association of clinical pathologists: 52nd ...menace increasing with time, namely, cancer. when...

J. c/in. Path. (1954), 7, 168.

ASSOCIATION OF CLINICAL PATHOLOGISTS:52nd GENERAL MEETING

The fifty-second general maeting of the Association of Clinical Pathologists was held at Harrogatefrom April 8 to 10, 1954.

For the first session the chairman was Dr. J. V. Wilson.

Myelofibrotic Anaemia in Hodgkin's Disease

J. M. FULLERTON.Said that, although anaemia had beenrecognized as a constant feature in Hodgkin's disease,only one recorded case of an aplastic or myelofibrotictype is recorded-in the literature.A male patient was seen showing the features of

anaemia, loss of weight, a palpable spleen, and a fewenlarged peripheral lymph nodes. Five marrow punc-tures, including a trephine, suggested the diagnosis ofmyelofibrotic anaemia or aplastic anaemia. A lymphnode biopsy six ,weeks before death suggested thepossibility of a diagnosis of Hodgkin's disease.

Post-mortem findings showed a typical Hodgkin'spicture of microscopical involvement of bone marrowof ribs, vertebrae, stemum, iliac crest, and longbones.

The Saline Fragility of Leucocytes

H. G. H. and D. L. RICHARDs (Winchester) des-cribed a technique for measuring the saline fragility ofleucocytes.The results are plotted on a graph in the form of two

curves, one representing the total cell bodies per c.mm.

of blood added to each tube, and the other a curve

representing the number of cells still remaining refractilein the solution.The median leucocyte fragility for 50 normal bloods

and a large number of abnormal bloods has beendetermined. Eighty-four per cent. of normal bloodshave median leucocyte fragility between 0.300% and0.350%. The extreme limits of normal are 0.250% to0.385%.

The Deficiency Theory of Blast Cell Leukaemias

E. K. BLACKBURN (Sheffield) and L. G. LAJTHA(Oxford) presented evidence against the theory thatacute blast cell leukaemia is a deficiency disease.

In more than 60% of over 200 normal bone marrowcultures an absolute increase in the number of poly-morphonuclear leucocytes was found during the first24 hours of the culture. Not infrequently, cultures fromcases of chronic myelocytic leuikaemia showed a similarincrease in the number of polymorphs. On the otherhand, no rise in the number of polymorphonuclearleucocytes was observed in 24 series of cultures from15 patients with acute myeloblastic, paramyeloblastic,or monoblastic leukaemia. Features of non-specificdifferentiation from blast cells could not be identifiedwith normal maturation. No differencecould be detectedbetween blast cells cultured in normal as opposed toacute leukaemic sera.

Study of daily blood counts before and after 52transfusions in 39 patients with blast cell leukaemiarevealed definite improvement in three cases, dubiousimprovement in seven cases, rapid deterioration in fivecases, and probable deterioration in four cases. Inthe remainder, 33 out of 52 transfusions, there was nosignificant change.

Frequent or serial fresh plasma transfusions in twocases of acute leukaemia failed to induce significantclinical or laboratory improvement.

For the second session on the opening dayDr. W. H. McMenemey was in the chair.

The Serum Antithrombin Test in Fibrocystic Disease ofthe Pancreas

J. C. W. MAcFARLANE said that the use of the anti-thrombin content of plasma as an aid to laboratoryconfirmation of the clinical diagnosis of fibrocysticdisease of the pancreas was originally suggested byInnerfield, Angrist, and Benjamin (1951). With aslightly modified technique and using serum in place ofplasma, this test has been used at The Hospital for SickChildren, Great Ormond Street, since December, 1951.The technique employed has not altered from thatpublished by MacFarlane (1952).

