- Email: [email protected]
Idiopathic Thrombocytopenic Purpura
494 the child the
No fever. civil liberties for responsible citizen give away must of but not the the we liberty nothing ; protect adult to make money as he pleases at the cost of failing to protect the child’s freedom to grow up without lasting deformity of character.
fight
to catch
typhoid
will
Idiopathic Thrombocytopenic Purpura IT used to be thought that idiopathic thrombocytopenic purpura was a form of hypersplenism ; the spleen sequestrated and destroyed the circulating platelets, and the megakaryocytes in the bone-marrow multiplied in an effort to replace the loss. This hypothesis was supported by the effect of splenectomy, which was usually followed by return of the plateletcount to normal and disappearance of the purpura. But from the first it was realised that this explanation was incomplete. Splenectomy unaccountably failed to relieve some patients in whom the diagnosis was firmly established ; while in others the platelet-count
increased at first, but fell later-sometimes without recrudescence of the purpura. Moreover, the severity of the bleeding into the skin or from mucous mem-
converse
experiment of transfusing blood from patients thrombocytopenia into healthy people,
with idiopathic
and showed that in many this caused temporary
thrombocytopenia. They also detected platelet agglutinins in the blood of 21 out of 31 patients with idiopathic thrombocytopenic purpura ; and in 4 of these the agglutinins acted against the patient’s own platelets. TULLIS6 found that serum from some patients with such purpura caused agglutination and even lysis of normal platelets in the presence of complement. These, and similar reports, seemed to confirm that a circulating antiplatelet-antibody was present and was detectable irt a fair proportion of cases of idiopathic thrombocytopenic purpura; and this presumably was responsible for the thrombocytopenia and the purpura. Further experience has yielded results which spoil this attractively simple picture. HARRINGTON et a1.5 noted that thrombocytopenia was still induced in healthy people by blood from patients whose plateletcount had reverted to normal after splenectomy. Further search revealed platelet-agglutinins in the blood of patients without purpura who had been transfused
who had been
pregnant; and STEFANINI branes did not necessarily correspond to the level of et al. described platelet-agglutinins in the blood of the platelet-count. These anomalies, and doubts who had never been transfused or been about the necessity for, or the timing of, splenectomy healthy people The techniques of demonstrating plateletin individual patients, have stimulated a search for pregnant. other factors in the pathogenesis and course of the agglutinins have proved difficult and unreliable, and disease. Recent work on platelet agglutinins and there is much difference of opinion about the interpre. tation of results. The reduction in the platelet-count lysins shows that the search is well justified. The idea of platelet-antibodies stems from observa- of healthy people transfused with blood from patients tions on gl1.ineapigs by BEDSON,1 who prepared an with idiopathic thrombocytopenic purpura is also not specific ; thus STEFANINI et al.8 found that transantiplatelet serum which caused thrombocytopenia fusion of normal plasma causes reduction of platelets, and damaged the endothelium of the capillary bloodthe only difference with plasma from patients vessels. Interest in this aspect of purpura has been and re-awakened by two researches. Firstly, ACKROYD2 )Vith thrombocytopenic purpura is that the effect showed that the thrombocytopenic purpura caused sometimes lasts longer. ACKROYD9 concludes that the to which idiopathic thrombocytopenic purpura by’ Sedormid ’ is due to the development of an anti-3 extent to an antiplatelet factor is not easily judged, due platelet factor in the blood. Secondly, EvANs et awl. is there is evidence of such a factor in
noted that some patients with acquired hsemolytic Since the anaemia also had thrombocytopenia. h2emolytic anaemia was known to be caused by antibody destruction of red cells, they thought that the thrombocytopenia might similarly be due to an antibody ; and they detected platelet-agglutinating factors in the blood of these patients and of some with idiopathic thrombocytopenic purpura. EvANS et al. considered that the
spleen acted more as an antibodyproducer slaughterhouse of red cells and also platelets. They pointed out that children born to women who at the time had thrombocytopenic purpura often had transitory thrombocytopenia, which suggested that a platelet-destroying factor had passed across the placenta. STEFANINI and DAMESHEK,4 and others, have worked out techniques for transfusing platelets and following their fate in recipients. They found that normal platelets transfused into patients with a low platelet-count due to aplastic ansemia or leukaemia survived for two to five days ; whereas platelets transfused into patients with idiopathic thrombocytopenic purpura survived for from half an hour to twenty-four hours. HARRINGTON et awl. made the than
"
"
as a
Bedson. S. P. J. Path. Bact. 1922, 25, 94. 2. Ackroyd, J. F. Clin. Sci. 1949, 8, 269. 3. Evans, R. S., Takahashi, K., Duane, R. T., Payne, R., Liu, C.K. Arch. intern. Med. 1951, 87, 48. 4. Stefanini, M., Dameshek, W. New Engl. J. Med. 1953, 248, 797. 5. Harrington, W. J., Sprague, C. C., Minnich, V., Moore, C. V., Ahlvin, R. C., Dubach, R. Ann. intern. Med. 1953, 38, 433. 1.
