1127

neurological

diseases

associated with M.v., and

found.

tients with

until a suitable donor can be found.

healthy controls) were kindly provided by Dr Wallace A. Tourtelette through the auspices of Dr William E. Reynolds of the National Multiple Sclerosis Society, New York. To avoid bias, the sera were identified by code only, and identification of the sera with proper diagnosis was revealed only after completion and reporting of the study.

Eventually partial artificial hearts and cardiac allografting should be able to be used together to save the lives of some very ill patients. The partial artificial heart could solve the biggest logistic problem of cardiac transplantation-supporting the prospective recipient

not

REFERENCES

Viruses Am. J. Cardiol. 1977, 39, 1073. Norman, J. C., Fuqua, J. M., Hibbs, C. W., Edmonds, C. H., Igo, S. R., Cooley, D. A. Archs surg., Chicago, 1977, 112, 1442. 3. Norman, J. C., Cooley, D. A., Igo, S. R., et al. J. thorac. cardiovasc. Surg. 1977, 74, 709. 4. Ott, D. A., Cooley, D. A., Norman, J. C., Sandiford, F. M. Cardiovasc. Dis. Bull. Texas Heart Inst. 1975, 5, 15.

1. 2.

Katz, A. M., Tada, M.

CANINE DISTEMPER VIRUS AND MULTIPLE SCLEROSIS ADALBERT KOESTNER

STEVEN KRAKOWKA

Department of Veterinary Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, U.S.A.

Serum samples from patients with multiple sclerosis (M.S.), patients with subacute sclerosing panencephalitis (S.S.P.E.), and controls were examined for virus-neutralising antibodies against measles virus (M.V.) and 2 strains of canine distemper virus (C.D.V.). M.S. and S.S.P.E. patients had higher M.V. antibody titres than controls. In contrast, no significant differences were observed in mean C.D.V.-neutralising antibody titres between M.S. patients and controls. The results, though obtained from a small number of patients, fail to implicate C.D.V. in the ætiology of M.S.

Summary

Measles virus (Edmundson strain), adapted to growth in African green monkey (vero) cells, was kindly supplied by Dr David Wolfe, Department of Microbiology, Ohio State University, Columbus, Ohio. Two distemper-virus strains adapted to growth in vero cells were used. One strain, Ondersperpoort (Ond-c.D.v.), was originally obtained from Dr M. J. G. Appel, Cornell University, and has been maintained in our laboratory since 1971. The in-vitro properties of the second strain, a viral isolate (R252-c.D.v.) capable of causing C.N.S. demyelination in dogs, have been described elsewhere.

Virus-neutralisation Tests On the day of testing, sera were thawed in a 37°C water bath and heat-inactivated at 560C for 30 min. Samples were tested in quadruplicate in a microtitre system with each viral isolate for neutralising titres. All tests were done at the same time to avoid potential losses in titre due to freezing and thawing. Sera of dilutions (0-025 ml) were mixed with 0.025 ml viral inocula containing 100 T.C.I.D’50 and incubated for 1 h at 37°C. The mixtures were inoculated into microtest wells (Falcon plate no. 2090) containing 24x104 vero cells per well, incubated at 37°C in 10% CO2 for 3 days (Ond-c.D.v. and M.v.) or 4 days (R252-c.D.v.). For accurate determination of titre end-points, monolayers were fixed in 10% formalin for 4 h, stained with Giemsa stain for 45 min, washed and read on an AO microscope at xlO magnification. 50% titre end-points were calculated with the Reed-Meunch method.

Introduction THE aetiology of multiple sclerosis (M.S.) is unknown. Vascular compromise, toxicities, and autoimmunity have all been implicated as causes of the characteristic perivenous plaques of demyelination.1 The viral theory of mt.s. has received indirect support. Serological surveys have indicated that M.S. patients have higher antibody titres to measles virus (M.v.) in serum and cerebrospinal fluid than do age-matched controls.2-4 However, attempts to recover M.V. from M.S. patients or demonstrate M.v. viral antigens in M.S. tissues have been unsuccessful. Several investigators have, however, isolated and characterised a parainfluenza virus from M.S. tissues.5-7 One report has suggested an association between M.S. and the presence of pets in the immediate household environment,8 implicating transmission of animal viruses as a possible pathogenetic pathway for M.S. in man. This hypothesis would apply particularly to dogs, since canine distemper virus (c.n.v.), an endemic viral pathogen of Canidae, is closely related serologically and biologically to M.V.9 and causes a demyelinating encephalomyelitis (a lesion also characteristic for M.S. in man) in some infected animals. 10 We have examined sera from M.S. patients and controls for c.D.v. and M.v. neutralising antibodies, to determine the likelihood of c.D.v. as a cause of M.S.