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ASSOCIATION OF CLINICAL PATHOLOGISTS MEETING

The test has been used in 102 cases of fibrocysticdisease of the pancreas, confirmed by examination ofthe duodenal juice, and in 92 of them, or 90%, theserum antithrombin content has been found to beconsiderably lower than that found in normal serum.The results have ranged from 18% to 68% of normal.Some 750 " normal " sera have been examined, thecases being of the same age group, including 114 casesof recurrent chest infections, 36 cases of coeliac disease,45 cases of " failure to thrive," 27 cases of fatty diar-rhoea, and 73 relatives of 22 proven cases. There havebeen six " false positive " results; one a case of eczema,one of advanced miliary tuberculosis, and four showingchronic respiratory infections.No rationale for the test can be offered, but it is

thought to offer a simple and reliable, if empirical, aidto diagnosis.

REFERENCESInnerfield, I., Angrist, A., and Benjamin, J. W. (1951). J. Pediat.,

39, 287.MacFarlane, J. C. W. (1952). Lancet, 2, 311.

Risks from Chronic Irradiation and their HaematologicalControl

R. H. MOLE said that in human cases of seriousanaemia due to radiation little if any warning was givenby the white cell count preceding the illness. Hediscussed the evidence, both clinical and experimental,and it was concluded that it was not likely that changesin the blood count would be observed unless exposureto radiation was many times the maximum permissible.Damage to the gonads occurred with smaller dose ratesof radiation. Physical measures of control were con-sidered preferable to haematological methods.

[We hope to publish this paper in full in a future issueof the journal.-ED.]

Observations on Temperature Levels in Hot AirOvens

R. BARRINGTON BROCK and E. M. DARMADY (Ports-mouth) described how multipoint thermocouples wereused to test ovens loaded with syringes. Observationswere made on two gas, three electric, and two electricovens with fans. The experiment showed the variationsover 400 C.-50° C. in the gas oven and that in manysites the temperature was considerably lower than thatof the thermometer reading. In the electric oven thefinal variation of temperature varied from 280 C. to120 C., and the take-up of heat was slow and variable.In the electric ovens fitted with fans the final variationof temperature was less than 10° C., and the take-upof heat was immediate and reliable. Tightly packingthe syringes prevented the absorption of heat in whateveroven was used. The loading of syringes while the ovenwas hot made no difference to the amount of heatabsorbed provided the temperature was allowed toregain the selected degree. In the ovens fitted with fansheat was probably taken up more quickly and moreevenly. It was suggested that heat treatment in these

ovens need not be so long as in the electric oven butthat the gas oven could not be regarded as reliable.A plea was made for the description of ovens whenloaded rather than the normal practice of describingwhen empty, since, apart from one gas and one electric,all the ovens investigated showed variation when emptyof less than ± 30 C. The tight packing of syringes wascondemned. Preliminary experiments with autoclavesshowed similar discrepancies.

On April 9 the chairman at the first session wasProfessor R. A. Willis and at the second Dr. R. W.Fairbrother.

In the afternoon Professor C. H. Gray took thechair.

During the afternoon on April 9 demonstrationswere shown at the Royal Bath Hospital, Harrogate.

Pneumocystis Carinii in Interstitial PlasmacellularPneumonia

H. S. BAAR described the first case of interstitialplasmacellular pneumonia outside the European conti-nent. The finding of characteristic honeycombedmasses in air-spaces, which were identified by Vanekand Jirovec as the protozoon Pneumocystis carinii, wasconfirmed. Histochemical reactions of the honey-combed masses were reported. The case was associatedwith cytomegalic inclusions of salivary glands and thesignificance of this association was discussed.

Nephrocalcinosis and Hypercalcaemia in an InfantI. M. P. DAWSON and W. S. CRAIG (Leeds) described

a boy aged 5 months who presented with anorexia,vomiting, constipation, and hypotonia, persisting, withperiods of irregular fever, till death at 11 months.Investigations showed raised serum calcium, bloodcholesterol, and urea nitrogen levels. Other biochemicalfindings, including plasma bicarbonate, alkaline phos-phatase and chlorides, were normal. Pus cells werefound in the urine which was acid. Radiographsshowed increased density of the skull and long bones.Necropsy revealed bronchopneumonia, without para-thyroid hyperplasia or gross changes in other organs.

