ENDOMYOCARDIAL FIBROSIS

48

being closely applied to the corresponding parts of the bony canal. In case 4 granulation tissue and pus were found anterior to the cord, and I suspect that the responsible bone lesion was in the body of the vertebra thus producing this reaction in the dura. Staphylococcal infection more commonly affects the laminae, pedicles, or transverse processes. In 2 of my cases there was also an accompanying perinephric abscess, the firing off into this space probably postponing the onset of serious cord lesions. There is, of course, usually an element of intradural reaction as shown by increased cell-count and protein levels, even if not actual organisms, in the cerebrospinal fluid. I agree with Dr. Hirson that the sudden onset of paralysis is of vascular origin, which stresses the need to refer such cases to the neurosurgeon at the earliest possible moment. One physical sign that I think may be of significance in these cases was present in 4 of mine-namely, that, although flexion of the spine was resisted and unattainable because of spasm, hyperextension was possible and without pain. One of my orthopaedic colleagues said that this excluded tuberculous bone-disease. Such was the pattern of this condition thirty years ago; but in these days of antibiotics, with the tendency there is to prescribe one or more when faced with a case of pyrexia of unknown origin, even if associated with spinal pain, and especially in children, the picture may be different and less dramatic, the juxtadural inflammatory reaction being modified or reduced to a fibrotic thickening of the epidural fat, thus producing vague discomfort and confusing neurological signs. Nevertheless, as Dr. Hirson so well demonstrates, the hot case still exists, and it is a potentially dangerous condition. F. A. R. STAMMERS.

CEREBROVASCULAR ACCIDENTS SIR,-In your annotation (Dec. 11) you comment on the different frequency of cerebrovascular accidents in teaching and district hospitals. In my experience, the comparison can go further. Among a series of 2221 necropsies on subjects over the age of sixty-five (performed by the late Dr. A. P. Piggot at St. James’ Hospital, Balham) there were 119 examples of cerebral haemorrhage and 50 of cerebral infarction.! In 106 octogenarians coming to postmortem examination in the geriatric unit of St. John’s Hospital, Battersea, there were 9 instances of cerebral infarction and 1 of cerebral haemorrhage.2 Among 125 subjects, aged sixty-five or more, from Maida Vale Hospital, cerebral infarction outnumbered haemorrhage by two

respond to psychiatric treatment. Prolonged small doses of prednisolone had previously been given to two of the five patients, depressing corticotrophin (A.C.T.H.) production. In the other three patients with this abnormal pigmentation, the response of the adrenal cortex to corticotrophin injections, metyrapone tests, and other investigations suggested a unitrophic pituitary deficiency of corticotrophin. No cause for this deficiency was found. These patients appeared to be upset by the most trivial stress, physical and emotional. It was considered that their symptoms were due to a poorly functioning hypothalamic-pituitary-adrenocortical axis. The excess pigmentation might result from an enzyme defect, which prevented the formation of corticotrophin and so allowed accumulation of the related melanophore-stimulating hormone. Replacement therapy in two patients first with cortisone and later with corticotrophin failed to cause any improvement in their symptoms. The lack of response to replacement therapy is not surprising if the mental state is directly attributable to abnormal pigment formation. It would seem reasonable to try the effect of a lowcopper diet and penicillamine on these and similar patients. Charing Cross Hospital, P. B. S. FOWLER. London, W.C.2.

ENDOMYOCARDIAL FIBROSIS SIR,-We have read with great interest the report (Oct. 30) by Dr. McKinney and Dr. Crawford on the production of fibrosis in guineapig heart by plantain diet. Especially intriguing to us was the demonstration of fibrin on thickened endocardium. We recently concluded a serological and immunohistological study in patients with endomyocardial fibrosis (E.M.F.), in which the salient feature was the ubiquitous presence of fibrin deposits in heart, kidney, spleen, liver, pancreas, thyroid, and

lung. Other interesting findings were a high incidence of circulatheart antibodies, predominantly reactive with endomysial tissueand the frequent occurrence of cryoprecipitates composed of an IgG/IgM complex. The serum from one patient reacted with his own heart as well, which indicates the auto-

ing

to one at

necropsy. The statistics of the Registrar General for England and Wales suggest that the numbers of deaths from cerebral hxmorrhage fell from 30,000 to 28,000 between 1942 and 1962. On the other hand, deaths from cerebral infarction rose from 16,000 to 38,000 in the same period. This change was associated with an increase in age at death and a peak-mortality occurring five years later. These examples suggest that the epidemiology of cerebrovascular accidents is worthy of more intensive study than it has so far received. TREVOR H. HOWELL.

