6155ARTICLESFURTHER ONE D OXFDCAMB MRCPDM OXFD FRCSG BM W ADELAIDE Sir - PDF document

1 6155ARTICLESFURTHER ONE. D. OXFDCAMB., M
6155ARTICLESFURTHER ONE. D. OXFDCAMB., M.R.C.P.D.M. OXFD, F.R.C.S.G. B.M. W. ADELAIDE, Sir William Dunn of Radcliffe briefly by Chain is here presented itsdevelopment to the stage isdescribed.Mouldwill grow and produce avariety of but used by (1932) is easy givesas a of as others containing horse-muscle This modified Czapek-Doxmedium consists g., KC10-5 FeS04.7H2O with hasas for has thethe mould medium, by sown asuspension sterile in screw-capped bottle containing a themould grown and freely. delicate be with difficulty bottom of The becomes voluminous the liquid layer thick, this the of and usually inparticularly around by day whole surface of themycelium, which 24hours appears begins turn first of theday growth The underwetted, brownish and lst day the culture-vessel isdisturbed the to glomerate ropes of of these only secondary growths ;this have should be for but not invariably may or.may not appear surface the mould, never them. colour of thebecomes faded changes mould by changes in the and 7 3 as the mycelium forming. reaching as the appears.At a theand traces penicillin can continues to titre of thebecomes more faded the rises it seldom 8-8. usually at about 7, may stant may The pH most useful of apart for The development be greater less than thatdepending largely depth of systematic study factors begun, not be completedowing to the very to fact that assay-method use large titre. Theconclusions, however, could be drawn :production seems over aoxygen mould grow2. satisfactorily C. At is harvesting thein have studied, being about limit his description statedand attempts to change the of or value resulted in incorporation oftimes of cm. cm. is visibly inadequate,for distinct layers upper yellow, the lower 5. the is fit to be off under the fresh which penicillin required for initial production. medium this 6. The must the under conditions isdestroyed by bacteria and 7. The of (Gladstone of mould not theIn large-scale growth have always in made contain but the 2%. of the yeast impaired prolonged or malt have the yield is greatly either by byhalving the of the 9. sodium is lactatethe 3 and ceases. 6-5 developmentpenicillin produced.nitrate wholly of muscle, glucose, withoutmaterially the penicillin.Occasionally or Although tamination in could not and the penicillin be variable and from batches, of had and none. of former and ninelatter were medium could between any of lines, the"mould The possi-due to mould was investigated, but found.lowest concentration penicillinthat prevent of isand to This its for chemical tions, the be would seems penicillin be partially on Seitzpads. method of adopted 178nutrient

2 agar seededorganism-Staphylococcus aureu
agar seededorganism-Staphylococcus aureus organism to flow the then for in the at 37’ C. rack Petri dish half lower part. the plates the and the one made from the dimensions]inset of fig. are The rlevel and has that the thin 14 penicillin sink into value concentration through assay seal. the size shape, the non-bevelled have proved fluid block at 370 C. placed the incubator shelves moisturemay lids of Petri dishes and thus the most has and by circular whereoccurred. the concentration the being shown in fig. 1. The this assayyet been fully followingpoints may be noted.of inhibition (which have called the " value ") when than it The assay value unaffected by the fested, strongly range inhibition is produced by saturated aqueoussolution of or by water free of hours, assay 14 of arethan after a the is cannot cylinders, if fluid is the bacteria to the is limits 7. assay value varies with different of For uneven seeding the be avoided.8. zone of surrounded ainhibition, a almost for, controlling, this phenomenon discovered.be assayedplasma serum must used, layer immediately top the which the leads low be this method assay, done in (preferably threedifferent if the is so as value of curve is probablythan : 25% considerably less.We evidence under suitable is inferior in to the serial dilutionand quicker. tion, of fluid required for each activity.