase deficiency. Arch Dis

Child 1983; 58: 595-97. Method for assay of intestinal disaccharidases. Anal Biochem 1964; 7: 18-25. 4. Ament ME, Perera DR, Esther LJ. Sucrase-isomaltase deficiency: a frequency misdiagnosed disease. J Pediatr 1973; 83: 721-27. 5. Gardiner AJ, Tarlow MJ, Symonds J, Hutchinson JG, Sutherland IT. Failure of the hydrogen breath test to detect primary sugar malabsorption. Arch Dis Child 1981; 56: 368-72. 6. Saltzberg DM, Levin GM, Lubar C. Common pitfalls in interpreting hydrogen breath test. Gastroenterol 1985; 88: 1566. 3.

Dahlqvist A.

PROGNOSTIC FACTORS IN HODGKIN’S DISEASE

SIR,-Dr Haybittle and his colleagues (April 27, p 967) report a multivariate analysis of factors influencing prognosis on 743 patients with Hodgkin’s disease clinical stages I and IIA. We have done a similar analysis on 1139 patients in clinical stages I and II in three EORTC controlled clinical trials.’ To compare Haybittle’s data and ours we extracted from our series the 606 patients in stages I and IIA who were treated by radiotherapy alone (table A). Table B shows the results obtained from the whole group of patients. On several points, the two series are in accord. For example, the great prognostic significance of the erythrocyte sedimentation rate (ESR) was confirmed, and we found that although ESR is strongly correlated with the presence or absence of systemic symptoms, it has independent prognostic significance.In our data, age is the variable that has by far the greatest impact on survival, especially survival after relapse. 1,3 This is consistent with the data ofHaybittle 4 et al and of Bergsagel et al. which our data diverge. For example, Haybittle et al found that mediastinal involvement was associated with a poor survival, whereas, in our data, in which the number of affected lymphatic sites was one of the variables of the multivariate analysis, the independent impact of mediastinal involvement was very slight, probably because it is strongly correlated with the number of affected lymphatic areas and also perhaps because the treatment technique was different. One conclusion to emerge from our data is the strong interaction between treatment and the significance of the various prognostic factors. In our study, the two prominent prognostic factors were a combination of ESR and the presence or absence of symptoms and the number of affected lymphatic areas. However, the impact of lymphatic areas varied with the type of initial treatment.5 The usefulness of laparotomy was studied in one of the EORTC trials in which, to assess the prognostic significance of laparotomy, all patients undergoing laparotomy, whatever the findings, received the same treatment.The relapse-free survival was significantly lower in patients with a positive laparotomy but because of the’ efficacy of salvage chemotherapy, the long-term survival was identical in patients with a positive or a negative laparotomy as well as in those treated by spleen irradiation. 3,6 This observation can be generalised to the other prognostic factors and to other types of treatment. In all controlled trials relapse-free survival has been higher in patients treated by chemotherapy and radiotherapy combined than in those treated by radiotherapy alone, but long-term survival has been the same in the There

are

points

*2 = &bgr;v var ((3). tHistology (mixed celIuIanty/difTuse lymphocytic); ESR (O40 mm/h or >30 for B); sex (male); MI = mediastinal involvement.

for A

and 50

radiotherapy alone. Combination chemotherapy is delivered to all relapsing patients but this protocol avoids the toxicity associated with administration of MOPP (gonadal damage and carcinogenesis) in over two-thirds of patients.

Institut Gustave 94805 Villejuif, France

M. TUBIANA M. HENRY-AMAR M. HAYAT P. CARDE R. SOMERS,

Roussy,

For the EORTC

Radiotherapy-Chemotherapy Group

on

systemic

two arms.

The current policy of our group is to restrict combination chemotherapy to the unfavourable subset of patients, those in whom relapse-free survival is low after radiotherapy (patients with

B symptoms and an ESR above 30 mm/h and/or with three or more affected lymphatic areas) and to treat all the other patients with

1. Tubiana

2

3

4. 5. 6.

