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of another firm which obtained butter from the samewholesaler were also affected ; that the managers of thestores and their families-who presumably were able toobtain large quantities—were particularly affected;and that in one family three children who ate this butterdeveloped typhoid, while their parents who had giventheir family fresh butter and themselves had eaten someolder, slightly rancid, butter from a family parcel, hadescaped. Incidentally, of these three children, one hadbeen inoculated against typhoid and had only a slightattack;. of two not immunised, one died and the otherhad a severe attack. The actual derivation of theinfection proved impossible to track down, because ofthe numerous sources of origin and the habit of vendorsat that period of mixing various butters to produce an" average " product for retail sale.The notifications fell from 446 in May to 304 in July

and 106 in August. Though the fatality-rate is not

given, the infection seems to have been clinically severe.

LYSOZYME, BIOTIN, AND AVIDINIT seems possible that the studies of Meyer and Laur-

ence into the relationship between avidin and lysozymemay produce some useful results-though not the onesexpected. Avidin is a protein constituent of egg-whitewhich inactivates biotin by forming a complex with it.Lysozyme is a bacteriolytic enzyme also present in egg-white, as well as in tears, sputum, and other secretions,which rapidly lyses certain cocci, notably the test

organism Micrococcus Zysodeikticus. Meyer 1 found thatavidin preparations possessed lysozyme activity roughlyproportional to their avidin activity. He found also thatthe bacteriolytic activity of lysozyme was increased 8 to250 times by the addition of traces of biotin. Laurence 2

found that egg-white lysozyme possessed avidin activity,while varioussamples of avidin possessed parallel avidinand lysozyme activity. It was suggested that these resultscould be satisfactorily interpreted by regarding lysozymeas an avidin-biotin complex. A previous annotation 3mentioned some objections to this view: Thus Woolleyand Longsworth reported that the iravidin preparations,very much purer than those of Meyer and Laurence,possessed no lysozyme activity. There appear also tobe considerable differences between the molecular

weights of lysozyme and avidin, though the availablefigures have not been fully confirmed. FurthermoreMeyer failed to dissociate lysozyme into avidin andbiotin, although biotin can be readily separated fromthe normal avidin-biotin complex by steaming. It was

apparent that the crux of the question lay in the purityof the preparations used (some of the avidin concen-trates evidently contained only a few per cent. of pureavidin) and that judgment would have to be postponeduntil the work had been repeated with comparativelypure avidin and lysozyme. ,

.

This necessary check has now been made by Alderton,Lewis, and Fevold,5 who cannot confirm the results ofMeyer and Laurence. Using highly purified avidinand crystalline lysozyme, as well as preparations oflower purity, they find no stimulation of lysozymeactivity by the addition of biotin. Pure lysozymepossesses no avidin activity and pure avidin possessesno lysozyme activity. Pure lysozyme contains negligibleamounts of biotin ; the quantity found (0009 part permillion) is comparable with that reported by otherworkers for quite unrelated purified proteins such as

insulin, casein, and tobacco mosaic virus. It appearsprobable therefore that lysozyme and avidin have nosimple biological relationship and that the resultsobtained by Meyer and Laurence were due to the im-perfect separation of the two proteins. Both are basic

1. Meyer, K. Science, 1944; 99, 391.2. Laurence, W. L. Ibid, p. 393. 3. Lancet, 1944, ii, 216.4. Woolley, D. W., Longsworth, L. G. J. biol. Chem. 1942, 142, 285.5. Alderton, G., Lewis, J. C., Fevold, H. L. Science, Feb. 9, 1945,

p. 151.

proteins, and they have similar isoelectric points (lyso-zyme pH 10ó8 andavidin pH 10’0) ; so it is hot surprisingthat simple methods of purification fail to separatethem.

While the interpretation Meyer and Laurence put ontheir observations has not stood the test of further

investigation there is no reason to doubt the accuracy ofthe observations themselves. With one exception theyare of the kind that would be expected from the use ofvery impure preparations. The exception is the stimu-lating effect of biotin on lysozyme activity. Meyernoted that as little as 10 pg. of biotin could increase thebacteriolytic action of lysozyme, against both live andkilled cocci, 250 times. Although Alderton and his

colleagues found that biotin had, no effect on the lyticaction of their highly purified lysozyme preparations, themagnitude and apparent reproducibility of the effectdescribed by Meyer make it impossible to dismiss it as anerror of observation. The impurities in Meyer’s biotinclearly deserve further investigation.