-When to be made large introduced for the 7 a standard set on each plate theassay values be been using is made up saturated with ether in the It an average value mm. far can be seen has not months been use. have adoptedthe (until penicillin obtained chemic-ally 1 c.cm. of as this The in human tests contained of and many types tainers had shape and whichThe are on reduces easier to on top other. of a venient way in they can be for sowing so separated thebut space is the autoclave the be wetted.medium 1-7 a is set up medium is whichare a of2C. an testnottouched until is and re-FIG. culture penicillin-con- stacxea is and with fresh To fromeasy needs thorough precautions. Into hasten of we attemptedto firstsatisfactory that have some still ontrial and therefore be withdrawal culture-medium being sterile original the refilling simple pouring,finally introduced, beingconveniently carried " by the of a to hinged slabs on vessels raised rim -C prolonged into a on forward.The is not A, but athat on depressing handle D the vessel not merely but thesuctionthe of special E, twosterilised G. F sterilising, and through blown current (sterile) a faster thanJ. Macintyre porcelainassay 2. penicillium been Fleming 179fluid is tube G. and arecontrolled by the single trigger H of for every o

3 f four vessels changedtwo batches. Both
f four vessels changedtwo batches. Both tubes are and one end tube FIG. trolley. ’fitted the the paper use. From harvested passes in which filtered bag. The filtered to the collecting bottle not on pin aboutvessel to in are to manipulate and bottle medium.CULTURE Principle.-Penicillin from anto organic be re-phosphate-buffer is at room first must carried lowtemperature. solvent is some was. toweekly output of litres of the crudecontaining up hand A continuous extraction wascannot included this crude filtered and is special jetsit up togiven The isbefore jets, so that theaqueous a for few seconds before the is a surrounded destruction place. Phosphoric acidification as of the first dissociation it own buffer correlation ofthe solution big the con-tinuously column, from thean amount collected 1/10-1 5 of crude the been many been eliminated.used purified only tothe salt was at time active probablyhad 1/10 of activity peutic batch for injection manfirst on mice. mouse was injection in c.cm. became ill mg., though itrecovered in When intravenouslyto human 100 mg. of same materiala with a of inhour. other sameleft no doubt a pyrogenic in used of uniform weight little over 2 (67° the day food and is hourly. used 1 of about but " below) no purification described intravenous purification.-Batches of each as from with five amounts using baryta adjustpH The solutions have alreadyfor used order decreasing The further working but a sixth extract with so watery acetate, which may contain a small ofInthe of periodically removed extraction by thorough washing.extract shaking with about andThe other The acidified successive of ether ; extracts through Brockmannalumina. solid but which remains behind the chromatograms vary, zones can be their to some from top :1. dark whose depth the amount of for the decolor-and absent layer 2. the none of the pyrogen. -orange contains someof reddish-violet layer penicillin. column by passing successive smallamounts through into the fourth is discarded. Theothers with successive of M/15buffer the the the is back water using hydroxide to the the is greatest adding the alkali, for rapidlydestroyed alkaline " therapeutic which contains perhaps 80% throughextracted water, allbeen rinsed is adeep reddish-orange yellow dilute solution, witha but characteristic smell bitter 180Yields and crude medium, 1 and units thedried purified has units A of units, yield of 1 of peutic 45,000 units, so third of the is tracted form suitable injection.are occur far possible but owing to overlapping batches the working up and been to the losses accurately. Nobig loss, stage.Storage strong with ether quite

4 is stored refrigerator, or dried by lyop
is stored refrigerator, or dried by lyophilicthe of the sodium water ice-chest 3 months lose any barium dry at temperature desiccator retained its least In dispensing for venous that the solution most of be removedby suction before measured ACTION OF PENICILLINpurified a timescrude material employed able more the and of other important Method.