925MEDICAL SOCIETY FOR THE STUDY OF VENEREAL DISEASES.

mixed infection with B. coli and B. proteus. Alkalinetreatment encouraged the B. proteus while acidsencouraged B. coli. If the patient happened to getan unconnected tonsil or throat infection the kidneycondition became much worse at once, though thereason for this was not known.

MEDICAL SOCIETY FOR THE STUDY OFVENEREAL DISEASES.

A MEETING of this Society was held in the roomsof the Medical Society of London on April 24th,Colonel L. W. HARRISON, the President, being in thechair.

TOXIC EFFECTS OF ARSENOBENZOL TREATMENT.

Mr. DAVID LEES opened a discussion on the toxiceffects of arsenobenzol treatment and their prevention.He said that these toxic effects, both after intravenousand intramuscular injection, were produced in manyways, and many factors entered into consideration.The chief determining factors were the health of thepatient prior to administration, the preparation ofthe patient, the drug used, the method of preparing itin solution, and the technique of administration.Physical exertion on the part of the patient, especiallyjust before or after administration, might play apart in some of the reactions that were observed.The daily regulation of the bowels, again, was essential.With regard to the drugs, the " 606 " group were moretoxic in general than the " 914," and in the case of" 606 " it was very necessary to be careful and slowin administration. Indeed, in all the drugs given forthe treatment of syphilis this slowness in administra-tion was an important factor. He was a strongbeliever in dilute solutions, and he believed also infiltration. There was no doubt that any undissolvedparticles would open the way to accidents, which mightbe avoided by using completely soluble preparations.In a great many patients psychic reactions occurredat the first administration ; they could be overcomeusually by careful technique and by having the patientin the lying posture. The fact that the beginning ofthe injection caused pain to the patient might set upfainting and other minor reactions. Some patients,no matter what precautions were taken, would reactadversely to either intravenous or intramuscularinjections of arsenic. He discussed the variousreactions, first those which occurred immediately onor after administration or within the first 24 hours,and then those which occurred later, up to a period ofmonths. In the immediate reactions were includedheadache, vomiting, and diarrhoea. It was probablethat more than one cause was present in the acutereactions which occurred after treatment with Iarsenobenzol. In his own experience, with care in the Ipreparation of the drug, and especially in the dissolvingof the drug, its filtration before use, and its slownessin administration, the incidence of the immediatereactions, both minor and major, was exceedinglysmall. Occasionally a sensitive patient was encounteredand it was necessary to consider what steps shouldbe taken to safeguard him. Mr. Lees found thatwith atropine desensitisation there was less likelihoodof the patient having cardiovascular upset than withadrenalin. Of the reactions which occurred within24 hours, skin eruptions, such as herpes and urticaria,were of little importance except as danger-signals.Special care should be taken to watch the kidneys ofsuch patients. He spoke of vasomotor disturbancesand gave particulars of cases.With regard to later reactions, albuminuria often

presented considerable difficulty. Was the albuminuriadue to drug therapy or to syphilis ? Only by waitingand watching could one possibly decide. One of themost interesting reactions was a gross exfoliatingdermatitis. There were certain individuals who hada special idiosyncrasy of the skin to therapeuticirritants, and these showed undoubtedly a greater

tendency to such a condition. From the experienceof the past ten years he could not agree with theobservation that the joint exhibition of arsenicaland mercurial therapy predisposed to the onset ofdermatitis. There was no actual proof that thedermatitis was due to over-excitation of the tissuesby metallic arsenic, as suggested by McDonagh, andone was left to assume that it was due to hyper-sensibility to arsenic on the part of the patient.Patients made a slow and uninterrupted recoveryunless complications set in. Of the complications themost dangerous was broncho-pneumonia, while otherswere peripheral neuritis and jaundice. If these com-plications could be avoided the prognosis was good.The drug most useful in the treatment of this conditionwas one of the sulphur compounds. In arsenicaldermatitis the Wassermann test frequently becamenegative and might remain negative for a considerabletime. Some workers had stated that such a patientnever again showed any manifestation of syphilis,but this he believed to be very dangerous teaching.With regard to jaundice, many considered that thiswas due to the toxic action of arsenobenzol on the livertissues. The predisposing factors were constipationand intestinal toxaemia. A very considerable numberof the mild cases of jaundice one met with were notdue to the salvarsan, although that might be a con-tributory factor, irritating, as it did, the mucous surfaceof the intestinal canal. It was a small matter forthe inflammation to extend from the bowel throughthe biliary tract and set up a liver condition. In otherwords, salvarsan was more likely to injure the liverin a person infected with syphilis who, in addition,had an intestinal toxaemia and a possible predispositionto catarrhal jaundice. For treatment, rest in bodyevacuation of the bowels, and careful dieting werenecessary, also the administration of alkalies inassociation with salicylate of soda, glucose givenintravenously, and - a diet rich in glucose. As aroutine procedure he had recently been giving 50 c.cm.of glucose by the mouth to every patient half an hourbefore treatment with arsenic. This fortified theliver against the arsenic action, and he had had veryfew cases of catarrhal jaundice.

