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could be virus-associated. The nuclear envelope particles are verynumerous and very easily identified by routine electron microscopicmethods. In four patients, electron-dense particles were foundwithin membrane-bound structures in the cytoplasm; these wereusually spherical particles 25 nm in diameter but some wereelongated, measuring 25-65 nm (d and e). A crystal-likearrangement of particles was seen in one case (c). Nuclear bodies andclusters of dense particles distinct from perichromatin granuleswere seen in two patients (f); these particles resembled thosedescribed in non-A and non-B hepatitis.l The nuclear envelopeparticles and the membrane-bound spherical particles are unlikethose reported to date in hepatitis A, B, or non-A, non-B. 1-12 Thefindings of similar nuclear envelope particles in the five cases andtheir association with other virus-like particles in the liver raises thepossibility of a common aetiology, possibly viral, for these cases.

Departments of Pathology,Pediatrics, and Virology,

University of Torontoand Hospital for Sick Children,

Toronto, Ontario M5G 1X8 Canada

M. JAMES PHILLIPSVERNON D. EDWARDSGLEN P. TAYLORLESLIE EIDUSKEVIN J. GASKINPETER J. MIDDLETON

ANOREXIA NERVOSA, VISUAL DISTURBANCE, ANDLAURENCE-MOON-BIEDL SYNDROME

SIR,-Quigley and Doane13 ask for reports of anorexia nervosa inthe visually handicapped. We have diagnosed anorexia nervosa in agirl with Laurence-Moon-Biedl syndrome, a conditioncharacterised by retinitis pigmentosa, adiposity, genital hypoplasia,mental retardation, and polydactyly.The patient, born in 1944, is the only child of parents who are first

cousins. She had polydactyly of her feet and has been partly sightedfrom birth. As a child she used to grope about before picking upwhatever toys she happened to drop. She was considered to be lazyand nothing was done about her sight until, at the age of 5 years, shewas seen by an ophthalmologist and was fitted with spectacles. Shewore spectacles until she became completely blind at the age of 21.The patient describes her vision during this period as "being more adifficulty in focusing things properly than a difficulty in actuallyseeing them." However, she attended a school for the partly sightedfrom the age of 8’/z. Her IQ at 9 years was 74. Her milestones,especially language acquisition, were delayed. As a child she wasobese, weighing 15 kg at the age of 11 months, her birthweight being4 kg. At the age of 8 years she was put on a diet but weighed 64 kg at

1. Shimizu YK, Feinstone SN, Purcell RH, Alter HJ, London WT. Non-A, non-Bhepatitis: Ultrastructural evidence for two agents in experimentally infectedchimpanzees. Science 1979; 205: 197.

2. Marciano-Cabral F, Rublee KL, Carithers RL, Galen EA, Sobieski TJ, Cabral GA.Chronic non-A, non-B hepatitis: ultrastructural and serological studies. Hepatology1981, 6: 575.

3. Huang SN, Lorenzo D, Gerety RJ. Electron and immunoelectron microscopic study onliver tissue of marmosets infected with hepatitis A virus. Lab Invest. 1979; 41: 63.

4. Huang WN, Millman IL, O’Connell AI, Aronoff A, Gault H, Blumberg BS. Virus-likeparticles in Australia antigen associated hepatitis: an in vivo electron microscopicstudy of human liver. Am J Pathol 1972; 67: 453.

5. Popper H, Dienstag JL, Feinstone SM, Alter HJ, Purcell RH. The pathology of viralhepatitis in chimpanzees. Virchows Arch A. Path Anat Histol 1980; 387: 91.

6. Lapis K, Schaff Z. Acute viral hepatitis. In: Johannessen JV, ed. Electron microscopyin human medicine. Vol VIII, the liver. New York: McGraw Hill, 1979: 124.

7. Vitvitski L, Trepo C, Prince AM, Brotman B. Detection of virus-associated antigen inserum and liver of patients with non-A, non-B hepatitis. Lancet 1979; ii: 1263.

8. Hantz O, Vitvitski L, Trepo C. Non-A, non-B hepatitis: identification of hepatitisB-like virus particles in serum and liver. J Med Virol 19800; 5: 73.

9. Jackson D, Tabor E, Gerety RJ. Acute non-A, non-B hepatitis. Specific ultrastructuralalterations in endoplasmic reticulum of infected hepatocytes. Lancet 1979; i: 1249.

10. Tsiquaye KN, Bird RG, Tovey H, Wyke RK, Williams R, Zuckerman AJ. Furtherevidence of cellular changes associated with non-A, non-B hepatitis. J Med Virol1980; 5: 63.

