215

therapeutic inspirations; in contrast, they are

showing signs of a new dimension. Just now theketoacid saga looks set to become a classic exampleof being right for the wrong reason, for, even if theamount of urea-nitrogen reutilised in their transami-nation is small, ketoacids nevertheless appear to havea profound effect on protein metabolism. WALSERet al. 16 showed that the net synthesis of urea by patientswith advanced chronic renal failure became negativewhen they were given a-ketoacids either in place ofseveral essential aminoacids or to supplement theirsupply, and that the decrease in net urea production(and the associated improvement in nitrogen balance)was greater than the amount of nitrogen required toconvert all the ketoacids to aminoacids; the efficiencyof transamination of these compounds is probablynot greater than 50%,1’ so a considerable improve-ment in nitrogen economy remains unexplained.The blood-urea of these patients fell (even when thediet seemed to contain sufficient essential aminoacidsin protein) and their clinical condition for a time

improved. Apparently the essential ketoacids hadmodified basal protein synthesis, either slowingprotein turnover or increasing the efficiency of theprocess.

’

Dietary investigations upon people with advancedrenal failure are not easy and the results are oftendifficult to interpret. The complementary investiga-tion of the effect of daily infusions of essentialketoacids on the nitrogen economy of starving obesepatients by SAPIR et a1.I8 is therefore of the greatestinterest. The nitrogen excretion of 5 of 11 obeseindividuals who had fasted for 37 days remainedconstant for the next two weeks. The other 6 obeseindividuals received daily infusions of the a-ketoacidsof five essential aminoacids, together with lysine,threonine, tryptophan, and histidine. Amination ofthe ketoacids was confirmed by significant increasesin plasma valine, leucine, isoleucine, alloisoleucine,phenylalanine, and methionine. The urinary urea-nitrogen decreased by a larger amount than thequantity of nitrogen needed to aminate all the infusedketoacids. Thus far, the results are confirmatoryand not revolutionary, but 5 days later the nitrogenexcretion was lower than it had been at the end of theperiod of infusions, and in 2 individuals studied for9 and 17 days after the last infusion the urinarynitrogen excretion was still less than that of thecontrol group. In contrast, plasma-aminoacid levelsalways returned to preinfusion levels within 20 hoursof an infusion. Under these circumstances ofstarvation-circumstances not perhaps intrinsicallydifferent from those early in recovery from majorsurgery or prolonged infective illness-the essentialketoacids had a substantial and prolonged protein-16. Walser, M., Coulter, A. W., Dighe, S., Crantz, F. R. J. clin. Invest.

1973, 52, 678.17. Rudman, D. ibid. 1971, 50, 90.18. Sapir, D. G., Owen, O. E., Pozefsky, T., Walser, M. ibid. 1974,

54, 974.

sparing effect. How this effect was achieved andwhether the therapeutic potential of these compoundsis as great as it seems to be at first sight remains tobe determined.

NOISE-INDUCED HEARING LOSS

NEARLY htty years ago legislation was introduced inRussia to reduce noise-induced hearing loss, but in theUnited Kingdom it was not until 1963 that advisorydocuments on noise and the worker were published.In 1972 a code of practice on reducing noise exposurewas introduced and the first suit, an unsuccessful one,was heard in 1969. Not until 1971 were damagesawarded for N.I.H.L., in Berry v Stone Manganese.N.I.H.L. was one of the subjects discussed at theFourth British Academic Conference in Otolaryngologyin London last week.

N.I.H.L. may be presumed to have occurred wherethere has been exposure to noise, for adequate timeand at adequate levels, causing progressive sensori-neural deafness with or without tinnitus. High tonesare usually involved symmetrically and there shouldbe no diagnostic competitors (such as Meniere’s

disease). In 10% of applicants a non-organic hearingloss (NO.H.L.) has been found-not surprisingly whenthere is the prospect of compensation. Clinicalassessment of speech comprehension, a flat audiogram,and disparity between the pure-tone and speechaudiograms are helpful in differentiating betweenN.I.H.L. and N.O.H.L.The structural changes caused by exposure to noise

can be seen clearly in surface preparations of theguineapig cochlea. Exposure to 140dB for only30 seconds produces gross distortion of the outer haircells in the basal turn of the cochlea and tears themoff the basilar membrane. 130dB for 20 minutes

produces a slightly less dramatic effect, and 72 hours’exposure at 120dB produces only just visible damage.When the animals are killed a year after exposure to120dB, patchy loss of the hair cells is seen with

retrograde degeneration of the neurons. Noise below90dB seems to produce no morphological damageeven after long exposure. It is of course difficult torelate these results in guineapigs directly to man sincethere may be considerable species variability.

In 1958 the American Academy of Otolaryngologyarranged a conference to try and determine a methodof assessing the degree of handicap caused by N.I.H.L.Eventually they decided to use the somewhat un-

satisfactory method of taking the average of thepure-tone-audiogram results at 500, 1000, and 2000Hz. Each dB loss over 25dB was regarded as 1%disability up to a maximum of 100% disability at 92dB.One criticism of this method is that the ability to hearpure sound does not necessarily mean that speech canbe understood. The Department of Health regulationsfor compensation at present are an average of the lossat 1000, 2000, and 3000 Hz, starting at 50dB, which isregarded as 20% disability, with 100% disability at90dB loss. This loss has to be corrected for presbya-cusis, and there are tables for calculating this.Pre-employment audiograms, now being performed

in the U.S.A., make assessment of future N.I.H.L. much

216

more accurate, and it is becoming a condition of

employment there to wear ear-protectors in noisyfactories. Ear-plugs will give adequate protection upto 100dB, but muffs are required over these levels.The employee must of course wear the protectors,not merely be issued with them. Unfortunately it ischeaper to employ inspectors to check on this thanto reduce noise levels. According to one estimate, itwould cost in the United States$14 billion to reducenoise levels in industry to 90dB. As the article onp. 203 shows, the question of non-industrial noise isstill thornier.