Results After completion of all neutralisation tests, the identification code was broken, and the mean antibody titres of duplicate and triplicate serum samples were calculated and tabulated (see figure). Mean c.D:v.-neutralising-antibody titres for both c.D.v. strains were less than

1/30

in all groups

(control,

non-M.v.

neurological

Methods

Sera 61

ul:ltublt! m

serum

samples

from 21

subjects (patients

with M.S., pa-

manI

Virus-neutralising antibody titres

wJ

in human

sera.

dis-

1128

M.S.) except s.s.p.E. No statistical differences between these groups in mean C.D.V. titres were observed. In contrast, all but one serum from patients with M.S. and both S.S.P.E. sera contained antibody to M.v. on titres 1/236 (the highest dilutions tested), whereas control M.v. titres, as a group, were signifi-

ease, and

Preliminary

EARLY PRENATAL DIAGNOSIS OF

cantly lower.

NEURAL-TUBE DEFECTS BY titres for titres for measles in M.s. pa-

However, ratios of group

mean

antibody

C.D.V. isolates versus mean tients and controls (normals plus non-M.s. neurological disease) revealed modest differences between groups in their responses to c.D.v. For M.s. patients C.D.V./M.V. ratios were 9.5 and 10.8 for R252-c.D.v. and Ond-c.D.v., respectively, Calculated ratios in the controls were 8 - 8 and 7-9.

the possible implication of causative agent of M.s. was tested serologically. Samples from 21 subjects (10 with M.S., 2 with S.S.P.E., end 9 normal or neurological controls) were examined for the presence of disteriper-virus and measlesvirus neutralising antibodies. The presence of antibody to C.D.V. in all subjects (M.s. and controls) and antibody to M.v. confirms previous studies. 13-15 It has been assumed that M.v. serum antibodies in the human population are acquired by intentional immunisation with M.v. or by spontaneous infection and that c.D.v. antibodies observed are cross-reactive with M. V.16 However, differences were noted when the ratios of C.D.v./M.v. antibody levels were compared in M.s. patients and controls. It was shown that M.v. titres as well as the ratio C.D.V./M.V. were higher in M.s. than in controls. If C.D.V. titres observed were attributable strictly to cross-reaction with M.v., higher levels of C.D.v. antibody in M.s. sera should have been obtained and c.D.v./M.v. ratios in both groups should have been equivalent. This was not so. The results tend to eliminate C.D.V. linkage to M.s. and further support the implication of M.v. in the setiology of M.S. Many dogs are immunised with attenuated M.v. to prevent c.D.v. infection, 17 and if M.v. as a cause of M.s. in man is confirmed, this vaccination practice may be a human health hazard. The possibility that dogs are a source of M.v. has not been investigated. The relatively high c.D.v. titres in the two S.S.P.E. patients deserve further attention, although it is well docu-

preliminary study,

C.D.v. as a

of its variants cause s.S.p.E.18 titres of antibody to c.D.v. in S.S.P.E. sera have been noted elsewhere.19 In that study, the possibility of superinfection of S.S.P.E. patients with c.D.v. was raised. The present study, in a small number of patients, failed to implicate c.D.v. in the aetiology of M.s. Studies in a larger series of patients at various stages of illness and appropriate viral-antigen absorption experiments are needed to exclude C.D.v. definitely as a cause of M.s. in man. mented that

M.v. or some

Inordinately high

We thank Ms Addajane L. Wallace for her excellent technical assistand Dr Wallace W. Tourtellotte, VA Wadsworth Hospital Center, Los Angeles, for providing serum samples and histories. This work was supported by grant no. ROI-Al-09022-08 from the Institute of Allergy and Infectious Diseases, National Institutes of Health. ance

