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Bismuth preparations were most promising 1

because bismuth is less toxic than the arsenical r

compounds when given by routes other than the i

intravenous, and therefore its administration icould be more safely left in the patient’s hands 1for a limited period. The search seems at last ;

to have been successful. lIn 1937 HANZLIK, LEHMAN and RICHARDSON 1 (

introduced a preparation called Sobisminol, anorganic compound of bismuth obtained by theinteraction of sodium bismuthate, tri-isopropanol-amine and propylene glycol and containing about20 per cent. of bismuth metal. Experimentalwork indicated that this substance was readilyabsorbed from the gastro-intestinal tract and wastolerated in sufficient dosage to produce as largean excretion of bismuth in the urine as that whichresults from ordinary intramuscular injection ofbismuth or its salts. Moreover, sobisminol takenby mouth seemed to be as effective as otherbismuth preparations given intramuscularly in

causing the disappearance of Treponema pallidumfrom surface lesions and in healing these lesions.Two recent studies by MEININGER and BARNETT 2and by SCHOLTZ, McEACHERN and WOOD 3 haveconfirmed these findings. MEININGER andBARNETT found that the optimum daily dosagewas six capsules each containing 0-2 g. of the drug.In all 192 patients were treated but in only 143of these was it possible to assess the antisyphiliticeffect; 49 took their capsules irregularly or failedto cooperate in other ways. All were treated asoutpatients, and it was therefore necessary to relyon the patients’ statements as to how regularlythe capsules were taken. Attempts were madeto check this evidence by estimating the bismuthcontent of the urine and blood. The resultsvaried widely and there was no discernible rela-tionship between concentration of bismuth in theblood and therapeutic effect. The drug was welltolerated by almost all the patients. About athird of them complained of slight gastric dis-turbances, and a few had diarrhoea or transitorystomatitis, but in only 5 was it necessary todiscontinue the drug because of severe gastro-intestinal reactions. Sobisminol alone was givenfor the first fourteen days to 14 patients with sero-positive primary syphilis and 37 with secondarysyphilis and cutaneous lesions. Patients withsero-negative primary syphilis were given otherremedies as well so as not to jeopardise theexcellent prognosis which is the rule in such cases.In 11 cases of primary syphilis the sores healedin from two to fourteen days; in the other 3

healing was estimated as 90 per cent. after four-teen days. In 26 cases of secondary syphilishealing was complete in from four to fourteendays. In the remaining 11 the average degree ofinvolution at the end of fourteen days was 70 percent. Daily scrapings of the lesions were car-ried out in 33 cases and in 29 of them treponematadisappeared from the surface lesions in an averageof about four days ; in the other 4 the organisms1. Hanzlik, P. J., Lehman, A. J. and Richardson, A. P. Amer. J.

Syph. 1937, 21, 1.2. Meininger, W. M. and Barnett, C. W. J. Amer. med. Ass. 1939,

113, 2214.3. Scholtz, J. R., McEachern, K. D. and Wood, C. Ibid, p. 2219.

were still present at the end of fourteen days.The routine adopted made it impossible to esti-mate the effect of the drug on the serum testsin these early cases. A further 28 patients withlate cutaneous lesions were treated with sobis-minol alone for from one to twelve weeks until

healing was complete, and 73 with late syphilisof various kinds received the drug alone for periodsof from four to seven months. No satisfactoryassessment of these results was possible but posi-tive serum tests were reversed in a few casesand some of the patients recorded subjectiveimprovement. Comparison was made between aseries of patients treated with Neosalvarsan andsobisminol and another in which intramuscularIodobismitol was combined with neosalvarsan.No particular difference was found in clinical orserological response or in the proportion of laterserological and neurological relapses. SCHOLTZ,McEACHERN and WOOD regard four capsules, or

