MAY, 1951Vol. 4. No. 2.
JOURNAL OF
CLINICAL PATHOLOGY
EDITED FOR
THE ASSOCIATION OF CLINICAL PATHOLOGISTSBY
A. GORDON SIGNY
ENTORIAL BoARD
E. N. ALLOTr R. J. V. PULVERTAFT
J. V. DACIE DOROTHY S. RUSSELL
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And the Editor of the Britihb Medical Journal
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J. cilin. Path. (1951), 4, 243.
ABSTRACTSThis section of the JOURNAL is published in collaboration with the two abstracting
journals, Abstracts of World Medicine, and Abstracts of World Surgery, Obstetrics andGynaecology, published by the British Medical Association. In this JOURNAL some ofthe more important articles on subjects of interest to clinical pathologists are selectedfor abstract, and these are classified into four sections: bacteriology; biochemistry,;haematology; and morbid anatomy and histology.
BACTERIOLOGY
Synthetic and Fermentation Type Chlor-amphenicol (Chloromycetin) in TyphoidFever: Prevention of Relapses byAdequate Treatment. SMADEL, J. E.,BAILEY, C. A., and LEWTHWAITE, R.(1950). Ann. intern. Med., 33, 1.
A continuation of the studies on the useof chloramphenicol (" chloromycetin ") inthe treatment of patients with typhoid feverindicates that the synthetic form of the drugis as efficacious as the natural antibioticobtained by the fermentation process fromStreptomyces venezuelae. The same totalamounts of either type drug are equallyeffective when given in divided doses at 2- to6-hour intervals or in larger doses once ortwice daily.
There was a definite relationship betweenthe duration of chloramphenicol treatmentand the occurrence of relapses in typhoidfever. Slightly more than half of thepatients who were treated for 8 days or lesshad a recrudescence of the disease whichbegan about 10 days after treatment wasstopped. No relapses occurred in the groupsof patients treated for longer periods of time.The present data suggest that a 14-day periodof treatment is sufficient to prevent relapses.In spite of the dramatic therapeutic effective-ness in patients with typhoid fever, seriouscomplications such as intestinal haemorrhageand perforation may be expected in treatedpatients since the stage is generally set forsuch developments before therapy is insti-tuted and time is required for the healing of
Q*
the typhoidal lesion of the intestine. In thepresent group of 23 patients, 2 had haemor-rhage sufficiently severe to produce shock.Two other patients suffered intestinal per-foration; the course in one of these wasfurther complicated by severe haemorrhageand the disease terminated fatally. Neitherof the patients with perforation was givensurgical treatment; chloramphenicol therapycontrolled or suppressed the usual signs ofgeneralized peritonitis.On the basis of the present observations,
it would appear that the adequate treatmentof typhoid fever in the adult consists of aninitial oral dose of 3.0 to 4.0 g. of chloram-phenicol, followed by 1.5-g. oral doses givenevery 12 hours during the febrile period andby single daily 1.5-g. doses for 7 days; there-after the dose may be reduced to a single1.0-g. dose and continued until the 14th dayof antibiotic therapy, after which the drugmay be discontinued. Particular attentionshould be given to the recognition of intes-tinal perforation in treated patients, sincethe classical signs of this development withthe ensuing generalized peritonitis may bepartially masked by the antibacterial effectof chloramphenicol.-[Authors' summary.]
In vitro Activity, Absorption and Excre-tion of Chloromycetin. TUNEVALL, G., andFRISK, A. R. (1950). Scand. J. clin. Lab.Invest., 2, 162.
Using 0.05 ml. of a 10- 3 dilution of 18-hourcultures as inocula, the authors comparedthe effects of chloramphenicol (in brain-heart infusion) in vitro with those of
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aureomycin (in thioglycollate broth). Chlor-amphenicol was assayed in the brain-heartinfusion medium, with a strain of Klebsiellapneumoniae (sensitive to 0.4 Vg. per ml.) astest organism. With 8 strains of Gram-positive organisms, aureomycin was some 30to 100 times more active and with 8 strainsof Gram-negative organisms (except forProteus vulgaris) some 5 times more activethan chloramphenicol.
Single oral doses of 1 g. chloramphenicolgave maximum levels in blood in 1 hour(10 jig. per ml.) and the antibiotic had dis-appeared in 24 hours. With 1 g. 8-hourly, amean level of 4 to 10 ptg. per ml. in blood wasattained. Urinary excretion was also veryrapid, 80% being excreted in 4 hours, andexcretion was complete in 8 to 12 hours.Conjugation starts rapidly and the antibioticis largely excreted in the urine in the inactiveform. Thus chloramphenicol is absorbedand excreted more rapidly than aureomycin,and the optimum interval between oral dosesshould be 4 hours. Malcolm Woodbine.
