51

mottling without development of a true rash, or generalsymptoms without either rash or enlarged glands.The Weil-Felix and Paul-Bunnell reactions were negative

in all cases tested.From two cases in Tel Aviv, in which the practitioner

concerned could obtain comparatively precise dates as to timeof contact and removal therefrom, the incubation periodappeared to be 4-5 days.Milian under the heading Roseole Infectieuse, refers

briefly to a somewhat similar condition which had

previously been noted by Trousseau (roseole saisonniere),and Fournier (roseole simple), but I have not been ableto examine the latter articles.

I could arrive at no conclusion as to cause or method of

spread, but arthropod vectors were most unlikely andthe occurrence of encephalitis suggested that the condi-tion might be due to a virus infection.

Folkestone. F. R. FLETCHER.F. R. FLETCHER.

1. Milian, G. Nouvelle pratique dermatologique. Paris, 1936;vol. 2, p. 803.

CANCER OF THE FEMALE BREAST

A. McKENZIE.General Register Office.

London, W.C.2.

SiR,—The point made by Dr. Holtzer (Dec. 24) is

important, and perhaps I should have explained fullyhow the rates were adjusted rather than make the baldstatement " the five-year survival-rates have beencorrected for age."The denominator used to calculate the corrected

survival-rate for any age-group is not the total number ofwomen that fall within that age-group but the numberexpected to be alive at the end of the five-year period,under the normal conditions of mortality. Thus the 65-69age.group contained 1250 women of whom 367 were alivefive years later, but according to the current life table1035 should have been alive.

The crude iive-vear survival is of course

but when corrected for age it is

NOR ANY DROP TO DRINK?

W. K. DUNSCOMBE.

SIR,-Your article under this heading (Dec. 17) coversalmost all aspects of Civil Defence in the thermonuclearage. I should like here to put forward only three points :

(1) The Ministry of Housing and Local Government havehad for some time arrangements for " mutual aid " for waterundertakings, though as far as I am aware no full survey ofpotential water-supplies has been made-at least not in thisarea.

(2) On the question of the contamination of water-suppliesby fission products I think that perhaps we (and you) may betoo pessimistic, as the Atomic Energy Research Establishmenthave been into this already and have taken samples in variousplaces to determine basic levels. One supply in this area(from an underground working from which pitchblende wasobtained many years ago) was found to have a degree of radio-activity vastly higher than any other place in this country ;yet the inhabitants are just as healthy as those near by whodo not drink the same water. There is also a place in Swedenwhere the water has a radioactivity 100 times greater eventhan that just mentioned, but there is no information thatthe people living there are not healthy.For reservoirs, owing to the relatively short half-life of

some at least of the most dangerous fission products, storagewould help ; while, where there are filters, using an alumfloc and the actual physical scraping of the sand surface wouldremove more. It is highly unlikely that there would be anyelectricity for a number of days ; so pumps for water andsewage would not be working unless Diesel-operated.In such circumstances it is obvious it would be criminal

to waste a drop, and this should be impressed on the FireService, which under present arrangements seems to imaginethat unlimited quantities of water will be available to put outfires. The answer is of course that houses would have to bedynamited for fire breaks and the rest left to burn.

(3) The teaching of " field hygiene," especially to sanitary

inspectors, was recommended by the medical officers of healthcourse at the Civil Defence Staff College as long ago as May,1951. But no action has been taken by the appropriatedepartments.With regard to (1) and (2) I would refer you also to the

contamination of the Wabash River after the historic"

Trinity " test, and also to a paper by Tsuzuki,1

Penzance. W. K. DUNSCOMBE.

1. Tsuzuki, M. Münch. med. Wschr. Aug. 5, 1955, 97.2. Peabody, F. W. Doctor and Patient: Papers on the Relation-

ship of the Physician to Men and Institutions. New York,1930.

3. Ryle, J. A. The Natural History of Disease. London, 1948.

NEEDLE BIOPSY OF THE KIDNEY

SiR,-We were delighted with the conservative attitudeof your editorial of Dec. 10. My colleagues and I havedone over 400 renal biopsies in the past few years. No

patient has died as a result of the procedure; the

morbidity has been slight ; and in no patient was surgicalexploration necessary. None the less, we believe that,for the time being at least, the procedure should be donein special centres and only by those who have been trainedin this technique.We were interested in several points raised by you :You state that " several patients have already had as many

as four successive biopsies, giving detailed information of

progressive renal disease which could not have been obtainedby other means. This is not, however, an adequate justifica-tion for a potentially dangerous operation ; and biopsy shouldbe used only when the information it gives will be of directadvantage to the patient, and not merely a rather academicaddition to medical knowledge."

