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and adjusted to give the cost per inpatient per week,based on the total number of beds with deductions forvacant beds and a notional allowance for outpatient work.If the actual cost for outpatient work is known this

figure is used, but the report gives no clue when this hasbeen done.- This costing figure may provide some basisfor accouritancy comparison ; but it does not reflect the

efficiency of the hospital, which could be better shown bycalculating the cost per patient treated. The hospitalthat appears expensive is often the efficient hospital witha rapid turnover and high bed occupancy ; and here thecost per patient treated may, in fact, be under half thatof a poorly staffed and ill-equipped, but much cheaper,hospital. The figures published may be of some value incalculating costs for road accidents or pay-beds, but thepresent overemphasis on cost per bed per week constitutesa real injustice to the efficient hospital. It would be ofconsiderable interest to find hospitals in each of thedifferent categories where both the profession and theMinistry agree that the level of staffing and equipment isoptimal for really good work, and to use thee costs as abasis for comparison.une 01 the principal objects of publishing these

statistics is to enable hospital authorities to make broadcomparisons in terms of performance, staffing, and so on,between hospitals for which they are responsible andsimilar hospitals elsewhere, and in this way to considerthe possibilities of increased efficiency. For any con-structive criticism, however, comparison of two hospitalsneeds a very intimate knowledge of their particularcircumstances. The Ministry is now considering howbest to present these statistics for 1953 and future yearsto enable an accurate comparison to be made. Theeditions published so far have revealed any grossdifferences in costs, and for these there have usually beenadequate explanations. It is very doubtful whether sucha detailed breakdown of figures is necessary at all ; itwould be valuable to have a much simplified analysiswith emphasis on figures which demonstrate volume andefficiency of the hospital service, as shown, for example,by the bed-occupancy rate, bed-turnover rate, and costper patient treated, giving some comparison with previousyears. Such an analysis, together with regional sum-maries, in one volume, could be both informative anddigestible.There is no limit to the statistical analyses which could

be made of public services : it might be interesting, butit would not necessarily be useful, to know the number ofletters handled per postman in each postal district orthe running-costs of every railway station. Althoughfull of fallacies, the figures for hospitals that havehitherto been issued have served a good purpose byfocusing attention on the need for better costing systemsand improved turnover ; but the time has surely comefor complete revision of the method of presentation.

THE ANATOMY OF FACIAL PALSY

Tschiassny suggests that lesions of the facial nervecan be defined by carefully analysing the type of palsyand its accompanying signs. In addition to the well-known supranuclear lesion, with preservation of emotionaland paralysis of voluntary movement and relative escapeof the forehead, he lists seven levels at which lesionsmay be recognised. At the nucleus, though all movementis abolished, reflex " tearing " and taste are unaffected,since fibres for these join the nerve in the midbrain and atthe geniculate ganglion respectively. Extracerebrally,but above the geniculate ganglion, tearing is lost buttaste preserved. At the ganglion taste is also lost.Below this, tearing is again unaffected since fibres for thispass via the ganglion to the greater superficial petrosalnerve. Further down, the nerve to stapedius leaves

,

the facial trunk, and lesions below this level no longercause hyperacusis to loud sounds. Next, the chordatympani segregates taste-fibres and lesions after thisno longer cause loss of taste. Finally, just at the stylo-mastoid foramen a motor branch passes to the digastricmuscle, and below this level the slight deviation of thechin caused by paralysis of the digastric is absent.

Application of these signs to cases of Bell’s palsytends to confirm that the site of the lesion varies. In

practice, however, the tests described by Tschiassnyoften give equivocal results. The important distinctionsare of upper from lower motor-neurone lesions, and ofBell’s palsy from other types of lower motor-neuronelesion. Fortunately, both these distinctions can usuallybe made on the history and clinical findings.

1. Tschiassny, K. Ann. Otol., &c., St. Louis, 1953, 62, 677.2. Garrod, A. E. Lancet, 1908, ii, 1, 73, 142, 214.3. An Introduction to Human Biochemical Genetics, by H. HARRIS,

M.A., M.D. Eugenics Laboratory Memoirs, XXXVII. CambridgeUniversity Press. 1953. Pp. 96. 15s.