A Case of Brili's Disease in London.HAWKSLEY, J. C., and STOKES, E. J. (1950).Lancet, 2, 97.The history of Brill's disease is given.The present authors describe the case of a
woman aged 49 who developed a febrileillness, with headache and pains in the limbs,which was treated with sulphadimidine(" sulphamezathine ") without effect. Thesymptoms had not changed by the 8th dayof illness, when the patient was admitted tohospital. The temperature was then 1020 F.(38.90 C.) and there was suffusion of theconjunctivae, but no rash was present andthe spleen was not palpable. Her tempera-ture began to fall after admission to hospitaland was normal after 8 days. The patientwas born in Poland and had typhus there in1915; she migrated to Berlin in 1919, andto London in 1939. A tentative diagnosis ofBrill's disease was made and investigations(blood count, blood culture, faeces culture,agglutination tests, etc.) were undertaKen.All were negative except the Weil-Felixtests, in which an agglutination titre of 1 in700 to Proteus OX19 antigens was obtained
on the 16th day of illness, subsequentlyfalling rapidly. Samples of serum were sentfor further investigation to Felix, whoseopinion was that the marked drop inthe OX19 titre was to be accepted asconfirming the clinical diagnosis. Speci-mens of serum were also sent to Wash-ington for rickettsial agglutination andcomplement-fixation tests, the reactionsbeing reported as " definitely epidemic intype and . . . consistent with a diagnosis ofBrill's disease."
A Note on a Case of Brill's Disease inLondon. FELIX, A. (1950). Lancet,2, 99.Apart from one case reported by Mooser
and Loeffler in 1946 in Zurich, all thereported cases of Brill's disease haveoccurred in the coastal towns of the north-eastern United States. Although the major-ity of cases have been in Jewish immigrantsfrom eastern Europe, the incidence is notlimited to any racial group. It seems likelythat the disease will occasionally be seen inany country whose population includes anappreciable proportion of persons previouslyexposed to louse-borne typhus.The clinical diagnosis of Brill's disease
is not easy, as the disease is alwayssporadic and the clinical course milderthan in the primary attack of louse-borne typhus. In the present case thepatient did not even develop a rash, whichis the most helpful of the few diagnosticsigns. Laboratory tests are indispensable fordiagnosis, and, although agglutination andcomplement-fixation tests became availablerecently and are valuable in differentiatingthe varieties of typhus, the case underreview shows clearly that it was possible toconfirm the diagnosis by the use of theProteus OX19 reaction; incidentally, itbecame positive at an earlier stage than therickettsial agglutination test.
It is important, however, that the Weil-Felix test be standardized by internationalagreement. The customary use of Dreyer'stechnique is unsatisfactory because of theheat-lability of 0 agglutinins. The propertechnique entails the use of round-bottomed
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ubes and incubation at 370 C. (Felix, Trans.R. Soc. trop. Med. Hyg., 1944, 37, 321).How great is the need for standardization isshown by results published by Murray et al.(J. Amer. med. Ass., 1950, 142, 1059), whonoted that only 3 out of 14 sera from patientswith Brill's disease gave a diagnosticagglutination titre in the Weil-Felix test.The indications are that the techniqueemployed was unsatisfactory, dilutions aslow as 1 in 10 being used. In the Londoncase the tests carried out in two laboratoriesshowed a fourfold difference in titre.From the epidemiological point of view
Brill's disease is of interest as a possiblesource of dissemination of louse-bornetyphus, and, in view of the widespreadepidemics of this form of typhus during thelast war and the subsequent movement oflarge groups of people from one country toanother, the disease may come into promi-nence in many parts of the world.
J. V. Armstrong.
BIOCHEMISTRY
Plasma Protein Studies of 200 Cases ofy-Hyperglobulinaemia and their ClinicalApplication. WUHRMANN, F., WUN-DERLY, C., and DE NICOLA, P. (1950).Z. klin. Med., 147, 73. Bibliography.
