1153 sometimes difficult to decide when this change is taking place, For this reason we studied patients with established polycythaemia to see if any immunoglobulin cellinclusions could be found. So far, our examinations both of patients’ own leucocytes and patients’ sera plus healthy polymorphonuclear cells have been negative. None of these patients were considered to be "converting" to myelofibrosis. Among those whom we have classified as having myelofibrosis, 2 had established fibrosis yet still retained an increased red-cell mass. Both our techniques showed that these patients had immune complexes, which suggests that the immunological abnormalities associated with myelofibrosis may form at a relatively early stage in the disease. Clearly we need to study more patients with myeloproliferative disorders to determine when this change takes place. It may well be important for management, especially since we believe that myelofibrosis is better not treated with busulphan or phosphorus-32 at the stage of imminent myelofibrosis, because these agents may well aggravate the fibrosis in the bone-marrow. Examination of a patient’s white cells or serum for the presence of immune complexes might enable us to make an earlier diagnosis in the transition from polycythasmia rubra vera to myelofibrosis, so that more appropriate treatment can be instituted. Requests

for

reprints

should be addressed

to

G.D.P.

cebo-treated patients. Thus, (+)-cyanidanol-3 be of benefit in acute viral hepatitis.

Introduction AT present, there is no effective treatment for acute viral hepatitis. A new substance, the flavonoid, (+)cyanidanol-3,’ has been shown to decrease the hepatotoxicity of ethanol and other compounds in laboratory animals,2-4 and to be a powerful free-radical scavenger.s In addition, (+)-cyanidanol-3 has been reported to decrease serum-bilirubin in patients with acute viral hepatitiS.6-8 In order to establish the value of (+)-cyanidanol-3 in the treatment of acute viral hepatitis, a multicentre, double-blind trial was carried out. The results are

encouraging. Patients and Methods

A prospective, double-blind, placebo-controlled trial of cyanidanol-3 was carried out in patients with acute viral hepatitis in five departments of medicine. 106 consecutive adult inpatients with acute viral hepatitis were randomised. Patients with an alcohol consumption of more than 100 g/day and/or jaundice for more than 4 weeks before admission were excluded. Viral hepatitis was diagnosed on the history, clinical

examination and liver-function tests. If there had been jaundice in the previous year, or if the diagnosis was doubtful, a liver biopsy was carried out. All 11 biopsies were read by one

pathologist (H.P.). Treatment

REFERENCES 1. Lewis, C. M., Pegrum, G. D. Unpublished. 2. Hurd, E. R., Andreis, M., Ziff, M. Clin. exp. Immun. 1977, 28, 413. 3. Pfueller, S. L., Luscher, E. F. Immunochemistry, 1972, 9, 1151. 4. Mantovani, B., Rabinowitch, M., Nussenweig, V. J. exp. Med. 1972, 135, 780. 5. Boivin, P., Bernard, J. F., Hakim, J., Woroclans, M. Acta hœmat. 1974, 51, 91. 6. Lang, J. M., Obeiling, F., Mayer, S., Heid, E. Biomedicine, 1976, 25, 39. 7. Wyatt, J. P., Sommers, S. C. Blood, 1950, 5, 329. 8. Kelemen, E., Kraszanai, G., Endes, P., Szinay, G. Acta hœmat. 1972, 57, 171. 9. Minok, G. R., Buckman, T. E. Am. J. med. Sci. 1923, 166, 469. 10. Ikkala, E., Rapola, J., Kotilainen, M. Scand. J. Hœmat. 1967, 4, 453.

(+)-CYANIDANOL-3

A. L. BLUM W. DOELLE K. KORTÜM P. PETER G. STROHMEYER

P. H. S. H.

BERTHET GOEBELL

PELLONI

POULSEN N. TYGSTRUP

Departments of Medicine, Triemli Hospital, Zürich, Switzerland; University Hospital, Tübingen; University Hospital, Ulm; University Hospital, Düsseldorf, Federal

Republic of Germany; Rigshospitalet, Copenhagen and Hospital, University of Copenhagen, Denmark

Hvidorre

Summary

A double-blind trial of

(+)-cyanidanol-3 (2 g/day) versus placebo tablets was carried out in 100 patients with acute viral hepatitis. 51 received the drug and 49 placebo. (+)-Cyanidanol-3 accelerated the disappearance of HBsAg from the blood, lowered serum-bilirubin, and relieved symptoms such

was

started within 24 hours of randomisation.

(+)-cyanidanol-3 was given in a dose of 2 g daily for 4 weeks, and placebo in a dose of two tablets four times daily. No dietary restrictions were imposed, but patients with severe anorexia, nausea, and vomiting (8 on [+]-cyanidanol-3, 7 on placebo) received intravenous glucose. Likewise, bed rest was not imposed. Patients with prothrombin concentrations 0.1). Follow-up data for at least 6 months is available for 96 patients but not for the following 4 patients. 2 placebo-treated patients

were

last

seen

in Ulm 1 month

after completion of treatment, when they were symptomTABLE III—CHANGE IN

HBsAG

STATUS

*No. of days between date of appearance of first symptom and date of

admission to hospital. tLogarithmic distribution is normal.

placebo (1 male and 3 females, and with initial bilirubin values of 16-0, 5.0, 16.0, 7.0 mg/100 ml respectively). Their data were not included in analysis. Therefore, 100 patients remained in the trial (tablesi and II). Hepatic precoma was not present in any patient before the trial, but developed in 1 patient during treatment with placebo. All patients survived the acute illpatients had been

on

aged 24, 44, 35, 50,

ness.

The effects of (+)-cyanidanol-3 on symptoms for all patients in the two groups are shown in fig. 1. If analysis is confined to data from the 75 patients with HBsAgpositive hepatitis, the drug had a statistically significant beneficial effect on abdominal discomfort (P