ARTHRITIS APHORISMS

IN discussing common mistakes in the handling ofpatients with arthritic and allied complaints, Comroe,lwriting from the arthritic clinic of the Hospital of

Pennsylvania University, complains that doctors com-rnonly treat their arthritic patients without first estab-lishing the diagnosis, while others too often allow con-tractures to develop and pains to persist because theythink only in terms of diagnosis. He urges that everypatient with joint symptoms should have a completehistory and physical examination, and the appropriatelaboratory tests, but this does not mean that affectedjoints should not be splinted or mild analgesics givenduring the period of study. He goes on to extract amultitude of lessons from the experience at the clinic,which may be summarised as follows :Do not depend too much on the sedimentation-rate in the

diagnosis of joint disease. This test should be used inconjunction with common sense, a carefully taken

history, and a thorough physical examination, blood-count, urine analysis, serological test for syphilis, andX-ray films of the involved joint.

Do not tell the patient that the joint is normal merely becausethe X-ray findings are negative. ,

It is an error to diagnose gout frequently in females ; 95-98%of all gout occurs in males..

Other diseases besides local ones may cause pains and aches injoints and muscles.

Extensive hypertrophic changes in the-spine may be foundwithout symptoms.

People over 50 nearly all show X-ray signs of degenerativejoint disease, usually symptomless.

Do not attribute pains low down in the back to arthritismerely because there are hypertrophic changes in thelumbar vertebrae or sacroiliac region. Backache is mostcommonly due to ligamentous and muscular strain.Chronic foot strain often causes pain not only in the footand lower leg but also in the knee and low back.

Syphilis may mimic any form of joint disease.Conjunctivitis and tenosynovitis are extremely commonly

associated with gonorrhoeal arthritis.There is no specific magic bullet for the treatment of rheuma-

toid arthritis-certainly not a gold one, and gold may betoxic.

Always remember you are treating a human being’ and notmerely a few joints.

Do not tell the patient with rheumatoid arthritis to go to bedfor a long period without proper exercise and massage ;if he lies in bed like a lump of putty, much harm maybe done.

Physical therapy alone will not cure most cases of arthritis.It is easier to prevent a deformity than to correct one.If you are a physician do not scorn to learn to apply plaster

in your cases of arthritis.Never manipulate joints that are acutely inflamedNo particular form of vitamin deficiency has ever been shown

to nroduce rheumatoid arthritis.

1. Comroe, B. I. J. Amer. med. Ass. Feb. 17, 1945, p. 392.

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All bath-water is buoyant, whether it is in the patient’s home, or in a high-priced spa.We do not yet know the role of focal infection in most cases of

rheumatoid arthritis.A protracted need for narcotics in a patient with joint symp-

toms suggests neoplasm.Less than 10% of patients with rheumatoid arthritis who

become pregnant are relieved of their rheumatoidarthritis for more than 4 to 6 weeks after delivery.

The injections of vaccines, sulphur, chaulmoogra oil, foreignproteins or the like will not straighten chronicallydeformed ankylosed joints.

On the whole, Comroe’s experience with rheumatoidarthritic is encouraging, for though he advises the

physician never to promise a cure he would tell thepatient that nine cases out of ten can be definitelyimproved. In the United States, as in England, there isan urgent need of hospital beds for " rheumatic "patients where a well-planned therapeutic programmecan be applied without delay.

ABDOMINAL PAIN IN CHILDHOODTHERE is probably no more interesting, uncertain,

or hazardous clinical domain in childhood than acuteconditions in the abdomen, and pain is the presentingsymptom, the warning signal that something has gonewrong and that it may be serious." It is this backgroundof possible catastrophe that makes every child patientwith abdominal pain such an urgent problem. In hisreview of abdominal pain in childhood, of which this wasthe opening sentence, Brennemann 1 included tendernessas an essential part of the story, and he put the majority Iof the more serious abdominal conditions heralded andaccompanied by pain into two main categories-thosedue to obstruction and those due to infection. Colicof infancy he put in a class by itself, pointing out thatit is probably more frequent in the breast-fed than in thebottle-fed infant and principally caused either by over-feeding or by the presence of excess of " gas " in thealimentary tract, itself either swallowed air or producedby fermentation. Of the obstructions in early life hestressed the importance of intussusception, with often adeceptive calm after the dramatic onset. A conditionless commonly diagnosed, though described by Brenne-mann as not rare, is congenital ano-rectal stricture withincreasing distension of the abdomen and screamingattacks, relieved by a brief course of daily digitaldilatation. I

