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1. Kettel, K. Arch. Otolaryng., Chicago, 1947, 46, 427.2. Hall, A. Ibid, 1951, 54, 475.3. Morris, W. M. Lancet, 1936, ii, 1172.4. Ballance, C., Duel, A. B. Arch. Otolaryng., Chicago, 1932, 15, 1.

services-the National Health Service and the local-

authority school service-would threaten the future

development of the latter. It would certainly be hard topredict the consequences of having part of the work

paid for by fees per item of service while the rest wasperformed by dentists receiving a salary which is at

present below the average for N.H.S. general dental

practitioners. But the essential argument against theassociation’s plan is surely that it offers a short-term

palliative rather than a solution to the problem. It seemsa pity that some means cannot be found to make greateruse of the help offered by the dental profession, but themillion half-hour appointments which the associationbelieves that private practitioners would set aside eachyear for child patients could affect only about 250,000additional children. Only so many would be able toreceive reasonably full dental care, and the vast majorityof the young would still only be able to obtain emergencytreatment for relief of pain. On the other hand, theMinister of Health would be rash to assume that prolonga-tion of the present depressed state of general dentalpractice is going to abolish the staffing difficulties of thepublic services, or that it could be the basis of a soundschool service.

Discussions will remain unrealistic until both sides

recognise that the dental profession is too small to fulfilall its tasks, and will soon be growing smaller. The

present slacking in demand for adult treatment does notindicate that the community has suddenly ceased toneed dental care : it is simply a measure of the public’sindifference to, and ignorance of, the importance ofdental health. It would be unfair to consider either theMinister of Health or the British Dental Association

guilty of complacency about this, though their exchangeof letters does not suggest that either has given muchthought to its significance.

CORTISONE IN BELL’S PALSY

MANY different pathological processes can give rise toparalysis of the facial muscles, but in most cases the causeis an apparently intrinsic peripheral lesion of the facialnerve. It is to this type that the name Bell’s palsy hasbeen given ; and, as Kettel 1 points out, this title coversall cases of facial paralysis in which no clear local causeis evident. Speculation about the origin of this conditionhas resolved itself into two main channels. Kettel 1 andHall,2 among others, believe that the prime cause islocal ischæmia ; whilst Morris 3 holds that it is an

inflammatory process in the nerve and its sheath. Mostworkers agree, however, that the nerve is compressedwithin the fallopian canal, and that this compressioncontributes to the impairment of neural function. Itwas to alleviate the long-term effects of such compressionthat Ballance and Duel4 devised their operation of

decompression of the nerve; their technique has beenemployed by the protagonists of both schools, each schoolvery reasonably supporting this practice by its own

theory of the lesion. Most cases of Bell’s palsy recoverspontaneously ; usually recovery begins after about threeor four weeks, and usually this recovery is complete.Those who consider doing decompressive operations areguided both by the persistence of the paralysis beyondthe first four weeks and by the absence of response tofaradism. The operation tends, therefore, to be donesome time between the sixth and tenth weeks.

This latent period-the natural consequence of thera-peutic prudence-is undesirable if the enduring and dis-figuring paralysis seen in certain cases is really due tothe compressive effect of inflammatory oedema. A report 5. Rothendler, H. H. Amer. J. med. Sci. 1953, 225, 358.

6. Lancet, March 7, 1953, p. 475.7. Gould, J. C., Bowie, J. H., Cameron, J. D. S. Ibid, Feb. 21, 1953,

p. 361.8. Eagle, H., Fleischman, R., Levy, M. New Engl. J. Med. 1953,

248, 481.9. Chain, E., Duthie, E. S. Lancet, 1945, i, 652.

by Rothendler 5 is therefore of special interest both forits therapeutic and for its setiological implications.Believing that the palsy is due to a non-specific acuteinflammatory reaction, Rothendler decided to try theeffects of cortisone. He treated 5 cases within five daysof onset, 1 at nine days, and another at ten days. Thecortisone dosage varied, but the course amounted toabout 3 g. given orally or intramuscularly over a twelve-day period. In 6 of the cases recovery began in the firstweek and was complete at the end of the second. In the7th case, in which the treatment was unsuccessful, theparalysis was very severe and had already been presentfor ten days when treatment began. In the first 6 casesthe rapid and complete recovery was clearly not spon-taneous. Rothendler expresses the view that cortisonerelieves the acute cedema and inflammatory reaction inthe nerve and its sheath ; and indeed the success of thistreatment constitutes prima-facie support for the

inflammatory hypothesis of causation. It may well bethat the old name " rheumatic facial paralysis " deservesmore respect than has been accorded to it by modernauthorities. _

Cortisone is still difficult to obtain in this country, andits administration is associated with certain hazards.Nevertheless, the striking benefit from so short a courseof treatment, and the implied avoidance of the danger ofpermanent disfiguration, certainly justifies an extendedtrial of this drug in Bell’s palsy-always provided, ofcourse, that it is given in the first few days after theonset of the disease.

