967

6. Hunt, T. ibid. p. 3.7. Stollerman, G. H. Amer. J. Med. 1954, 17, 757.8. Bywaters, E. G. L., Thomas, G. T. Brit. med. J. 1958, ii, 350.9. Bywaters, E. G. L., Hallidie-Smith, K. ibid. i, 1234.10. Catanzaro, F. J., Stetson, C. A., Morris, A. J., Chamovitz, R., Rammel-

kamp, C. H., Stolzen, B. L., Perry, W. D. Amer. J. Med. 1954, 17, 749.11. Lim, W. N., Wilson, M. G. New Engl. J. Med. 1960, 262, 321.12. Sanderson, G., St. Hill, C. A., Chamberlain, E. N. Brit. med. J. March

26, 1960, p. 913.

Dr. Thomas Hunt 6 says that publication of the newjournal is justified both by the special interests of thisspecialty and by the size and authority of the society. Thefirst issue helps to vindicate his claim.

PROPHYLAXIS OF RHEUMATIC FEVER

NOWADAYS most physicians dealing with rheumaticfever, especially in children, pay much attention to

prophylaxis against streptococcal respiratory infections.This measure, applied continuously during the years ofgreatest susceptibility to recurrence after an attack,provides a high degree of protection against furthercardiac damage. Much of the work on prophylaxis hasbeen done in the U.S.A., where a high recurrence-ratein unprotected cases seems to be the rule. In the UnitedKingdom recurrence-rates, though rather poorly docu-mented, are apparently lower; but evidence has beenforthcoming that here too prophylaxis is worth while,8and efforts have been made to overcome objections toit.’ One of the main difficulties is in securing regularadministration : continuous prophylaxis with oral peni-cillin or sulphonamide depends on a close understandingbetween family doctor, parents, and children. The

difficulty of making sure that patients continue to taketheir tablets increases as the interval since their lastrheumatic attack lengthens; and when recurrences dooccur it is equally difficult to establish whether prophy-laxis has in fact been omitted. Daily prophylaxis isusually regarded as more efficacious than administrationof penicillin only for treatment of respiratory infections-although this method, properly and consistently used,can undoubtedly protect against recurrence.toLim and Wilson 11 in New York studied ambulatory

rheumatic children attending a rheumatic clinic monthlyfor six years. One group of patients (group 1) receivedcontinuous oral penicillin prophylactically and were

also treated with penicillin when respiratory infectionsoccurred. Another group (group 2) received penicillinonly for treatment of respiratory infections. In each

group, treatment consisted of a full ten-day course of anoral preparation, started at the onset of symptoms.B-haemolytic streptococci were isolated from the two

groups with about the same frequency (the organisms wereapparently not serologically grouped) and the incidence ofupper respiratory infections was also similar. Likewisethe recurrence-rates were not significantly different: therecurrence-rates per 1000 patient-months were 7’5 in

group 1 and 4-6 in group 2 for cases in which the lastattack had been recent, and 3-9 and 2-4 when the intervalsince the last attack had been longer. In two British

series,8 12 in which prophylaxis had been continuous, therewas a smaller but still significant recurrence-rate (about aquarter of that reported by Lim and Wilson).

It may thus be argued that the risk of recurrence is nogreater when penicillin therapy is confined to the treat-ment of respiratory infections than it is with full prophy-laxis. But this has been shown to apply only wherecareful medical supervision minimises the hazard ofinfections remaining untreated. Continuous prophylaxisis surely at present the most generally effective protectivemeasure against recurrences.

1. Selby, G., Lance, J. W. J. Neurol. Neurosurg. Psychiat. 1960, 23, 23.2. Mac Keith, R. Brit. Heart J. 1944, 6, 1.3. Pugh, R. C. B., Gresham, G. A., Mullaney, J. J. Path. Bact. 1960, 79, 89.4. Zimmerman, I. J., Biron, R. E., MacMahon, H. E. New Engl. J. Med.

1953, 249, 25.5. Rosenberg, L. M. ibid. 1957, 257, 1212.6. Farley, S. E., Smith, C. L. J. Urol. 1959, 81, 130.

MIGRAINE

MIGRAINE may be viewed narrowly as an episodic head-ache with features suggesting a vascular origin, or as asyndrome with more widespread bodily disturbances.What initiates either the vascular change in cranialarteries or the visceral dysfunction ? Careful clinicalstudies can still be useful here; and Selby and Lance 1have reviewed five hundred cases confirming manyprevious observations, some of which are well known.