-To mediumgraded of penicillinwere tube a series was inoculated standard drop of a 24 hours fluidculture investigation. the case-ofsuch as Staphylococcus culture was usually diluted 100 All done Complete absence of 24 hours thecontrol culture partial was clearly of . table species are in of but actual be taken reserve.As work progressed was becoming that in may sometimes lossof penicillin sterilised Seitz-needs only a few species have been tested one with a of whichobserved such cannot be place in the order they great be that the cutthe distinctions. andhave a variability sensi-to strains of thetypes. It likely an mental comparison effects two a wide of modes testing of was Owingstability growth of the it merely incorporate the the at outset.was in glycerol-broth,was added every days aas to maintain at the stated for14 days. well in Ahad already done by Dr. L.similar results.that even partialinhibition growth not delicate action. In somewhat dilutions is retarded, as has been (Gardner 1940), a the indicative defective fission, often macr.osco,piCj1lly virulence of it is the effect be peutic one typhi whereas the visible, inhibition at elongation microscopically to which may a therapeutic tofind questions TABLE OF PENICILLIN VARIOUS EFFECTS HAVE * Another strain inhibited up 32,000. Grown inhibition and strains appear at different in 181themselves inhibitory they do by penicillin-destroying enzyme has saprophytes commensals1940), aureus some months few daily subcultures increased the least nine weeks, with every a 7 weeks able a penicillin a times greater in while completely ingrew in 1000.expectation general- thein and activities. was with parent a ferment-substances, and was found although afterboth strains showed no in dulcitol ; liquefaction acid strain a lag, instead to lactose, 4 for mannitol, to coagulate milk. A reduction nutrient and also blood-agar delayed.strains gave a coagulase reaction.weeks) and end toin adapted strain enzyme in coccus. adaptedwas two batches20 rolled bottles, in obtain asufficient bacterial bodies to used bacterial and Thewashed off after fuged, centrifuged up to consistency. thenhours. was centrifuged at revs. for 20 thesign of penicillin-after this period. There is evidencethat the on the the In earlier discovering insusceptible is

5 power of containing non-inhibitory tion
power of containing non-inhibitory tion (1/400). a, rich of the and was dilutions on Staph. 1/500,000, which titre batch of could be Bact. caused anypenicillin.EFFECTS OF SERUM, the known products autolysis on action sulphon-amides, it to look for a penicillin. None, Serum.-To exclude such action the was with human and on by thedescribed above.modified the this then c.cm. of or on the top. atbelow the and abovethe of growth. A inoculum gave the results-e.g., broth diluted c.cm. of glucose with thusin comparison the water, both in the ofinhibition millimetres :23-24 (2) In water...... 22 23-24therefore, in way interferes with the and diffusibility the Whole two inthe whole blood, is enough say that one experiment a cillin 1 in Strep. pyogenes which, plated, producedper inoculated agreed that therewas regard to following failed to action.Some pus Staph. aureus incubated for 3 days at to " thin " it ; fugalisation the fluid withthrough Seitz ofof was added, making adilution 1/50,000. a thepus was Both drop c.cm.) of a 1/1000dilution broth culture aureus. of cocci in the inoculum the tubestaphylococcus the showed from and 20,in c.cm. that least most been sincethe of 1 in over 6million) was inhibit growth.similar experiment done sample urinewith to with coli In the 1/450,000 and The inoculum of was same due incubation the complete staphylococcalgrowth, the two weaker the of pus-broth occurred. titre the used the experiment gives noof ofliver from of Potter Elvehjem and the for 37° was no gas during the incubation noputrefactive smell the of The suspension had liquified it yellow obtained.fluid at hoursa solution (0-1 containing mg.the crude material. A peni-cillin was period.When after solutions assayed, found had destroyed of the penicillin.are devoid of antagonistic usual assay method agar containing peptonemedium for the CHARACTERISTICS ANTIBACTERIAL The penicillin strepto-staphylococci is that known, heavy the acridine &c.antiseptic ; it directimmediate bactericidal action. was observations. uptake of coccal any penicillin concen-tration 1/1000, period hours. incubation in containing penicillin 182colonies on only effect that we was of streptococci fluid 1/50,000 compared pure its action, resembles bacterio-sulphonamide on theiraware following significant power penicillin staphylococci much of the sulphonamides, when tested (small media, Saturated show completeon assay plate, penicillin gives appreciable zone.action streptococci lococci, that in-minor extent be the are lated millions of or aconcentration as low as the even This property for treatment heavily on which sulphonamide to have but little 3.