11. Pfeifer U, Thomsen R, Legler J, Battcheu U, Gerlich W, Weinmann E, Klinge O.Experimental non-A, non-B hepatitis Four types of cytoplasmic alteration inhepatocytes of infected chimpanzees Virch Arch B Cell Pathol 1980; 33: 233.

12. Burk RH, Cabral GA, Dressman GH, Peters RL, Alter HJ. Ultrastructural changesand virus-like particles localized in liver hepatocytes of chimpanzees infected withnon-A, non-B hepatitis J Med Virol 1981; 7: 1.

13. Quigley B, Doane B. Anorexia nervosa and visual experience. Lancet 1981; ii: 1113.

the age of 10 years. She was teased at school and became obsessedwith losing weight at about the age of 13 years. Friction developedbetween the patient and her parents over her eating.Optic atrophy and retinitis pigmentosa were diagnosed at the age

of 17 years and she lost her vision completely at 21 years of age,perception of light and hand movements being noted up to the age of20 years. At the age of 22 years she was first admitted with marked

weight loss and amenorrhoea, her weight on admission being lessthan 38 kg. At this time she explained that her dieting was anattempt to make herself more attractive and expressed a fear of beingugly through being overweight. Anorexia nervosa was diagnosedand she was treated with chlorpromazine and modified insulintherapy. In 1971, soon after being told by an ophthalmologist thatshe would remain blind permanently, she developed persistentvomiting 5-10 min after meals, pain in the chest, and features of adepressive illness. Her weight at the time was 47 kg. She wasreadmitted in 1972 with amenorrhoea and vomiting after meals. Herweight was then 41 kg. She recovered after treatment with

antidepressants and modified insulin therapy.In the 14 years that she has been known to the psychiatric services

she has a dread of even normal body weight, seeking constantreassurance about her body size. She regulates her weight by meansof a strict diet and by the daily use of laxatives. The patient’scondition is associated with difficulties in the family relationships,including an ambivalent and often resented interdependence.This patient is also of interest in that both Laurence-Moon-Biedl

syndrome and anorexia nervosa have been postulated as beingassociated with hypothalamic disturbance.

Walsgrave Hospital,Coventry CV2 2DX

T. L. DUNNP. R. COOREY

REOVIRUS TYPE 2 IN STRAINS OF KOREANHAEMORRHAGIC FEVER VIRUS

SIR,-Reovirus type 2 was isolated in primary African greenmonkey kidney cells (AGMKC) inoculated with strain 76-118 ofKorean haemorrhagic fever virus (KHF) in our laboratories at theNational Institutes of Health (N.I.H.). Subsequently, additionalstrains of KHF, being studied at the Institute for Viral Diseases,Korea University Medical College, were shown to be similarlycontaminated with reovirus.A study was undertaken to adapt KHF virus to growth in vitro in

cells other than the A-549 human lung carcinoma cell line, since thevirus is not cytocidal in those cells and is detectable only by thedemonstration of viral antigen by the indirect immunofluorescencetest (IF). The sixth rat passage of rat-adapted 76-118 strain ofKHFvirus,2 originally isolated from trapped field mice (Apodemusagrarius coreae),3 was inoculated into primary AGMKC cultures.Primary passage of the virus in AGMKC was associated withaccumulation of antigen detected by IF; however, the number ofcells with KHFV antigen diminished on two serial passages ofAGMKC culture, and by the third and subsequent serial passagesno antigen was detectable by the IF test.

’

In contrast, cytopathogenic changes appeared in the AGMKCcultures on the 12th day, affecting less than 25% of the AGMKCmonolayers of the third serial passage of the KHF virus. On

subsequent passages, devoid of KHF virus by IF, there waswidespread destruction of greater than 50% of the monolayer ofcells and a significantly shortened incubation period before thedevelopment of cytopathic effects (CPE).Electron microscopic examination of thin sections of AGMK cell

cultures showing cytopathic changes and preparations of the virus,made by caesium chloride density gradients of ’Freon’ treated

suspensions of infected cells, revealed particles morphologically

1. French GR, Foulke RS, Brand OA, Eddy GA, Lee H-W, Lee P-W. Koreanhemorrhagic fever: propagation ofthe etiological agent in a cell line of human origin.Science 1981; 211: 1046-48.

2. Lee P-W, Amyx HL, Gibbs CJ Jr, Gajdusek DC, Lee H-W. Propagation of Koreanhemorrhagic fever virus in laboratory rats. Infect Immun 1981; 31: 334-38.

3. Lee H-W, Lee P-W. Korean hemorrhagic fever I. Demonstration of causative antigenand antibodies. Korean J Intern Med 1976; 19: 371-83.