2
203 platelets. This theory has since held the field against all attacks and has recently been confirmed again by SALTZMAN in Sweden and SCHWARZ 2 in America. Using the dark-ground illumination techniques applied by WALLGREN to ’the study of cytoplasmic structure, SALTZMAN found that the cytoplasm of megakaryocytes and the blood-platelets share some features of arrangement that are found only in these cells, and there are many other points of similarity that occur in few other bone-marrow and blood cells. No signs of life were recognised in the platelets ; the odd protrusions and blisters with granules in brownian movement appear to be quite unchanged by the addition of potassium cyanide to the prepara- tions. SCHWARZ has studied the formation of granules in megakaryocytes. The typical megakaryocyte of bone-marrow, with a uniformly granular cytoplasm, originates from a smaller megakaryoblast that has non-granular cytoplasm. In the megakaryoblast and the next stage-the promegakaryocyte-a relatively pale zone appears in the cytoplasm next to the indentation in the nucleus ; it is within this area that the granules first appear. SCHWARZ calls this pale zone the " functional area," and, by studying many preparations from suitable bone-marrows, he has found that as the megakaryocyte develops, this functional area stains pinkish and the granules become blue; the area spreads as the cell develops until eventually it occupies the whole cytoplasm except for a narrow peripheral rim. DE LA FUENTE 3 described a similar development, but he thought that granule formation began in several areas simul- taneously. When the megakaryocyte divides, the functional area is not involved and remains unaltered in size and shape ; the nucleus appears to take no part in granule formation. The megakaryocyte, SCHWARZ points out, thus behaves like any other cell ’whose cytoplasm develops a " specific functional transformation." It is only when the cytoplasm is fully granular that platelets are formed, by the breaking up of pseudopodia. SCHWARZ also discusses the appearances of the megakaryocyte in thrombo- cytopenic purpura, which is well known as a primary disease and also occurs as part of other syndromes such as aplastic anaemia. Splenectomy is effective treatment for most, though not all, of the primary cases but is useless in the secondary type. Since the blood-platelets are so much reduced in this form of purpura the megakaryocytes have naturally been carefully studied in the hope of finding a clue to the aetiology of the disease and explaining the occasional failures of Splenectomy.. SCHWARZ finds that the megakaryocytes usually look quite normal ; granule formation in the cytoplasm proceeds in the way described above. There is often hyperplasia of the megakaryocytes, and-exactly as with hyperplasia of other types of marrow cells-early forms are relatively increased. On the other hand, cases have been reported in which the megakaryocytes were reduced or even absent. In another group distinctly abnormal megakaryocytes have been found ; a recent example is the description by DAMESHEK and MILLER 4 of odd megakaryocytes with non-granular cytoplasm that 1. Saltzman, G.-F. Acta med. scand. 1949, 132, suppl. 221. 2. Schwarz, E. Arch. Path. 1948, 45, 333, 342. 3. De la Fuente, V. Arch. intern. Med. 1946, 79, 387. 4. Dameshek, W., Miller, E. B. Blood, 1946, 1, 27. they call " lymphoid forms." Differences of technique make comparison between different reporters difficult, but deficient granule formation is common to all. SCHWARZ examined the marrow from 26 patients with primary thrombocytopenic purpura and found deficient granule formation in only a single case. The early megakaryocytes of this patient had a " functional area " that appeared and enlarged as in normal cells, but -no granules developed in the area. There thus seem to be three types of primary thrombocytopenic purpura: e (1) the common type with normal megakaryocytes, (2) a type in which granule formation fails, and (3) one in which the megakaryocytes are degenerate or show cytotoxic changes. The second type, in particular, has had undue publicity, but ScgwAtz’s estimate that orily- about 4% of patients show abnormal marrow pictures will surely be supported by anyone with experience in this difficult field. Consequently statements that splenectomy in thrombocytopenic purpura should only be recommended if a characteristic marrow picture is found 5 are premature. The knowledge that the clinical syndrome of thrombocytopenic purpura has a varied marrow picture may enable us to sort out those whom splenectomy is less likely to benefit, but the evidence has yet to be produced. Annotations ROYAL MEDICAL BENEVOLENT FUND ‘’ Letters of inquiry from medical men which reach the office from time to time lead the Committee to conclude that deserving cases fully entitled to relief fail to be directed to the Fund." Mr. R. M. Handfield-Jones,6 chairman of the committee of management of the Royal Medical Benevolent Fund, reports that in spite of the efforts of the central office and the local secretaries, the ladies’ guild, and the British Medical Association, many doctors are still unaware of the work and scope of the Fund. How wide this scope is may be judged from the Fund’s " proud tradition for a great many years that no applicant, medical man or woman, wife, widow, or child, is refused assistance if the need is real." Moreover, it is not only subscribers, or the relatives of subscribers, who are entitled to apply for help : the Fund is ready to help the whole profession. At the case-committee meetings none of the members knows whether the applicant has been a subscriber or not. Those who have contributed regularly to the Fund realise this already ; but in order to explain the work of the Fund to the profession at large the annual report is this year being sent to every doctor in England, Scotland, and Wales. Since the little booklet is filled mainly with accounts, it does not take five minutes to glance through the four pages allotted to Mr. Handfield- Jones. The information he packs into them has a. personal interest for us all, since as he says " an honour- able and learned profession should be able to cope with its own casualties." He foresees many years of necessary work for the Fund, despite national insurance ; for even the most benevolent of national schemes cannot take account of all the ills that flesh is heir to, all the disasters which may overtake a doctor’s family when he is disabled or struck down. Mr. Handfield-Jones quotes two cases characteristic of those which came before the Fund : an aged doctor, infirm with failing vision, is trying to carry on practice to support an invalid wife ; 5. Scott, R. B. Brit. med. J. 1949, i, 1063. 6. Annual report, 1948. Obtainable from the secretary, 1, Balliol House, Manor Fields, Putney, London, S.W. 15.