In discussing appendicitis, Brennemann voiced theopinion of all children’s physicians who are honestwith themselves when he wrote : " I still approached "{i.e., after all his experience) " the acutely painfulabdomen in a child with more apprehension and a greaterfeeling of uncertainty than any other domain in child-hood." He described the pain as only rarely intenseand the fever as rarely more than a "few degrees."Early residual tenderness at a definite point is importantand is usually at McBurney’s point, though with a retro-coccal appendix it may be higher or more in the flank.Rectal examination he,regarded as seldom adding any-thing to a careful abdominal examination. (This is in con-trast to teaching in this country often crystallised in theaphorism attributed to Sir Robert Hutchison: "Ifyou’ll put your finger in the rectum you won’t put yourfoot in it.") The diffuse dull pain in the region of theumbilicus with some tenderness, occurring in the courseof upper respiratory throat infections, Brennemannattributed to mesenteric lymphadenitis, but he confessedthat he did not know how to distinguish satisfactorilybetween this condition and appendicitis, adding thewarning that more than half of all cases of the latter arecausally related to throat infections. In discussing hispaper, Joseph Colomb quoted two tips : (1) the patientwith diaphragmatic pleurisy or pneumonia is too sicktoo soon to have appendicitis; and (2) a child who is

1. Brennemann, J. J. Amer. med. Ass. 1945, 127, 691.

conscious and not forcibly held, who on deep palpationmakes no attempt to remove your hand, probably doesnot have a surgical condition of the abdomen-theconverse is not true.Abdominal pain due to food allergy, according to

Ratner,2 is caused by spasm of smooth muscle, byweal formation or vascular spasm in the gastro-intestinalwall, or by a combination of these factors. He pointsout that skin-tests are not helpful. The same point ismade by Blamontier,3 who describes an adult whoseallergic trouble with mutton appeared to be due to somedisintegration product of the meat protein rather thanto the protein itself, for whjch skin-tests were negative.Ratner makes his diagnosis rest on careful history-taking,on prompt relief from pain after subcutaneous adrenalineor oral atropine, and on X-ray observations that thesuspected article of food will provoke pylorospasm withdelayed gastric emptying, and hypertomicity and hyper- °

peristalsis of the intestine. " The longer I practiseallergy," he remarked in discussing his paper later," the more often I make the diagnosis of no allergypresent." His treatment, apart from the avoidance offoods to which the child is sensitive, which may notalways be possible, is to give a well-cooked diet, on theview that coagulated albumins cannot act as allergens.’

It is perhaps fitting to end with Brennemann’s closingwords : " the majority of abdominal pains ... have, inmy experience, been of unknown nature and unknownaetiology."

AN INDIAN SCOURGE

CHOLERA, an epidemic of. which is said to have begunin Calcutta among the civilian population, has long beena curse of India. It is essentially a water-borne disease,and outbreaks usually originate from the contaminationby carriers of unprotected wells and tanks used for drink-ing purposes. Widespread epidemics occur in famineyears through the failure of the monsoon and winter rains,with resultant scanty and bad water-supplies both foragriculture and for domestic purposes. In India

epidemic cholera is more particularly associated, innormal times, with the movements of millions of pilgrimsthrough the densely populated endemic areas. Thesepilgrims acquire the infection and distribute it as theygo on their way.Some personal protection against infection can be

obtained by prophylactic vaccine inoculation ; but thisis only temporary, and has to be reinforced by repeatedinoculation every few months to maintain the immunityobtained. Equally important in the avoidance of thedisease is abstention from all uncooked food or unboiledwater or milk, and the seclusion of all foodstuffs from theattentions of the innumerable flies. Water-supplies,apart from the more obvious safeguards against pollu-tion, can be treated with potassium permanganatesufficiently to make them pink-a measure which, whenproperly and universally applied in rural areas, is heldto be a useful check on the spread of the disease.Treatment of cholera is directed towards the correction

of the deficiencies created by it and towards combatingthe toxaemia resultant on the infection. So far no drugcan be regarded as exerting a specific action on the choleravibrio. Sir Leonard Rogers based his original treatmenton an appreciation of the pathology of the disease, and hisresults were very encouraging in that he reduced thefatality-rate considerably. The aim is to replace thefluid and salts lost in the choleraic diarrhoea, to equili-briate the body temperature, and to neutralise as far aspossible the toxins produced by the organisms. Anti-cholera units have been created in India with the

necessary personnel and equipment ready to proceed tothe epidemic areas when the disease breaks out. Similarunits are in existence in the Army in India, and the

2. Ratner, B. Ibid, p. 692.3. Blamontier, P. Pr. méd. March 31, 1945, p. 162.