0-8 g. of sobisminol, as an adequate daily dosage.Their results in 90 patients corresponded roughlywith those Of MEININGER and BARNETT. Of their3 patients with gummatous changes in bones ormucous membranes 1 failed to respond to thistreatment but the other 2 healed in about fortydays. Another group of 23 patients were sufferingfrom various forms of late neurosyphilis. In mostof these there was some improvement of symp-toms and in 10 the symptoms were almost com-pletely relieved.No full assessment of any antisyphilitic drug

is possible in less than a period of years, butmost of the present evidence suggests that thisbismuth preparation given by mouth is as effectiveas those given intramuscularly. There are

obvious reasons why it is unlikely to replace itsintramuscular counterparts for routine use. Toomuch reliance would have to be placed on thememory and intelligent cooperation of the patient,and regular skilled observation is essential to safeand effective antisyphilitic treatment. For thesame reasons it would be unsafe if such a prepara-tion were open to unrestricted purchase by mem-bers of the public. But given the properrestrictions there is an important though limitedplace for it in the treatment of seamen and thelike, who because of their work are unable toobtain regular treatment, and those few in whomintramuscular bismuth produces enough localtissue reaction to cause serious discomfort or

pain. Another possible field for this drug is in thetreatment of inherited syphilis in young children.

MENIÈRE’S DISEASETHE symptom complex of vertigo, tinnitus and

deafness is a fairly common affliction, although itis not often disabling. Each of the symptoms canvary in intensity independently of the others andwithout relation to the prognosis—CHARCOT’s dic-tum that the vertigo ceases when the deafnessbecomes absolute is a fallacy. The name" Meniere’s disease " was formerly attached tothe condition although nothing was known of itsmorbid anatomy or pathological natural history,but later it was thought that a number of widely

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differing causes could provoke the symptoms andthe cautious physician and otologist began to

favour " Meni’ere’s syndrome," or if giddinesswas the most prominent feature " aural vertigo."The pendulum is now swinging back and thebelief is growing that a large group of the cases aresuffering from a clinical entity, a chronic pro-gressive disease of the labyrinth, the remainderhaving more or less accidental lesions of that

organ. Several independent methods of investi-gation-biochemical, clinical and histological-have been responsible for this reaction, and mostof the information about the pathology hasresulted from empiric attempts at treatment.The first biochemical approach was made by

S. H. MYGIND and DIDA DEDERDING, who havepublished their findings in a series of papers dat-ing from 1924. They started with the premisethat the disease resembles glaucoma and is a

hydrops of the labyrinth; they therefore tried torelieve the acute attacks by a dehydratingregimen. In this they were often successful, butthe treatment did not strike at the root of thetrouble they postulated-namely, the cause of alocalised accumulation of fluid in the labyrinths ofpatients with otherwise normal metabolism.However, a break with the surgical tradition hadbeen more or less successfully made and an

impetus given to thought and experiment alongfresh lines. Adopting this same premiseFURSTENBERG and his colleagues 1 showed that theadministration of sodium salts to these patients,causing water retention, often precipitatedattacks. Thev devised a treatment based on adiet poor in such salts with the periodical additionof ammonium chloride and obtained favourableresults as did other otologists who tried it.TALBOTT and BROWN 2 have investigated the acid-base constituents of the blood in 48 patients beforeand after a period on this diet. In all but 4

(where the serum-potassium was raised and thesodium lowered) the concentrations of sodium,potassium, calcium, chlorides, carbon dioxide,phosphate, protein and non-protein nitrogen werefound to be normal. In the 4 exceptions theblood was examined actually during an attack.These findings seem to rule out the idea that thesymptoms are produced by gross retention in thebody of water or sodium chloride, because if thiswere so one of three changes should be present.There should be an increase in the sodium andtotal fixed base concentration with an unchangedwater and protein content; or a diminution ofsodium and fixed base concentration with an

increased water and protein content; or a decreasein concentration of protein without a change inthe sodium and total fixed base concentration. Toconfirm their findings TALBOTT and BROWN

deliberately produced the first of these conditionsby administering massive doses of sodium salts to4 patients without however succeeding in inducingan acute vertiginous attack. To explain the clini-