In conclusion, he emphasised the great necessity ofcareful preparation of the patient for administrationand careful examination, especially of the urine, priorto administration. Next he emphasised care in dosageand in the technique of administration. Alcohol mustbe avoided throughout the whole course of the treat-ment. As to the amount and frequency of the drug,moderate doses should be given with a safe interval(one week), the average course of injections extendingover eight weeks and the intervals of rest eight toten weeks. Except in the early stage of the disease,heroic therapy by massive doses was not of so muchvalue as moderate, safe, and prolonged dosage. Intra-muscular administration was to be preferred to intra-venous, especially in the later stages.

Dr. J. C. BUCKLEY said that in his clinic for thefirst two years, while the novarsenobenzol was of theold " Rochester Row pattern" not a single case ofjaundice occurred, but during the last five years hehad seen about 120 cases of jaundice, all of them verymild, except one, which proved fatal, the patient dyingfour and a half months after the administration of thedrug. Of these 120 cases about 20 occurred amongpatients who had been put down as provisionally cured,having had a negative Wassermann for two years,and coming up every six months or so for a provocativedose or a test. As to dermatitis, the worst case heever saw was long before " 606

" was introduced.

Dr. T. ANWYL DAVIES thought the most importantlesson to be gathered was that the prophylacticagainst arsenical intoxication was intramuscularadministration. In addition this had greater thera-peutic value, and undoubtedly brought about anegative Wassermann sooner than did any otherform of administration.

Dr. FONVLER WARD said that he had had formerly agood many cases of stomatitis, but now he made a

926 BRISTOL MEDICO-CHIRURGICAL SOCIETY.

practice the first week of giving arsenic and the secondweek of giving mercury intramuscularly with thearsenic, and since then very few cases of stomatitishad occurred.

Dr. D. N. NABABBO did not think that the psychiceffect could be attributed to the drug itself. He foundat Great Ormond-street that the same children weekafter week were sick after injections, and one nervouschild used regularly to vomit before the injection wasstarted. Recently he had been treating an adultcase who had malaise and nausea after each intra-venous injection of arsenic ; he tried intramuscularinjection of bismuth, and the patient stated that hehad the same symptoms. Vasomotor disturbanceswere very rare in children, and when they did occurhe thought they were due to too big a dose for thesize of the child. Jaundice was also very rare amongchildren. Some years ago he had one case of dermatitisoccurring after a fourth injection of novarsenobenzol ;the rash appeared on the first or second day afterinjection. Unfortunately, the child was not broughtdirectly back to the hospital, but was taken first toan outside doctor. When later it came to the hospitalthe rash looked exactly like measles. The child wastaken into a special observation ward and died.

Dr. H. C. SEMON had had one case of dermatitis,but never a case of jaundice. He was surprised thatfor the treatment of jaundice Mr. Lees did not suggestthiosulphate of soda ; he had himself found that drugvaluable.

Dr. C. H. MILLS said that in the earlier days of" 606 " patients were prepared as for a major operationand were starved. This course had been proved to beerroneous, and now patients were not starved; theywere told to avoid physical exertion and the use ofalcohol, and constipation was corrected. What wasstill wanted was some reliable test which could beapplied in the out-patient department for the detectionof intolerance.

The PRESIDENT said that he had previously venturedthe opinion that the use of thiosulphate as a prophy-lactic might interfere with the therapeutic action ofthe remedy, but he now desired as the result of furtherwork and consultation to retract that opinion. He.also emphasised the effect of cold in increasing thepredisposition to dermatitis.

Mr. LEES, in reply, urged that it was a very soundprocedure to filter the solution in intramusculartherapy; it made for less pain and discomfort.He said it was more desirable to bring the patient’sgeneral health up to the highest possible level thanto fill him up with salvarsan or its substitutes.

Clinical Cases.Dr. H. M. HANSCHELL showed two clinical cases.