6 power of antagonised appreciable breakd
power of antagonised appreciable breakdownproducts tissue pus, bacteriostatic of the suppurating possible successful treatment of infections abundant place.EFFECT OF CELLSLEUCOCYTESis little that substances which bactericidal only to for their curative the organismswhile the are from In leucocytes " other bacteriostatic which present both and indebted to C. TheJessop Sheffield, sending details of leucocytes. solution has used, leucocytes solution containing urea0-3 glucose 1-61 g., NaH2P04.H2O 0-425 g.,KC1 g., MgCl, CaCl, g. alitre of 10% of serum added timeof the experiment. test substance diluted forthe addition of the serum. The control saltsolution and serum. The leucocytes came the donor as serum. of to coverslip the incubated C. 30min. in dish containing the red blood-cells away salt and the coverslip reversed solution. leucocytes stuck to and could under slide and kept atC. a controlled Penicillin, the flavines the sulphonamides were obtainedpowders and dissolved in the obtained the electrolytic use,contains % not was 30% solution the salt solution was as the given the solutionsthe salt 3 at C. the centrifuged the with Albucid beslightly when buffered than once ; sistent. range of used ments results dilution immediately ; 1/250 livedfor for which watched-but the survivors were the end.control. -hemisulphate) at 1/50,000.leucocytes but active for sameIn lower dilutions leucocytesstained of an and at by the of 2 hours.Leucocytes killed by 7-diamino-acridine monohydrochloride but 1/20,000at 1/8400 1 mixed bloodthe on slide- over form a film. ours it see discrepancyarises, of killed 2 hours were with activity.1/500 after 2 hours, showed only formation move-At i/1000 their all alive. gave and atremained active hours, they were watched. Sulpha-and of After some of the in sulphapyridine the preparations were thoughsome were inactive that the flavines with recent studies) suitable use concentration on lesions The strength for lethal it may beinactivated tissue. sulphon-amides general inhibitory leucocytes, which strengthens Penicillin is to than sulphonamides and should an admirablefor infected surfaces. might rapid further tests can is so.irrigation repeated would case the 1/500 appear vitro contrasts complete on and -in vitro at at It leucocytes inafterintravenous Complementary ’those on tissue P. Medawar of theZoology Department, us his employed had the,of inhibitory power drugs takes of the fact that tissues into a blood-plasma incubated tem-perature resistance to depends source cellular composition 183of the suppress fibroblasts ventricle for 24 hours at The from a each is of five ten grown in of the

7 medium. after it the the drug for total
medium. after it the the drug for total Results.-The for at this feeble is arrested after24th hour of andtoif the drug isprolonged. The concentration so examined bymethod, 1/6000, still toxic experiment for 48 each is thenfor hour Ringer and medium, it possible to give estimate of which standard just withstand 48 hours changesirreversible this concentration is 1/1200 than after48 subjection to 1/1600 are factnormal growth 3 or 4 a normal medium.to figures penicillin-1/800 minimum The are 1/120,000 1/250,000.action of embryo lung, kidney)be by small fragments of series of containing tissues coagula containingpenicillin. be obtained as 1/1000. Penicillin differentialfor epithelia ; . from a TABLE PENICILLIN ON BLOOD PHAGES A SINGLE GROWTH source, fibroblasts and the influence drug, grow.of magnitude of are to These may to than Significance culture only when they exertsecondary action, obscure antoxicity. exertsno reaction of this penicillin " highly actions identical, be taken to F. Jacoby, Birming-University, effects of cultivated table 11 penicillin in various macro-phages in vitro.appears toxic hen’s fibroblasts APPLICATIONThe effect central under inserted cisternal a few drops cerebrospinal had a burette containing1/1000 penicillin in normal saline to theofwas which caused rapidcerebrospinal the blood-streamwith consequent the the space. Weed (1922) showed underthe influence of fluid duced passed sheaths and of cerebral this instance c.cm. penicillin in minutes in After the cisternal anaesthetic had passed neitherfunctional histological by Dorothy