HUMAN BIOCHEMICAL GENETICS

THE pathologist’s long-term aim is to describe all diseasein terms of the physics and chemistry of the cell. His firstsuccesses are likely to come in disorders due to the primaryaction or inaction of a genetic factor, rather than in thedisorders where some external agent, such as infection, isimportant. Genetic factors must operate first among thechemical elements in the nucleus ; and mutations, changesin genetic factors, must produce some variation from thenormal in cell biochemistry. Work on lower organisms,such as the fungus neurospora, suggests that in manyinstances one genetic factor controls the production orfunctions of one enzyme. In man it is difficult to studywhat is going on in the cell, and knowledge of biochemicalvariation is mostly limited to that which can be studiedin blood, saliva, and urine. The first biochemical disorderto be recognised was alkaptonuria, because here theabnormal metabolite not only appears in the urine butturns this black on standing. These abnormalities werefirst fully discussed by Garrod.2 Harris has now ablysummarised present knowledge in a monograph from theGalton Laboratory.3The genetically determined variations in metabolism

can be placed in certain broad groups. One group arethose in which the end-product differs from the normal,or, if there is no normal, may be present in severalalternative forms. Another group are those in whichthere is an apparent block at some intermediary stage sothat normal metabolites accumulate in abnormal amounts.A good example of the first group are the variants

of haemoglobin. That found in patients with sickle-cell anaemia and, in smaller amounts, in those withthe sickle-cell trait differs from normal adult haemoglobinin its much slighter solubility in the reduced state andalso in the electrophoretic properties of some of itsderivatives. This physical difference in solubility is

chemically important, but it must depend on only smalldifferences in the chemical composition of the molecules.Chemical analysis of these types of hemoglobin shows

THE commonest cause of facial weakness in an other-wise healthy adult is Bell’s palsy. This eponym wasassigned to the disorder well over a century ago ; yetthe cause is still obscure. Usually the patient feels avague ache behind the ear, which is accompanied orfollowed by a facial weakness that often rapidly becomesmore severe ; previous exposure to draught is common.If, in addition to the facial palsy, there is some loss of tasteon one side of the tongue, the diagnosis is further con-firmed. This clinical picture portrays only the site ofthe lesion-namely, between the geniculate ganglion,through which taste-fibres leave the nerve-trunk, andthe -origin of the chorda tympani, at which they join it.Taste is not always involved, however, and it seems thatin Bell’s palsy the nerve may be attacked at differentlevels, at any rate between the geniculate ganglion andthe iltylomastoid foramen.

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only differences in the relative proportions of the differentamino-acids found, and X-ray analysis of the crystalsgives a picture identical in every detail. Different indivi-duals with the sickle-cell trait vary in the proportion ofsickle-cell haemoglobin present. This depends on othergenes present, since within families there is less variationin this respect. Two other genetically determinedabnormal types of haemoglobin are known. Another

example of genetically determined variation, chemicallysmall but clinically important, is that between the A,B, and 0 blood-group substances. These substances havebeen thoroughly analysed, and again the only differencesfound are in the relative proportions of the differentamino-acids present. Yet another example is the con-genital methaemoglobinaemia that has been found infour generations of one family where the globin moietydiffered from that in normal haemoglobin. It is note-

worthy that the examples in this group, comprisingvariations in the end-products of metabolism, are mostlydue to genetic factors which take appreciable effect inthe heterozygous state and in this sense are dominant.The best examples of the second group come at the

moment from the biochemistry of the amino-acid,phenylalanine. Alkaptonuria represents a block at a latestage in the breakdown of phenylalanine. In phenyl-ketonuria, on the other hand, the block appears to be atthe first stage of its metabolism-the conversion to

tyrosine. Phenylalanine in normal people is an essentialconstituent of diet, and tyrosine is not ; but in phenyl-ketonuria any phenylalanine fed can be recovered fromthe urine in the same quantity, as phenylalanine or oneof its near derivatives, such as phenylpyruvic acid. Inaddition to these two well-known conditions one case of

tyrosinosis has been described in which tyrosine andp-hydroxyphenylpyruvic acid were present in the urinein amounts which varied according to the amount of

tyrosine or phenylalanine fed ; here the block must lieat a stage between that in phenylketonuria and that inalkaptonuria. Fructosuria, pentosuria, and the recessivetype of congenital idiopathic methaemoglobinaemia alsoprobably depend on enzyme deficiencies. So presumablydo the storage diseases such as glycogen-storage disease,the amaurotic family idiocies, Gaucher’s disease, andgargoylism. In this group, comprising blocks in inter-mediary metabolism probably due to specific enzymedeficiencies, the genetic factors responsible mostly takeeffect only in the homozygous state, and in this sense arerecessive. In some pedigrees, however, alkaptonuria andalso Gaucher’s disease behave as if due to dominant

