J. clin. Path. (1959), 12, 380. ASSOCIATION OF CLINICAL PATHOLOGISTS: 62nd GENERAL MEETING The 62nd general meeting was held at the Medical School, University of Manchester, from April 16-18, 1959. Summaries of the papers read there are presented below. The Myeloproliferative Disorders H. E. HUTCHISON (Glasgow) reviewed the morbid histology and marrow cytology of the myelo- proliferative disorders, beginning with the typical case. Thereafter atypical examples were used to illustrate the relationship to the leukaemias, refractory anaemia both normoblastic and megaloblastic, and reticulum-cell tumour of the haemopoietic system. The value of trephine biopsy and reticulin staining of the marrow was illustrated. Separation of Red Cell Mixtures by Centrifugation H. E. M. KAY and M. CONSTANDOULAKIS (Royal Marsden Hospital, London) said that the young red cell, in particular the reticulocyte, is known to have a lower density than the mature cell and can by centrifugation be concentrated in the top layer of the red cell column. Experiments were described which demonstrated the degree of segregation so obtained. It was further shown that, where blood transfusion or bone-marrow transplantation had produced a mixture of circulating erythrocytes, it is usually but not always possible to establish the genotype of the functioning bone marrow by means of such a separation. (See page 312.) The Principles of the Investigation of Acute Bleeding States Complicating Pregnancy and Childbirth G. I. C. INGRAM (St. Thomas's Hospital, London) said that the literature describing the acute coagulation disorders which have complicated pregnancy and childbirth was now sufficiently extensive for the principles of the investigation of these disorders to be worked out in detail. Four processes have been thought to cause these defects. They are: (1) Defibrination, which implies a continuing, slow coagulation proceeding in the mother's blood so that the red cells eventually are circulating suspended in serum, with a deposition of the fibrin in various organs. (2) Fibrinolysis, by which is meant an activation of the normal fibrinolytic mechanism of the mother's blood. (3) Release of heparin into the mother's blood. (4) An excessive utilization of clotting factors in an attempt to procure haemostasis at the placental site. In addition, it has been suggested that an insufficient synthesis of clotting factors may contribute in a shocked patient. These conditions have been seen variously associated with abruptio placentae (concealed ante- partum haemorrhage), retained dead foetus, "amniotic infusion," hydatidiform mole, and septic and criminal abortion. The processes of defibrina- tion and fibrinolysis are thought to be initiated by the entry of tissue substances from the conceptus into the maternal circulation, and in these two conditions there have been found thrombocytopenia and reductions in antihaemophilic globulin (A.H.G.), factor V, occasionally factor VII, and fibrinogen. It is thus apparent that tests might be applied in these cases to detect at least the following abnormalities: thrombocytopenia, heparin - like activity, and depletions of A.H.G., factor V, and fibrinogen. It is important to identify any heparin activity before making other coagulation tests since the presence of heparin will interfere with other techniques. It is suggested that the tests might be arranged in the following order: (1) Platelet Count, and (2) Thrombin Clotting Time of Citrated Plasma.-If the thrombin time is longer in the patient's plasma than in the control this might be due either to a reduction in the fibrinogen content or to the presence of heparin. If abnormal, the test should therefore be repeated, adding to both the patient's and the control plasmas first purified fibrinogen and then toluidine blue 1/1,000. This test also provides a method for detecting fibrinolysis, by incubating citrated plasma and repeating the thrombin time on samples withdrawn at intervals over an hour or two; a progressive lengthening of the thrombin time apparent in the patient's plasma but not in the control plasma is strong presumptive evidence of this process. (3) Fibrinogen Determination.-It is probably more useful to estimate fibrinogen as fibrin, i.e., what clots, than in terms of a salt precipitate. (4) One-stage Prothrombin Time. This will be prolonged where there is a marked diminution in factor V activity. It should be noted in this connexion that in late pregnancy the prothrombin time is shorter than in the non-pregnant state, so that even small prolongations of the patient's time over that of a non-pregnant control should be taken seriously. (5) Thromboplastin Generation Screening Test (Hicks and Pitney).-Using some convenient platelet substitute, this will detect a reduction in A.H.G. on April 16, 2021 by guest. Protected by copyright. http://jcp.bmj.com/ J Clin Pathol: first published as 10.1136/jcp.12.4.380 on 1 July 1959. Downloaded from
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J. clin. Path. (1959), 12, 380.
ASSOCIATION OF CLINICAL PATHOLOGISTS:62nd GENERAL MEETING
The 62nd general meeting was held at the Medical School, University of Manchester, from April16-18, 1959. Summaries of the papers read there are presented below.
The Myeloproliferative DisordersH. E. HUTCHISON (Glasgow) reviewed the morbid
histology and marrow cytology of the myelo-proliferative disorders, beginning with the typicalcase. Thereafter atypical examples were used toillustrate the relationship to the leukaemias, refractoryanaemia both normoblastic and megaloblastic, andreticulum-cell tumour of the haemopoietic system.The value of trephine biopsy and reticulin stainingof the marrow was illustrated.
