PLATELET BEHAVIOUR AND BLEEDING

421 valuable improvements on my tables. draw attention to the last paragraph of his letter. The treatment of tetanus has remained in the doldrums for decades. This is principally due to our inability to describe the disease in a manner appreciated by others. There appears to have been little reduction in mortality since the introduction of the barbiturates, though the phenothiazines and diazepoxides have reduced morbidity and nursing requirements. If the mortality and morbidity are to be further reduced, then a simple classification comparable for all areas is required. I have suggested such a classification notas an end but as a beginning. It is open to modification and improvement, but not I hope complication. If, among those of us interested in the disease, we can work out and accept some such system, then we can start to learn from the experience of others. Colonial War Memorial Hospital, L. A. PHILLIPS. Suva, Fiji.

ing suggestions are Particularly would I

ULLRICH’S SYNDROME should like briefly to record our experience with SIR,-We some 40 female patients who apparently have a clinical condition, with neck webbing, similar to the one described by Dr. Nora and Dr. Sinha (July 29, p. 256) under the eponym of Turner phenotype, and for which we1 have used the name of Ullrich’s syndrome, as suggested by Caflisch.2 These patients attend with somatic anomalies reminiscent of those described by Turner, with webbing of the neck as a central feature, but are distinct in possessing normal ovaries as judged usually by normal ovarian function at puberty. The syndrome therefore generally cannot be confidently diagnosed before puberty, though a normal female sex-chromosome complement in the presence of these anomalies can be taken to make this diagnosis likely, allowing one, as it does, to predict with some assurance the emergence of normal secondary sex development at puberty. In our experience, this condition, which is clinically related to and overlaps congenital arthromyodysplasia, subdivides as follows: it may be transmitted in a dominant manner or, at other times, apparently in an autosomal recessive way; it may be caused by an autosomal structural anomaly; or, much more commonly, it may present sporadically in a family, in a person who has a chromosome complement indistinguishable from normal. Some of these latter cases may be due to structural chromosome errors which cannot be detected by our present techniques; others may be due to other mutational events, possibly point mutations, and may be related to the cases with dominant transmission; and others may represent mostly environmentally triggered phenocopies. The dominant examples, of which we have three or possible four families, show transmission from mother to daughter only. Some patients with Ullrich’s syndrome have dermatoglyphic peculiarities, with unusual and sometimes striking tendency of the palmar ridges to course longitudinally, which are less extreme than but resemble those in the example of Wilder,s the hand noted by Kanaseki et al,4the case of Holt and Lindsten5 (patient no. 54), and the two patients of Wolf et al.While some of the combinations of terminations of palmar main lines in some patients with Ullrich’s syndrome tend to be like those found in a greater proportion of XO subjects with Turner’s syndrome, other dermatoglyphic criteria distinguish between the two groups of patients. We have stressed that the diagnosis of Ullrich’s syndrome rests on evidence of ovarian normality, generally normal function after puberty. However, we think that there are subjects in whom ovarian function is not wholly normal, and Bishop, P. M. F., Lessof, M. H., Polani, P. E. in Sex Differentiation and Development (edited by C. R. Austin): Memoirs of the Society for Endocrinology, no. 7; p. 162. Cambridge, 1960. Polani, P. E. Br. med. Bull. 1961, 17, 200. 2. Caflisch, A. Das Pterygium und sein Vorkommen bei verschiedener Zuständen multipler Abartungen. Zürich, 1952. 3. Wilder, H. H. Biol. Bull. mar. Biol. Lab., Woods Hole, 1916, 30, 135. 4. Kanaseki,T., Miyauchi, E., Wada, I. J. med. Ass. Formosa, 1939, 38, 989. 5. Holt, S. B., Lindsten, J. Ann. hum. Genet. 1964, 28, 87. 6. Wolf, U., Brehme, H., Reinwein, H. Humangenetik, 1964, 1, 149. 1.

even some

with evidence of

clearly be clinically related

dysgenetic gonads. These would to the syndrome described by

Turner. Paediatric Research Unit, Guy’s Hospital Medical School.

P. E. POLANI R. ANGELL N. POLANI.

COMA DUE TO ACUTE HEPATIC NECROSIS

SIR,-In the article by Dr. Jones and his colleagues (July 22, 169) the diagnoses given in table I include two cases of " halothane necrosis " , in four cases " virus hepatitis was diagnosed by excluding other possible causes of acute hepatic

p.

necrosis "-the clear implication is that if any of these four patients had received halothane, the diagnosis would have then become " halothane necrosis ". The National Halothane Study1 covering 850,000 aneesthetics was unable to correlate acute hepatic necrosis with halothane anaesthesia, and this has been the conclusion from other large series.2 While we are aware that the article of Dr. Jones and his colleagues was not concerned with this specific matter, it is a pity that a group who speak with authority on liver disease should use this diagnosis as though it were an established entity. J. G. ROBSON Royal Postgraduate Medical School, M. D. A. VICKERS. Ducane Road, London W.12.