Electrophoretic analysis of sera in 24cases of myelomatosis revealed a signifi-cant decrease in y-globulin mobility com-pared with eight normal sera. In 23 casesof hepatic disease, tuberculosis, or malig-nant disease, there was no change.Electrophoretically homogeneous y globu-lin was prepared in eight cases of myelo-matosis, by methanol precipitation of thesera at pH 6.8, in the cold. Extinctioncoefficients, at 280 mrA. and pH 2 and>12, differed widely, lying above andbelow the normal. These results supportthe hypothesis of the heterogeneity of the'r globulins. In the electrophoretic pat-terns, the peaks of myeloma y globulinwere steeper and narrower than corre-sponding peaks in other diseases. Theauthors consider the shape of the peak to
indicate the degree of heterogeneity of they globulins, the ratio of height to widthof base (Q) decreasing with increasingheterogeneity.Out of 800 sera analysed by electro-
phoresis, 200 had a raised y-globulin con-tent, that is, this globulin formed morethan 20% of the total protein (normal =14 to 18%). In each case, the diagnosisand the figures for protein and Q arerecorded. In 150 cases the cadmium sul-phate turbidity test and Weltmann calcium-chloride heat-coagulation test were per-formed.
In myelomatosis, y globulin forms about40% of the total protein, the amount ofthe latter being also raised. The cadmiumreaction is positive and there is a markedshift to the right in the Weltmann reac-tion. The empirical protein reactions arestrongly positive. The erythrocyte sedi-mentation rate is typically raised and Qis increased, this change being almostpathognomonic.
In malignant disease all three globulinfractions increase, but there is a subnormalor low value for total protein. The cad-mium reaction is positive and there is ashift to the left in the Weltmann test.
In alcoholic cirrhosis of the liver theamount of y globulin is moderately in-creased while those of a and f8 globulinare slightly raised. The cadmium reactionis positive and the Weltmann test shows awidened range of coagulation. In acuteinfections a globulin increases in amountas well at y globulin. In chronic infectionsthe results are variable. M. Lubran.
Serum and Urinary Potassium in SurgicalPatients. SNYDER, C. D., and SNYDER,H. E. (1950). Arch. Surg., Chicago,61, 62.In 38 consecutive surgical cases involv-
ing major operation (including 15 on thegastrointestinal or biliary tracts) and fiveinvolving minor operation, completeanalyses of the blood, urine, and gastricreturn were made at frequent intervals:whenever possible, the plasma potassium
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concentration was determined 24 hoursand 12 hours before operation, imme-diately after operation, and then 24-hourly until a normal level was reachedand every 48 to 72 hours thereafter duringthe remainder of the patient's stay in hos-pital. The clinical management of thepatient was not altered in any way andparenteral fluids were given in accordancewith the usual routine; potassium therapywas not given unless it was consideredessential [presumably on biochemicalas well as on clinical grounds].A plasma potassium level below
3.8 mEq. per litre was found [at one ormore readings?] in 26 cases. The levelsat different intervals were extremelyvariable, sometimes fluctuating widelybetween one estimation and the next. Of26 cases in which the immediate pre-operative and post-operative plasmapotassium levels were determined, in 13there was a rise after operation, and in13 a fall. The lowest average reading inthe 38 major surgical cases was 3.25 mEq.per litre, and the highest 4.97 mEq. perlitre. [Presumably these averages refer tothe complete period of study for eachpatient.] It is apparent, therefore, thatany conclusions drawn from the averageplasma potassium values in the differentperiods studied would have no value.Urine volume and urinary excretion ofpotassium also tended to vary ratherwidely; the urinary excretion rates forwater were higher, and for potassiumwere lower, than those reported by otherworkers. The nearest approach to a setpattern of reduction in plasma potassiumvalues associated with a rise in urinaryexcretion of potassium was exhibited bythe six patients who had undergonecholecystectomy. Potassium therapy hadbeen considered essential (and had beengiven) in seven of the 26 cases in whichhypopotassaemia was found; the clinicaland biochemical findings indicated that itcould have been given with advantage in11 other cases. Clinical notes with graphsare given of some typical cases, includingthree in which potassium therapy could be
regarded as life-saving. The series in-cluded many elderly patients and a numberof poor operative risks; infusion therapycould not be considered a factor in thethree deaths which occurred.In a series of cases in which plasma
potassium values were determined less fre-quently, levels below 3.8 mEq. per litrewere found in 9 of 30 patients under-going operations on the biliary tract, andin 8 of 42 other surgical patients. In all,100 major surgical cases were studied. Itis concluded that " studies on surgicalpatients have clearly demonstrated thenecessity for a knowledge of plasmapotassium levels in the management ofcomplicated surgical cases."
[The authors of this important papercould have been more informative. Howmany of the patients, for instance, showedone or more plasma potassium levelsbelow, say, 2.3 mEq. per litre in the im-mediate post-operative period?]
Joseph Parness.