Separation of Red Cell Mixtures by CentrifugationH. E. M. KAY and M. CONSTANDOULAKIS (Royal
Marsden Hospital, London) said that the young redcell, in particular the reticulocyte, is known to havea lower density than the mature cell and can bycentrifugation be concentrated in the top layer of thered cell column. Experiments were described whichdemonstrated the degree of segregation so obtained.It was further shown that, where blood transfusionor bone-marrow transplantation had produced amixture of circulating erythrocytes, it is usually butnot always possible to establish the genotype of thefunctioning bone marrow by means of such aseparation. (See page 312.)
The Principles of the Investigation of Acute BleedingStates Complicating Pregnancy and Childbirth
G. I. C. INGRAM (St. Thomas's Hospital, London)said that the literature describing the acutecoagulation disorders which have complicatedpregnancy and childbirth was now sufficientlyextensive for the principles of the investigation ofthese disorders to be worked out in detail. Fourprocesses have been thought to cause these defects.They are: (1) Defibrination, which implies a continuing,slow coagulation proceeding in the mother's blood sothat the red cells eventually are circulating suspendedin serum, with a deposition of the fibrin in variousorgans. (2) Fibrinolysis, by which is meant anactivation of the normal fibrinolytic mechanism ofthe mother's blood. (3) Release of heparin into themother's blood. (4) An excessive utilization ofclotting factors in an attempt to procure haemostasisat the placental site. In addition, it has beensuggested that an insufficient synthesis of clottingfactors may contribute in a shocked patient.
These conditions have been seen variouslyassociated with abruptio placentae (concealed ante-partum haemorrhage), retained dead foetus,"amniotic infusion," hydatidiform mole, and septicand criminal abortion. The processes of defibrina-tion and fibrinolysis are thought to be initiated by theentry of tissue substances from the conceptus intothe maternal circulation, and in these two conditionsthere have been found thrombocytopenia andreductions in antihaemophilic globulin (A.H.G.),factor V, occasionally factor VII, and fibrinogen.
It is thus apparent that tests might be applied inthese cases to detect at least the followingabnormalities: thrombocytopenia, heparin - likeactivity, and depletions of A.H.G., factor V, andfibrinogen. It is important to identify any heparinactivity before making other coagulation tests sincethe presence of heparin will interfere with othertechniques. It is suggested that the tests might bearranged in the following order:
(1) Platelet Count, and (2) Thrombin Clotting Timeof Citrated Plasma.-If the thrombin time is longer inthe patient's plasma than in the control this might bedue either to a reduction in the fibrinogen content orto the presence of heparin. If abnormal, the testshould therefore be repeated, adding to both thepatient's and the control plasmas first purifiedfibrinogen and then toluidine blue 1/1,000. This testalso provides a method for detecting fibrinolysis, byincubating citrated plasma and repeating the thrombintime on samples withdrawn at intervals over an houror two; a progressive lengthening of the thrombintime apparent in the patient's plasma but not in thecontrol plasma is strong presumptive evidence of thisprocess.
(3) Fibrinogen Determination.-It is probably moreuseful to estimate fibrinogen as fibrin, i.e., what clots,than in terms of a salt precipitate.
(4) One-stage Prothrombin Time. This will beprolonged where there is a marked diminution infactor V activity. It should be noted in thisconnexion that in late pregnancy the prothrombintime is shorter than in the non-pregnant state, so thateven small prolongations of the patient's time overthat of a non-pregnant control should be takenseriously.
(5) Thromboplastin Generation Screening Test(Hicks and Pitney).-Using some convenient plateletsubstitute, this will detect a reduction in A.H.G.
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Having made these tests it should be possible toadvise the obstetrician whether special infusions, e.g.,purified fibrinogen, are required and whether itwould be safer to await natural delivery or tointervene under the appropriate cover. The progressof the case may then be followed by repeating thosetests shown in the initial investigation to have beenabnormal; and in particular, the fibrinogendetermination is convenient for following progresssince the test is rapid and accurate, the concentrationvaries fairly rapidly in the plasma following changesin the clinical state or as a result of infusion, and theresponse to an infusion can be controlled bycomparing the expected with the observed increase inthe fibrinogen concentration of the plasma.For these tests (apart from the platelet count) the
only requirement is citrated plasma. The reagents forthe thrombin-fibrinogen-toluidine blue tests are notdifficult to obtain or to prepare and may be stored at-200 C.
It seems advisable to provide the clinicians with asimple screening test such as a rapid fibrinogendetermination and to suggest that they call in theclinical pathologist in consultation whenever this testshows abnormal results. The clinical pathologistmust therefore provide a service covering 24 hours,but if this can be assured he may be able to offeradvice to his obstetric colleagues which is bothdecisive and life-saving.A rapid side-room method for estimating
fibrinogen was demonstrated, depending upon theincrease of turbidity which occurs when plasma clots.A review of the literature with the full account of
the proposed tests is appearing in the Journal ofObstetrics and Gynaecology of the British Empire.
Acute Erythraemic Myelosis (Di Guglielmo's Disease)E. NEUMARK (Department of Pathology, St. Mary's
Hospital Medical School, London) said that, since DiGuglielmo's first description of a case of acuteerythraemic myelosis in 1926 which followed nineyears after he had postulated the existence of such acondition (Di Guglielmo, 1917), more than a hundredcases had been reported in the medical literature.The first case recognized and published in Englandwas Israels's (1939), who called the condition"immature cell erythraemia."