CONTINUOUS OR DISCONTINUOUS PENICILLIN

WE have lately drawn attention to the desirability ofbasing the dosage of antibiotics on the in-vitro sensitivityof the infecting organisms. 6 The work of Gould et awl. 7

has shown that the logical interpretation of laboratorytests can lead to successful treatment with doses verymuch less than the " standard " ones, at any rate in

urinary tract infections. Undesirable side-effects are

diminished or eliminated by this means, and the dangerof producing resistant strains of bacteria seems to bemuch less than might have been expected. Gould andhis colleagues gave the drugs at 6-hourly intervals;and a report by Eagle et al.8 now suggests that attentionto the spacing of doses may still further increase theefficiency of treatment. They investigated the relationbetween the dosage, the interval between injections, and.the therapeutic efficiency in streptococcal infections ofmice.

Chain and Duthie 9 demonstrated that penicillinexerted its greatest bactericidal action on organisms inthe logarithmic phase of growth. This indicated that the

efficiency of therapy might be increased if the intervalbetween two injections was such that dormant organismshad begun to multiply by the time of the second injection.Eagle et al., however, conclude that the greatest efficiencyis achieved when the penicillin concentration at the siteof the infection is continuously maintained at the levelwhich exerts the maximal bactericidal action in vitro.They found that a penicillin-free interval between

injections prolonged the total duration of treatment

necessary for cure. They injected large numbers of miceintramuscularly with a highly virulent strain of group-Astreptococcus, and penicillin was then given to thesemice, according to a number of different treatmentschedules. The intervals between injections were

3/4, ll/2, 3, 6, 12, and 24 hours, and the number of injec-tions varied from one to sixteen. On each schedule mice

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were injected at each of seven dosage levels (0-05, 0-2,08, 3.2, 12-5, 50, and 200 mg. per kg. body-weight).The 50% survival-rate of each group was then determined.The full mathematical analysis of the series was compli-cated, but the authors selected for detailed commentthose aspects directly connected with the problem underinvestigation. For example, six to eight injections, eachof 3.2 mg. of penicillin per kg. body-weight, given atintervals of 3/4 hour, were needed for a 50% survival inone group of mice. If injections of the same dose weregiven three-hourly, only two or three injections gave thesame survival-rate. Increasing the intervals to 12 hours,however, necessitated three or four injections. Com-

parable results were found with all other doses investi-gated. It is clear that if the intervals were too short,penicillin was still present in effective concentration atthe time of each injection, so that the full benefit of thepreceding injection was lost. If the intervals betweeninjections were too long, then the organism multipliedand longer treatment was necessary. The total treatmenttime required for mice injected every 3/4 hour was 4’-/2to 6 hours ; with 3-hourly injections it was 6 to 9 hours ;and with 12-hourly injections 36 to 48 hours. Theinterval between injections also had a pronounced effecton the total dose of penicillin required to effect a cure.For example, when four injections were given at intervalsof 3/4 hour, a total dose of 68 mg. per kg. was needed.When the four injections were given at 3-hourly intervals,however, the total dose needed was only 3 mg. per kg.,while for four 12-hourly injections the total dose forcure was 7.6 mg. per kg.The streptococcus used by Eagle et al. was killed at a

maximum rate in vitro by 0-024 µg. of penicillin per ml.Approximately half of the penicillin in the blood-streamis bound to serum-protein, so that a serum concentrationof about 0-05 tJ.g. per ml. would be needed to providemaximum bactericidal action in tissue fluids. Eagle andhis colleagues have determined the total time for whichthe serum-penicillin level was at or above this criticallevel in groups of mice treated by various schedules untilthey were cured. They call this the " aggregate penicillintime." The number of injections varied from one totwelve, and the intervals between injections from 3/4hour to 12 hours ; but the aggregate penicillin timeremained remarkably constant at about 4 hours through-out the series. Increasing the interval between injectionsto 24 hours, however, caused a sharp rise in the penicillintime necessary for cure, apparently because of bacterialmultiplication between injections. These results indicatethat the efficacy of penicillin treatment is determinedprimarily by the total time for which the drug remainsat effective levels at the site of infection, provided thatthe interval between injections is not long enough toallow bacterial multiplication.