Requests for reprints should be addressed to S. K., Coffey Road, Columbus, Ohio 43210, U.S.A. Ilc/crrrces at Juut cf ncxt culunru

tory, 1925

ULTRASOUND-GUIDED FETOSCOPY S. CAMPBELL

C. H. RODECK

Department of Obstetrics and Gynœcology, King’s College

Hospital, London SE5

Summary

In three fetuses with neural-tube defects

(N.T.D.S) the lesions were clearly seen by in the second trimester. In a fourth fetus, in which the diagnosis of N.T.D. was suspected because of raised amniotic-fluid alpha-fetoprotein, spina bifida was excluded by fetoscopic examination and a normal baby was delivered at term. Ultrasound-guided fetoscopy has a place in the diagnosis of N.T.D.S when the results of other investigations are conflicting or inconclusive, and may be useful in assessing the severity of a lesion.

fetoscopy

Discussion In this

Communications

Goss Labora-

INTRODUCTION

NEURAL-TUBE defects (N.T.D.s) can be diagnosed either amniotic-fluid alpha-fetoprotein (A.F.P.) estimation’1 or by ultrasound scanning of the fetal spinel These two methods complement each other,2 but ultrasound scanning may miss low lesions and A.F.P. may be raised in the presence of a normal fetus3 or by other abnormalities;’-" conversely, it may be normal in the presence of closed defects." While early attempts with fetoscopy were not very encouraging,14 our recent experience with fetoscopy guided by real-time scanning (R.T.S.) suggests that this method provides a definitive diagnosis when the results of A.F.P. estimation and ultrasonography are not consistent or are inconclusive.

by

TECHNIQUE Direct inspection of the fetus is carried out with the ’Needlescope’ (Dyonics, Inc.),15 but ultrasound scanning is essential at every stage of the technique. Initial amniocentesis should be

DR

KRAKOWKA, DR KOESTNER: REFERENCES

Soll, R. W Postgrad. Med. 1972, 52 113. Adams, J. N., Imagawa, D. T. Proc. Soc. exp. Biol. Med. 1962, 111, 562. Pette, E., Kuwert, E. Arch. ges. Virusforsch. 1965, 16, 141. Salmi, A., Gollmar, Y., Norrby, E., Panellus, M. Acta path. microbiol. stand. 1973, 81, 627. 5. Raisne, C. S., Peineas, J. W., Sheppard, R. D., Bornstein, M. B., DuboisDalcq, M. J. neurol. Sci. 1977, 33, 13. 6. ter Muelen, V., Koprowski, H., Iwasaki, Y., Käckell, Y. M., Müller, D. Lancet, 1972, ii, 1. 7. Iwasaki, Y., Koprowski, H., Müller, M. D., ter Muelen, V., Käckell, Y. M. 1. 2. 3. 4.

Lab. Invest. 1973, 28, 494. Cook, S. D., Dowling, P. C. Lancet, 1977, i, 980. Appel, M. J. E., Gillespie, J. H. Virol. Monogr. 1972, 2, 1. McCullough, B., Krakowka, S., Koestner, A. Lab. Invest. 1974,31,216. Confer, A. W., Kahn, D. E., Koestner, A., Krakowka, S. Infect. Immun. 1975, 11, 835. 12. Reed, L. J., Muench, H. Am. J. Hyg. 1938, 27, 493. 13. Hopper, P. K. Acta pœdiat. scand. 1959, 48, 43. 14. Karzon, D. T. Pediatrics, Springfield, 1955, 16, 809. 15. Carlström, G. Acta pœdiat. scand. 1956, 45, 180. 16. Imagawa, D. T. Prog. med. Virol. 1968, 10, 1960. 17. Strating, A. J. Am. vet. med. Ass. 1975, 167, 59. 18. Johnson, R. T. J. infect. Dis. 1970, 121, 227. 19. Sato, T. A., Yamanouchi, K., Shishido, A. Arch. ges. Virusforsch. 1973, 42,

8. 9. 10. 11.

36.

Canine distemper virus and multiple sclerosis.

1127 neurological diseases associated with M.v., and found. tients with until a suitable donor can be found. healthy controls) were kindly prov...
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