Russell the thatthe and on the brainin 3 rabbits by had Falconer to discovered.results, taken in with and cultures, strongly theview local of quite OF PENICILLINhas penicillin is subcutaneous mice, urine have been further investigated rabbits,and always the of The have been compared intravenous, intestinal same As substance in not considered worthwhile study the adminis-tration into the observations normal and sorption from the tract beenstudied by direct penicillin thea man a standard dose experiments rabbit units. otherwisethe was catheter, the bladderwashed the were assay. necessary ansesthetic was to injection and theIn 1 received each After no detectable 184observed (one or hr.14% and 5-3% activewere afterthere no in 1 and 50 at hr.,hr. hr. yields in urine however, 44% and produced a the the twosamples hr. in the14-5% the rabbit after 1 none the since urine passed a cage activity may in of the was On the that the inactivated liver, were from portalvein and 20, intervals1 t no blood sample detected,urine end of 2 hr. of theinjected penicillin. Bile from

8 the common ducthaving showed up In aals
the common ducthaving showed up In aalso under penicillin injectedthe ear vein. wasa thebile were Aexperiment on the same result. The good return urine after intravenous a returnof 20% after administration the intestine.can detected in blood whatever given. excretion in bile. in the blood " loss "which appears to associated equivalent to thestandard penicillin three routes. a was the blood at -1 hr.(2 experiments} experiment) the urinethe intravenous and observed in the and and theand 52% of the Inblood cat taken half for ainjection, could detected seen of again.with nembutal tied. Penicillin injected the Activity the portal and blood taken hr. bile had 15 little second and was maintained duringsecond hour, similar inblood a 4 in the urine 6 the bile reached its in the urine showed small after decerebrated and prepared in way andhere the injection was given wasthe liver the whole 6 of the (only the the amount was the active cat anses-extended of ofintravenouslyhigh in bile for the not at all fifth. secreted also saliva, but here centration present in 1 the penicillin in the urine Cat 7prepared a result, the end of theproved inactive. that alone was inactive on plate juice did not the rabbitmaintaining an antibacterial concentration the least hr. after and intestinal differs the no doubt connected-inthe 50% of penicillin, route.In injection not used man,but from preliminary and from the casesa about the and administration. with that single of been given. The one subject intervals from until 2 hr. 5 min. after injection.to tracewas occurring min. was in a ofcollected 14th detectable in blood the endrepeated doses a found the blood an had five hourly 200 Thebest from the view estimating theonand 5, whose urine output measured the In total substance and 30% was actually recovered lost in process). which in saline of the antibacterial reappeared in theand 54% was recovered for further use.passed and duodenum fluoroscopy. thousand units (about mg. dissolved c.cm. of water were c.cm. water. this thebacterial 3 urinary 6 inhibitory level wassteadier persisted for after The dose was maximum it is quite that larger for by the intestinal route.Nevertheless the are is possible way penicillin.A wards penicillin rabbit one hand and giving 400 a rabbit no activity could inthe blood end an in the was for at least 1 the little the could the and considerable in the appears to more catthan Apparently rabbit a morefor the penicillin other two administered all substance appears in urine. " Incubation for at 37° penicillin blood and with kidney, lung andfrom no diminution of afterwith rabbit-bile, with is the material rec

9 overed in during a titre again into pati