It is a far cry from mice to men, but in this instanoethe same factors are likely to govern the response of bothspecies. The work of Eagle et al. suggests that penicillinshould be given to man in a way that ensures that theconcentration at the site of infection remains continuouslyin excess of that necessary to kill the infecting organismin vitro. The exact timing of the injections woulddepend upon the preparation and dose of penicillin used,but the most economical regime, and the one which wouldproduce the most rapid cure, would be that in which eachinjection was given when the penicillin concentration atthe site of infection had fallen to the in-vitro bactericidalconcentration for the organism concerned. Knowledgeof the concentrations of antibiotics that can be attainedin the tissues is at present scanty, but advances in thisdirection, combined with rational interpretation ofbacterial sensitivity tests, should clearly lead to a

reduction in the. massive doses of antibiotics at presentgiven, and therefore to less side-effects and unnecessary- expense. -

TREATMENT OF COUGH

1. Amer. J. Med. 1953, 14, 87.2. Boyd, E. M., Lapp, M. S. J. Pharmacol. 1946, 87, 24.3. Boyd, E. M., Machlachlan, J. Canad. med. Ass. J. 1946, 50, 338.4. Boyd, E. M., Palmer, B., Pearson, G. L. Ibid, 54, 216.5. Boyd, E. M., Pearson, G. L. Amer. J. med. Sci. 1946, 211, 602.6. Alstead, S. Edinb. med. J. 1940, 47, 693; Glasg. med. J. 1940,

134, 125; Lancet, 1939, ii, 932 ; Ibid, 1941, i, 308 ; Practitioner,1947, 158, 149.

7. Howell, T. H. Chronic Bronchitis. London, 1951.8. Herxheimer, H., McAllen, M. K. Lancet, 1952, i, 1213.9. Davenport, L. F. Publ. Hlth Rep., Wash. 1940, suppl. no. 158,

p. 61.10. Hillis, B. R. Lancet, 1952, i, 1230.

IT is not alwavs easv to decide when to interfere witha cough-particularly a postoperative one. Even whenthe decision to treat it has been made, the choice ofremedies is enormous, though the really effective drugsare few. A conference at Cornell University has latelydebated these questions.The majority of the drugs which are said to stimulate

the respiratory secretions are emetic when given in largeenough doses, but it is extremely doubtful whether theyhave any real effect in the doses usually given. Boydet al.2-5 have shown that in lightly anaesthetised catsammonium chloride and carbonate, ipecacuanha, tinct.camph. co., potassium iodide, creosote, and several ofthe essential oils will all increase the volume of fluidsecreted by the respiratory tract. In man, however,there is no such evidence. Both Alstead 6 and Howell,7who have made long and painstaking studies of thevolume of the sputum secreted by chronic bronchitics,failed to show that it was influenced at all by any of alarge number of expectorants used in conventional doses.But Herxheimer and McAllen 11 have recently suggested amethod of using potassium iodide intermittently in dosesof gr. 15-25 which they claim does produce a real increasein respiratory secretion. Probably one of the best

expectorants is a hot drink; many a chronic bronchiticand sanatorium patient will testify to the value of hisearly morning cup of tea as a loosener of phlegm. This

probably explains the popularity of the celebratedhot-water mixture (mist. sod. chlor. N.F.).

Of the opiates and their derivatives and the few otherdrugs, such as methadone, which depress the coughreflex, linctus diamorphinae is incomparably the mosteffective, but the danger of addiction means that itmust be kept strictly in reserve and used only when allsafer drugs have failed. One speaker at the Cornellconference advocated the wider use of small doses of

morphine, but, for the same reason, few would agreewith him. The main discussion concerned the dosageof codeine. The preparations normally used in this

country contain quite small doses. For example, theordinary linctus codeinse N.F. contains gr. 1/8 to thedrachm and the strong linctus gr. 1/4’ Many people,including Alstead, have recommended larger doses-e.g., gr. 1 four-hourly. On the other hand, Muschenheim,at the Cornell conference, made a plea for smaller dosesat shorter intervals. He quoted an experiment carriedout before the war in an American sanatorium byDavenport 9 who found that out of 475 patients withtroublesome cough only 21 required more than gr. 1/6of codeine to control it-only one-third of the traditionaldose formerly given in this institution. But Hillis 10

found no evidence that the action of codeine, even inlarge doses of up to gr. 3, was any greater than could beexplained by the factor of suggestion. In experimentallyproduced cough in man he was impressed by the impor-tance of the psychological factor in contributing to thesuccess of various drugs-which may well account forthe divergent views on the optimum dosage of codeine.The dry hacking cough of tracheitis and acute bron-

chitis is helped by warm moist air;- and the Americansfavour continuous treatment with a steam-kettle ratherthan the intermittent treatment with jug and _ towel,which is perhaps more popular in this country. The

wheezing cough is helped by antispasmodics ; and one