The Effect of Diethylstilbestrol on theCalcium, Phosphorus and NitrogenMetabolism of Prostatic Carcinoma.SCHILLING, A., and LASZLO, D. (1950).J. clin. Invest., 29, 918.
The metabolism of a patient with diffuseosseous metastases from a carcinoma ofthe prostate was studied before and duringfour months' oestrogen therapy at theMontefiore Hospital, New York. Urinaryand faecal excretion of calcium, ab-normally high before, decreased duringtherapy, and the calcium balance changedfrom negative to positive. The serumacid-phosphatase level fell markedly; theserum alkaline-phosphatase level roseslightly. Nitrogen and phosphorusmetabolism was little affected. Thetheoretical phosphorus balance, based on anitrogen/phosphorus ratio of 15:1 and acalcium/phosphorus ratio of 2.2: 1, wascalculated. Throughout the period therewas retention of phosphorus, unaccount-able theoretically, which was less aftertreatment that before. P. Mestitz.
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Hypercalcemia in Osteolytic MetastaticCancer of the Breast. SWYER, A. J.,BERGER, J. S., GORDON, H. M., andLASZLO, D. (1950). Amer. J. Med., 8,724.
Working at the Montefiore Hospital,New York, the authors of this paper havestudied a series of 71 patients withosteolytic bone metastases from cancer ofthe breast. In 10 of these they observeda syndrome, consisting of gastro-intestinaldisturbances, mental changes, and renalinsufficiency, which was associated withhypercalcaemia. In these 10 cases theserum calcium content ranged from 12.3to 20 mg. per 100 ml., whereas theserum inorganic-phosphorus and alkaline-phosphatase levels did not consistentlyvary from normal. The patients frequentlyshowed evidence of dehydration, and an
elevated blood urea-nitrogen level and im-paired renal clearance were found in allcases. The authors believe actual bonedestruction by the tumour to be the mostimportant factor in the development ofthe hypercalcaemia, but they discuss otherfactors, including immobilization and renalinsufficiency, which they regard as contri-buting factors.Treatment took the form of restriction
of calcium intake and improvement ofhydration by the parenteral administrationof fluids, with sodium citrate in some cases,
to facilitate calcium excretion. Althoughthe ultimate prognosis was not affected,response to treatment is described as fre-quently dramatic, and was associated withthe return of serum calcium content andblood urea level to normal.
H. A. Sissons.
Regulation of Sodium Excretion in Nor-mal and Salt-depleted Subjects. BLACK,D. A. K., PLATT, R., and STANBURY, S. W.(1950). Clin. Sci., 9, 205.
The osmotic stability of the body fluidis maintained by keeping the serum sodiumlevel constant. This level is kept constantby a renal excretion of sodium which
effectively compensates for changes in thesodium intake and in the amount of sodiumlost by sweating. It has hitherto been be-lieved that the amount of renal excretionis influenced by serum sodium level andthe glomerular filtration rate (GFR)Xwhich in turn depends on the sodium load-presented to the kidney for excretion. Theauthors, by studying the excretion ofsodium and other substances like chloride,bicarbonate, potassium, urea, sulphate, andphosphate in normal and salt-depleted sub-jects, were unable to confirm this hypo-thesis. They found that, in all subjects, in-crease in the sodium load which directlyaffects the GFR did not lead to increasein sodium excretion even after the serumsodium level and inulin clearance had beenraised to normal figures or figures abovenormal. This means that sodium re-absorption occurs in the tubules whichmust, therefore, play a significant part indetermining the amount of sodium excre-tion. The authors found that in salt-depleted subjects sodium reabsorption wasnot only greater but also more prolonged,and was maintained for a few days. Theytherefore believe that the slowness withwhich the readjustment to normality takesplace suggests that a hormonal mechanismmay be concerned, and that there may bean overproduction of adrenal corticalhormones during salt depletion. [Fullexperimental plan and methods are givenand the results are well tabulated.]
S. Karani.
HAEMATOLOGYThe Relationship of Polycythemia Vera toLeukemia; A Critical Review. [InEnglish.] SCHWARTZ, S. O., and EHRLICH,L. (1950). Acta haemat., Basel., 4, 129.Bibliography.