or
though strong the blood of some patients with the disease. Accordingly, the clinician cannot look to information about platelet-agglutinins to help him in deciding whether splenectomy is advisable, or whether cortisone or corticotrophin should first be tried. But experience over the years has helped to clarify the division of idiopathic thrombocytopenic purpura into an acute type, which does not often call for splenectomy, and a chronic type, in which sooner or later splenectomy will probably be necessary. The acute cases, which are very alarming, were formerly treated by emergency splenectomy, but the results were often disappointing. The present practice of watchful waiting has shown that the condition often remits spontaneously after a period varying from a few weeks to three or four months ; in some instances the disorder eventually becomes chronic, but in occasional tragic cases the patient dies from uncontrollable haemorrhage that is uninfluenced even by splenectomy. Cortisone may help to tide over the waiting period ; platelet-transfusions have been given, but have severe limitations.1O In the chronic cases the platelet-count is persistently
Tullis, J. C. New Engl. J. Med. 1953, 249, 591. Stefanini, M., Pitman, G. I., Dameshek, W., Chatterjea, J. B. Mednicoff, I. B. J. Lab. clin. Med. 1953, 42, 723. 8. Stefanini, M., Dameshek, W., Chatterjea, J. B., Adelson, E., Mednicoff, I. B. Blood, 1953, 8, 26. 9. Ackroyd, J. F. Brit. med. Bull. 1955, 11, 28. 10. See Lancet, 1953, ii, 605. 6. 7.
495 low for many months, and the purpura tends to vary Occasionally peptic ulceration defies all surgical is the treatstill endeavours ; PRIESTLEY et al.16 mention a patient who quite independently. Splenectomy ment of choice ; and the timing of this operation had five operations and ultimately required total depends greatly on such considerations as whether the gastrectomy. In such cases the underlying factors haemorrhages are persistent or damaging, whether can hardly be gastric, since ulceration continues to the patient is likely to become pregnant, or whether recur after most of the stomach has been removed. the central nervous system is involved. Unfortunately, WALTERS et al.14 suggest that the continual presence 11 as STEFANINI and DAMESHEK point out, it is still of free HCI in the stomach or stomach remnant is whether the disorder will important, and base their surgical approach to recurto predict impossible at respond to splenectomy, but in least two-thirds of rent ulceration on its elimination. FRENCH et al.17 In have found that in monkeys stimulation of the cases the results of operation are satisfactory. children idiopathic thrombocytopenic purpura tends hypothalamic area induces secretion of HCl. Section of the vagus nerve might have been expected to stop to be milder than in adults ; but more cases are acute, with the risk of serious complications in the first this response if their experiments had not also pointed month of the illness. KOMROWER and WATSON 12 to an extravagal pathway from the posterior hyporeport that of 28 cases in children aged 6 years or less, thalamus through the pituitary-adrenal system; stimulation caused a delayed secretion which was blocked no fewer than 24 presented as acute cases, 12 with severe and 12 with mild bleeding ; 6 of the children only by adrenalectomyJ8 If acid is a factor in with severe bleeding died, but the other 18 recovered ulceration, and if stress stimulates the hypothalamus, completely without treatment. In the chronic cases this might explain the rare recurrence of ulceration in children the onset is less dramatic, and symptoms after adequate gastric resection followed by vagotomy. tend to persist in an irregular fashion for more than FRENCH et a1.19have induced in monkeys ulceration in six months. KOMROWER and WATSON agree that in prepyloric and postpyloric areas by protracted stimuthe acute cases splenectomy is hazardous, and they lation (thirty to seventy days) of the medial prefer treatment with corticotrophin or cortisone for diencephalic axis from preoptic to postmamillary at least the first month after onset. For the chronic regions. This circumstantial evidence does not prove But that a similar mechanism operates in man. cases splenectomy should be considered after six months, but the necessity for this depends on the clinical observation caused CUSHING 20 to consider the role of stress and its impact via interbrain to midbrain disability the disease is causing. The successful management of idiopathic thrombo. and so on to the vagal centres in the medulla. His or was aroused by two cases in which acute in adults still children interest cytopenic purpura depends or duodenal perforations followed craniotomy on accurate diagnosis and on clinical assessment of the gastric condition and prognosis, as much as on information for cerebellar lesions. The several perforations were from clinical pathology. The detection of platelet- located in areas of erosion-in. the stomach in one case, agglutinins is not yet a helpful laboratory test, but and in the duodenum in the other. Ulcers that follow technical refinements may make it so. operations on the brain are apparently of two types : one is characterised by diffuse petechiæ and even gross haemorrhage, and the other by gelatinous softenPeptic Ulcer and the Brain and perforation.21 DAVIS et al.22 have erosion, ing, VAGAL section may be indicated in cases where the found that the incidence of perforation or haemorrhage anastomosis ulcerates after comprehensive gastric after 7000 neurosurgical operations was 0-7% ; but resection for duodenal ulcer ; and as a supplement to after craniotomies (943) and also after suboccipital the Billroth-i operation for duodenal ulcer it may craniectomies (350) it was about 2-5%. 