PLATELET BEHAVIOUR AND BLEEDING SIR,-We have read with interest the preliminary communication by Dr. Hardisty and Mr. Hutton.3 Recently, we presented4a group of patients showing the following defects at a meeting of the Turkish Medical Association on April 18, 1967. A platelet-aggregation defect was shown in 3 patients with Hodgkin’s disease, 2 with lymphosarcoma,1 with reticulum-cell sarcoma, and 1 with acute monocytic leuksemia, out of a series of 40 patients with malignant lymphoma or acute leukaemia with normal platelet-count. In these patients the bleeding-time was prolonged and adenosine diphosphate (A.D.P.)-induced platelet aggregation was defective, as shown in the accompanying table. In cases where A.D.P.-induced aggregation was LABORATORY

FINDINGS IN DEFECT ("

PATIENTS

ACQUIRED

WITH PLATELET-AGGREGATION ATHROMBIA ").

defective at a concentration of A.D.P. of 0-4-8 g. per ml. the defect still persisted when the concentration was raised to 40 g. per ml. The Borchgrevink and Salzman tests were defective, and the platelets were individually dispersed in the bloodsmears. Clot retraction was normal. Except in the patient with acute monocytic leukaemia platelet-factor-3 activity was normal. Similar defects were also noted in three out of a group of 50 patients with pulmonary tuberculosis accompanied by haemop-

tysis. We have named this

syndrome " acquired athrombia ". The

Bunker, J. P. J. Am. med. Ass. 1966, 197, 775. Mushin, W. W., Rosen, M., Bowen, D. S., Campbell, H. Br. med. J. 1964, ii, 329. Henderson, J. C., Gordon, R. A. Can. Anœsth. Soc. J. 1964, 11, 453. 3. Hardisty, R. M., Hutton, R. A. Lancet, 1967, i, 983. 4. Balkuv, Ş., Bayrak, G., Ulutin, O. N. Turk Tib Cemiy. Mecm. (in the press). 1. 2.

422 term " athrombia," which was coined by Frank 3 in 1925, is used for defects of aggregation and adhesion of platelets. We use the term " thrombocytopathia " only for defective plateletfactor-3 activity. From the standpoint of nomenclature, the syndrome described by Dr. Hardisty and Mr. Hutton is a type of athrombia, and we are of the opinion that the term " throm" bopathia should not be used for such patients. In our studies we have observed the disaggregation described by Dr. Hardisty and Mr. Hutton in a patient with " periodic fever " with prolonged bleeding-time. In our patient, the aggregation induced by 0.8 g. A.D.P. per ml. disaggregated in 3 minutes at room temperature. After further addition of 0-8 g A.D.P. per ml. to the disaggregated platelet-rich plasma, aggregation occurred, and disaggregation took place in 14 minutes. This preliminary observation suggests that there may be a factor present in the rapid disintegration of exogenous A.D.P. Division of Hæmatology, Cerrahpaşa Medical Clinic, Istanbul University.

ORHAN N. ULUTIN ŞENGÜN BALKUV.

BLADDER-PHÆOCHROMOCYTOMA METASTASES and Gresham4 presented the findings in a of 48 years who was operated on for a phaeochromocytoma of the bladder. She had had symptoms during micturition, starting at the age of 13. The partial-cystectomy specimen and biochemical tests confirmed the diagnosis. The tumour was deemed to be completely removed, there was no evidence of metastases, and she remained well with a normal blood-pressure (B.P.) for 6 years. In August, 1964, the patient was seen again with right hemiplegia and B.P. 240/110mm.Hg. Biochemical testing was negative at that time for phmochromocytoma but became positive during the next 6 months. Cystoscopy was normal and all investigations to detect the site of the tumour were unreward-

SIR,-Lumb

woman

ing. The patient was treated until November, 1966; her B.P. controllable then only by phenoxybenzamine (’ Dibenyline ’) or propranolol, neither of which she could tolerate any longer, and she therefore underwent laparotomy. Tumour tissue was found in the right iliac and obturator lymph-nodes. The para-aortic nodes at the bifurcation were normal; above this point no lymph-node enlargement could be seen or felt. All obvious tumour tissue was excised. This necessitated removal of the right external iliac vein, which was infiltrated by tumour, and ligation of the right internal iliac vein. She made an uneventful recovery, and surprisingly had no oedema of her right leg. Her B.P. fell to 160/100 immediately postoperatively; however, as was not unexpected, after a further 4 months it rose again, and there was biochemical evidence of active tumour tissues. 1 of the 3 patients of Higgins and Tresidder 5 with phasochromocytoma of the bladder had involvement of the iliac lymph-nodes at the time of operation and had had haematuria for 12 months before. Moloney, et al. described a patient whose symptoms had been present for 11 years when operated upon, whose lymph-nodes were involved, and who died of widespread metastases 4 years later. They acknowledge the reports of Pughand Poirier and Robinson8 as being the only other recorded cases of malignant phtochromocytoma of the bladder. This patient we think is unique for two reasons: firstly, because of the long period (41 years) between the onset of symptoms and the establishment of functioning metastatic tissue; and, secondly, because this is the only recorded case of late metastases occuring from a phaeochromocytoma of the was

3. 4. 5. 6.