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platelets. This theory has since held the field againstall attacks and has recently been confirmed againby SALTZMAN in Sweden and SCHWARZ 2 in America.Using the dark-ground illumination techniques

applied by WALLGREN to ’the study of cytoplasmicstructure, SALTZMAN found that the cytoplasm of

megakaryocytes and the blood-platelets share somefeatures of arrangement that are found only in thesecells, and there are many other points of similaritythat occur in few other bone-marrow and blood cells.No signs of life were recognised in the platelets ;the odd protrusions and blisters with granules inbrownian movement appear to be quite unchangedby the addition of potassium cyanide to the prepara-tions. SCHWARZ has studied the formation of granulesin megakaryocytes. The typical megakaryocyte ofbone-marrow, with a uniformly granular cytoplasm,originates from a smaller megakaryoblast that hasnon-granular cytoplasm. In the megakaryoblast andthe next stage-the promegakaryocyte-a relativelypale zone appears in the cytoplasm next to theindentation in the nucleus ; it is within this areathat the granules first appear. SCHWARZ calls this

pale zone the " functional area," and, by studyingmany preparations from suitable bone-marrows, hehas found that as the megakaryocyte develops, thisfunctional area stains pinkish and the granules becomeblue; the area spreads as the cell develops untileventually it occupies the whole cytoplasm exceptfor a narrow peripheral rim. DE LA FUENTE 3

described a similar development, but he thoughtthat granule formation began in several areas simul-taneously. When the megakaryocyte divides, thefunctional area is not involved and remains unalteredin size and shape ; the nucleus appears to take nopart in granule formation. The megakaryocyte,SCHWARZ points out, thus behaves like any othercell ’whose cytoplasm develops a

"

specific functionaltransformation." It is only when the cytoplasm is

fully granular that platelets are formed, by the

breaking up of pseudopodia. SCHWARZ also discussesthe appearances of the megakaryocyte in thrombo-cytopenic purpura, which is well known as a primarydisease and also occurs as part of other syndromessuch as aplastic anaemia. Splenectomy is effectivetreatment for most, though not all, of the primarycases but is useless in the secondary type. Sincethe blood-platelets are so much reduced in this formof purpura the megakaryocytes have naturally beencarefully studied in the hope of finding a clue to theaetiology of the disease and explaining the occasionalfailures of Splenectomy.. SCHWARZ finds that the

megakaryocytes usually look quite normal ; granuleformation in the cytoplasm proceeds in the waydescribed above. There is often hyperplasia of themegakaryocytes, and-exactly as with hyperplasia ofother types of marrow cells-early forms are relativelyincreased. On the other hand, cases have been

reported in which the megakaryocytes were reducedor even absent. In another group distinctly abnormalmegakaryocytes have been found ; a recent exampleis the description by DAMESHEK and MILLER 4 of oddmegakaryocytes with non-granular cytoplasm that

1. Saltzman, G.-F. Acta med. scand. 1949, 132, suppl. 221.2. Schwarz, E. Arch. Path. 1948, 45, 333, 342.3. De la Fuente, V. Arch. intern. Med. 1946, 79, 387.4. Dameshek, W., Miller, E. B. Blood, 1946, 1, 27.

they call " lymphoid forms." Differences of techniquemake comparison between different reporters difficult,but deficient granule formation is common to all.SCHWARZ examined the marrow from 26 patientswith primary thrombocytopenic purpura and founddeficient granule formation in only a single case.The early megakaryocytes of this patient had a" functional area " that appeared and enlarged as innormal cells, but -no granules developed in the area.