Since 1948 (Britton and Neumark, 1949), when thefirst case of acute erythraemic myelosis had beenshown to the Association, another six cases had beenobserved at St. Mary's Hospital, but preparationsfrom more than 30 cases had now been seen.Clinically they usually show pyrexia, pallor, andpurpura. Most are rapidly fatal.
Haematologically they show anaemia, whichoccasionally is macrocytic, wide variations of thewhite blood cell picture ranging from neutropenia tomyeloid crises, thrombocytopenia, but occasionallythrombocythaemia, and usually absence of evidenceof haemolysis. The marrow shows erythroidhyperplasia sometimes resembling megaloblasts.Pathologically the red bone marrow is increased, but
infiltration of other organs is only apparentmicroscopically.
REFERENCESBritton, C. J. C., and Neumark, E. (1949). S. J. Leitner's Bone
Marrow Biopsy. (Trans.,rev., and ed. by Britton and Neumark.)J. & A. Churchill, London.
Di Guglielmo, G. (1917). Folia med. (Napoli), 3, 386.- (1926). Haematologica, 7, 481.Israels, M. C. G. (1939). J. Path. Bact., 48, 299.
Platelet Serotonin and Normal HaemostasisH. E. HUTCHISON and J. M. STARK (Glasgow). It
has often been suggested that the vasoconstrictor,serotonin (5-hydroxytryptamine, 5HT), released fromplatelets during clotting might take part in normalhaemostasis. With the discovery that reserpine candeprive the platelets of this 5HT and prevent furtheruptake, it has become possible to test haemostasis inthe absence of 5HT. No abnormality could bedemonstrated when the following investigations werecarried out in 12 patients given reserpine: bleedingtime, Hess's test, capillary response to injury, siliconeclotting time, prothrombin time, prothrombinconsumption index, thromboplastin generation test(with platelet dilutions), platelet count, plateletadhesiveness, and plasma clot retraction. From thisno evidence was obtained to suggest that 5HT playsany part in normal haemostasis.
Non-healing Granuloma of the Upper Air Passages:Granuloma Gangrenescens
E. W. WALTON (Dundee) said that, though over 300cases of granuloma which would not heal had nowbeen reported, understanding of it had progressedlittle since the late Sir Robert Muir wrote in 1897," The disease does not correspond to any type withwhich we are familiar." A personal study of 23 casessuggests that " non-healing " granuloma is a tripartitegroup: classical malignant granuloma, which is aprogressive, non-neoplastic but lethal form ofulceration; Wegener's syndrome, which is adisseminated granuloma of hyperergic typeoriginating in the respiratory tract; and granulomagangrenescens, which is a malignant neoplasm.
Five cases of this third type, having similarclinical and pathological features, were described, andat least 24 others had been reported previously.
Typically, granuloma gangrenescens begins as aprolonged nasal or palatal ulceration: after a latentperiod of six to 12 months, metastatic lesions develop.Most often, the cervical and mediastinal lymphnodes, liver, skin, kidney, spleen, and lung areaffected, with relatively frequent involvement of theheart, brain, small intestine, and gonads. Themetastases consist grossly of pale-grey infiltrates andcharacteristically focal tumours do not occur outsidethe upper air passages. Histologically theseinfiltrates are highly cellular and pleomorphic withmany mitoses; round and vesicular nuclei arecommon, and multinucleate cells are quite frequent.The absence of haematological abnormality duringlife and the absence of atypical cells from vessels intissue sections support the view that granuloma
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gangrenescens is not a leukaemia. There are none ofthe characteristic features of Hodgkin disease, andmost pathologists consider that it is a form ofreticulum-cell sarcoma, originating in the nose.
Further Observations Regarding Rheumatic Diseases(Including Rhmtoid Aritis) and Deficency of
Secretion of the Mucosa of the Small IntestineARNOLD RENSHAW (Manchester). A continuance
of former work, some of which had been previouslyreported and which had begun in 1939, stated theresults obtained to date by the use of the group ofenzymes known as erepsin in the treatment ofrheumatic diseases, including rheumatoid arthritis.Some 1,200 patients had now been treated with thisenzyme put up in tablet form, the latest preparationbeing known as "arthrepsin." In addition, at least10,000 injections of this specially purified enzyme hadbeen given trom time to time to these patients invarious areas requiring treatment.The results obtained had on the whole been
extremely good. Long-standing and short-standing,severely and slightly affected cases had been includedas they presented themselves. In many instancesother methods of treatment at present available hadbeen used in various patients without permanentsuccess-cortisone, other medicinals, including largedoses of aspirin, sedatives, gold, etc.-before theypresented themselves for this treatment. Of 1,200patients suffering from either rheumatoid arthritis,osteo-arthritis, fibrositis, and various other conditions,such as Paget's disease, spondylitis, Still's disease,90.9% were improved to some degree and only9.1% not improved or worse. Of these, 49% weremuch improved and were practically normal and quitewell able to earn a living. Of 533 patients withrheumatoid arthritis, 218 were much improved, 257were improved, 55 not improved, and only three(0.6%) worse while on treatment and underobservation for what is to be regarded as a deficiencydisease of intestinal secretion. This latter figurecompares with a series of untreated cases ofrheumatoid arthritis reported by other observers inwhich 33% of the patients were worse over five yearsor so of observation. Improvement occurs in thesedimentation rate, the albumin/globulin ratio, andin the general condition. In patients with osteo-arthritis with hyperpiesia the blood pressure may fallin 12 months or so from 210 mm. to 170 mm. Hg orthereabouts. Patients look five to 10 years youngerafter a year or so. Associated migraine practicallyceases after about three or four months' treatment.
