R. B. McConnell

Experimental Studies on the Prevention of Rh Haemolytic Disease

In the context of haemolytic disease of the newborn, ABO incompatibility means that the father’s blood is unsuitable for transfusion into the mother, and our interest in this stems from the work of Levine (1943), who noted a deficiency of such mating types in the parents of affected children. He deduced, therefore, that ABO incompatibility affords a degree of protection against Rh haemolytic disease, and this has been confirmed by many workers. Of particular interest are the experiments of Stern et al. (1956), who showed that male volunteers could be much more easily sensitized to Rh if the injected blood were ABO compatible.

Further Experimental Studies on the Prevention of Rh Haemolytic Disease

In a previous report (Finn et al., 1961) we gave reasons for thinking that the rapid removal of Rh-positive foetal erythrocytes from the circulation of a mother who was Rh-negative would prevent her from becoming immunized and producing Rh antibodies. We have now investigated the matter further, and the present paper describes the completed results of the earlier work (Experiment I) and then gives details of some subsequent observations (Experiments II and III). The reasoning involved and the scope of the investigations are first discussed.

Secretion of Blood Group Antigens and Peptic Ulcer

Although there is no evidence at Cambridge that undergraduate suicides have increased in number in recent years, certain post-war developments may have had an adverse effect. One of these has been the increase in the number of students, which adds to the difficulties of supervision even though the tutorial body may have been strengthened to some extent; in the period 1948 to 1957 the numbers at Cambridge have increased by over 1,200. In a big university the detection of the earliest stages of mental ill-health must almost inevitably fall on those with whom undergraduates are in daily contact. When it is suspected that trouble is brewing the patient can be guided to where specialized help can be obtained. The increase in the number of undergraduates must mean that tutors find it more difficult to get to know each man personally so that they are in a position to detect small, but possibly significant, changes in personality or performance. Nor do present economic trends make this part of a tutors work any easier. That cases of mental ill-health are sometimes not detected in the earliest stages is unfortunate, but under present conditions is not surprising. The crux of the problem has recently been admirably summed up by one of Her Majestys coroners: The truth is that suicide is a most complex phenomenion and highly unpredictable; our knowledge of its roots is scanty indeed (Thurston, 1958). Student suicides are an end stage of the problem of mental health in universities about which undoubtedly far too little is known even by those most directly concerned. Figures of incidence of mental ill-health have been given for certain universities (Still, 1954 ; Malleson, 1954), but none are available for those universities with the highest incidence of suicide. Information and statistics are the bricks and mortar of prevention, and until mental di ease in university students is regarded in the same way as any other illness, as a misfortune and not something of a stigma, it is unlikely that much progress will be made in preventing its occurrence.

P.T.C. taste response and thyroid disease.

The deaths from leukaemia in England and Wales for the period 1945 to 1957 have been classified under three headings-acute leukaemias of all types, chronic myeloid leukaeniia, and chronic lymphatic leukaemia. The age-specific mortality rates have been calculated for each type of leukaemia, for each sex, and for three periods of time-1945 to 1949, 1950 to 1954, and 1955 to 1 957. A study of these data suggests that the principal feature in the real increase in leukaemia is a change in the incidence of acute leukaemia. This is compatible with the concept that an increased exposure to ionizing radiations plays some part in the changed incidence of the disease.

Prevention of Rh-Haemolytic Disease: A Third Report

In two papers (Finn et d., 1961; Clarke it al., 1963) we described experiments which were successful in preventing Rh immunization in Rh-negative male volunteers. The basis of the procedure was to remove rapidly from the circulation previously injected chromium-tagged Rh-positive red cells by giving hightitre incomplete anti-D either as an infusion of plasma or as gamma3-globulin. In our second paper we stated that the next steps should be to find out whether foetal red cells could be cleared equally well as adult and whether female volunteers could be protected in the same way as men. The results of experiments to test these points form the first part (I) of the present paper. The second part (II) concerns two factors of great importance in the application of the technique to preventing Rh immunization due to pregnancy. These are the frequency with which transplacental haemorrhage from foetus to mother occurs during pregnancy as distinct from at delivery, and the relation of the production of immune antibodies to the size of transplacental haemorrhage assessed after delivery. In the third part of the paper (III) we discuss some of the details of the clinical trial, recently started in Liverpool, of anti-D gamma2-globulin injection given to Rh-negative Women after delivery.