The whole literature relating to the co-incidence of polycythaemia vera andleukaemia is critically reviewed, but only30 cases out of the 83 reported in theliterature are accepted by the authors asadequately proved. In 25 of these 30
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cases irradiation treatment had been givenfor polycythaemia before leukaemia becamemanifest, in three others such treatmentmay have been given, and in another theleukaemia developed at the time of startingradiotherapy. In only one case of poly-cythaemia did leukaemia undoubtedlydevelop without any previous irradiation.The type of leukaemia which develops
in cases of polycythaemia after x-raytherapy may be either of the acute or ofthe chronic granulocytic type, whereas inall those cases recently reported of leuk-aemia following treatment of poly-cythaemia with radioactive phosphoruswere of the acute granulocytic type. Theauthors regard the evidence of a causativerelationship between irradiation and thedevelopment of leukaemia as proven.
A. Piney.
Microscopic and Histochemical Studies onthe Auer Bodies in Leukemic Cells.ACKERMAN, G. A. (1950). Blood, 5,847.Auer bodies were found in the abnormal
leucocytes in 16 cases of acute monocyticleukaemia and four cases of acute myelo-genous leukaemia out of a total of 185 casesof acute leukaemia occurring in the haema-tological clinic at Ohio State Universityduring a period of 34 years. Histochemicalstudies were made on blood specimens fromseven of the cases of monocytic and threeof the cases of myelogenous leukaemia,the method including the examination ofsupravital preparations both by direct andphase contrast microscopy. The stainingproperties of the Auer bodies are des-cribed. It is suggested that they are formedby the fusion of newly formed " normal "cytoplasmic granules which take place inyoung cells in which the granules are ofa relatively acid pH. P. C. Reynell.
Myeloid Metaplasia. BLOCK, M., andJACOBSON, L. 0. (1950). J. Amer. med.Ass., 143, 1390. Bibliography.Twelve cases of myeloid hyperplasia
seen within a period of 18 months are des-
cribed. In two cases the condition occurredas the terminal stage of polycythaemia andin three cases as a result of carcinoma withskeletal metastases ; two cases were asso-ciated with tuberculosis, one case was dueto sclerosis of the bone marrow, and fourappeared to be " primary." The clinicaland haematological features correspondwell with those already described in theliterature. The bone-marrow findings werevariable; only in one case was myelo-sclerosis generalized, but in six of them onesternal puncture failed to produce enoughcells to make adequate smears. In thehyperplastic marrow the erythroblast wasthe dominant cell, in marked contrast tothe findings in leukaemia. The importanceof hepatic and splenic biopsy examinationin diagnosis is stressed. Extramedullaryhaematopoiesis was demonstrated by thesemethods in every case in which they werecarried out. The differential diagnosisfrom leukaemia is discussed in detail.[This is a lucid review of a subject whichoften causes difficulty.] P. C. Reynell.
Nine Blood-group Antibodies in a SingleSerum after Multiple Transfusions.COLLINS, J. O., SANGER, R., ALLEN, F. H.,and RACE, R. R. (1950). Brit. med. J.,1, 1297.
A Connecticut woman aged 40 years hadtwo pregnancies, the first ending in tox-aemia and premature stillbirth, and thesecond in normal delivery. At this timesplenomegaly was noted, which was saidby the patient to have been present for 12years. No abnormality was found onexamination of the blood on three occa-sions. Four years later splenectomy wasperformed, the spleen weighing 1,100 g..after which anaemia developed and twoblood transfusions were given. During thenext 12 years the patient was given afurther 18 transfusions for anaemia due toosteosclerosis, and on four occasionsdeveloped a transfusion reaction. On ex-amination of the patient's serum, nineblood-group antibodies were found, asshown in the following table:
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System Pheno- Genotype Antibodies intype ye the Serum
ABO .. 0 00 Anti-A and anti-BMNS .. MsMs MsMs Anti-N and anti-SRh .. CDe/cde or Anti-E and anti-Cu
CDe/cDeKell .. K- kk Anti-KLewis*.. Le(a- b-) ?LecLec Anti-Lea and anti-LebP . . P- ppLutheran* Lu(a-) LubLub
* See Andresen et al., Nature, 1949, 163, 580.
Of these antibodies, those to E, Kw, C,Lea, and S were probably immune inorigin and the remainder naturally occur-ring. It is surprising that among thiswealth of antibodies, five of which are veryrare, no anti-P was found, since the patientlacked the antigen P and she must surelyhave received some P+ blood.
John Murray.
Multiple Antibody Response to RepeatedTransfusions. MALONE, R. H., andCOWEN, J. (1950). Brit. med. J., 1, 1299.A woman of 64 received transfusions of
blood from 24 donors "compatible" inrespect of A, B, 0, and D blood antigens,as a result of which she developed anti-bodies to E, M, and P. The authors statethat routine methods of cross-matching areinadequate to detect the rarer antibodies,and that special techniques should be em-ployed in cases of repeated transfusion.They suggest that a search for rare anti-bodies in the sera of patients who havebeen repeatedly transfused with so-calledcompatible blood will reveal that these anti-bodies are of much more frequent occur-rence than is generally believed.