There thus seem to be three types of primarythrombocytopenic purpura: e (1) the common typewith normal megakaryocytes, (2) a type in whichgranule formation fails, and (3) one in which themegakaryocytes are degenerate or show cytotoxicchanges. The second type, in particular, has hadundue publicity, but ScgwAtz’s estimate that orily-about 4% of patients show abnormal marrow pictureswill surely be supported by anyone with experiencein this difficult field. Consequently statements thatsplenectomy in thrombocytopenic purpura should

only be recommended if a characteristic marrow

picture is found 5 are premature. The knowledge thatthe clinical syndrome of thrombocytopenic purpurahas a varied marrow picture may enable us to sortout those whom splenectomy is less likely to benefit,but the evidence has yet to be produced.

Annotations

ROYAL MEDICAL BENEVOLENT FUND‘’ Letters of inquiry from medical men which reach the

office from time to time lead the Committee to concludethat deserving cases fully entitled to relief fail to be directedto the Fund."

Mr. R. M. Handfield-Jones,6 chairman of the committeeof management of the Royal Medical Benevolent Fund,reports that in spite of the efforts of the central officeand the local secretaries, the ladies’ guild, and the BritishMedical Association, many doctors are still unaware ofthe work and scope of the Fund. How wide this scopeis may be judged from the Fund’s " proud tradition fora great many years that no applicant, medical man orwoman, wife, widow, or child, is refused assistance if theneed is real." Moreover, it is not only subscribers, orthe relatives of subscribers, who are entitled to apply forhelp : the Fund is ready to help the whole profession.At the case-committee meetings none of the membersknows whether the applicant has been a subscriber ornot. Those who have contributed regularly to the Fundrealise this already ; but in order to explain the workof the Fund to the profession at large the annual reportis this year being sent to every doctor in England,Scotland, and Wales. Since the little booklet is filled

mainly with accounts, it does not take five minutes toglance through the four pages allotted to Mr. Handfield-Jones. The information he packs into them has a.

personal interest for us all, since as he says " an honour-able and learned profession should be able to cope withits own casualties." He foresees many years of necessarywork for the Fund, despite national insurance ; for eventhe most benevolent of national schemes cannot takeaccount of all the ills that flesh is heir to, all the disasterswhich may overtake a doctor’s family when he isdisabled or struck down. Mr. Handfield-Jones quotestwo cases characteristic of those which came before theFund : an aged doctor, infirm with failing vision, is

trying to carry on practice to support an invalid wife ;5. Scott, R. B. Brit. med. J. 1949, i, 1063.6. Annual report, 1948. Obtainable from the secretary, 1, Balliol

House, Manor Fields, Putney, London, S.W. 15.

Page 2: ROYAL MEDICAL BENEVOLENT FUND

204

a man under fifty with malignant hypertension, whosewife must stay at home to nurse him, has three childrenwho need help to complete their education.

In such circumstances as these, grants are vain unlessthey are generous, and therefore the Fund has need ofmore than all the money it raises. In the last thirteenyears subscriptions have increased from f13,500 yearlyto 23,900—an increase of more than 10,000 yearlyover a period which includes the second world war.Last year the Fund’s income was E36,968 ; and E32,000of this went out to relieve poverty and distress. Some,moreover, went to maintain Westmoreland Lodge, theresidential home at Wimbledon now happily occupied bytwelve elderly ladies, beneficiaries of the Fund, who hadbeen living lonely and straitened lives in single rooms.Over E2300 was distributed in Christmas gifts to thefund’s benenciaries.

No appeal for funds has ever been made to the generalpublic : this is our own responsibility and one whichthe profession as a whole can well carry. It is surelyright that such an intimate and benevolent undertakingshould, as the report says, claim the interest of everymember of our profession.

POSTERIOR CULDOSCOPY

IN the United States some gynaecologists are usingendoscopy of the pouch of Douglas through the posteriorfornix as an alternative to exploratory laparotomy, andthe bastard French-Greek term " culdoscopy " has beenapplied to this procedure. Abdominal peritoneoscopyhas never caught on widely here, though it is nearly fortyyears since it was first thought of, but this approachthrough the posterior fornix is said to avoid the unde-sirable features of abdominal puncture. Decker 1 givesa detailed description of the technique. The patientmust be examined in the knee-chest position or theview will be obscured by coils of intestine. Unfor-

tunately, this is the most disconcerting of all positionsfor the unanaesthetised patient. With the help of

procaine local anaesthesia the trocar is inserted throughthe posterior fornix, and a pneumoperitoneum results atonce if the pouch of Douglas has been successfully per-forated. Either carbon dioxide -or. air can thus beadmitted and the intestines tend to fall out of the way.The electrically lit culdoscope is then inserted and thepelvic cavity visually explored. Decker describes his