The first was a Chinese seaman with ulceratinggranuloma of the penis. The other was a European,about 30 years of age, who, four and a half monthspreviously, had primary syphiloma on the prepuce,and the Sp. pallida was found. The Wassermanntest was doubly positive; there were no secondarysymptoms. After five intravenous injections atweekly intervals of stabilarsan, totalling 2-7 g., andfive weekly injections of bismuth in glucose suspension,totalling 1 g., he developed severe purpura coveringthe trunk like a bright purple jersey. The liverbecame enlarged 3t in. below the costal margin, thespleen 2 in. below. There was no fever or malaise,and the patient insisted on continuing his work, whichwas that of a carman. There was no albuminuriaor glycosuria, and the Wassermann was still doublypositive. Treatment was suspended. A weekpreviously he developed jaundice. The urine was ofdeep orange colour, there was no bile, no albuminuria,no glycosuria, the liver was not tender (though it wasstill 3 in. below the costal margin), the spleen wasnot palpable. The purpuric area was now stainingbrown. When first seen four and a half monthspreviously there were abdominal pains. On palpationof the abdomen at that time no enlargement of liver Ior spleen was detected. I

BRISTOL MEDICO-CHIRURGICAL SOCIETY.

A MEETING of this Society was held at the Univer-sity, Bristol, on April 8th, Dr. J. 0. SYMES, thePresident, in the chair, when Mr. A. RENDLE SHORTread a paper on

Diagnosis of the Dyspepsias.His observations were based on a series of 100 casesof non-malignant dyspepsia, all studied on a definiteplan, all verified by operation, and mostly followedsubsequently. The growth of accuracy in the diagnosisof dyspepsia was due to : (a) Better knowledge ofphysiology; (b) disregard of haematemesis as a

diagnostic point; (c) watching the movements of thebowel by means of X ray screen ; and (d) betterclassification. Knowledge of physiology had grownin several ways. It was now known that both thehypersthenic and the hypotonic types of stomachmight exist in perfectly normal persons. In theformer, the viscus emptied quickly ; such persons wereapt to have an excess of acid, and were " hungryfolk." On the other hand, achlorhydria was notnecessarily a sign of disease, any more than wasvisceroptosis. Again, we now knew that nervous,reflex mechanism controlled the sphincters of thealimentary canal, so that delay in any one part mightupset matters all along the line, and produce symptomsreferred to a region distant from the actual site ofthe disease. Thirdly, minute lymph nodules werefound especially along the lesser curvature of thestomach; these might ulcerate and bleed. Haemat-emesis might be the only symptom of disease, orthere might be dyspepsia due to causes outside thestomach and duodenum, accompanied by dangerousbleeding, or finally there might be bleeding froma chronic ulcer. In the series, 1 in 3 of the gastricand duodenal ulcers were accompanied by bleeding,and 1 in 6 of the cases of appendicular dyspepsia.Mr. Short said that he classified dyspepsia as (1) func-tional, (2) organic, or (3) reflex. Functional did notmean hysterical, but disturbance of function, as withacute and chronic gastritis of alcoholism, dyspepsiaof phthisis, anaemia, anorexia nervosa, and so forth-all these were the province of the physician. Thereflex dyspepsias were (a) gall-bladder dyspepsia-flatulence and vomiting prominent, the vomitingcoming especially after certain foods, alkalies did nothelp, there was often some gastric delay ; (b) appendixdyspepsia, pain is usually not very severe, was

continuous, but worse after food-often vomit withoutrelief of pain; (c) undiagnosable reflex dyspepsia-pain and vomiting were not related to each otheror to food.

Organic disease of the stomach or duodenum mightgive rise to several types of dyspepsia : (A) Gastriculcer. These cases tended to show a definite sequence,thus-food, relief, pain, vomiting, relief. The relieffollowing a meal tended to be rather over half anhour. The pain was severe and vomiting the rule.A test-meal was useless in diagnosis, but X raysmight give great help. If later pain becamecontinuous and was felt in the back, pancreaticinvolvement might be suspected. (B) Duodenalulcer. Vomiting was less common, only half the casesshowing it. Relief obtained by food lasted usuallyover an hour. The pain was severe. Test-meal wasof little service, though hyperchlorhydria was therule, but deformation of the skiagraphic duodenalcap was characteristic when seen. The stomach usuallyemptied rapidly, but this was a cause rather than aconsequence of the ulcer. (C) Duodenal ileus mightoccur by itself or be a symptom of other disease.Flatulence and nausea were marked, vomiting wascommon, pain was not severe, and the relation tofood was obscure. The skiagram might be definite,showing great delay and distension of the second andthird parts of the duodenum ; duodeno-jejunostomybrought about a cure. (D) Periduodenal adhesionsmight give rise to bad pain, even after taking water.! Vomiting was usual, bleeding absent. The X rays