1. Furstenberg, A. C., Lashmet, F. H., and Lathrop, F. Ann.Otol., &c., St. Louis, 1934, 43, 1035.

2. Talbott, J. H., and Brown, M. R. J. Amer. med. Ass. Jan. 13,1940, p. 125.

cal benefits obtained with the diet they stressedthe importance of the potassium content of theblood, since it has been observed to vary in certaindiseases in which the conduction of nerve

impulses is disturbed. In normal diets the propor-tions of sodium and potassium are about equal,but in the Furstenberg diet a relative increase inthe potassium is unavoidable. Since this diet istherapeutically beneficial they investigated theeffects of a normal one together with an extraamount of potassium. After eighteen months theywere able to assert that this was a successfulmethod of treatment. Its precise action isunknown. The conduction of a nerve impulse isperhaps associated with an optimum concentrationof potassium. In 4 cases they found that duringan attack the serum-potassium was high, indi-

cating its loss from the tissues (by analogy witha high serum-calcium), and it seems reasonabletherefore to try to compensate for this loss. In

addition, the diuretic effect of potassium causesan increased excretion of sodium and water, repro-ducing the condition obtained by a low sodium dietand ammonium chloride. The clinical resultswere confirmed by WALSH and ADSON 3 and themethod clearly has fruitful possibilities.

Clinical data have been provided by a numberof workers. From observations on patients beforeand after division of the eighth nerve CROWE 4concluded that the attacks in this disease are dueto abnormalities both in the normal pressure andthe chemical constitution of the endolymph. Hesuggests that the mode of action is excitation, ahyper-function of the labyrinth, but his argumentis not convincing. However, he is certain thatthe symptoms are produced by a specific andcommon cause. WRIGHT 5 agrees, although hearrives at the conclusion by a different route. Hehas studied about 100 cases and has found a focusof sepsis in a large proportion of them. Hebelieves that a bacterial intoxication of the laby-rinth which he calls " focal labyrinthitis

"

resultsfrom this focus, and has found that eradication ofthe sepsis is followed by cure. Although otherotologists have not observed so high a proportionof cases with septic foci they recognise that thistype of case does exist and to this extent theyconfirm the validity of WRIGHT’s S hypothesis.Again, DANDY 6 has divided the eighth nerve inwhole- or part (vestibular portion) in a largenumber of these cases without a single death andwith almost uniform cure of the vertigo, althoughnot always of the tinnitus. This places the originof the symptoms in Scarpa’s ganglion or in thelabyrinth. CHEATLE suggested many years agothat decreasing the intra-labyrinthine pressuremight cure the symptoms, as he was struck bythe clinical resemblance to glaucoma. LAKE ’[

demonstrated the accuracy of this deduction, andMOLLISON showed that destruction of the labv-rinth by alcohol cured the vertigo, although it

3. Walsh, M. N., and Adson, A. W. Ibid, p. 130.4. Crowe, S. J. Medicine, 1939, 17, 1.5. Wright, A. J. Proc. R. Soc. Med. 1937, 31, 87.6. Dandy, W. E. J. Amer. med. Ass. 1937, 108, 931.7. Lake, R. Lancet, 1904, 1, 1567.8. Mollison, W. M. Proc. R. Soc. Med. 1935, 28, 1597.

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also destroyed the hearing. These findings placedexactly the seat of the disease and showed thatthe intra-labyrinthine tension is an importantfactor, as well as possibly the chemical constitu-tion of the endolymph.

’ An opportunity recently arose of correlatingthese biochemical and clinical observations withthe morbid anatomy. Such an opportunity is

rare, for the disease is not fatal and when deathoccurs from other causes there is rarely anyoneat hand sufficiently interested or knowledgeable tosecure helpful information. Here, however, 2

patients with these symptoms succumbed to theoperation of intracranial division of the eighthnerve and their temporal bones were removed andexamined microscopically. 9 The labyrinths ofanother patient dying of secondary haemorrhageafter an intranasal antrostomy were similarlyinvestigated.10 In each case the chief finding wasa dilatation of the endolymph system affectingchiefly the scala media and saccule. In addi-tion, the soft connective tissue surrounding thesaccus endolymphaticus was absent, and thistissue is thought to be the site of absorp-tion of the endolymph. The stria vascularis inthe scala media (the supposed site of formation of