SCHIZOPHRENIA-MELANOSIS SiR)ŇDr. Greiner and Dr. Nicholson3 have assumed, with good reason, that melanogenesis is increased in schizophrenia. Their finding that pigmentation is decreased by a low-copper diet plus penicillamine, and that this regimen improves the mental state, is of great interest. I have seen five patients with round discrete patches of pigmentation at the junction of the hard and soft palate. Three had profound mental disturbances. One had schizoid features, and two appeared to have a gross psychoneurosis; but a psychiatrist found them difficult 1. 2. 3.

to

classify, and thev have failed

Howell, T. H. Geront. clin. 1965, 7, 193. Howell, T. H. Br. J. geriat. Pract. 1963, 2, 155. Greiner, A. C., Nicolson, G. A. Lancet, 1965, ii, 1165.

to

Fibrin deposits in the heart.

immune nature of this reactivity. In the hearts fibrin deposits were found on the surface and in the depths of the thickened endocardium and also throughout the myocardium surrounding individual myofibres (see accompanying figure). Bound y-globulin was also demonstrated in these hearts, localised mainly in sarcolemmal and subsarcolemmal sites in myofibres and to a much lesser extent in the endocardium. In the kidneys extensive deposits of fibrin were observed together with complement, IgG, IgM, and occasionally IgA. However, the bound immunoglobulins were far less widely distributed than fibrin and complement. 1. van der Geld, H. Lancet, 1964, ii, 617.

49 These abnormalities were not found in tissues from patients with myocardial infarction and hypertensive heart-disease. We suggest that in endomyocardial fibrosis cardiac necrosis induces the formation of circulating heart-antibodies, and that the cryoprecipitates are instrumental in the deposition of fibrin. Although the mechanism remains to be elucidated fully, there is evidence suggesting that coagulation may be directly initiated by antigen-antibody complexes, rather than being secondary to tissue damage. Robbins and Stetson2 showed that antigen-antibody complexes accelerated clotting in vitro. More recently it has been demonstrated that the presence of large amounts of immune complexes in the circulation accelerated coagulation, resulting in widespread fibrin deposits in capillaries, especially in the glomeruli.3 These observations suggest that in E.M.F. patients the widespread fibrin deposits and circulating IgG/IgM complexes may be causally related. Secondary organisation of the fibrin could conceivably lead to extensive fibrosis, especially in view of the propensity of darkly pigmented races to keloid formation. It is of interest that IgM-IgG cryoglobulinsemia was recently postulated to be an autoimmune phenomenon.45 Laboratory of Immunopathology, University of Amsterdam, P.O.B. 200, Amsterdam, H. VAN DER GELD. The Netherlands. Makerere University College Medical School, Mulago Hospital, P.O.B. 2072, Kampala, K. SOMERS. Uganda, East Africa. Laboratory of Immunopathology, University of Amsterdam, P.O.B. 200, Amsterdam, F. PEETOOM. The Netherlands.

ASPECTS OF CARDIAC RESUSCITATION SIR,-Dr. Gilston’s article (Nov. 20) prompts me to report here the results of cardiac resuscitation at this hospital since we began to record details seven months ago. During this time, the emergency team (registrars in anxsthesics, medicine, and surgery) has been called to 52 patients with unexpected circulatory arrest: in the wards or corridors (37), the surgical intensive-treatment unit (12), the operating-theatre suite (2), and the X-ray department (1). 14 of these 52 patients were successfully resuscitated, and have been discharged from hospital; 1 of these 14 had survived a first episode of cardiac arrest thirteen months before. Of the 38 failures, 7 had massive pulmonary embolism, 3 dissecting aortic aneurysm, and 1 a ruptured heart; in the remaining 28, the initial or subsequent resuscitation attempts were ultimately abandoned when it was clear that the brain was irretrievably damaged or that the heart was mechanically defunct, even though QRS complexes might still be visible in the electrocardiogram. The survival-rate for the surgical intensive-treatment unit (4 survivors out of 12, or 33%) is little different from that for the rest of the hospital (25%), but the figures for the unit are weighted by some patients with severe heart-disease under observation after cardiac surgery. The survival-rate for patients with circulatory arrest in the early days after frank myocardial infarction was 5 out of 14 (36%), and might have been improved by routine cardiac monitoring, since few badly shocked patients are admitted here. Circulatory arrest was due to ventricular fibrillation in 27 patients, and 11 of these survived after defibrillation by directcurrent (D.C.) shock through the closed chest. Ventricular asystole was found in 12 patients: 3 of these survived-2 were maintained by endocardial pacing until resolution of their post-infarction auriculoventricular block, and 1 resumed sinus rhythm spontaneously after external massage only. In 13