In almost a quarter of their cases symptoms startedbefore the age of 10 years. In 15% there was a familyhistory of epilepsy, and in 38% one of allergy. 67%regarded emotional upsets as a clear precipitating factor.18% had clouding or complete loss of consciousnessduring attacks. Such disturbances of consciousness,which usually are not apparently epileptic, may occur onlyfor a limited time-perhaps during adolescence or at themenopause. In treatment the value of ergotamine tartratewas confirmed. Histamine as an intravenous infusion

(not administered for slow graded " desensitisation ")also proved valuable, though Selby and Lance wonderwhether this acted primarily on soma or on psyche.

In considering the migraine syndrome we may bemisled by too exclusive attention to the headache. Gastro-intestinal disturbances and peripheral vasomotor symp-toms occur; and abnormalities of fluid balance are notuncommon. These may be secondary to disturbancesof neural control; but possibly the imbalance, the electro-lyte changes which accompany it, or some associatedendocrine abnormality plays a primary part in the attack.

PHÆOCHROMOCYTOMA OF THE

URINARY BLADDER

PH.OCHROMOCYTOMAS (chromaffin paragangliomas)may arise in any part of the scattered extra-adrenal chro-maffin-tissue system, which is situated in the preverte-bral tissues of the abdomen as well as in the adrenal

gland itself. Mac Keith 2 collected 165 reported cases, ofwhich 152 were of adrenal origin and 13 arose in theretroperitoneal tissues between the kidneys. Thetumours, which are usually benign, may cause paroxysmalhypertension or the adrenal sympathetic syndrome,leading to death if the tumour is not removed; or theymay have no hormonal effects.

Pugh et al.3 have described 4 cases of phxochromo-cytoma of the urinary bladder; only 3 other such caseshave been reported previously.4-6 These 7 cases are of

great clinical and pathological interest. All the patientswere females, whereas adrenal phseochromocytomasoccur with about equal frequency in the two sexes. Theages ranged from 16 to 74 years, though in at least 3cases symptoms had remained undetected or latent for

many years before the diagnosis was established.The presenting symptoms may be due to the presence

of a tumour in the bladder, or may be due to hormonalactivity. 5 cases presented with haematuria, 6 with hyper-tension (paroxysmal in 2), and 3 with headache, tachy-cardia, or facial flushing; and in 1 case distension of thebladder with 100 ml. of water caused headache and a riseof blood-pressure. Operation usually caused a sudden

968

fall in blood-pressure. The symptoms regressed afterremoval of the tumours, except in 1 case where the

blood-pressure rose. 5 patients are still alive. 1 died

forty months after operation from a cerebral hemorrhage,and 1 immediately after operation in circulatory failureowing to the hormonal effects of manipulating thetumour.

The tumours were found in all parts of the bladder,and their size and weight varied considerably. A strik-ing feature of the gross specimens was the alteration incolour during fixation in formol-saline, accompaniedsometimes by yellow-brown discoloration of the fixa-tive itself. Pigmentation of this type is well known inadrenal phasochromocytomas, and is thought to be dueto the formation of an adrenochrome from the adrenalineprecursors in the tumour. The chromaffin reaction waselicited in only 2 cases, but this reaction is capricious andrequires special and rapid fixation. An excess of nor-adrenaline was demonstrated in the tissue of 2 of thetumours. 6 were benign, and 1 was malignant withmetastases. Metastases are the only reliable criterion ofmalignancy, because the tumour cells lie in the musclecoat of the bladder wall and even grow into the peri-vesical tissues, thus simulating infiltrative growth. Suchan anatomical distribution supports the belief that thetumours arise from paraganglia related to the autonomicnerves of the bladder wall.

The analysis of these 7 cases suggests that diagnosisbefore operation should be possible in some two-thirdsof the cases. Haematuria combined with the adrenal

sympathetic syndrome is almost pathognomonic. Hsema-turia with hypertension, especially if paroxysmal, is sug-gestive. The effects of adrenergic-blocking agents, theestimation of the urinary catechol amines, and bioassayof the excised tumour will substantiate the diagnosis inmost cases. Rosenberg draws attention to two featuresof vesical cases. First, the excretion of urinary catecholamines may not return to normal until about a monthafter the tumour has been removed, and a temporarilyraised level in the immediate postoperative period shouldnot be regarded as evidence of a second tumour or ofmetastatic spread (nevertheless, in the case of Farley andSmith a polypoid tumour obscured the right uretericorifice and at operation a second nodule of tumourtissue was found at the bifurcation of the hypogastricvessels). Secondly, Rosenberg induced a hypertensiveattack in his patient by distending the bladder with fluidintroduced through a urethral catheter.