7. 8.

Frank, E. in Handbuch der Krankheiten des Blutes und der Blutbilden Organe; vol. n (edited by A. Schittenhelm), Berlin, 1925. Lumb, B. R. B., Gresham, G. A. Lancet, 1958, i, 81. Higgins, P. McR., Tresidder, G. C. Br. med. J. 1966, ii, 274. Moloney, G. E., Cowdell, D. M. Lewis, C. L. Br. J. Urol. 1966, p. 38, 461. Pugh, R. C. B. ibid. 1958, 30, 432. Poirier, H., Robinson, J. O. ibid. 1962, 34, 88.

bladder in which (macroscopically) the lymph-nodes were free of tumour at the time of partial cystectomy. Department of Urology, DAVID E. YOFFA Addenbrooke’s Hospital, J. F. R. WITHYCOMBE. Cambridge.

MEGALOBLASTIC ANÆMIA AND VISION

SIR,-It was with particular interest that I read the report of Dr. Adams and his colleagues (July 29, p. 229) and their finding of optic neuritis in one patient with addisonian pernicious anxmia who was a lifelong non-smoker. I am in complete agreement with the view expressed that it is possible that the optic neuritis in this patient was the result of exposure to cyanide from some source other than tobacco, for it is now well recognised that besides being present in tobacco-smoke and alcohol, cyanide is also widely distributed in the plant kingdom.1 This would also be one possible explanation for the finding of optic neuropathy in 4 of 102 subjectively healthy persons in Finland infected with the fish tapeworm who had low serum-vitamin-B12 levels, since 3 of the 4 were nonsmokers and took no alcohol.22 Our original thesis, that the aetiology of retrobulbar neuritis in pernicious anaemia could not be satisfactorily explained by a deficiency factor alone, was based on a critical review of 31 cases.3 We were able to determine the following facts from this analysis. Firstly, there was an overwhelming male preponderance of cases of retrobulbar neuritis in patients with pernicious anaemia (of 31 reported 28 were in men): yet in pernicious anaemia males and females are equally affected. Secondly, it was evident that the development of amblyopia in patients with pernicious anaemia was not related to the duration of the disease, to the presence or degree of anaemia, or to neurological involvement. These findings suggested to us that there must be an additional factor responsible for the development of retrobulbar neuritis in pernicious anaemia which is far commoner in males than females, and which acting alone

does not cause anaemia or subacute combined degeneration of the cord; we presented evidence in support of our hypothesis that this responsible factor was to be found in tobaccosmoke. Our previous work on the aetiology of tobacco amblyopia undertaken in Bristol some 10 years ago had clearly shown in all 13 patients studied that serum-vitamin-B12 levels were significantly lower than in the normal controls, and the effect of parenteral cyanocobalamin in improving the visual acuity and completely reversing the changes in the visual fields was most encouraging, even if the use of tobacco was continued.4 One of these patients, a known case of treated pernicious anaemia, was particularly instructive in that when he was very anxmic, with a haemoglobin of 33%, he had no amblyopia and at that time he had been a lifelong non-smoker. However, when we first saw him with severe retrobulbar neuritis some 2 years later, his haemoglobin had risen to 93%, though the serum-vitamin-B12 level was low at 130 li4kg. per ml.-and he had started smoking 12 months before. Thus this degree of vitamin-B12 deficiency was not now sufficient to produce anaemia or signs of peripheral neuropathy or spinal-cord involvement, though it was severe enough to cause retrobulbar neuritis once he started smoking. In further support of this hypothesis that the responsible factor producing retrobulbar neuritis in patients with pernicious anaemia was present in tobacco-smoke was the fact that no patient in our series of 31 cases was reported as being a non-smoker, and, although most of the visual fields described were incomplete, those analysed showed changes similar to the characteristic ones found in patients with tobacco

amblyopia. An earlier

suggestion

that the

hydrogen cyanide in tobacco-

1. Heaton, J. M. Trans. ophthal. Soc. U.K. 1962, 82, 263. 2. Björkenheim, B. Lancet, 1966, i, 688. 3. Freeman, A. G., Heaton, J. M. ibid. 1961, i, 908. 4. Heaton, J. M., McCormick, A. J. A., Freeman, A. G. ibid.

1958, ii, 286.