Microscopically, the lungs showed unresolved pneu-monia. In the kidneys there was patchy hyaline changein some glomeruli, and both calcium-containing andeosinophilic casts in distal and collecting tubules, withsome calcium deposition in surrounding tissue. Theproximal tubules showed vacuolation and degenerationwith calcium deposits in degenerate areas. The casewas considered similar to those described by Lightwood(1952) as idiopathic hypercalcaemia. The pathologicalchanges were those of a nephron nephrosis of unknownaetiology, and the biochemical disturbances probablysecondary to primary renal damage.

REFERENCELightwood, R. (1952). Arch. Dis. Childh., 27, 306.

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The Pathology of Ulcerative ColitisCUTHBERT E. DUKES said that the modem surgical

treatment of ulcerative colitis by colectomy had provideda new opportunity for the study of the lesions in severecases. These always include widespread inflammationof the mucosa, often accompanied by extensive super-ficial ulceration, congestion of the submucosa, thepresence of inflammatory polyps and strictures.A patient with severe ulcerative colitis is threatened

with many dangers such as haemorrhage, toxaemia, andperforation. There is also a less obvious yet persistentmenace increasing with time, namely, cancer. Whencancer follows chronic ulcerative colitis the malignanttumours are frequently multiple and atypical in appear-ance, grow rapidly and metastasize early.Almost all who during recent years have enquired

into the relationship between ulcerative colitis andcarcinoma have reached the conclusion that colitispredisposes to cancer and that the extent of this predis-position has been underestimated in the past becauseof difficulties in diagnosis, both clinical and pathological.

Dr. Dukes explained that his experience was basedchiefly on the examination of colons removed by colec-tomy from severe cases of ulcerative colitis. In aconsecutive series of 120 cases of severe colitis carcinomawas found seven times, an incidence of 5.8%. Theaverage age of these patients was 42 years. The averageduration of symptoms of ulcerative colitis before theonset of cancer in this series of cases was 15 years.

If the question is asked, "How often does cancerfollow ulcerative colitis ? ", the answer must obviouslydepend on the severity of the disease and on the durationof symptoms of the cases being considered. Such aquestion can only be answered in general terms by sayingthat any patient in whom severe ulcerative colitis haslasted more than 10 to 15 years has entered a phase oflife when intestinal cancer has become a serious risk.

Some Observations on the Pathology of Sjogren'sSyndrome

B. S. CARDELL reported the necropsy findings in threecases of Sji6gren's syndrome and discussed them inrelation to four cases recorded in the literature. Thereappeared to be two main components, (1) atrophy ofcertain glands and dryness of their associated mucosaeand (2) rheumatoid arthritis. In the first component theessential lesion was in the conjunctival, lacrimal, andsalivary glands and the submucous glands of the res-piratory and upper alimentary tract. The distributionof the glandular lesion in the seven necropsy cases waslacrimal and salivary, seven, conjunctivae, six, mouth,tongue, and larynx, five, oesophagus, four, nose andtrachea, three, and bronchi, two. In the earlier stagethere was a predominantly lymphocytic cellular infiltra-tion producing glandular enlargement and parenchymalatrophy which resulted in impaired function. Eventuallyboth parenchyma and the cellular infiltrate disappearedand were ieplaced by fibro-adipose tissue. Dryness ofthe associated mucosae was a result of the glandularatrophy.

The nature of the underlying pathological processremained obscure. It was possible that the glandularatrophy and the rheumatoid arthritis were both mani-festations of collagen disease. This theory receivedsome support from the observation that cortisoneproduced symptomatic improvement in these cases andfrom the occurrence of polyarteritis nodosa in two ofthe seven necropsy cases.