In some cases recovery may appear to be delayed.A full protein diet is required. All purgatives andsedatives should be stopped. Adequate vitaminsshould be given.
Slides were shown of the condition of the proteinsin the swollen bursae when examined by the electronmicroscope and the effect on these of incubation witherepsin. A cine film also illustrated the improvementin several severe cases.
Cytological Examination of Gastric WashingsA. I. SPRIGGS (Oxford) described the results of
cytological examination of gastric washings from 155patients for malignant cells. A simple salinewashing technique was used. Comparativecytological and histological examinations were alsomade on a series of 24 fresh, surgically excisedstomachs.Of 28 cases with carcinoma, malignant cells were
identified in 55% in the first specimen. This figure islower than many in the literature, but has not beenweighted by the results of multiple examinations incases with strong clinical suspicion, nor by theexclusion of " unsatisfactory specimens." There wasone false positive report.A brief review was given of the techniques used by
previous workers in this field, such as abrasiveinstruments, proteolytic enzymes, and the use ofsections of fixed sediment. The last is recommendedas a method of relatively low sensitivity, but whichrequires no special training for technicians orpathologists and takes relatively little time. Theexamination of smears (which Dr. Spriggs stainseither with haematoxylin and mucicarmine or withPapanicolaou's stains) reveals malignant cells in ahigher proportion of cases but is extraordinarilylaborious.Coloured slides were shown of some of the
principal appearances, mostly in wet-fixed smears butalso in sections and in dry films stained by aRomanowsky method.
Some Observations on Drying HandsK. B. ROGERS (Children's Hospital, Birmingham).
The requirements for drying hands in hospitals aredifferent from those demanded anywhere else, and asa busy nurse takes only 10 to 14 seconds to dry herhands any method that is slow is undesirable. Theusual method of drying the hands is by employingsome form of towel, but it is obvious that a towelwill be useless if the act of drying infects the hands.At present nearly all hospital towels are liable toinfect the hands.
All the modern hot air hand dryers deliver acurrent of air that is too narrow to dry a largesurface and none dry the hands fast enough for usein hospitals. Moreover, many of the presentmachines have their air inlets too near the floor, sothat infected particles are liable to be sucked up fromthe floor and discharged into the air.
It must be emphasized that any hospital towelshould be covered until it is used, as infected particlesfall on it if it is exposed. Paper towels are relativelycheap and provide single disposable towels. Manypaper towels are rather rough, tending to scratch thehands, and very few dry the hands when only oneis used, so that the time taken to dry the hands isrelatively prolonged. Single cloth towels are tooexpensive to discard and the cost of launderingmilitates against their use.
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Several distributors market towels in long lengthswhich provide a dry and aesthetically clean surfacefor drying the hands. The makers are reluctant toalter the design of the machines which deliver thetowels, although the present cabinets make it verydifficult to use the piece of towel that has been mostrecently pulled off the unused roll of towel, so thatthese towels are just as liable to be contaminated asany other exposed towel in a ward in which there ismuch infection. This has been demonstrated byblowing a small number of very fine particles of wooldust, impregnated with fluorescine, into the air of aroom in which such towels are placed. By means ofthe ultra-violet light from a Wood's lamp it is easy toshow how these particles of dust fall on the exposedsurfaces.A cabinet has been designed which will provide a
continuous warm, dry, and sterile towel. Thecabinet contains boiling water, the steam from whichwill kill any non-sporing organisms on the surface ofa towel, which is drawn through the top of themachine. Experiments showed that there was nodamage to the cotton fibres of towels which wereplaced under tension and exposed to steamcontinuously for three weeks. The production of thismachine is held up because of the cost, as each musthave safety devices to prevent over-heating andliberation of steam, and the market would be limitedas the demand for these machines would only comefrom hospitals.
Haemagglutination Reactions with StreptococcalCultures
F. S. STEWART (Dublin) said that two types ofserological change were found in human red cellswhich had been incubated with streptococcal culturesupernatants:
(1) The development of an antigenic modificationidentical with that occurring in cells modified byexposure to influenza virus (FM1 strain). The agentresponsible for this type of change was found in allcultures of pneumococci examined, in a majority ofcultures of viridans streptococci, in a minority ofcultures of streptococci possessing Lancefield grouphaptens, and was not demonstrable in cultures ofStaph. aureus, neisseriae, and various Gram-negativeorganisms, with the exception of one strain ofSalm. typhimurium. Although not formally proved.the agent responsible for this type of change wasbelieved to be the receptor-destroying enzyme.
