487

tion and hepatic copper content may be observed in othercauses of chronic hepatitis, whereas the serum-caeruloplasminis invariably normal or raised in these other conditions.We conclude that, despite its low incidence, Wilson’s disease

should be kept in mind when dealing with young patients whopresent with chronic active hepatitis.

Stepping Hill HospitalStockport SK2 7JE

G. J. ARCHERR. D. H. MONIE

EARLY DIAGNOSIS OF CONGENITAL ADRENALHYPERPLASIA

SiR,-We have measured serum concentrations of

17-OH-progesterone (17-OHP) serially during the early new-born period in a male infant. The infant was studied becauseof a family history of congenital adrenal hyperplasia. Therewas spontaneous onset of labour at 40 weeks, but delivery wasby cxsarean section because of fetal distress. At birth, clinicalexamination was entirely normal. Serum-17-OHP concentra-tions, determined by radioimmunoassay, were: mixed cordblood 183 nmol/1 and 2, 8, and 16 h and 5 day values 4$, 42,15, and 3 nmol/1, respectively. The raised concentrations incord blood and during the first few hours of life presumablyreflect the placental production of 17-OHP. Thereafter, theconcentrations fell rapidly to normal, thus excluding a diag-nosis of congenital adrenal hyperplasia secondary to C21-hyd-roxylase deficiency. These results are in striking contrast tothose obtained from a male infant with congenital adrenal hy-perplasia. Mixed cord serum-17-OHP concentration was 225nmoi/1, and at 2, 8, and 16 h and 5 days age the levels were109, 188, 488, and 188 nmol/1, respectively. The raised17-OHP concentrations persisted after birth; subsequently,biochemical confirmation of congenital adrenal hyperplasiawas further substantiated by increased urinary excretion of17-oxosteroids and pregnanetriol.The 17-OHP assay should be of value in the early diagnosis

of congenital adrenal hyperplasia due to C21-hydroxylase defi-ciency, especially in newborn males in whom clinical examina-tion is usually entirely normal.

Tenovus Institute for Cancer Research,Welsh National School of Medicine,Cardiff CF4 4XX IEUAN A. HUGHES

Neonatal Unit,St David’s Hospital,Cardiff

D. H. WILLIAMSA. D. BIRCH

UPPER GASTROINTESTINAL HÆMORRHAGE

S)R,—The interesting article by Dr Franco and her col-leagues (Jan 29, p. 218), highlighting the association betweenstress factors and acute drug-independent mucosal erosions inhepatic cirrhosis, should increase our understanding of thepathogenesis of acute upper gastrointestinal haemorrhage inthis condition and help in correct management. We have seena very similar pattern in patients with fulminant hepatic fail-ure admitted to the acute liver-failure unit, King’s CollegeHospital. In a series of 105 consecutive cases, 54% developedsevere upper gastrointestinal bleeding from acute mucosal ero-sions.’ There was a significant correlation between hmmor-rhage and the complications of hypotension, renal failure, car-diorespiratory distress, and sepsis, similar stress factors to

those described by Dr Franco and her colleagues.However, where there is haemorrhage from acute erosions in

patients with chronic liver disease and gastro-oesophageal var-ices, the definition of the predominant site of bleeding is moredifficult. In our experience there are three additional possibili-ties to be considered. Firstly, because variceal bleeding is often

1. Bailey, R. J., Macdougall, B. R. D., Williams, R. Gut, 1976, 17, 389.

intermittent, an initial emergency endoscopy may reveal activehaemorrhage from acute erosions only, whereas repeat endo-scopy for subsequent haemorrhage, often within a few hours,may then demonstrate variceal haemorrhage in addition to ero-sions. Secondly, endoscopy in bleeding patients is notoriouslydifficult, and haemorrhage from a gastric varix high in thefundus of the stomach may be overlooked in the presence of

bleeding mucosal erosions. Thirdly, liver function may deterio-rate rapidly after variceal haemorrhage, and this, in additionto other stress factors, may lead to the development of acutemucosal erosions.We would advocate caution in the interpretation of bleeding

from acute erosions in these patients. After the start of defini-tive therapy for gastrointestinal haemorrhage, either from var-ices or erosions, repeated assessment is essential because thepattern of bleeding may alter from one episode to the next.

Liver Unit,King’s College Hospital,London SE5 9RS

B. R. D. MACDOUGALLK. J. MITCHELLP. G. WHEELERROGER WILLIAMS

MULTIPLE SCLEROSIS AND DOGS

StR,—The evidence increasingly favours a viral aetiology formultiple sclerosis (M.s.).’ None of the hypotheses,2-4 however,seems to me to explain the epidemiological -data satisfactorily.In particular, the positive correlation of M.s. prevalence withlatitude is unlikely to be due to sanitary conditions2 or diet,3since the same correlation is found in areas (e.g., U.S.A., Wes-tern Europe, Australia) where living standards and styles varylittle with latitude. I should like to propose an alternative

hypothesis.I postulate that dogs are the main carriers of the M.s. virus

and that, as in canine hepatitis, the virus is transmitted amongdogs via urine. Dogs are particularly prone to inhale materialfrom the urine of other dogs, but often long after the urine hasbeen excreted. Thus, if we assume that the virus in canine urineis inactivated by sunlight, we can account for the correlationwith latitude. In Japan, where ns.s. is very rare even in northernareas,7 dog ownership8 runs at a third to a fifth of that in Bri-tain and the U.S.A. Furthermore, in Japan "it is not custom-ary to exercise dogs."8

If M.S. infection in dogs has a long incubation period, thenbecause dogs have a relatively short life each dog carrying thevirus might act only briefly as a source of infection. Thus, theinfection focus for man would be mainly restricted to the im-mediate family owning the dog. The age-distribution of M.S.patients, suggests that susceptibility to infection is highest dur-ing childhood and adolescence, which would explain much ofthe data of familial incidence. Thus, the risk for two siblingsis much higher,9 because they face common exposure duringthe short infectivity of a family dog. The increased incidenceamong cousins9 is also consistent with the hypothesis, sincecousins can be expected to visit fairly frequently and to havecontact with the family dog. The increase in dog ownershipwith affluence could also account for its correlation with M.s.among social groups within a country. 10 11

1. Carp, R. I., Merz, G. S., Licursi, P. A. Infect. Immun. 1974, 9, 1011.2. Poskanzer, D. C., Schapira, K., Miller, H. Lancet, 1963, ii, 917.3. Swank, R. L. A Biochemical Approach to Multiple Sclerosis. Springfield,

Illinois, 1961.4. Alter, M. Lancet, 1976, i, 456.5. Acheson, E. D. in Multiple Sclerosis: a Reappraisal (edited by D. McAlpine,

C. E. Lumsden, and E. D. Acheson); p. 55. Edinburgh, 1972.6. Poppensiek, G. C., Baker, J. A. Proc. Soc. exp. Biol. Med. N.Y. 1951, 77,

279.7. Okmaka, S., McAlpine, D., Miyagawa, K., Suwa, N., Kuroiwa, Y. Shiraki,

H., Araki, S., Kurland, L. T. Wld Neurol. 1960, 1, 22.8. Carding, A. H. J. small Anim. Pract. 1969, 10, 419.9. Schapira, K., Poskanzer, D. C., Miller, H. Brain, 1963, 86, 31510. Miller, H., Ridley, A., Schapira, K. Br. med. J. 1960, ii, 343.11. Beebe, G., Kurtzke, J. F., Kurland, L. T., Auth, T. L., Nagler, B. Neuro-

logy, 1967, 17, 1.