John Murray.
Dangerous Universal Donors. II. FurtherObservations on in vivo and in vitroBehavior of Isoantibodies of ImmuneType Present in Group 0 Blood. ERVIN,D. M., CHRISTIAN, R. M., and YOUNG,L. E. (1950). Blood,. 5, 553.The authors describe the occurrence of
severe haemolytic reactions in three group-A (sub-group A1) individuals on transfu-sion with group-O whole blood or plasma.In one case 10 ml. of a commercial pre-paration of soluble A and B factors had
been added to 500 ml. of whole bloodbefore transfusion. The anti-A antibodiesdemonstrated in the donors' serum fixedcomplement, acted as haemolysins, weredifficult to neutralize with soluble A andB factors, and were capable of giving apositive reaction to Coombs test, whiletheir ability to agglutinate group-A erythro-cytes was enhanced by normal humanserum. In other words, they had thecharacteristics of antibodies observed inserum from donors known to have beenactively immunized against the A factor byprevious transfusion of group-A erythro-cytes, by transfusion of A factor, or bypregnancy. A history of such a stimuluswas, however, lacking in the case of thesedonors. Small amounts of immune A anti-body were consistently demonstrated in 12of 100 random samples of group-O serumwhich, after neutralization, gave indirectpositive Coombs tests with A. erythro-cytes and agglutinated Al erythrocytes sus-pended in compatible normal humanserum.The authors conclude that there is no
longer any justification for regardinggroup-O blood as universally safe fortransfusion purposes. They stress that,while outward clinical manifestations ofa haemolytic reaction may be slight, thelaboratory findings may be dramatic. Theaddition of group-A and group-B substanceis not at present sufficient to render allgroup-O blood safe, and they suggest thatall group-O blood should be screened.Many dangerous donors would be elimi-nated if their serum, diluted 1 in 50, 1 in100, or 1 in 200 with saline, were testedwith a saline suspension of group-A andgroup-B erythrocytes. If group-O plasmawhich in such dilution failed to agglutinateerythrocytes of either group were neu-tralized with soluble A and B factors, somereduction in hazard would be achieved.Tests of neutralized serum against group-Aand group-B erythrocytes suspended in therecipient's own serum would serve as anadditional precaution in selected cases,especially those receiving multiple transfu-sions from universal donors.
Janet Vaughan.
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Coagulation Defects associated with Pre-mature Separation of the NormallyImplanted Placenta. WEINER, A. E.,REID, D. E., and ROBY, C. C. (1950).Amer. J. Obstet. Gynec., 60, 379.
The authors suggest that alterations inthe blood coagulation mechanism may beassociated with premature separation ofthe placenta, and investigations on threesevere cases of this condition are described.
In the first case described the bloodcomponents were normal one week beforeseparation of the placenta. Three hoursafter separation, and without rupture ofthe membranes, the fibrinogen plasmaand prothrombin levels were 50% ofnormal and there was evidence of a cir-culating fibrinolysin. The blood findingswere normal again three days after de-livery. In the second case the plasmafibrinogen value four hours afterplacental separation was one-third ofnormal. There was a spontaneous increase20 hours after rupture of the membranes,and a further increase due to blood trans-fusion at delivery. The prothrombin acti-vity, which was 80% after the onset ofsymptoms, fell to 30% at delivery, but alsoimproved with transfusion. A circulatingfibrinolysin was present before artificialrupture of the membranes. In the thirdcase the coagulation mechanism was nor-mal four hours after placental separation.Two hours later, in spite of transfusion,fibrinogen was absent, prothrombin activitywas diminished, and a circulating fibrino-lysin was present. There was persistentbleeding after delivery, with no sign ofclotting. A total of 2,400 mg. of fibrinogenwas given intravenously in solution over
a period of half an hour, and bleedingceased. The blood fibrinogen level hadrisen by then to 187 mg. per 100 ml.The authors believe that the changes
in the coagulation mechanism followrather than precede premature separationof the placenta. In 15 other patients,apparently bleeding from a partial separa-
tion of placenta, the coagulation mechan-ism was normal. It is felt that there is
a need for a rapid test which will detecta critical reduction in blood fibrinogenconcentration, and observation of the sizeand stability of the clot in a sample ofincubated venous blood is suggested as a
suitable test. Transfusion of 1,500 ml. ofblood, with the addition of 2,000 to6,000 mg. of fibrinogen, is an importantpart of treatment when clot stability isinadequate. Margaret C. S. Binnie.