overed in during a titre again into patients It is to that material passage body.OF PENICILLIN- uncer-of intestinal first Since and 185the was outset was felt intermittent give the sion tissues repeated tem-porary raising the the highest be administration of quantity.To frequent ainto vein connected to dripand Kekwick of 0-8% sodium Each penicillin was 2 c.cm. into the rubber dripand in with a little inconvenient owingto maintaining intra-infusion but itwas thought thatif therapeuticcillin method giving In case in1/1000 normaland as vein raised to The thiswell. Higher method of medication is the most is serious to stomach.It may be to the stomach the of Experiments as magnesium silicate described are required. strongly drug wasmaintained 7 giving it by together sodium bicarbonate. In this case we were up an antibacterial concen-in the urinary not in the of which willthrough stomach has not been butsome tentative experiments salol-coated were discouraging. LaWall stated that passed satisfactorily ; have while a scarce substance toadministration tried subject, substanceand that faeces probably by bacterialaction. was introduce strong of penicillin intra-owing uncertainty the More 1 which shown to innocuous of of fluid. 1 c.cm. intramuscularlycaused up quickly.IN 12, of from mouth a earlier. infection aureus; Strep. Sulpha-given from Dec. 19; drug-rash. Jan. incision on right showed on 1941, after 3 pain ; incised, gave Staph. aureus pus.eye ; cornea perforated Jan. 21.Eye 3. pints all this tongue heavily furred. right chemosis, Staph. aureus bothLungs w th pyogenic cocci. cells 1,800,000. Penicillin intravenously ; 3-hourly, intravenoustwo Slight after firstno reactions. 800 24 hours. scalp-discharge seemed before faint A.M.none. penicillin mg.Feb. 14:much fusion pints:100 injectioninto total inFeb. trans-fused mg. 3-fand white-cell in case had improvement ; 74%. Right left eye and arm. Shortage ofinterrupted from noon to 6 P.M. ; chloride being injected drip, 3-hourly ; no 17: g. days. felt of in face, scalpand coughing ; contained Strep.N. catarrhalis. right humerus stillsuppurating. Blood-urea 30 per 100 Condition days, deteriorated, Autopsy picture ofwith 12, (polymorphs 11,200; 18th, 11,000 (polymorphs 88%).attempt was it that could over of 5 a fall granular cells Apartthis effect, has not in subsequentand the slight inthe no use its since at and laterexperience showed that the dose penicillin administration well, andnot after 2.-Boy, aged 15. Admitted 29, forhaemorrhage of Proseptasinefrom Jan. to 3, two soluble intravenously and 9th, and twobut swinging 22 : looked over right discharging sero-pus. 6

10 2% ; cells 3,000,000 ; white cells (poly
2% ; cells 3,000,000 ; white cells (polymorphs Blood-culture Blood-urea 32 100 At 100 penicillin injected into 2-hourly After interval 100 mg. 186rigor ; Feb. general better, to purerstopped ; g. hadonly shown slight antibacterial Feeling condition 29 c.cm.White cells 8300 74%).pints. 26 : 3-4 almost normal treatment.samples in thishad been from thecase no The samples, shivers, third although had through ancolumn they The Here there localhæmolytic hadto todoses of therapyby patient’scondition, the dose being insufficientto maintain concentration penicillin con-tinuously the CASE 48, AdmittedMay in. scapula for now Staph. bronchial for Left 106% ; red cells May penicillin 200 for by into then hourly. Noactivity continuously much slight dropped to mg.2-hourly and 3-hourly. 10 : resolved ; axillary nasal mg. 6-hourly 4 dosesthen 90% ; cells white 37 mg. per c.em. normal. Temperature, which had kaolin poultice sulphate for hours dry as skin carbuncle almost neuritis cleared quickly, from arm 23,000 19,200 ;19,800; In concentration of maintained the no rapid resolution the without without formation. additionchronic and were cleared.white count on the 5th days spite the beingthrombosis from left face measles 5 before. Had in before admission. urine (fig. 6a), left, proptosis.Complete bilateral external dioptresof papilloedema ; Kernig’s sign andboth Liverfinger-breadths gave a under III).citrate saline 10 9 days,the site changed times). 100 mg. for four doses, then mg. hourly. May pus made into Staph. aureus. ray : opacity antrum, blood an hour dose showed no increased hourly. improvement. better ;swelling subsided. May FLUID OF after fluid stood hours.general condition (see responsesreduced Smallcorneal eye treated penicillin 1 caused 22 : with Chest pyrexia due inthromboses injections May 26 : progressTemperature General excellent.only patch consolidation and shadow to signs condition no A.M. vomited and had generalLumbar under necksign spastic 28 :May 29 : g. in died Autopsy T. Robb-Smith).-Brain showed nomain venous sinuses ; adhesions haemorrhage old andregion and cerebellum due toof artery. oedematous carotid partiallyoccluded b ythrombus cavernousandin bony scat-air-cysts yellowishmembrane;FIG. (a) beginning of treatment ;(b) llth treatment.material not Histologically whether in lung tissues regionssmall of containing around a granulation formed ofhistiocytes containing and neutrophil 187this vascularised there in periphery. cavernous region of contain organising and to be infected, but as large breaks elastica thesebe probably of organschange.autopsy that the had been almost overcome, and that we