episodes

the basic

arrhythmia

was

not

determined, usually

because evident cerebral death at the time of the team’s arrival made electrocardiosraohv suoerfluous. 2. Robbins, J., Stetson, C. A. J. exp. Med. 1959, 109, 1. 3. Vassali, P., McCluskey, R. T. Ann. N.Y. Acad. Sci. 1964, 116, 1065. 4. van Loghem-Langereis, E., Peetoom, F., van der Hart, M., van Loghem, J. J., Bosch, E., Goudsmit, R. Int. Congr. Blood Transf. (in the

press). 5. Peetoom,

F.,

van

Loghem-Langereis,

E. Vox

Sang. 1965, 10,

281.

Intravenous or intracardiac adrenaline has occasionally proved useful in rendering fine ventricular fibrillation coarser and so more susceptible to reversion by D.C. shock. Intravenous calcium chloride has appeared to enhance ventricular ejection after defibrillation. Propranolol, intravenously and later orally, has seemed to suppress ectopic ventricular rhythms, and may thus have prevented recurrences of ventricular fibrillation. Expert attention to the respiratory problems of the immediate post-arrest situation has been invaluable. These results contrast favourably with the available data for the preceding sixteen months during which there were only about 6 long-term survivals from over 100 resuscitation attempts by a similar team. The principal reasons for this improvement are, probably: (1) the more prompt and skilled immediate treatment by the nursing, medical, and auxiliary staff on the spot; and (2) the much greater use now made of intravenous bicarbonate to combat metabolic acidosis. It is now standard practice to give 50-100 mEq. sodium bicarbonate to every patient with circulatory arrest of more than thirty seconds’ duration, and to give three or four 50 mEq. increments during the ensuing ten to thirty minutes if spontaneous heart-action is not quickly restored. In the patients reported here, external massage only was used, and this was rarely continued beyond thirty minutes. But a young patient with cardiac arrest, which occurred during anxsthesia at a sister-hospital, had external massage for fifteen minutes followed by internal massage for a hundred and fifteen minutes before ventricular defibrillation was accomplished by the first D.c. shock adminiftered, alternating-current shocks having failed. He received a total of 750 mEq. sodium bicarbonate during the period of cardiac arrest, and his arterial pH and standard bicarbonate were respectively 7-42 and 26 mEq. per litre three hours after resumption of spontaneous heart-action. He made a complete recovery. Viable patients with asystole, whether " primary " or induced by a defibrillating shock, may pose particularly difficult problems in management, since external cardiac pacing is rarely effective, and the establishment of intracardiac-electrode pacing takes time. Perhaps in such cases, when precordial blows, external massage, ventilation, shocks, and drugs (including atropine) have failed to restart the heart, the chest should be opened and skilled internal cardiac massage commenced without undue delay. In this way, the brain may be kept alive long enough to make installation of a temporary pacemaking system a practical possibility in a higher proportion of cases. Queen Elizabeth Hospital, D. W. EVANS. Birmingham, 15.

RENAL AUTOTRANSPLANTATION

SiR,—The report1 of Dr. Serrallach-Mila and his colleagues a new method of revascularisation of the kidney by autotransplantation is hardly new. This surgical procedure must have been advocated by those German surgeons who were pioneering kidney transplantation at the beginning of this century. But I strongly advocated this procedure in Modern Trends in Urology (1953) as follows: " The clinical need for autotransplantation of the kidney is no doubt extremely small. ’If, however, a ureter is extensively involved in a tumour about

of the colon and rectum, it may be desirable in an occasional case to conserve the kidney if the other is not present or is not in good condition. With further improvements in operative and restorative techniques, it may not be so formidable a procedure to carry on and autotransplant the kidney on to the iliac vessels and re-implant the sectioned ureter into the bladder ". My own experiments had shown by this time that normal function could be expected from a kidney properly autotransplanted to the pelvis. I spent a lot of time autotransplanting kidneys, and the clinical application was constantly in mind. Again, in 1962 in Operative Surery Service (part 15, p. 15),

growth

1.

Serrallach-Mila, N., Paravisini, J., Mayol-Valls, P., Alberti, J., Casellas, A., Nolla-Panadés, J. Lancet, 1965, ii, 1130.