An Incidence of Miliary Tubercles in Bone MarrowRelated to Diagnostic Needle Biopsy

J. L. EMERY and N. M. GIBBS (Sheffield) said thatthe clinical diagnosis of miliary tuberculosis using thepresent methods of radiological appearance of the lungsand examination of the eye for choroidal tubercles wasknown to reveal the disease in a little less than half ofthe cases.A systematic study of 0.1 ml. of bone marrow from

44 children who had died with generalized miliary tuber-culosis revealed miliary tubercles in 13 cases.

In these 44 children a clinical diagnosis of miliarytuberculosis had been made by radiography of the chestin 13 and examination of the eye in 14 cases. Thesetwo methods in conjunction produced the diagnosis in18 cases. Marrow biopsy would theoretically haveenabled the clinical diagnosis to be made in a furtherfive cases.

It was suggested that bone marrow aspiration biopsyhad a place in the diagnosis of generalized miliarytuberculosis.

Cristobalite Granuloma

T. C. MORTON said that cristobalite was a rarecrystalline form of silica occurring in nature. Quartzand amorphous silica are converted into cristobaliteby heating them above 800° C.The case reported was that of a single woman of

44 who had a simple appendicectomy carried out in1940. Thirteen years later a lumbar sympathectomywas carried out retroperitoneally on the right side anda small lymph gland found incidentally was sent downfor biopsy. This was at first suspected to be the siteof a hyperplastic tubercular lymphadenitis. Owing tothe success of the operation a left lumbar sympathectomywas carried out through an abdominal incision and achain of grossly enlarged para-aortic lymph glands wasfound on the left side. There were no peritoneal adhe-sions or the usual talc granulomatous plaques or nodules.The lymph glands were removed and showed a markedforeign body reaction with numerous inclusion bodiesvisible in ordinary stained sections, especially veryprominently under Nicoll's prisms. A re-examinationof the original biopsy from the right side under Nicoll'sprisms showed identically similar particles. ProfessorKing and Dr. Nagelschmidt showed that these inclusionbodies were cristobalite in addition to talc.

It is known that the talc dusting powder in use in1940 was of inferior quality and it is surmised thatquartz was present as a contaminant together withcristobalite. The interesting feature was the widedispersion from the site of the operation and the fact

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that the proliferative foreign body reaction was confinedsolely to the lymph glands.

M. J. H. SMITH and M. E. H. PESSELL reportedexperiments and results of " The Estimation of SerumAcid and Alkaline Phosphatase Activity with 4-Amino-antipyrine." This paper will be published in theAugust issue of the joumal.

A Calcium Tolerance TestB. E. C. NORDIN (Postgraduate Medical School of

London) described an intravenous calcium tolerance testwhich might assist in the diagnosis of certain types ofmetabolic bone disease. Calcium gluconate (15 mg.calcium per kg. body weight) was given intravenouslyin normal saline over a four-hour period after thesubject had been on a low calcium diet (100 mg.) forthree days. In nine normal subjects the mean urinarycalcium excretion during the 12 hours following thestart of the infusion was 50.7% of the administereddose: two standard deviations either side of the meangave a normal range of 38 to 62%. In seven cases ofproven osteomalacia the excretion was always less than25%. In nine cases of osteoporosis the excretion waswell above the normal range in three (all young adults)but within the normal range iii six (all post-menopausalosteoporosis). An interesting aspect of the test was thefall in urinary phosphate clearance which followed theinfusion and which was most marked in the osteomalacicgroup. It seemed possible that this was due to suppres-sion of activity in the parathyroid gland.