11 ll advanced.due ruptured andto recrudesc
ll advanced.due ruptured andto recrudescence accident the patient restored from amoribund condition apparent Nothe noticed.Staphylo-early of fall 6 days grew aureus. Given g. between with little benefit. 17: hip-joint explored, contained little sterile poly-urine. Embolicrash. Extension by traction X neck destruction Dis-charge ill, temperature tomuch in and contained74% ; cells Blood-mg. per infusion and white-cell in penicillin normal c.cm. anhour. Infusion 90 during which 3-5 in blood. improved. June tenderness. transferred veinand (1 in 13 sudden risestemperature without apparent cause ; traced ofmonths and penicillin recovered boy’s used.another50 then 4-hourly for Stopped June dosage 29 mg. June red cells of quite July extension removed. afebrile No pain in leg. hip almost full.White 11,400 ; 12th, 7500 ; 13th, 9400 ; 14th16th, 8400 ; 17th, 7600 ; 18th, 6200 ;11,800 ; 12,400.This case of staphylococcal localisingin hip-joint, which been of early stages. extremely had the casesthere striking improvement period in region cleared histemperature to normal. the time there in ORAL CASE 6.-Boy, 6 Admitted 1941. fortnight with general-in skin. (x 40). ’vn’all of " lipoid-containing wall vascular which there large numbers of lipoid-containing lymphocytes only tissue the of lipoid-containing plasma-proliferation.cells 50many cells). 60 per contained pus ; and but becausec.mm. After ammonium mandelate remained. 3 :cells cells (polymorphs 600). mg. perc.cm. June attempts to duodenal tube by 2 sodium bicarbon-3 then 3-hourly. specimensof urine bacteriostatic concentration ofpenicillin. pus reduced to 3-hourly. Vomited 2-3 times daily.June polymorphs up to1000 per per c.cm. Junepenicillin June blood’-urea mg. 70% ; cells June sterile though and casts and red dition to still aureus.This case to maintain aconcentration penicillin the by Although the obscure doubt of urinaryinfection by Staph. the this infection.LOCAL APPLICATION THE In 4 1/5000 penicillin to a It caused no and of eye improved. eye on in Eye Hospital.aged corneal of the 4 byArgentum, boracic lotion mercuro-ultraviolet In ulcer 3 later similar ulcer right6 then as but without and upper quadrantsof conjunctiva considerableeye with 1/5000 dropped hourly by day 188by been application bag fit eye solution run New bag eachabout 8 began refilling After day ofon concentration of penicillin of day eye greatlyconjunctiva slightly and cornealopacity remained, con-smaller. 1/2500 one day increased which caused June 9 (8 ulcer stained with but still injection.with of 1/500 penicillin, but June 20 : healed, residual had weekaged Burnt her admission ; burn became

12 and rash over Week admissionred, swolle
and rash over Week admissionred, swollen small impetigo-like spots bothof conjunctiva as with day eye-not almost of by and by 13 :On and June 1/500 in hydrated lanoline When on June 15 completely slight residual of 2 in some penicillin solution was to who told to drops the solution by CASE 9.-Man, aged eye with acid and argentum, painting lids silver Only given drops ; next 2 treatment June whencomplete.CASE 20. Developed muco-5, with lotion and lids nitrate. Penicillin on June and almost 4 cases, proved therapeutic in rapid relief pain and inflammation. In ill Discussionin has been assembled that combines astriking two agent-low toxicity Its multiplication covers of including some of the and which man may be infected, thisaction is no interfered by bodyfluids only a extent very efficacy chemo-is it aIn spite large-have enough material try a few cases. Cases 4, been forms of chemotherapy and some also by surgery. fact, further to could be proposed. Case all the tempera-the general and local improved.of it case administration