1347

ENCEPHALOMYELITIS AND ENTEROVIRUSES

SIR,-The cases reported by Dr. Innes (May 9, p. 969)are sufficiently remarkable to merit fuller documentation.

Isolation of enteroviruses from essentially normal cerebro-spinal fluid collected 4 months after acute illness is outsidemy experience. Were these isolations of Coxsackie virus B2(case 1) and echovirus 3 (case 3) confirmed by reisolationfrom the same specimens, and were later specimens testedto follow the duration of infectivity ? What were the anti-body responses of these patients to the isolated viruses ?

Interpretation of static titres of neutralising antibody toenteroviruses is difficult because infections with theseviruses are common, often clinically silent, or trivial, andbecause moderate antibody titres may persist for longperiods of time. By the usual techniques, the titre of 128to Coxsackie virus B2 in case 2 would not be considered assignifying more than infection with this or a related virussome time in the past-perhaps years previously. In case 4the Coxsackie virus B5 antibody titres of 1024 and 512 areindeed consistent with recent infection with this or a relatedvirus, possibly, but not necessarily, relevant to the illnessdescribed. Have these titres been maintained ?Perhaps the unnamed virologist could have helped to

provide a more detailed interpretation of the observations.

NORMAN R. GRIST.

Glasgow University Departmentof Infectious Diseases,

Ruchill Hospital,Glasgow N.W.

*** This letter was shown to Dr. Innes, who replies asfollows: " Except for repeat lumbar puncture, which I couldnot justify since the patients would not have benefitedtherefrom, the more detailed studies suggested by ProfessorGrist constituted my own ideal. Unfortunately this was notrealisable. I published in the hope that others encounteringthis syndrome would recognise it, and, by timely and moredetailed studies, establish the precise role of enteroviruses inthis condition."—Eo. L.

PLASMA-INSULIN IN DIABETES

SIR,-In your leader on this topic (June 6, p. 1212),there is a slightly ambiguous statement about the effectsof sex on insulin response to glucose. Although it is truethat in diabetics no such effect of sex has been reported,in non-diabetics there have been two reports showinghigher post-glucose insulin levels in women.1,2 Whateverthe reason for this may be-and oral contraceptives werecertainly not the reason in at least one of the studies 1-the difference between the sexes is sufficient to makematching for sex an essential of comparative studies.

R. J. JARRETT.

Department of Medicine,Guy’s Hospital Medical School,

London S.E.1.

HORMONES AND THE XYY MALE

SIR,-Dr. Skakkebaek (May 2, p. 949) alluded to myreport (March 21, p. 623) in which I described a raisedserum-luteinising-hormone (L.H.) level in a male with47,XYY chromosome constitution and similar or a

higher levels of L.H. in 2 of 5 controls with an 46,XYchromosome constitution. He suggested that results ofsperm analyses or testicular biopsy would be of valuebecause primary testicular failure results in an elevationof L.H. and follicle-stimulating hormone (F.S.H.).

Before testicular biopsy, seminal-fluid examination in

1. Boyns, D. R., Crossley, J. N., Abrams, M. E., Jarrett, R. J., Keen,H. Br. med. J. 1969, i, 595.

2. Welborn, T. A., Stenhouse, N. S. and Johnstone, C. G. Diabetologia,1969, 5, 263.

my XYY patient was normal. The sperm count was100,000,000 per ml. with normal morphology and motility.The histological appearance of all testicular-biopsy sectionsexamined was entirely normal, with intact seminiferoustubules and active spermatogenesis.Although this XYY patient’s increased serum-L.H. level

was not related to impaired gonadal function, I agree thatresults of sperm analyses and testicular biopsy would bevaluable in future reports of XYY males.

This work was supported in part by a grant from the BirthDefects Institute, New York State Department of Health(C-40629).

LAWRENCE R. SHAPIRO.

Cytogenetics Laboratory,Mental Retardation Research Unit,

Letchworth Village,Thiells, N.Y. 10984.

ASCORBIC-ACID TREATMENT FOR

OSTEOGENESIS IMPERFECTA

SIR,-We are interested in the possibility that nutritionalfactors may be useful in the treatment of collagen diseases,and we should like to report the results of a trial of ascorbicacid in osteogenesis imperfecta.

Osteogenesis imperfecta is a metabolic bone condition in whichthe protein matrix of the bone is believed to be the site of theabnormality. Collagen, the chief component of the matrix, is

unique in containing a high proportion of hydroxyproline, whichis formed in vivo by hydroxylation of proline. Oxygen, ferrousiron, ot-ketoglutarate, and ascorbic acid are required cofactors forthe proline-hydroxylase enzyme,’,3 Urinary excretion of hydroxy-proline is regarded as an indicator of collagen metabolism in thebody. In animals made scorbutic, hydroxyproline excretiondecreases. 4 In contrast, when normal people have been madescorbutic, excretion has been shown to increase.5 This increasein human beings may represent turnover of partially hydroxy-lated collagen precursors or increased degradation of collagen.Ten patients with osteogenesis imperfecta, aged 5-27

years, were studied for 12-17 days in the clinical studycentre of The Children’s Hospital, Columbus, Ohio, andsubsequently followed at home. The patients had historiesof total fractures ranging from 4 to over 250. Four normalcontrol subjects were selected, representing the two pre-dominant age-groups. They followed the same dietaryregimen, but were not admitted to hospital. A lowhydroxyproline diet was given throughout the study, andafter an initial 4-day period, 1 g. of L-ascorbic acid was

given daily.Ascorbic-acid retention, calculated as intake minus

urinary excretion, ranged from 255 to 612 mg. after 3months. In the young controls, retention also remainedrelatively high, but a much smaller retention was observedin the older controls. A decrease in urinary hydroxyprolineexcretion was observed after the 3-month period in six ofthe ten patients. It may be postulated that there wasincreased deposition of more stable collagen or decreasedcollagen degradation. Further evidence of a change incollagen metabolism is a decrease in the incidence ofbroken bones. At the previous rate of breaks, 20-22fractures could have been expected in the time period sincethe start of the ascorbic-acid supplement. Actually, only5 were reported. 2 of these resulted from substantialtrauma; the other 3 were typical of the disease. Thisdecrease in the number of breaks is dramatic, and indicatesthat this approach is promising for the treatment of this,and possibly other, collagen diseases. That the approach1. McKusick, V. V. Heritable Disorders of Connective Tissue; p. 233.

St. Louis, 1966.2. Udenfriend, S. Science, N.Y. 1966, 152, 1335.3. Hutton, J. J., Tappel, A. L., Udenfriend, S. Biochim. biophys. Res.

Commun. 1966, 24, 179.4. Martin, G. R., Mergenhagen, S. E., Prockop, D. J. Nature, Lond.

1961, 19, 1008.5. Burkley, K. Am. J. clin. Nutr. 1969, 22, 547.