genetic factors.Harris includes in his account a third group in which

the essential abnormality appears to be failure of renaltubular function. These are errors of metabolism inthat the specific dysfunction of the renal tubular cells

probably depends on the failure of one or other ofthe syntheses which normally makes possible the reabsorp-tion of these substances from the glomerular filtrate.The details of these syntheses are not yet known. Inthis group he places renal glycosuria and also the typeof cystinuria in which cystine stones often form and inwhich greatly increased amounts of the three amino-acids, cystine, lysine, and arginine, are found in theurine, although the plasma levels of these three substancesare within normal limits. There is at the moment noobvious reason why these three particular amino-acids should be affected together ; presumably their

reabsorption involves the same biochemical synthesis.The inheritance both of renal glycosuria and of thecystine-lysine-arginine type of amino-aciduria is not

straightforward. p

Advances in histochemistry are certain to lead to rapidadvances in biochemical genetics. When these come thegeneticist will no longer be limited to the study ofconditions in which chemical variations can be detected

in the blood, saliva, and urine. It is reasonable to

suppose, for example, that in achondroplasia, due inmost instances to a dominant factor, and in Morquio’sdisease, due in most instances to a recessive factor,specific biochemical abnormalities will be found in theosteoblasts and osteoclasts. In the same way specificabnormalities in the nerve-cells will be found, for example,in Huntington’s chorea, which is dominantly inherited,and in Kinnier-Wilson’s disease, which is recessivelyinherited. -1 In Kinnier-Wilson’s disease there is in fae’already some evidence that there is abnormal depositionof copper in the brain and liver and an abnormally lovlevel of protein-bound copper in the plasma. Bearr

suggests that the sequence is a low level of copper in""Lplasma, increased absorption of copper from the gut,deposition of copper in the tissues with damage to thebasal nuclei of the brain and to the liver, and increasedexcretion of copper in the urine bound to amino-acids.No doubt the time will come when individual differencesin resistance to infection-for example, to the tuberclebacillus-can be described in terms of individual varia.tions in biochemistry, but that is looking some way ahead.

4. Beam, A. G. Amer. J. Med. 1953, 15, 442.5. Waldbott, G. L. Ann. intern. Med. 1953, 39, 1026.

"SMOKER’S COUGH "

TOBACCO-SMOKING is a hazardous pastime. Whilecontributing to the yearly 1:617 million tobacco tax, thesmoker may, it seems., raise his blood-pressure, diminishhis vital capacity, have anginal pain, and lay the founda-tions of a, bronchial carcinoma. He may also suffer from" smoker’s cough," chronic pharyngitis, wheezing, short-ness of breath, and a tendency to respiratory infections-a combination that has been termed " smoker’s respira-tory syndrome." Waldbott 5 has found the pharyngealand bronchial mucosa in this condition fiery red andstreaked with mucopus ; the patients had wheezing, aproductive cough in the mornings, " rhythmic dartingand angina-like " chest pains, and a sensation of con-striction beneath the sternum. When they stoppedsmoking two-thirds of them improved, and most becamecompletely well. Some who did not improve hadadvanced emphysema, and Waldbott assumes that thiswas the end-result of chronic irritation by nicotine,pyridine, collidine, ammonia, and hydrocyanic acid.

" Smoker’s cough " is not new. A German who visitedLondon in 1598 noted that the English were constantlyseen smoking the nicotean weed " and puffing out thesmoke along with plenty of phlegm and defluction fromthe head." Nor are smokers unaccustomed to havingtheir indulgence attacked, though seldom so vehementlyas in King James’s " Counterblaste to Tobacco." Smokingwas very widespread at that time. According to a

declaration introducing the tax of 6s. Sd. a pound in1604, it was " through evil custom and the tolerationthereof, excessively taken by a number of riotous anddisorderly persons ... who do spend most of their timein that idle vanity ... and also do consume [their]wages... not caring at what price they buy the drus;."It has been suggested that the very excess of smokingby all classes in the 17th century may have led to thegrowth of the snuff habit, which gradually replacedsmoking in the 18th. Snuffing itself also developed tofashionable excess, but yielded to cigarette-smoking inearly Victorian times. The immoderate cigarette-smoking of the 20th century may some day becomeunfashionable and snuff-taking return-but perhaps noton the lavish scale of the past, when Samuel Johnsoncarried his snuff loose in his waistcoat pockets, Coleridgesuggested that snuff might be the final cause of thehuman nose, and a certain Mrs. Thompson requestedthat at her funeral her faithful servant should wait:before the coffin and distribute every twenty yards a