Paper Chromatography of Urinary 17-KetosteroidsSHEILA MCDONOUGH and ARTHUR JORDAN said that

a considerable number of neutral 17-ketosteroids hadbeen found in urine, but the methods hitherto employedfor their separation had not been suitable for routineuse. Chromatography using impregnated filter papercan give excellent results but in our hands proved to bevery uncertain, but satisfactory separations using acyclohexane when a 20% (v/v) methanol system onWhatman No. 31 paper and working at a temperatureof 34.80 C. had been found satisfactory. The amountof 17-ketosteroid on the paper must not exceed 400 ,ug.From this amount, an extract from a normal male givesfive or six spots. Work is in progress to identify thesespots. The least mobile spot is not yet identified. Thenext appears to be aetiocholan-3a:1 I,-diol-17 one, thenext aetiocholan-3a-ol- 1 1:17-dione. The fourth spot isnot yet idtntified, it may be androstan-3a :1l1l-diol-17-one; the fifth spot is not always present, it consists ofandrost-5-en-3#-ol-17 one. The sixth, and most mobile,spot contains three components : androsterone(androstan-3a-ol-1 7-one), aetiocholan-3a-ol-1 7-one, and3,8chloro-androst-5-en- 17-one.

Haemoglobin S and Haemoglobin C-A Case with SickleCell Haemoglobin C Disease

H. LEHMANN and G. M. EDINGTON said that sixhuma;i haemoglobins were now known of which five

seemed to be alleles genetically: adult (A), sickle cell (S),C, D, and E. Foetal haemoglobin (D) is not usuallyfound after the first year of life, except in thalassaemiaand in sickle cell anaemia and in some other anaemias,particularly those which started before the physiologicalhaemoglobin F formation in the infant came to an end.Haemoglobin F is characterized by its resistance toalkali. A, S, and C haemoglobins differ in their beha-viour on paper electrophoresis, and, in addition, afeature of S is its tendency to gel at reduced 02 tension.At pH 8.6 A migrates fastest, S less so, and C is slowerthan both A and S. Various chemical differences havebeen alleged to exist between A and S: the number ofSH groups, or the number of " active " SH groups, orthe number of valine molecules are said to be different.The only definite chemical differentiation is shown byelectrophoresis atpH 11 and 4 (Scheinberg). As the twohaemoglobins migrate differently at pH 11, the differencecannot be due to the NH2 groups which are inactive atthis pH. They do, however, migrate at equal speeds atpH 4, suggesting that the different migrating rates at theotherpH ranges are due to carbonyl groups. D has thesame electrophoretic properties as S but does not gel atreduced °2 tension, E migrates at alkaline pH at thesame rate as A but differs from A at acid pH. D andE have so far been found in one family each, but Sand C seem to be widely distributed and their incidencepattern is of anthropological interest. Much work hasbeen done on S in that respect but little so far on C.The present case is the first to be reported from outsidethe U.S.A. A survey recently carried out jointly withDr. D. F. Roberts in Southem Sudanese Nilotes,including 75 unrelated Dinkas, failed to show C in thatgroup, a population which also does not have the Shaemoglobin. A systematic survey of C incidence inWest Africa is now in progress and plans are made toextend this to other parts of Africa.

S can give rise to sickle cell anaemia and it is importantto differentiate between the haemolytic anaemia and thesickle cell disease, the condition in which crises maylead to death. The anaemia is similar to that of acho-luric jaundice and to the newly discovered " target cellanaemia" associated with C, and to thalassaemia.Similarly as in acholuric jaundice, but to a lesser extent,it is now believed that the abnormally shaped cells areeliminated by the reticulo-endothelial system. Thecrisis is peculiar to the S-carrying red cell and it is dueto sickling of cells in vivo. A most important factorin their causation are infections.The therapy of the homozygous, giving rise to sickle

cell anaemia, and the heterozygous, giving rise to harm-less sickle cell trait, will have to be modified, and whileit will always be true that a very severe case of sicklecell anaemia will be a homozygote and a perfectlyhealthy S individual a heterozygote, there is a wide scalebetween the two. Sickle cell trait is not always harmnlessand in the U.S.A. a disease involving haematuria is nowfound more and more exclusively in S heterozygotes.There must be factors (modifiers) of which we know asyet little which determine the percentage of haemoglobin