ROGER BACON AND THE PHYSICIANS

WE do not know for certain the time or place of RogerBacon’s birth, or when he died; but probably he was bornin Somerset, about 1214, and lived till he was over eighty.He is reputedly buried in Oxford, and it was in that citythat he is likely to have carried out his most notablescientific investigations. That he invented spectacles, leftthe earliest recorded formula for gunpowder, and pre-dicted the development of the aeroplane, are matters offact. The myths which surrounded him even in his life-time credited him with the creation of a brazen head whichtalked, and his contemporaries held him to be a necro-mancer. All these things apart, he was certainly a man ofunusual scholastic attainments and was accomplished inGreek and Latin, Hebrew and Aramaic. It was not,however, his prowess in physics or chemistry, nor theprophetic gifts which enabled him to foresee, for instance,

the steam-engine and the telescope, but Bacon’s criticismsof the medical profession that Sir John Charles made thesubject of his Gideon DeLaune lecture, delivered or

April 20 before the Worshipful Society of Apothecaries.There are, he pointed out, at least eight Baconiat

treatises associated with medicine. Four are conceme(with the related questions of the preservation of youththe retardation of old age, and the prolongation of lifeThree more are mainly pharmaceutical treatises, and tbeighth is the racy and-despite its title-the helpfull;analytical book, On the Mistakes of Physicians. All ar,written in simple, easily flowing Latin, and abound i]vivid phrases (Mundo senescente senescunt homines, ageinpmen in an ageing world: Bacon regarded old age as beginning when the prime of life was over, at about forty-fiv,or fifty; and, like Shakespeare, he recognised phases i]the period of declination, and speaks of three groups-the old, the elders, and the decrepit). None of the othercan approach the De Erroribus in originality of thoughtor pertinence of expression. But it is the production, athey all are,

" of a man of singularly practical mind, whiwas not in practice and had ... few opportunities ogetting certitude by experience ": and it is based upo]Galen’s system of medicine, as modified by Avicenna an,the Arabic physicians, and accepted without questionThere is, then, little in the work which can be regardedeven remotely, as clinical. There are none of those bedsidvignettes we find in the ancient writers, brief and sharptdrawn in the case of Hippocrates, copious and discursivwhen Galen is in charge of the patient. Nor is it merel;an indictment of, or a diatribe against, contemporarpractitioners. Its significance lies in its constructivcriticism of the system, then prevailing, of what wwould now call Medical Education.

Bacon listed six principal impediments to those whlstudied medicine. Certain of them, Sir John remarkedare as relevant today as they were in the 13th centuryThe first was an ignorance of language, which denied t(many readers the original text of their source booksA second was an ignorance among doctors of the drug!they used: they could not recognise them, accepted olcpreparations in place of newly compounded ones, ancwere put off with substitute or sophisticated remediesAbove all, they did not know what they cost. Anotheiobstacle to progress was the time wasted in futile argu.ments, and in the discussion of ill-defined problems, tcthe neglect of practical study. Bacon’s next complaintreflects his enthusiasm for astrology, and he held tha1through failure to enlist its assistance a physician wouldbecome unduly dependent on chance and good fortune.Neglect of another subject, alchemy, was the theme of thefifth protest, and the term alchemy included not only theinfant science of chemistry but also the whole of botanyand zoology. Finally, Bacon considered a number of realdefects in our knowledge, detailing in particular a lack ofprecision in diagnosing disease and in classifying it, ourignorance of a specific cure for many conditions, and ourinability to explain their causation. All these gaps, heargued, might be made good by investigation usingexperimental methods. And, though Bacon was, through-out his life, an important and influential advocate of suchmethods, nowhere else has he expressed himself moreclearly than in the pregnant final sentence of De Erroribus:" Neither the voice of authority, nor the weight of reasonand argument are as significant as experiment, for thencecomes quiet to the mind."