ABO blood groups and secretor character in rheumatic carditis.

Case 16.-A man aged 46 had had shadowing in the right uppcr lobe since 1947, with local extension in 1949. This was regarded as probably tuberculosis in spite of repeatedly negative sputum examinations. In 1952 a further reactivation in the right upper lobe occurred, and he also developed severe bronchitis followed by a left spontaneous pneumothorax. This proved difficult to re-expand. There were numerous scattered opacities throughout both lung fields, particularly in the upper zones. It was decided to do a lung biopsy and at the same time identify an air leak. On thoracotomy (January 1, 1957) a large leak and small emphysematous bullae were present in the left upper lobe and apex of the left lower lobe. Both lobes were fibrotic, with numerous hard calcified nodules scattered throughout. Microscopical examination of a biopsy specimen showed lesions strongly suggestive of calcifying chronic miliary tuberculosis. He was put on antituberculous drugs for the first time.

A genetical study of the variations in ABH secretion

1. The sib pair data suggest that the amount of A, B or H antigen secreted by an individual is in part inherited.

Prevention of Rh-haemolytic disease: results of the Liverpool "low-risk" clinical trial.

A clinical trial is reported in which Rh-negative primiparae, just delivered of an Rh-positive ABO-compatible infant and in whom fetal cell counts after delivery suggested less than 0·2 ml of circulating fetal blood, were treated with about 200 μg of anti-D gammaglobulin. Three (0·36%) out of 844 women thus treated developed anti-D in the subsequent six months; this is 10% of the incidence in untreated controls. Three (1·8%) out of 171 treated mothers had anti-D at the end of the second Rh-positive pregnancy, and this is 18% of the incidence in controls. Possible reasons for the occasional failure of the treatment are discussed and the results of this trial are compared with those of a previous trial in which 1,000 μg or more of anti-D was given to a different group of mothers. The combined results of the two trials lead to the conclusion that the passive administration of anti-D gammaglobulin after delivery affords in this population of Rh-negative women a 95% protection rate in the postdelivery period and an 89% protection rate by the end of the subsequent pregnancy.

Data on linkage in man: ovalocytosis, sickling and the Rhesus blood group complex

1. Two families are reported in which linkage between the gene controlling ovalocytosis and that of the Rhesus blood group complex is present. In those individuals where cross‐overs could have been detected none was in fact found in either family.

Blood Groups and Disease: Previous Transfusion as a Potential Source of Error in Blood Typing

No relationship between the placental site and the duration of pregnancy or the length of labour was found. ADDENDUM.-One objection to the present study is that the assessment of the length of labour when the placenta has partially extended on to the uterine fundus may not adequately test Csapos hypothesis (personal communication, 1961) as he postulates an effect only when the placenta is completely fundal. Nevertheless, there were five completely fundal placentae in the present series, and the length of labour was very short in two of these cases (2 and 24 hours). REFERENCES Bieniarz, J. (1959). Amer. J. Obstet. Gynec., 78, 385. Csapo, A. (1956). Amer. J. Anat., 98, 273. (1961). Ciba Foundation Study Group, No. 9, p. 3. Fell, M. R. (1956). J. Obstet. Gynaec. Brit. Emp., 63, 760. Kushnirskaya, E. S., and Ivanova, E. F. (1958). Akush. i Ginek., 34, No. 1, p. 35. Pinkerton, J. H. M. (1961). Ciba Foundation Study Group, No. 9, p. 82. Ranney, B. (1956). Amer. J. Obstet. Gynec., 71, 1049. Stevenson, C. S. (1949). Ibid., 58, 432. (1950). Ibid., 60, 41. Torpin, R., and Faulkner, A. H. (1957). J. Obstet. Gynaec. Brit. Emp., 64, 582. Whitehead, A. S. (1953). Ibid., 60, 854.