9. Hallpike, C. S., and Cairns, H. Ibid, 1938, 31, 1317.10. Hallpike and Wright, A. J. Ibid, 1939, 32, 1646.

the fluid) is relatively unharmed histologicallyand perhaps even less so functionally since its

blood-supply is arranged so that it is protectedagainst a rise of pressure in the duct. Thus adefect in the absorption rather than the productionof endolymph is indicated as the cause of the raisedtension. It is possible that the formation of anabnormal endolymph of high ionic concentrationcould lead to an increase in endolymphaticpressure by osmosis from the perilymph throughthe membranous walls. But in any case, oncesuch a pressure exists anoxaemia of the end-organswill result with a lowered functional condition ofthe labyrinth. A relatively slight increase involume of the endolymph would result in a verygreat increase in pressure, consequent asphyxia ofthe end-organs and thus an attack of vertigo. Thematerial for examination is still scanty, but theargument is both consecutive and feasible.Applying these principles to treatment, we canchoose between the diet suggested by FURSTENBERGand modified by TALBOTT and BROWN, and thevarious surgical methods, decompression of thelabyrinth, its destruction, or intracranial divisionof the eighth nerve or its vestibular portion. It isperhaps wise to try the simpler and safer beforeproceeding to the more complicated and hazardousmeasures.

ANNOTATIONS

RATIONING OF MEAT

LAST Mondav meat was added to the list of rationedfoods. No-one can now spend more than Is. 10d. inany week on what is called butcher’s meat. A childunder six can only have 11d. worth. The restrictionwill hit quite severely those of us who are in the habitof eating freely of sirloin and steak. There is anattractiveness about the more select parts of the bovinemusculature, such as psoas and erector spinec and evengluteus maximus. But as a seasoned broadcaster hasalready told the listening public the hardship is

unreal, for the dietitian can make up a complete menuwithin the rationing scheme. The only real hardshiphas already been met by allowing the diabetic to

exchange his unwanted sugar for an additional rationof flesh. Many kinds of animal protein are in factnot rationed at all: there is poultry and game forthose who can afford it, rabbit and excellent fat fishfor those who cannot. And there is always cheese.Pies and puddings and sausages are exempt if theycontain no more than 50 per cent. of meat by weightand, for the first month at least, cooked meats will besold free of coupons. Actually it seems doubtfulwhether, as in the case of bacon, people generally canafford to buy up to their total meat ration, and theenhanced price of the cheaper cuts and the edihleoffals is something of a calamity. One has a feelingthat some readjustment may be necessary in the lightof experience, or this last stage of rationing may presshardly on poorer folk. The physiologist might criticisethe allocation from another angle. There shouldhave been some consideration for age. Most peopleover 50 and all over 60 would have been better withhalf a meat ration; the other half might well havebeen allotted to the young adults in whom the urge toeat flesh is strong, especially when they live outdoorlives.

A NEW VASODILATOR

BB HEX new substances with chemical structuresallied to that of an active drug are studied by pharma-cologists their actions are often found to be qualita-tively similar to that of the original drug, but theresults are more interesting when new actions appear.The study of a number of substances containing theiminazoline ring, which is similar to the iminazol ringin histamine, by Hartmann and Isler has shown that2 benzyliminazoline, which is known by the tradename of Priscol, has actions superflcially similar to,but fundamentally different from, those of histamine.Like histamine, it dilates small blood-vessels and thisaction is illustrated very effectively in an article byR. Meier and R. Müller’2 of the Ciba laboratories bycoloured photographs of the pads of a dog’s foot, of adog’s nipple and of a rabbit’s conjunctiva. Wheninjected iiitrai-eiiously, priscol causes a short-livedfall of blood-pressure and an increase in the blood-flow to a dog’s leg. The action has not yet beenstudied in full detail and it is not known whetherthe vasodilatation is confined to skin and mucous

membranes or whether all tissues are equally affected.Histamine causes similar effects by dilating capillaries,but priscol dilates small arteries and this effect, unlikethe corresponding effect of histamine, is particularlywell shown in experiments on rabbits. It also causesthe erection of hair, and comparatively large dosesstimulate isolated plain muscle and isolated heart andconstrict the coronary vessels. Priscol is most effectivewhen given by intravenous injection, but it is alsoactive when injected by other routes or when givenby the mouth. Strong solutions, locally applied, dilatethe vessels of a rabbit’s cornea for several hours and

1. Hartmann, M. and Isler, H. Arch. exp. Path. Pharmak. 1939,192, 141.

2. Schweiz. med. Wschr. 1939, 29, 1271.