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from each gene. In A-S heterozygotes A has up to nowalways been found to be >S: among S-C heterozygotesnone has been so far found in whom the relationshipwas not C<S.One difficulty is the discrepancy between observed

incidence of sickle cell anaemia and the calculatedincidence of S homozygotes. Evidence has recentlybeen brought forward to suggest the protection of Shomozygotes against malaria, and the question ariseswhether malaria protects homozygotes from sickle cellcrises. If this could be proven it would go far in helpingus to understand the increased finding of sickle cellanaemia in areas where malaria is being eradicated(U.S.A., Greece, certain parts of Africa). Better diag-nostic facilities and more intensive search for the con-dition will not serve as a complete explanation. Somerelationship between malaria and sickle cell anaemiawould serve as an additional explanation of the survivalat high frequency of the sickling gene in areas wheremalaria is endemic. Sickle cell crises have a sufficientlyserious prognosis to justify an examination of thepossible therapeutic value of malaria.

Protein and Protein-bound Polysaccharide Abnormalitiesin the Diagnosis of Amyloid and Allied Disorders by

Paper Electrophoresis

I. C. GILLILAND and E. STANTON said that diabeticnephropathy described by Kimmelstiel and Wilson (1936)shows deposits of hyaline-like material in the arteriolesand in the glomerulus. MacManus (1950), by periodic-acid-Schiff staining, showed it to be a polysaccharide-containing protein. He suggested that they might bedeposited from the blood.

Diabetic retinopathy shows similar changes of poly-saccharides in the hyaline arterioles and microaneurysms.Duguid and Anderson (1952) suggested that these alsoare deposited from the blood.

Initial observations required elaborate chemicalestimations (Gilliland, Hanno, and Strudwick, 1954),but it was now proposed to show that the same informa-tion could be obtained by a simple method suitable forroutine use.

Total proteins and total polysaccharides were measuredin the serum and further characterized by electrophoresison paper. Duplicate papers were run for each sample.Naphthalene black stain demonstrated the proteins andperiodic-acid-Schiff stain demonstrated the poly-saccharides. The colour density was read with therecording densitometer of Laurence (1954), the Gaussiancurves completed, and the relative areas measured byplanimetry.No evidence of abnormal polysaccharide was found

in a series of cases of diabetes, but a progressive rise inthe total protein-bound polysaccharides occurred as thecomplications of diabetes increased. The major com-ponent affected was the az globulin. The albumin fellas a2 rose, so that four groups could be well differen-tiated by comparing the albumin a2 ratio without the

need for chemical estimation of the total. As thepolysaccharides are protein-bound an indication can bederived from examination of the protein pattern alone.These protein changes are consistent and of diagnosticvalue in diabetes with Kimmelstiel-Wilson complications.A useful index ofcomplications could be obtained from

simple electrophoresis on paper of proteins and estima-tion on the albumin/a2 ratio so derived. This index wastested in a new series of diabetic patients suffering fromthree grades of diabetic retinopathy and the indexcorrelated with the severity of the complications.

It had been shown by many people (Gutman, 1948;Marrack and Hoch, 1949; Lever, 1951) that a rise inprotein-bound polysaccharides in the serum is notspecific for diabetes but occurs in a wide variety ofconditions. Acute rises in protein-bound polysaccharidesoccur after many feverish or traumatizing episodes, butreturn to normal. This has been studied particularly inrheumatic fever. Chronic rises more comparable todiabetes occur in rheumatoid arthritis and in untreatedtuberculosis amongst other conditions.

If the lesions of the diabetic complications occur asa result of the deposition of these protein-bound poly-saccharide materials in the vessel walls and in the kidneys,then similar changes should occur in these other con-ditions. Both rheumatoid arthritis and tuberculosismay terminate in amyloid disease and the kidneystained by periodic-acid-Schiff stain shows a remarkablesimilarity to Kimmelstiel-Wilson lesions. The serum ofpatients with proven amyloid disease examined by thesame electrophoretic technique was also similar to thoseof the diabetics with Kimmelstiel-Wilson lesions.