(2) Adsorption of heat-stable bacterial antigensprobably of polysaccharide nature. Four sensitizingantigens were identified, agglutinins reacting witheach being present in most normal human sera. Oneof these antigens was found to be widely distributedamongst the Gram-positive cocci, being present inmost Lancefield group streptococci in all strains ofStaph. aureus examined and in a minority of culturesof viridans streptococci. Except in one case it wasnot demonstrable in cultures possessing the cell-modifying enzyme. The remaining three antigens
were predominantly viridans antigens. The possiblevalue of these reactions in streptococcal classificationwas discussed. A species specific sensitizing antigenwas also identified in pneumococcal cultures.By the use of the sensitization technique it was
possible to demonstrate a high titre of antibody inthe sera of certain cases of presumed subacutebacterial endocarditis specific for sensitizing antigensin the homologous strain of streptococcus isolated onblood culture and it was suggested that the methodmight be of value in the diagnosis of this condition.
Benign "Tumours" of the LarynxS. S. EPSTEIN and I. FRIEDMANN (Department of
Pathology, Institute of Laryngology and Otology,London) presented a survey of benign " tumours " ofthe larynx, based on material seen in their departmentduring the years 1948-58 (see Table). This term wastaken to include non-neoplastic and benign neoplasticswellings.553 BENIGN " TUMOURS " OF LARYNX SEEN AT THEINSTITUTE OF LARYNGOLOGY AND OTOLOGY, LONDON,
Vocal cord polyps and their clinical variants,nodes and polypoidal degeneration, are by far thecommonest non-neoplastic laryngeal "tumours."They arise as a result of an exudate in the closedsubepithelial space of the membraneous cord. Theirstructure may be fibrovascular or oedematous, andthey may, for this reason, be misinterpreted asangiomas, fibromas, or myxomas, which in fact areexcessively rare in the larynx. Hyalinization in thevocal cord polyp is common, and when massive mustbe distinguished from the deposits of primarylocalized amyloidosis. Non-specific granulomas canoccur anywhere in the larynx, but are particularlycommon on the vocal process, where they may followthe trauma of endotracheal intubation (intubationgranuloma), or of forceful apposition of both vocalprocesses following abnormal patterns of phonation(contact ulcer granuloma).
Cysts and glandular hyperplasia may occur in thelarynx. When the glandular structure is conspicuous,compact, and unassociated with a significant inflam-matory exudate, they may be regarded as adenomas.Myoblastomas are also rare, and, while their preciseaetiological status is doubtful, are of special interestin that the overlying epithelium of the larynx mayassume a "pseudo-epitheliomatous " appearance.
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Laryngeal papillomas are the commonest benignlaryngeal neoplasms and when occurring in childhoodtend to be multiple and multicentric in origin. Adultpapillomas are more often solitary and localized tothe vocal cords and, when recurrent, the possibility ofa malignant change must be excluded. Papillaryprojections from a keratotic epithelium (papillarykeratosis) can, clinically and histologically, simulatepapillomas, but the conditions are quite distinct.Chondromas are rare and usually arise endo-laryngeally from the posterior plate of the cricoidcartilage. Angiomas, neurilemmomas, plasma-cytomas are rare.
Pulmonary Bone Marrow Embolism in AccidentReconstruction
J. K. MASON (Royal Air Force) discussed the useof pulmonary tissue embolism as a method for timinginjuries. Fat embolism, which had been suggested asbeing of value, was unsatisfactory because of thefrequency with which it occurs and confusionsurrounding its genesis. Pulmonary bone marrowembolism is accepted as arising only following traumato bone and its incidence had been studied in 102aircraft deaths associated with fracture. Emboliwere found in 40.2% of such cases. If a minimum offive slides had been examined in every case, theincidence would have approximated to 60%. Emboliwere distributed at random in the lungs.A correlation with injuries sustained shows that
emboli are uncommon when there is evidence ofwidespread, instantaneous destruction of the organsand, in particular, the cardiovascular system. Embolican only form in the presence of an intact circulation,but both fat and bone marrow emboli arise with verygreat speed, the latter being found in 37% of deathsbelieved to be immediate. Both become more markedwith increased survival time, but bone marrow emboliare resolved very much faster than fat emboli. Ananalysis of the two types of embolism can givevaluable information as to survival following injury.The application of these findings to accident
reconstruction was illustrated with reference to deathsfollowing escape from aircraft by ejection. Deathsdue to simple lack of height can be differentiatedfrom those associated with injury at altitude by meansof a thorough search for pulmonary bone marrowemboli.The possibility of extending such principles to
other types of accident was discussed.
Mesonephric Tumours of the Female Genital TractF. A. LANGLEY, Lois STENT, and T. WADE-EVANS
(Manchester) said that Schiller in 1939 described agroup of rare tumours characterized by the presenceof "glomerulus-like " structures and tubules linedby "hob-nail" cells. He called these tumoursmesonephromas because he thought that they werederived from the mesonephros. Teilum (1945) doesnot accept this view and considers such tumours tobe closely related to embryomal carcinomas and
chorion-epitheliomas. Teilum himself has describedan unrelated class of tumour which he considers to betruly mesonephric.A study was made of nine tumours belonging to the
class described by Teilum. These show muchvariation in histological pattern. Five main patternsare recognizable, namely, adenomatoid, tubular,cystic, papillary, and sheets, or cords, or eosinophiliccells. Several of these patterns are usually present inany one tumour.