penicillin. The only toxic seen due could and in spirits in the local applicationhas tried, it given been but many points which investigation supply of penicillin.Enough now to a new and chemotherapeutic and properties hitherto Summarydescription is given the other for of penicillinby and material peutic use on the and The material excreted in concentration in urine a cats’ less in rabbits’ has low toxicity sub-directly to toxic attributable " therapeutic cillin " injected crude penicillin which by suitable shown that the growth in vitro of many pathogenicis prevented purified dilution ofone more, that others degrees of sensitiveness, some being quite resistant.Proof is inability tissueto prevent of aureus to the been beennot be due to the penicillin-destroying enzyme.A the penicillin reasonsare why be to operatewhen ineffective.of in infections proved possible aconcentration of symptoms. intravenousa large substancerecovered from again.Pencillin five patients staphylococcal infections to baby with infection. It locally fourcases infection. all favourable therapeutic work E. Chain W.Florey. biochemical part of wascarried the E. P. Abraham.N. G. the andM. W. have conducted biological mentioned A. Gardner somespecial observations the growth of M.Fletcher (of the Nuffield has charge the the work to its stage been the concerned. wish physicians surgeons who placed their at ourto work technicians, adequate supplies ofcould have Callow, S. Cresswell, G. M. P. Vincent.indebted to a Foundation providing and foot 189PENICILLIN : P. and 837A., P. and H. J. Path. 41.V. H. and D. E. (1940) Med.

13 Florey, G., J. A. P. R. H. (1932) Bioch
Florey, G., J. A. P. R. H. (1932) Biochem. Cook, F. LaWall, 8th ed. G. A. J. Wigodsky, H. intern. Med. 67, Fleming, exp. Path. 10, A. Nature, Gladstone, G. P. and (1940) J. exp. 21, 161Medawar, P. B. and Willmer, E. N. In C. and A. (1940) Brit. Rogers, and Fleming, Lancet, H. 193.Medawar, B. (1940) roy. Soc. 129, V. C. A. J. Chem. D. Falconer, M. A. 472.Physiol. DRY HAMILTON BAILEY, F.R.C.S.SURGEON TO THE NORTHERN To soak infected apply can be borne are methods ofpostoperative in the medical time for to Let (the disadvantages It extremely remember dreadingtime my own fomentations, whichapplied at by hot. *swelling tenderness the the applications, due extension infected consequently accurate diagnosis of the pus delayed. in to causing pain, to and of uninfected (d) Sodden, tend to can METHODDuring the past ingly impressed dryof treating The bestway will to quote the of surgical tenosynovitisof from trainedpossible to contrast compare more ordinaryenlightenment.to four begun. had the back of index a the the finger thatpatient them u c hpain had diagnostic to observers.the tenoeyno-vitis because patient can nex the finger; it farbe completelyextended by voluntary By saw was had sulphonamidethe but the tem-the wereso great that septicaemia feared. waspulse-rate By palpation with a the of tenderness could be definedclearly over flexor surface of of second Kennon, 1929, med. J. 1934, anaesthesia sheath and corresponding both were and proximal sheath. Apiece of Gamgee length Cramer wire bandaged the piece between the Cramerdorsum of incised finger a which did not fixit atbase of the finger,carried the palm.sound bandaged to The to arm end of theCramer The that the com-and tempera-dressingnot should the positionthe be altered 48 day ofin shoulder;eased somewhatthe pillows, to lowered.the dressing was and the paste reapplied. about hand throb, patient was glad again, the the report the was to a pure ofthe uninfected back Cramer wire, were whose general condi-improved tofingers turn of While this dry, is a About vaseline drainis into antiseptic and washed. If are wound is irrigated ; is then dried reapplied. Whether the vaseline gauze drain replaced or the arm for 20days. 1 duringthis period the bandage was undone rays. 21st she up. wound of all the uninfected thethe cases I have for infectinga streptococcus. time thatchanged wet to the mightit was ing great benefits which haveaccrued therapy but case reported here adequate dry advance ; unlikely this my dry after-treatment uniformly informs me and of find is unsatisfactory. suchcases Sister Wray changes to what known " " about 48 hours. immobilised, 4 dressings a