Estimations of the albumin/a2 ratio in the serum ofpatients with uncomplicated rheumatoid arthritis ofvarying durations showed a steady fall with duration.The albumin/a2 ratio below 3 was of diagnostic help inamyloid disease.

Seibert et al. (1947) showed that the total serumprotein-bound polysaccharides are cumulative and thatthe presence of two diseases such as tuberculosis anddiabetes leads to a greater amount being present. Thealbumin/a2 ratio in a few patients with tuberculosis andrheumatoid arthritis showed albumin/a2 ratios diagnosticof amyloid disease which had developed in a period verynotably shorter than in the cases with uncomplicatedrheumatoid arthritis. In each of these cases the amyloiddisease was proved by biopsy.The albumin/a2 ratio in several cases of osteoarthritis

showed no change.Sera were examined from four cases of amyloid

disease occurring as a result of long-standing tuber-culosis and in these the albumin/a2 ratio was againbelow 3.A number of cases of uncomplicated sarcoidosis

proved by biopsy were also examined. The albumin/a2ratio was lowest in four cases characterized by grossenlargement of liver and spleen. One was shown tohave characteristic changes of para-amyloid disease atnecropsy.

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Our observations in rheumatic fever confirm the risein protein-bound polysaccharides initially, returning tonormal. The albumin/a2 index can be calculated fromthe figures given by Jackson et al. (1953) on 303 childrenwith rheumatic fever using the Tiselius method. Theseshow a progressive rise in the albumin/a2 index as thedisease progresses.Thus the albumin/a2 index gives useful information of

prognostic and diagnostic value in a wide variety ofdisorders.

REFERENCESDuguid, J. B., and Anderson, G. S. (1952). J. Path. Bact., 64, 519.Gilliland, I. C., Hanno, M. G., and Strudwick, J. I. (1954). In

the press.Gutman, A. B. (1948). Advances in Protein Chemistry, vol. 4,

pp. 115, 250. Academic Press, New York.Jackson, R. L., Kelly, H. G., Smith, E. K., Wang, P., and Routh,

J. 1. (1953). Amer. J. Dis. Child., 86, 403.Laurence, D. J. R. (1954). In the press.Lever, W. F. (1951). Bull. New Engi. med. Cent., 13, 160.Kimmelstiel, P., and Wilson, C. (1936). Amer. J. Path., 12, 83.MacManus, J. F. A. (1950). Medical Diseases of the Kidney. Lea

and Febiger, Philadelphia.Marrack, J. R., and Hoch, H. (1949). Journal of Clinical Pathology,

2, 169.Seibert, F. B., Seibert, M. V., Atno, J. A., and Campbell, H. W.

(1947). J. clin. Invest., 26, 90.

The meeting ended on April 10, when the chairmanat the first session was Dr. H. R. R. Mavor and atthe second Dr. A. G. Signy.

The Isolation of Pasteurella septica from the Sputumin Bronchiectasis

J. M. TALBOT said that Past. septica (s.yn. multocida)had now been described on numerous occasions ashaving been isolated from pathological conditions inman. The majority of examples were from woundsinflicted by animals, but there were a number of cases,most of which were reported from the U.S.A., in whichno direct animal contact was known. Prominent inthis latter group are those cases in which the organismseems to live as a symbiont in the respiratory tract ofthose patients with disease of the bronchi, lungs, ornasal sinuses, especially those with bronchiectasis. Thepersistent occurrence of this organism in the sputum ofa patient with bronchiectasis has not previously beenreported in this country, but such a case was here des-cribed in which the organism was satisfactorily identifiedby biochemical and pathogenicity tests. There is astrong possibility that more examples of this conditionmay be forthcoming if a careful watch is kept for them.