It is concluded that these tumours fall into twogroups: (1) Tumours which are truly mesonephric,being derived from vestiges of the mesonephros orfrom mesenchyme retaining mesonephric potencies;(2) tumours derived from vestiges of the rete ovariior from mesenchyme retaining rete potencies.testis.Tumours similar to these two types occur in the
REFERENCESSchiller, W. (1939). Amer. J. Cancer, 35, 1.Teilum, G. (1945). Acta obstet. gynec. scand., 25, 377.
Hyperephroma with Polycythaemia: UraemicAnaemia; Possible States of Over- and
Under-secretion of ErythropoetinH. F. BARNARD (Westwood Hospital, Beverley,
Yorks) said that the association of these states had, inrecent years, been reported a number of times. Thecase here described, a woman of 73, sufferedfrom haematuria, a haemoglobin of 135% repeatedly,and no other notable feature. A moderate-sizedtypical hypernephroma was removed by nephrectomy.Histologically the tumour was a typical clear celltype with no distinguishing features. The haemo-globin returned to normal and the patient remainswell with a normal haemoglobin a year later.
Polycythaemia occurs with probably 4% ofhypernephromas and may be the presenting symptom.Erythropoetin long suspected and now reasonablyestablished is probably secreted by the kidney. It hasbeen suggested that in polycythaemic cases thetumour may secrete erythropoetin.
In uraemic anaemia it is reported that erythropoetinin the plasma is low. It is of interest, therefore, thatby transfusing post-haemorrhagic plasma intouraemic anaemia reticulocytos s has been obtained.
Birth Injury to the NeckP. 0. YATES (Department of Pathology, University
of Manchester) said that all methods of delivery in-volved stresses of varying degree to the infant's neck.Out of 213 deaths occurring in the perinatal period, arandom selection of 60 were examined histologicallyfor evidence of trauma to certain cervical structures.Though only two, both breech deliveries, showedmarked bruising of the spinal cord, nine had nerveroot injuries, and in nearly half the total there wasdamage to the spine ligaments and the dura were tornin some.The most surprising findings were haematoraas in
the walls of the vertebral arteries in 24 cases. Many
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of these were large enough to cause narrowing of thearterial lumen. They were thought to arise fromtearing the origins of arterial twigs supplying nerveroots and spinal cord. These haematomas may beof considerable importance since ischaemic damageto the nuclei of the brain-stem would result incardiorespiratory embarrassment and dysfunction ofcranial nerves. Moreover, since the vertebral arteriesare responsible for the blood supply to the inner ear,the optic cortex, and in part the basal ganglia, thoseinfants surviving moderate degrees of ischaemia mightlater show deafness, blindness, or one of the formsof cerebral palsy. The bilateral symmetry of somecerebral lesions described in cerebral palsy which hasin the past been attributed to interruption of venousdrainage into the great vein of Galen could equallywell be accounted for by stenosis of a vertebralartery, since these vessels have, via the basilar artery,a bilaterally symmetrical distribution.
Serum Isocitric Dehydrogenase in the Investigation ofLiver Cell Damage
D. N. BARON and JOYCE L. BELL (Royal FreeHospital, London) reported that serum isocitricdehydrogenase (ICD) was estimated by the method ofWolfson and Williams-Ashman (1957), involvingspectrophotometric measurement at 340 m,u ofconversion of T.P.N. to T.P.N.H. during dehydro-genation and decarboxylation of D-isocitrate.Activity is measured in units similar to transaminaseunits: one unit is a change in O.D. of 0.001 /ml.serum/min. in a volume of 1.5 ml., corrected to25° C. (Qlo; 20'-30° C.= 1.7). Our normal rangewas 2.5-9 units; that of Wolfson and Williams-Ashman, converted to these units, was 3-15 units(1 O.D. unit= 15 Wolfson reactant units).
Hepatocellular damage raised the serum I.C.D.High values (up to 200 units) occurred in parallelwith transaminases in infective hepatitis, and a rise(20-60 units) was found following administration ofhepatotoxic drugs, e.g. iproniazid, in primary andmetastatic hepatic malignant disease, and usually incirrhosis. Serum I.C.D. was consistently normal inpost-hepatic obstructive jaundice, and this may provevaluable in differential diagnosis.
In clinical protein malnutrition (in Nigeria) serumI.C.D. rose (average 30 units), and slight increases(average 10 units) were found in villagers on a poordiet. Serum I.C.D. appeared more sensitive for liverdamage here than all other tests, includingtransaminases.
In uncomplicated myocardial infarction, serumI.C.D. was normal, but in cases with heart failure andliver enlargement moderate rises were found; in onecase with prolonged hypotension, the serum I.C.D.exceeded 200 units.
REFERENCEWolfson, S. K., and Williams-Ashman, H. G. (1957). Proc. Soc. exp.
Biol. (N.Y.), 96, 231.
The Diagnostic Value of Plasna Amylase withSpecial Reference to Gastrectomy
G. K. McGowAN (Bristol) said that over a seven-year period 53 patients who might have beendiagnosed clinically as acute pancreatitis were foundto have plasma amylase levels of over 1,000§omogyi units/ 100 ml. In 39 the diagnosis wascertainly or very probably acute pancreatitis, and infive the final diagnosis was uncertain. In nine thediagnosis was shown not to be acute pancreatitis.Of these nine "false positives," seven had had a
partial or total gastrectomy at a time which variedfrom 12 hours to four years before the attack,whereas none of the true cases of acute pancreatitishad had a gastrectomy. The two remaining "falsepositives" were suffering from perforation of apeptic ulcer.A further four patients on whom a gastrectomy had
been performed developed abdominal symptoms withplasma amylase levels of over 1,000 units, but noneof these were considered on clinical grounds to besuffering from acute pancreatitis.