experiences in 77 cases selected because of difficulty indiagnosis, and Te Linde and Rutledge 2 give a similarseries of 56 cases., In about 10% of the patients theoperation failed, either because of a loosely attachedperitoneum, which " rides ahead of the trocar " or

because of a pelvic mass or adhesions. Neither serieswas marred by visceral injury, haemorrhage, or peritonitis.The cases for which this investigation is regarded as

suitable are the differential diagnostic problems of

ectopic pregnancy, pelvic inflammatory diseases, acuteand " chronic " appendicitis, pelvic tuberculosis, andendometriosis, and for assessing the state of the pelvicorgans in sterility. The claims are too sweeping to beignored, but it is doubtful whether this procedure will beused much in this country. With accurate clinicalexamination and the accessory laboratory aids,such as leucocyte-counts and endometrial biopsy, theproportion of cases in which culdoscopy might be usefulshould be small. Then, it is in just the cases which ofteninvite visual inspection of the pelvic organs-e.g., casesof chronic pelvic pain with a tender fixed retroversion oran indefinite tender mass-that the risks of such an

inspection from perforating adherent intestine would’seem to outweigh its possible advantages ; moreover,in these cases the field would sometimes be obscured byadhesions, rrns. or tarrv blood. Of all the forms of

1. Decker, A. J. Amer. med. Ass. 1949, 140, 378.2. Te Linde, R. W., Rutledge, F. Amer. J. Obstet. Gynec. 1948,

55, 102.

gynxcological examination, this must be among the mostrigorous from the patient’s point of view-its use incases of sterility may lead the cynic to wonder whatnext these unfortunate women will have to endure in thenext hundred years. Nevertheless, when he considersthe frequency of errors in clinical diagnosis, the numberof unnecessary laparotomies done, and the temptation toradical surgery which abdominal exposure of thepelvic viscera presents, even the most conservativegynaecologist will acknowledge that culdoscopy offersattractions.

HOUSEWIFE’S LOAD

THE housewife is the freelance of the labour market;and the diagnostic sign of a freelance is that he is neverfree. The job which can be done " in any odd moment "is at the mercy of anyone who cares to interrupt it;and everybody borrows time from the one member ofthe family whose time is not sold in neat sections, peggeddown with a whistle at either end. Last year Dr. StellaInstone 1 made a study of 61 Sussex housewives, andfound that their state of health was not good enoughfor the lives they had to lead. They were nearly alltired, many had varicose veins -and postural defects,some had bad teeth or bad feet, some were stout andhypertensive. Their fatigue, she thought, was not due tolack of sleep, but rather to much standing in queuesand basket-carrying, and to faulty feeding (many ofthem making a practice of giving up their protein toother members of the family). Dr. Dagmar vVilson 2has now made two small studies, the first of 194Oxfordshire, Berkshire, and South Devon women, 127 ofthem townswomen and 67 rural. Unlike Dr. Instone,she heard few complaints about shopping. Most of thewomen were interested in cooking and satisfied withtheir cooking arrangements. Some complaired of havingto share their homes with additional relatives, but

spoke more approvingly of lodgers, who contributeto expenses without being so much of a strain on thetemper. More than half of them were married to skilledworkers, nearly a third to unskilled workers, and theremaining 4.3% to professional workers. Over three-quarters reported some sort of strain or stress—over-

crowding, deficient water-supply, and loneliness whenchildren had left home being among these. Only 7%were under medical care, but physical examinationsuggested that a further 31% needed medical or dentaltreatment. In addition, over three-quarters had foottroubles such as flat-feet, corns, or bunions, and 12%had varicose veins.The second survey was made on a group of 57 women

between the ages of forty and sixty who had lived fornearly three years on

" an estate of 250 houses situated

on a sandy hilltop near the city boundary and circum-scribed by fields and gardens." She found 20 of them in

good health ; the rest complained of such things as

menopausal symptoms, gynaecological disorders, respira-tory, and gastro-intestinal ailments, nervousness, anddiseases of the bones and legs. Only 3 of this grouphad foot troubles ; 1 had severe varicose veins ; 5 had

simple goitre and 1 was myxcedematous. Only 2 wereunder a doctor’s care at the time of the inquiry, but itwas felt that a further 11 should be having medicaladvice. In this group nearly a quarter were the wivesof professional workers, and nearly two-thirds wives ofskilled workers ; only about a tenth were married tounskilled workers. There was only 1 case of over-

crowding. All but 6 were satisfied with their cookingarrangements, and their food was probably adequatein caloric value, though they complained of monotony;and here again a large proportion of them gave up allor part of their protein ration to other members of thefamily. Unlike the first group they suffered little anxiety

1. Lancet, 1948, ii, 899.2. Publ. Hlth, Lond. April, 1949, p. 139.