This is a most important statement, for it emphasisesagain that the clinical investigator must be first a

clinician, whose chief consideration is the care of thepatient.2 As we have shown, in selected cases, serial

biopsy of the kidney has provided data which could nothave been obtained in any other way and which was of

great value in the care and management of our patientsand their illnesses. The serially taken biopsies haveincidentally provided new knowledge of the natural

history of diseases which, as John Ryle taught us manyyears ago on the wards of Guy’s Hospital,3 is not " merelya rather academic addition to medical knowledge."

Later you state " that in patients with the nephrotic syn-drome... therapeutic trial [of cortisone or corticotrophin]would give the same information [as renal biopsy] with lessdisturbance to the patient."

Unfortunately this is not true. Without histologicalinformation the response to cortisone or corticotrophinis always unpredictable ; this is hardly surprising if werecognise that " nephrotic syndrome " is but a syndromewith many underlying pathological causes. When thenephrotic patient is first seen the clinician is faced withthe problems of how to treat him, for how long, andwhether to treat a second time. This decision can bemade with far more confidence if the underlying pathologyis known. In our experience, no good has been achievedin patients with severe glomerular lesions who have beentreated with corticotrophin or steroid hormones. Andin some cases at least it is our opinion that their clinicalcondition has deteriorated greatly as a result of treatmentwith these hormones. As far as " disturbance to the

patient " is concerned, our patients who have needed abone-marrow or hepatic biopsy as well as a renal biopsyhave told us they have been least disturbed by the latterprocedure. It has also come as a surprise to us to findthat a number of our female patients were disturbedless by renal biopsy than by catheterisation of theirbladders.

You end by saying : " There are other interesting possi-bilities, but it seems unlikely that renal biopsy will achievethe importance that liver biopsy is now assuming. Many

52

lives have been saved by liver biopsy in the differentialdiagnosis of prolonged jaundice ; but accurate differentialdiagnosis of renal disease is rarely of such immediate andcrucial importance."We wonder whether this prognostication is based on

personal and comparative experience in the use of needlebiopsy in the care of patients suffering from either hepaticor renal disease.Our experience with hepatic biopsies goes back many

years and is much more extensive than with renal biopsy.To tell the truth, we are embarrassed to admit that wehave saved lives with hepatic biopsies, but even this earlyin the game we will admit having cured some patientswith renal disease as a result of biopsy of the kidney.On the basis of our experience with both types of biopsieswe suspect that biopsy of the kidney will be of greaterpotential value to patients with diseases involving thekidney than hepatic biopsy is to those with jaundiceand other types of hepatic disorder. As a matter offact, we find less use today for hepatic biopsies than wedid a few years ago. This is to be expected because,from hepatic biopsies, we have learned so much of thenatural history of the different diseases which producecirrhosis or result in jaundice that we are now able torecognise them early and clinically.

It is probable that few needle biopsies of the kidneywill be necessary twenty years hence, for by that timeclinical investigators will have sorted out, by renal biopsy,the early and treatable stages of the many diseases whichproduce the end-stage kidney. At present these are

lumped together by physicians under the all-inclusive" chronic glomerulonephritis "-the diagnosis of which isequivalent to a death sentence.

ROBERT M. KARK.Presbyterian Hospital,Chicago 12, Ill., U.S.A.

THE FORGOTTEN PATIENT

A. G. DUNCAN.Severalls Hospital,Colchester, Essex.

SiR,-The letter (Dec. 24) from the president andsecretary, Friends of Menston Hospital, states that thefindings of a Daily Express investigation "cannot bedismissed so airily as Dr. Duncan (Nov. 12) would haveus think." I can ignore the rebuke from Mr. Carter andMr. Cripps, but not their inaccuracy. My protest ofNov. 12 neither included nor implied reference to anynewspaper investigation or articles.

CERVICAL VERTIGO

T. J. WILMOT.Tyrone County Hospital,Omagh.

SiR,-I was interested in last week’s article by Dr. Ryanand Dr. Cope.They describe five cases of vertigo associated with

cervical abnormalities and attribute the vertigo in eachcase to interference with the tonic neck reflexes. In

describing each case they state that the aural findingswere negative. What does this mean ? If every eartested was clinically normal and gave normal audio-metric and caloric results, they should state this. If

aticliometry and caloric testing were not done theirobservations on the aetiology of the vertigo are valueless.