Van der

M, Henry-Amar M, Werf-Messing B, et al. A multivariate analysis of prognostic factors in early stage Hodgkin’s disease. Int J Radiation Oncol Biol Phys 1985, 11: 23-30. Tubiana M, Henry-Amar M, Burgers M, Van der Werf-Messing B, Hayat M. Prognostic significance of erythrocyte sedimentation rate in clinical stages I-II of Hodgkin’s disease. J Clin Oncol 1984, 2: 194-200. Tubiana M, Henry-Amar M, Hayat M, et al. The EORTC treatment of early stages of Hodgkin’s disease, the role of radiotherapy. Int J Radiation Oncol Biol Phys 1984, 10: 197-210 Bergsagel DE, Alison RE, Beau HA, et al. Results of treating Hodgkin’s disease without a policy of laparotomy staging. Cancer Treat Rep 1982; 66: 717-31. Tubiana M, Henry-Amar M, Hayat M, et al. Prognostic significance of the number of involved areas in the early stages of Hodgkin’s disease Cancer 1984; 54: 95-104. Tubiana M, Hayat M, Henry-Amar M, Breur K, Van der Werf Messing B, Burgers M. Five-year results of the E.O.R.T.C randomized study of splenectomy and spleen irradiation in clinical stages I and II of Hodgkin’s disease. Eur JCancer 1981; 17: 355-63.

CLINICAL VIRAL INFECTIONS AND MULTIPLE SCLEROSIS

SIR,-In an investigation into the role of coronavirus infection in the aetiology of multiple sclerosis (MS), we have closely followed up 39 cases and 39 community controls for a period of eight months (October, 1983, to May, 1984), chosen to include the coronavirus cold season. As Dr Sibley and colleagues have done, we recorded cold symptoms experienced as well as exacerbations of neurological deficits during this time. Cold symptoms were self-reported and neurological status was assessed by a physician in our MS clinic on a monthly basis. We also asked patients and controls how often they recall having had colds during the year before the study. There were 19 exacerbations of MS and 39 reported colds in the 294 patient-months of observation. Our monthly cold frequency (13-3%) is higher than the 4- 5% reported by Sibley et al and may reflect climatic differences, our inclusion of primarily winter months, and slight differences in case definition. However, this rate

’

166 almost identical

to the 13 7°7o seen in our controls (40 colds in months). The patient group claimed to have experienced 46 colds in the 12 months before entry into the study, marginally fewer than the 54 remembered by the controls. was

293

Of the 19 exacerbations seen in our MS group, 6 occurred in association with colds and 13 did not. Of the remaining 275 nonexacerbation months 33 were associated with colds and 242 were not. The rate of exacerbation was thus more than three times higher in cold months than in the non-cold months (p = 0 - 028, Fisher’s exact test, one-tailed). Our ratios are similar to those obtained by Sibley et al. 15% of infections were associated with worsening ofMS whereas 32% of MS exacerbations coincided with colds during this

period. Colds were most frequently reported during the winter months but there was little seasonality evident in the MS episodes. We are currently analysing serum specimens for coronavirus antibody titres in an attempt to determine whether these episodes of neurological impairment can be linked to a particular viral agent or if they represent a non-specific response to any ofa host of infectious

agents. Departments of Epidemiology and Community Medicine, and of Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1 H 8M5

S. NAROD C. M. JOHNSON-LUSSENBURG Q. ZHENG

MS Clinic, Ottawa General Hospital

R. NELSON

SIR,-Dr Sibley significant relation

and colleagues (June 8, p 1313) suggest a between clinical viral infections and multiple sclerosis (MS) exacerbations. In table v patients who had no infection were excluded: this exclusion will seem to strengthen any association between infections and exacerbations. Although care was taken to prevent the patients having any preconception of the aim of investigation, it is difficult to believe that patients, contacted monthly to complete a questionnaire, had no idea about the subject of the study. Moreover, patients are more likely to answer positively to questions about health problems when they have MS exacerbations. This could explain the relation between frequency of exacerbations and annual infection rate. MS exacerbations are often treated with drugs that can affect immunity. The lack of a significant relation between urinary tract infections and exacerbations does not rule out this hypothesis completely. Indeed, some MS patients have chronic urinary problems because of their neurological illness, so it is difficult to analyse data on this particular infection. ANNICK ALPEROVITCH CLAUDINE BERR

INSERM Unit 169, 94807 Villejuif, France

* This letter has

been shown

to

Dr

Sibley,

whose

reply

follows.-ED. L.