The Bacteriology and Pathogenesis of Brain Abscess

L. PARKER reviewed 70 cases of brain abscess investi-gated at the Manchester Royal Infirmary since January,1948.A comprehensive technique was used for the isolation

of the organisms. Blood agar plates were incubatedaerobically, microaerophilically, and anaerobically. Strictanaerobes were found on 12 occasions and many facul-

tative anaerobes grew better on anaerobic or micro-aerophilic culture than on aerobic culture when firstisolated. Chloral hydrate-blood agar was used whenthe presence of Proteus vulgaris was suspected. Liquidmedia, particularly a modification of Brewer's thio-glycollate medium, were valuable when only a smallnumber of organisms were present.The organisms most frequently isolated were:

Proteus vulgarisStaph. aureusNon-haemolytic streptococciBacteroides group . .Anaerobic streptococci

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No pneumococci or fungi were isolated.In 15 cases all cultures were sterile.The bacterial flora of an abscess was related to the

primary focus.In many of the abscesses due to direct spread of infec-

tion the route of spread was easily traced; in somecases there was a bone defect, and in others thrombosedblood vessels were seen.

In abscesses caused by blood-borne infection theroute of spread was less obvious. In a few cases therewas clinical evidence of bacteraemia before the presenceofthe abscess was recognized; but the relative importanceof bacteraemia and septic embolism (by the systemicarteries or the vertebral veins) in the pathogenesis ofhaematogenous brain abscesses is difficult to assess.

The Epidemiology of Proteus vulgaris InfectionsA. C. CUNLIFFE said that within recent years the

importance in surgical infections of Gram-negativebacteria, such as Pseudomonas pyocyanea and Proteusvulgaris, which are relatively insusceptible to penicillinand the majority of the new antibiotics, had increased.It is generally recognized that a large number of Ps.pyocyanea infections are the result of cross-infection inhospital. There is much less knowledge about theepidemiology of P. ulgaris.

In the work described the serological classification ofP. vulgaris had been developed to provide an accuratemethod of subdividing the species and by this meansthe epidemiology of Proteus infections in a number ofpopulations had been elucidated. The typing of strainsisolated at a general hospital and from patients in abums unit provided evidence suggesting that infectionwith Proteus vulgaris occurs in two ways; (a) as theresult of self-infection from the gut, and (b) by cross-infection.

Evidence for cross-infection was suggested by thefinding of the same type of P. vulgaris in seven of nineinfected bums in one ward of the bums unit. Thedistribution of types in this and other wards suggestedthat infection took place in the ward rather than duringdressings at the common dressing station. In the generalhospital no evidence of cross-infection was found; self-infection was suggested by the fact that in the majorityof patients the somatic and flagellar antigens of thestrain isolated from the faeces were identical with thoseof the strain isolated from the site of infection.

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A Seasonal Incidence of Toxoplasma Infection ?

J. K. A. BEVERLEY and C. P. BEATTIE said that thebirth dates of patients born with severe manifestationsofcongenital toxoplasmosis (hydrocephalus, intracerebralcalcification, and chorio-retinitis) showed a peak fromApril to July; of those born with minor manifestationsonly, a peak from October to March. If the birth datesof those born with severe manifestations are antedatedthree months and a histogram made by months fromthem it will be found to coincide with a histogram madeof the birth dates of cases born with minor manifesta-

tions. This is in keeping with the supposition thatchildren born of mothers infected during the middle oftheir pregnancy may show major manifestations andthose born of a mother infected late in pregnancy minormanifestations. It also suggests a seasonal incidence ofinfection in autumn and winter.

Carrier Medium in Pertussis DiagnosisD:. B. W. LACEY described his carrier medium for

isolation of B. pertussis and showed the greater ease ofisolation using his selection medium.

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association of clinical pathologists: 52nd ...menace increasing with time, namely, cancer. when...

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