Evidence is accumulating rapidly that labyrinthinevertigo is linked closely with the autonomic nerve-

supply to the vessels supplying the inner ear. It would

appear that interference with the cervical sympatheticchain might well have caused the vertigo in all fivecases by causing a temporary alteration in the blood-supply to one or both inner ears.The conception of " cervical vertigo " put forward

by Dr. Ryan and Dr. Cope merely increases the presentconfusion on this subject, and in laying stress on thecervical abnormalities present may tend to preventproper otological investigation of these cases in future.

STREPTOKINASE IN TREATMENT OFINFLAMMATION

SiR,—Professor Dubos, in his account of the Micro-environment of Inflammation, has reviewed a new fieldto which he himself has made many significant contribu-tions.The oedema fluid in inflamed areas contains large

amounts of fibrin. The deposition of fibrin in the tissue-fluids and the formation of thrombi in the arteries,capillaries, veins, and lymphatics help to wall-off thearea of infection by aiding in the formation of a limitingmembrane. This defence curtain has been correctlyregarded as a beneficial structure ; and its preservation,in order to inhibit the spread of infection, has beenconsidered a basic surgical necessity.The advent of streptokinase has produced a change

in thought about the barrier. The chemical nature ofthe limiting membrane might be changed by administra-tion of streptokinase ; for this will indirectly cause lysisof fibrin through activation of plasminogen to plasmin,which is the active lytic agent. Such a change wouldbe beneficial, since the antibacterial drugs, being borneby the blood, cannot pass through the limiting membranefrom without any more than can pathogenic bacteriafrom within. The inefficiency of the antibacterial drugsin the treatment of abscesses, walled-oN cellulitis, andsimilar infections is well recognised.

’ Varidase,’ which contains streptokinase and strepto-dornase, has been used as the source of streptokinase,since a pure preparation of streptokinase has not yetbeen made.2 (The streptodornase content can here bedisregarded.) Varidase was dissolved in physiologicalsaline so that the final concentration of streptokinase was10,000 units per ml. The solution must be stored in a

refrigerator ; and a fresh solution was made daily.5000 units of streptokinase in 0.5 ml. of physiologicalsaline was injected intramuscularly, usually in the glutealarea, twice daily for a total of six doses or more if

necessary. One of the antibacterial drugs must be given,either orally or parenterally, when streptokinase is

injected intramuscularly in the treatment of infection

and/or oedema. A spreading infection may result fromdissolution of the membrane if protection against thecontained bacteria is not provided.In 64 patients with abscess, cellulitis, empyema, epididymitis,

hsemarthrosis, thrombosed haemorrhoids, orchitis secondary tomumps, sinusitis, thrombophlebitis and oedema, 45 excellentand 15 good results were obtained. The 4 poor results werein a patient with paraplegia and extensive decubitus ulcerswhich were resistant to all forms of treatment, in 2 patientswith peripheral arteriosclerotic vascular disease with gangrene,and in a patient with thrombosed haemorrhoids who did notreceive sufficient treatment.

Of patients who were benefited the redness and cedemastarted to decrease in a few after several hours, and in allreceded considerably by the end of two days. In the patientswith granulating wounds, healing was hastened by reductionof the surrounding induration. Delay in healing was notseen in any of the patients. Pain and tenderness at thesite of injection, noted in about 60% of the patients, dis-

appeared about twenty-four to forty-eight hours after theinjections were stopped. The pain and tenderness were

probably due to the streptokinase in varidase, since theywere not encountered in patients given streptodornase alone.A granuloma at the site of injection was not seen in any ofthe patients. A rise in temperature attributable to the

streptokinase was noted in about 10% of the patients.A significant change in the total and differential white-blood-cell counts and in the prothrombin-time was not found;fibrinolysis, determined by the whole-blood technique, wasnot observed ; hsemorrhage, haematomas, and petechiae werenot seen ; and chills, cyanosis, or allergic responses were notnoted. Administration of anti-histamine drugs was not

necessary.

1. Dubos, R. J. Lancet, 1955, ii, 1.2. Miller, J. M., Surmonte, J. A., Ginsberg, M., Ablondi, F. A.

Maryland St. med. J. 1955, 4, 188.