THE NOT-SO-HARMLESS HAMSTER

THE natural host of lymphocytic choriomeningitis(L.C.M.) virus is the mouse, and the absence of overtdisease in mice congenitally infected with this virushas been a fruitful sphere of investigation for virologistsand experimental immunologists. Infection of manwith L.c.M. virus is happily a rare event, for, althoughthis may be silent, it is usually accompanied by fever,headache, and severe myalgia, occasionally terminatingin fatal meningoencephalitis. Human infections are

always secondary to contact with an infected rodent,although the precise mode of transmission is often indoubt. In the past, most recognised cases have arisenin persons living in rodent-infested houses, but

lately there have been substantial outbreaks of L.C.M-virus disease in man, reported from Germany andfrom the U.S.A., in which the source of infection wastraced not to household pests, but to household pets-specifically the hamster.1-3 Infected hamsters havealso been incriminated in another outbreak in the

U.S.A., but this involved personnel working in a .

medical centre which used hamsters in tumour re-search. 4

The clinical features of the different outbreaks werevery similar. The index case in the Rochester out-break was a young woman who was admitted to hos-pital with encephalomyelitis in January, 1974; L.C.M.-virus infection was diagnosed on the basis of sero-logical tests. Four members of her family developedmilder illnesses which were also caused by L.C.M.

virus. Inquiry revealed that the family had acquired apet hamster for Christmas, as had two other familiesin the same area in whom L.c.M. infection was alsodiagnosed. After these early cases and a Press releasedrawing attention to the possible hazard of infectionof man from pet hamsters, 57 serologically confirmedcases of L.C.M. infection were diagnosed in upperNew York State over a period of four months, all

having contact with hamsters obtained from a singlebreeder, though sold through several different retailers.The patients ranged from 3 to 70 years of age andseveral had quite severe illnesses, 11 being admittedto hospital, 2 with encephalitis, 7 with aseptic mening-

1. Ackermann, R., Stille, W., Blumenthal, W., Helm, E. B., Keller, K.,Baldus, O. Dt. med. Wschr. 1972, 97, 1725.

2. Biggar, R. J., Woodall, J. P., Walter, P. D., Haughie, G. E. J. Am.med. Ass. 1975, 232, 494.

3. Deibel, R., Woodall, J. P., Decher, W. J., Schryver, G. D. ibid.p. 501.

4. Hinman, A. R., Fraser, D. W., Douglas, R. G., Bowen, G. S.,Kraus, A. L., Winkler, W. G., Rhodes, W. W. Am. J. Epidem.1975, 101, 103.

itis, and 2 with an initial diagnosis of psychogenicillness. 3 young women had symptoms suggestive ofinfectious mononucleosis, another had a spontaneousabortion following infection, a 16-year-old boydeveloped orchitis, and several patients who hadinfluenza-like symptoms described their illness as theworst of their lives. Of 60 patients with L.C.M. anti-bodies, 55 kept hamsters as household pets, 4 workedfor the wholesalers or retailers of hamsters, and theremaining 1 had moved away before being fullyinvestigated. In virological studies on some of thehamsters under suspicion, L.C.M. virus was isolatedfrom 2 and 21 adult hamsters were shown to havecomplement-fixing antibodies against L.C.M. virus.The source of the infected hamsters was a breeder inAlabama, who apparently supplied hamsters over aconsiderable area, cases of human disease beingdetected in six States in addition to New York State.The medical-centre episode involved at least 48

people over a period of several months. Some of thevictims handled animals in the course of their work,but at least 17 persons denied such exposure and were

presumed to have been infected by the airborne route:infections in a hospital plumber and in a servicingengineer came into this category. L.C.M. virus wasisolated from each of 11 tumour-cell lines that hadbeen serially passaged in hamster cheek-pouches, butlines passaged in mice were free from infection.Infections ceased when all work with hamster tumourswas stopped, and they did not recur when studiesrecommenced six months later using animals andtumour lines free from L.c.M. virus.

L.C.M. virus has proved an invaluable model for thestudy of chronic, persistent, and generally symptomless

, infections in laboratory animals. There is a certain

irony in the fact that the most inoffensive of laboratoryanimals, the hamster, should be so clearly linked withsuch unpleasant illnesses in man.

NERVE GRAFTING IN LEPROSY

SENSORY loss can be a problem not only during theactive stage of leprosy but also after the disease hasbeen arrested or cured-in fact, for the rest of thepatient’s life. Absence of the protective sensation ofpain in hands or feet encourages carelessness in theuse of the affected limbs, and this in turn leads toabrasions, bums, trophic ulcers, cellulitis, osteo-

myelitis, and bone absorption. Impaired motor func-tion can be improved by tendon transposition andphysiotherapy, but no successful remedy has beendevised for sensory loss. Lately, a combined medicaland surgical team in Australia 1 have described a nerve-grafting technique designed to correct this disability.McLeod and others describe the results obtained afterinserting 23 nerve grafts into the peripheral nerves of14 leprosy patients. Median, ulnar, sciatic, and pos-terior tibial nerves were removed from cadavers within24 hours of death and stored in physiological saline at0-10°C for up to two weeks. They were then cut intosuitable lengths and the diameters were measured.The nerves were freeze--dried, placed in individually

1. McLeod, J. G., Hargrave, J. C., Gye, R. S., Pollard, J. D., Walsh,J. C., Little, J. M., Booth, G. C. Brain, 1975, 98, 203.