Investigations on the Role of Plasma Cellsas Antibody Producers. [In English.]GORMSEN, H. (1950). Sang, 21, 483.
The existing evidence for the globulin-forming function of plasma cells is brieflyindicated. In a study of sternal marrowfrom 800 patients with diseases other thanmultiple myelomatosis the author foundthat a plasma cell count of more than 5°%was invariably accompanied by hyper-globulinaemia. In patients with a serumglobulin level of more than 3.5 g. per100 ml. the converse was almost alwaystrue. Earlier work showed that rabbitshyperimmunized with polyvalent pneumo-coccal vaccine responded with an intensegeneralized plasma-cell proliferation. Theantibody content of tissue extracts was
related to the number of plasma cells inthe tissue. " Stilbamidine," although pro-ducing specific myeloma cell inclusions inpatients with myelomatosis, did not appar-ently interfere with antibody formation inexperimental animals. M. McC. Giles.
MORBID ANATOMY ANDHISTOLOGY
Multiple Cancers: Primary in the Lungand Other Sites. CAHAN, W. G., BUTLER,F. S., WATSON, W. L., and POOL, J. L.(1950). J. thorac. Surg., 20, 335.Among 1,493 cases of primary carcinoma
of the lung observed at the MemorialHospital, New York, over a period of 24years, 25 cases (1.6%) of multiple primarieswere encountered, two tumours being presentin all but one case, in which there were three.In 7 cases the tumours had different histolo-
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gical appearances (positive evidence); in 13the tumours had similar histological appear-ances, but on clinical grounds it was unlikelythat either was a metastasis from the other(probable evidence); and in 5 cases the lunglesion was associated with a basal-cellcarcinoma of the skin. The oral cavity (7),skin (5), and larynx (4) were the mostfrequent sites of the second tumour. In 15instances diagnosis of the 2 lesions was madewithin 6 months of each other, and in 10cases the second lesion was diagnosed morethan 6 months after the first.
Histogenesis of Papillary CystadenomaLymphomatosum (Warthin's Tumor) ofthe Parotid Salivary Gland. THOMPSON,A. S., and BRYANT, H. C. (1950). Amer.J. Path., 26, 807.This is a well-illustrated review of the
subject of adenolymphoma, the view beingsupported that this tumour arises fromparotid ducts, and that it and " oxyphilicgranular cell adenoma are related neoplasmsthat differ only in pattern and supportingstromal elements." Adenolymphomata fallinto two histogenetic groups: (1) those whicharise from parotid ducts included in lymphnodes; (2) those which arise in the parotidgland itself and are accompanied by an in-flammatory aggregation of lymphoid tissue.The close proximity of the lower partof the parotid gland to the submandibulargland probably accounts for the supposedorigin of some adenolymphomata from thelatter. [A full bibliography adds to the valueof this useful paper.] R. A. Willis.
Amyloid and Myeloma. DAHLIN, D. C.,and DOCKERTY, M. B. (1950). Amer. J.Path., 26, 58.Amyloid material, giving characteristic
reactions with methyl violet, methyl green,van Gieson, and Congo red stains, wasfound in 14 out of 66 personally studiedcases of plasma-cell tumours. In 2 of thecases intracytoplasmic inclusions, stainingweakly for amyloid, were present in thelarger tumour cells. It is suggested that thepresence of amyloid within a tumour of
debatable nature is almost diagnostic ofmyeloma; it is also thought that plasmacells produce amyloid or some precursor ofthe latter. Necropsy findings in 2 cases ofmyelomatosis are also described; in onethere were widespread amyloid deposits, inthe other local deposits only.
A. Wynn Williams.
Malignant Blood Vessel Tumors. A Re-port on 56 Cases of Angiosarcoma andKaposi's Sarcoma. MCCARTHY, W. D.,and PACK, G. T. (1950). Surg. Gynec.Obstet., 91, 465.A comparative survey of 20 cases of
angiosarcoma and 36 cases of Kaposi'ssarcoma is presented. An attempt has beenmade to clarify the confusion existing in thestudy of malignant blood-vessel tumours.Definite predilections in race, sex, andanatomical onset were noted in Kaposi'ssarcoma. The condition is bizarre or ful-minating in females. Similar predilectionswere noted in the patients with angiosar-coma.Trauma appears to be directly involved in
the development of angiosarcoma in 3 of thepatients described and was suspected in 2patients with angiosarcoma of the breast.Angiosarcoma has been observed to developfrom irradiated benign angiomata in 3patients after long intervals. Treatment isfully discussed.Two cases are added to the recent literature
describing a new disease entity in whichlymphangiosarcoma originates in the massivearms of women with post-mastectomylymphoedema.