SIR,-No patients were excluded from tables IV, VI, andvii, and we think that the conclusion that there is a causal relation between certain common viral infections and attacks of MS is supported by the data overall. Every attempt was made to avoid patient bias in this 8 year prospective study. Since questions about infection were asked amidst scores of questions about other events of the previous month, such bias can probably be discounted. No positive temporal relationships were found in other areas. The fact that urinary tract infections of an acute symptomatic variety were not a risk factor for exacerbations makes us feel that infection, per se, is not the triggering mechanism. It seem more likely that our data are explained by an antigenic similarity between certain viruses and brain proteins. Jahnke et al (in the July 19 issue of Scie?zce) describe aminoacid sequence homologies between certain viruses and

encephalitogenic proteins. Department of Neurology, Health Sciences

Center,

University of Arizona, Tucson, Arizona 85724, USA

WILLIAM A. SIBLEY

Commentary from Westminster The Warnock Recommendations: Mr Powell and his Fellow Opponents Renew their Campaign THE Government seems to have made a serious strategic in its approach to legislating on the recommendations of the Warnock committee on advances in biotechnology and genetics. Although the tactics chosen by DHSS Ministers allowed them to force through Parliament early the relatively uncontroversial ban on surrogate motherhood, their plans to codify medical and scientific responsibilities on other aspects of this subject seem to be increasingly in danger of lapsing into chaos. Their difficulties apparently arise because Ministers have utterly underestimated the nature of the opposition to one of the principal Warnock recommendations -that a non-Governmental body should be established to regulate the conduct and extent of experimentation on embryos. They were aware at the start that opposition would be organised against such experimentation in any form. In the hope of containing that opposition and defusing it, Ministers opted to postpone legislation on the whole range of the recommendations (apart from surrogacy) until this autumn. At the time that seemed a wise tactic. In the interval, however, the full strength of the Parliamentary opposition was revealed. MPs voted by an overwhelming majority to give a second reading to the Bill tabled by Mr Enoch Powell, which sought to ban all experimentation involving embryos. Backbench support came from within all parties, though with a preponderance of Conservatives, and it came in spite of the backbenchers’ knowledge that Health Ministers were in favour of allowing regulated experimentation to continue. (Ministers’ professions of neutrality on the issue were more a matter of Parliamentary convention in relation to private Bills than a matter of true neutrality.) In the event it was the Parliamentary ingenuity of a backbench minority opposed to the experimentation ban which blocked Mr Powell’s Bill, through the use of procedural devices as arcane as those applied by Mr Powell himself. Somewhat shell-shocked, and not entirely relieved, Ministers took stock and realised they were in danger of losing the whole of their planned legislation on the Warnock recommendations unless they could undermine the strength of the backbench opposition to error

embryo experimentation. The alternatives before them were either to accede to the still widely desired prohibition on all experiments or to drop the proposed regulatory body from the Government Bill and try to get it through Parliament separately. The second course would have guaranteed the passage of the Bill, but it would have been a lame piece of legislation without the regulatory body. Then Ministers discovered another option; they postponed the introduction of their Bill for another twelve months. It is now not expected to come before Parliament until the autumn of 1986. If Ministers hoped this stratagem would help to cool tempers on the backbenches and smooth the eventual passage of their Bill, that has turned out to be another miscalculation. Mr Powell and his supporters have announced that they plan to use the newly extended interval before Government legislation to launch a fresh campaign to secure a Parliamentary ban on embryo research, preempting the Government Bill. They are to try the same route of private members’ legislation which was previously blocked, but they will have more chances of success than last time. Their improved chances result from the increased numbers of backbenchers who now say they are willing to