After gastrectomy there are many possible factorswhich can contribute to a rise in the plasma amylaselevel such as resistance to the escape of pancreaticsecretions due to afferent loop obstruction or spasmof the sphincter after drugs like morphia; absorptionof amylase from the peritoneal cavity after escapeof pancreatic secretions due to leak from the gutor accidental secretion of accessory pancreatic ducts;secondary pancreatitis resulting from peritonitis;renal insufficiency in post-operative shock reducingthe excretion of amylase in the urine.
It was concluded that a high plasma amylase shouldnot be taken as indicative of acute pancreatitis if thepatient has had a gastrectomy, and that pathologistsshould emphasize this point when reporting suchraised values.
Serum Transaminase Activity in Cirrhosis of theLiver and Related Conditions
K. O'SULLIVAN and J. KoHN (Roehampton) hadclassified the 450 patients who comprised this studyas follows:Liver diseases .230 (114 cirrhosis)Miscellaneous diseases .155Patients with or suspected of cardiac infarction 35Normal subjects.30The S.G.O.T. and S.G.P.T. activity was observed
in a large number of cases of chronic liver disease andthe results compared with the flocculation liverfunction tests, the alkaline phosphatase, serumproteins, E.S.R.s, and electrophoresis of serumproteins.No direct correlation was found between these tests
and the serum transaminases. The conclusion wasreached that the serum transaminases are far moresensitive tests than the flocculation tests in theassessment of hepatocellular damage, and thatabnormal serum transaminase values quickly followhepatic necrosis. In acute cases the rise in serum
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transaminase may precede abnormal readings of allthe other liver function tests.
Alkaline phosphatase was estimated in 300cases in conjunction with the serum transaminasesand in 26 liver cases abnormal alkaline phosphataselevels were found. Of these 26, 80% also hadabnormal serum transaminases. On the other hand,68 liver cases with abnormal serum transaminaseswere found; of these only 31% had abnormalalkaline phosphatases. A greater percentage of casesof cirrhosis with a previous history of infectivehepatitis had abnormal serum transaminase valuesthan other cases of cirrhosis. The incidence ofinverted S.G.O.T.-S.G.P.T. ratios in chronic hepaticdiseases was noted. A reversed ratio was presentin 40% of liver cases with abnormal serumtransaminases and in 19% of liver cases with normaltransaminases.When the serum transaminases are estimated by the
colorimetric method of Reitman and Frankel (1957)corrections for temperature are unnecessary in therange of 20 to 30° C.
It is concluded that in chronic liver diseases theserum transaminases are a valuable adjunct inassessing clinical progress and as a guide toprognosis.
REFERENCEReitman, S., and Frankel, S. (1957). Amer. J. clin. Path., 28, 56.
The Effect of Heparin on the Early Stages ofBlood Coagulation
J. R. O'BRIEN (Portsmouth). Heparin in criticaldosage was found to have no apparent effect on anti-haemophilic globulin, factor V, factor VII, or onplatelet activity, and the activation of coagulation byglass (Hageman factor) was not affected. Evidencewas presented which strongly suggests that heparinactually combines with and inactivates Christmasfactor and that the addition of protamine sulphate tosuch a heparin-Christmas factor complex removes theheparin, thereby liberating the Christmas factoractivity. Heparin can apparently exist in two formsin plasma. It may be free and available to delayclotting, or it may be inactivated, presumably boundto some protein, and unavailable to delay clotting.The ability of coagulation factors to inactivateheparin was investigated; the clotting time of athrombin fibrinogen mixture was used to measure thepresence or absence of available heparin after theheparin had been added to the plasma fraction understudy. Plasma Christmas factor, and especiallyserum Christmas factor, and platelet protein, but notintact platelets, were shown to inactivate heparin.The platelet-like activity of serum (O'Brien, 1955) alsoinactivated heparin. The ability of whole nativeblood to inactivate heparin was monitored while theblood was clotting and the amount of heparin thatcould be inactivated was markedly increased in thesubsamples taken soon after the blood started to clot;this increased inactivating power of blood was duepresumably to platelets breaking up, and to theformation of platelet-like activity of serum and
serum Christmas factor, and these three occurrencesprobably accounted for all the heparin inactivated.Critical quantities of heparin added to whole nativeblood delayed clotting, probably due to its effecton Christmas factor. Thrombin generation andprothrombin consumption were normal and nodetectable heparin remained in the serum; presum-ably the heparin was inactivated by the mechanismsreported above before it could interfere with theintrinsic thrombin formed.
REFERENCEO'Brien, J. R. (1955). Brit. J. Haemat., 1, 223.
Problems in the Diagnosis of MegakaryocyticMyelosis
H. G. H. RICHARDS (Winchester). The mainclinical and laboratory findings in myelosclerosiswere reviewed, and the three stages of this diseasedescribed by Leonard, Israels, and Wilkinson (1957).A series of five cases of megakaryocytic myelosiswhich appeared to be a special form of myelo-sclerosis, and might be related to stage I, as describedby Leonard et al., were described.