Sclerosing Lipogranuloma. SMETANA, H. F.,and BERNHARD, W. (1950). Arch. Path.,50, 296. Bibliography.The authors discuss 14 cases of sclerosing
lipogranuloma, taken from the files of theArmed Forces Institute of Pathology, Wash-ington. They assign the term sclerosinglipogranuloma to those cases characterizedby tumour-like swelling of subcutaneous fatafter trauma ofany kind, with basic patholo-gical similarities and not already classified as
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ABSTRACTS
recognized clinical entities. Detailed histolo-gical appearances are given and comparisonsdrawn between these lesions and the onesfound in allied conditions such as fatnecrosis of the breast, Weber-Christiandisease, and lipoid pneumonia. The theoriesof aetiology and pathogenesis of sclerosinglipogranuloma and allied lesions are re-viewed. No definite conclusions are reached,but it is suggested that the lipogranulomatousreaction represents a specific process whichfollows its own course and has distinctclinical and pathological significance.
A. Ackroyd.
Two Cases of Dysgerminoma Ovarnl, oneOccurring in a Malignant Teratoma inAssociation with Acute Myelocytic Leu-kaemia. CHALMERS, J. A. (1950). J.Obstet. Gynaec. Brit. Emp., 57, 437.The author describes 2 cases of dysger-
minoma ovarii in young girls, one associatedwith local infiltration and distant metastasis,and the other with myeloid leukaemia. Bothcases were fatal, in spite of adequate surgeryin the second case. The first case was ofpathological interest inasmuch as there wasno lymphocytic infiltration of the tumourstroma [Novak (Gynaecological and Obstet-rical Pathology, 2nd ed.) states that this is aconstant feature ofthe tumour]. The tumourin the second case showed assorted embry-onic tissues, of which dysgerminoma wasonly one of the features.The author reviews the literature of
dvsgerminoma ovarii and describes thepathological features of both teratoma andleukaemia. He suggests the possibility of acommon origin of teratoma, leukaemia, anddysgerminoma from an undifferentiatedmesenchymal cell, a hypothesis which thesecond case seems to support.
M. Halden Lloyd.
A Histologic Study of Muscles andNerves in Poliomyelitis. DENsT, J., andNEUBUERGER, K. T. (1950). Amer. J.Path., 26, 863.In the early stages of poliomyelitis the
muscles showed an irregularity in stainingassociated with a granular fatty degeneration
of many fibres. Longitudinal fibrillationand sometimes necrosis were seen. Latermany fibres showed atrophic shrinkage(? disease atrophy) and some hypertrophy.Proliferation of sarcolemmal nuclei andformation of muscle giant cells were some-times conspicuous, but definite evidence ofregeneration was absent. In all stages thehistological appearances were characteristi-cally pleomorphic. Changes in the nerves(which were obvious by the third day) wereless severe than those in muscle, but itseemed that the degree of damage in themuscles and anterior horn cells ran parallel.The muscle changes, however, differed fromthose of simple central paralysis, and maypossibly be due to a direct action of the virus.
D. M. Pryce.
The Histogenesis of Granular-cell Myo-blastomta (? Granular-cell PerineuralFibroblastoma). EVERSON PEARSE, A. G.(1950). J. Path. Bact., 62, 351.A histological and histochemical examina-
tion of 6 specimens of granular-cell " myo-blastoma" is described, and the threehypotheses concerning the origin of theselesions-whether, from muscle cells, histio-cytes, or Schwann cells-are rejected. Thegranules in the cells are found to stainsimilarly to granules in fibroblasts. It issuggested that the growths are lipoid-containing granular-cell fibroblastomata.
R. A. Willis.
The Development of Giant-celled Tendon-sheath Tumours and Related Conditions(Chronic Villo-nodular Synovitis andCutaneous Histiocytomia). SPENCER, H.,and WHIMSTER, 1. W. (1950). J. Path.Bact., 62, 411.Their histological study ofspecimens taken
from 7 cases of villous synovitis and from 34cases of giant-celled tumour oftendon sheathsatisfies the authors [but not the abstracter]that the latter is a non-neoplastic " prolifera-tive response to chronic inflammation." Asimilar conclusion regarding the pigmented" histiocytoma " or " sclerosing angioma "of the skin is based on a study of 37 of theselesions. R. A. Willis.
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