Clinically, these cases featured refractory anaemiawith hepatosplenomegaly and wasting. Laboratoryinvestigations revealed a progressive anaemia withmarked erythropoikilocytosis, bizarre platelets incirculation, and a leucoerythroblastic blood picture.Marrow aspiration usually produced blood only. Atnecropsy (or by means of a surgical biopsy of themarrow) it was found that the marrow was hyper-cellular, with a superabundance of megakaryocytes,and an increase in reticulin stroma. The liversinusoids showed foci of haemopoiesis, includingmegakaryocytes, and the spleens, in availablesections, likewise showed the presence of mega-karyocytes with other evidence of myeloid ectopia.The differential diagnosis between megakaryocytic
myelosis and other conditions such as myeloidleukaemia, a necrotizing form of Hodgkin's disease,typical myelosclerosis. and leucoerythroblasticanaemia arising in secondary carcinomatosis of bonemarrow, was illustrated by examples.
Hypofibrinogenaemia in Pregnancy: Prevalenceand Prognosis
R. F. JENNISON (St. Mary's Hospitals, Manchester).A survey of the incidence of hypofibrinogenaemia inpregnancy was carried out at St. Mary's Hospital,Manchester, during a period of a little more thanthree years, the object being to assess the frequencyand severity of this condition.One hundred and ninety fibrinogen estimations
were carried out at all stages of normal pregnancy.The mean fibrinogen level in the first trimester was377 mg.%, in the second trimester 443 mg.%, and inthe third trimester 487 mg. %. The standarddeviation in the third trimester was ±102 mg.%, sothat the limits within which 95% of fibrinogen levelsin normal pregnancy should fall were 283 mg.% to691 mg.%, and, on this basis, when reviewing the
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patients in the survey, fibrinogen levels below 270mg.% were considered possibly to be due to somepathological condition.
In the survey, fibrinogen estimations were done on(1) patients with an accidental haemorrhage, (2)women with retention of a dead foetus in utero forlonger than one week, (3) patients with severe shockor with haemorrhage due to causes other thanaccidental haemorrhage and placenta praevia, (4)patients with severe toxaemia of pregnancy oreclampsia. Two hundred and six women with theseconditions were investigated and 52 were found tohave hypofibrinogenaemia.
Thirty-four women with low fibrinogen levels werefound in 117 patients with accidental haemorrhage.In 1956, 81 patients, in 1957, 100 patients, and in1958, 82 patients were admitted with accidentalhaemorrhage according to the hospital records. Theincidence of hypofibrinogenaemia in those years was9%, 13%, and 12% of the patients with an accidentalhaemorrhage. Of the 34 patients with low fibrinogenlevels, eight were below 50 mg.%, six between 50mg.% and 100 mg.%, and 10 between 100 mg.%and 200 mg.% The more severe deficiencies infibrinogen usually occurred in the patients with largeretroplacental blood clots. All but three of thesepatients had transfusions of blood and/or plasma.The treatment was usually started because of shockor haemorrhage and not because of the lowfibrinogen level. Of the 10 patients with fibrinogenlevels above 200 mg.%, only three had transfusions.The fibrinogen levels returned rapidly to normal inall cases irrespective of treatment.
Fifty-three women with a dead foetus retainedin utero were also investigated. Forty-one of theseretained the dead foetus for three weeks or more and13 of these developed hypofibrinogenaemia. In onepatient the fibrinogen level fell below 50 mg.%, intwo it was between 50 mg.% and 100 mg.%, and insix between 100 mg.% and 200 mg.%. There was aprogressive slow fall in all cases, the lowest levels
being reached in those women who retained the deadfoetus the longest. Only three of these patients hadtransfusions and the -fibrinogen levels returned rapidlyto normal. The only severe haemorrhage was in apatient delivered immediately on admission tohospital.Amongst the miscellaneous conditions were two
patients with haemorrhage associated with abortionand fibrinogen levels of 68 mg.% and 22 mg.%. Oneother patient was admitted with severe haemorrhageand a ruptured uterus. Her fibrinogen level onadmission was 150 mg. /O. Two other patients becameextremely shocked early in labour and a diagnosis ofamniotic fluid embolism was made. The fibrinogenlevel fell to 50 mg.% in the first patient. Nofibrinogen was detected in the second patient untilseven hours after delivery. Multiple transfusionswere required, but both patients recovered so that thediagnosis of amniotic fluid embolism could not beconfirmed by necropsy.No instances of hypofibrinogenaemia were seen in
toxaemia of pregnancy.Fibrinogen was only used in the treatment of these
patients on one occasion. When treatment other thanblood transfusion was thought to be necessary, triplestrength plasma was used.
All the patients, except one who had a caesareansection for suspe::ted placenta praevia, were deliveredvaginally.
In all the patients delivered in hospital a priorknowledge of the fibrinogen level has allowedextreme care to be taken in order to avoid unneces-sary trauma and following delivery the uterus hasbeen kept well under control.The patients who caused most concern were those
delivered either outside the hospital or withoutknowledge of the fibrinogen level, or those in whomsome abnormal condition made the obstetricmanagement difficult.
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