8 patients in insure against recurrence.13 A report from the Mayo their series had pre-existing gastro-intestinal trouble ; Clinic 14 indicates that, though gastric resection is after all 8 were seriously ill because of operation the operation of choice for ulceration after gastroand some of these died from this cause. haematemeses, enterostomy, vagotomy, with a low mortality of 1%, In some cases gastro-intestinal haemorrhage ensued gives excellent results in 70% of patients with stomal even when the operation had not been on the central ulcer after partial gastrectomy : indeed, compared with nervous system-for example, on the autonomic the few cases submitted to gastric reresection which nerves. Moreover, as CUSHING knew, disease of the were followed up, vagotomy was apparently more effeccentral nervous system, without neurosurgical trauma, tive. WELLS 15 has reported the outcome of vagotomy may be associated with perforation or haemorrhage ; in 25 patients with ulceration after partial gastrectomy WATSON and NETSKY 23 describe 6 such cases, and and 14 after gastro-enterostomy : two-thirds of the refer to 38 previously reported, in which the patient resection group were free from trouble after three died from one of these complications. In 30 of the years; but the results in the gastro-enterostomy group total of 44 cases the neurological disorder involved were disappointing, since ulceration recurred in 10. the hypothalamus. WELLS considers that vagotomy is worth trying in the gastrectomy group, since it is safer than further 16. Priestley, J. T., Walters, W., Gray, H. K., Waugh, J. M. Proc. Mayo Clin. 1954, 29, 638. resection. There are occasions when removal of yet 17. French, J. D., Longmire, R. L., Porter, R. W., Movius, H. J. stomach is well-nigh is then a last resort. more
impossible ; vagal
section
11. 12.
Stefanini, M., Dameshek, W. Komrower, G. M., Watson, G.
13. 14.
Capper, W. M., Welbourn, R. B. Lancet, 1954, ii, 193. Walters, W., Chance, D. P., Berkson, J. Surg. Gynec. Obstet. 1955, 100, 1. Wells, B. W. Lancet, 1954, i, 599.
502.
15.
Annu. Rev. Med. 1954, 5, 87. H. Arch. Dis. Childh. 1954, 29,
Surgery, 1953, 34, 621. 18. Porter, R. W., Movius, H. J., French, J. D. Ibid, 1953, 33, 875. 19. French, J. D., Porter, R. W., Cavanaugh, E. B., Longmire, R. L. Arch. Neurol. Psychiat. 1954, 72, 267. 20. Cushing, H. Surg. Gynec. Obstet. 1932, 55, 1. 21. French, J. D., Porter, R. W., von Amerongen, F. K., Raney, R. B. Surgery, 1952, 32, 395. 22. Davis, R. A., Wetzel, N., Davis, L. Surg. Gynec. Obstet. 1955, 100, 51. 23. Watson, J. MacD.,
72, 426.
Netsky, M. G.
Arch. Neurol.
Psychiat. 1954,
No fever. civil liberties for responsible citizen give away must of but not the the we liberty nothing ; protect adult to make money as he pleases at the cost of failing to protect the child’s freedom to grow up without lasting deformity of character.
fight
to catch
typhoid
will
Idiopathic Thrombocytopenic Purpura IT used to be thought that idiopathic thrombocytopenic purpura was a form of hypersplenism ; the spleen sequestrated and destroyed the circulating platelets, and the megakaryocytes in the bone-marrow multiplied in an effort to replace the loss. This hypothesis was supported by the effect of splenectomy, which was usually followed by return of the plateletcount to normal and disappearance of the purpura. But from the first it was realised that this explanation was incomplete. Splenectomy unaccountably failed to relieve some patients in whom the diagnosis was firmly established ; while in others the platelet-count
increased at first, but fell later-sometimes without recrudescence of the purpura. Moreover, the severity of the bleeding into the skin or from mucous mem-
converse
experiment of transfusing blood from patients thrombocytopenia into healthy people,
with idiopathic
and showed that in many this caused temporary
thrombocytopenia. They also detected platelet agglutinins in the blood of 21 out of 31 patients with idiopathic thrombocytopenic purpura ; and in 4 of these the agglutinins acted against the patient’s own platelets. TULLIS6 found that serum from some patients with such purpura caused agglutination and even lysis of normal platelets in the presence of complement. These, and similar reports, seemed to confirm that a circulating antiplatelet-antibody was present and was detectable irt a fair proportion of cases of idiopathic thrombocytopenic purpura; and this presumably was responsible for the thrombocytopenia and the purpura. Further experience has yielded results which spoil this attractively simple picture. HARRINGTON et a1.5 noted that thrombocytopenia was still induced in healthy people by blood from patients whose plateletcount had reverted to normal after splenectomy. Further search revealed platelet-agglutinins in the blood of patients without purpura who had been transfused
who had been
pregnant; and STEFANINI branes did not necessarily correspond to the level of et al. described platelet-agglutinins in the blood of the platelet-count. These anomalies, and doubts who had never been transfused or been about the necessity for, or the timing of, splenectomy healthy people The techniques of demonstrating plateletin individual patients, have stimulated a search for pregnant. other factors in the pathogenesis and course of the agglutinins have proved difficult and unreliable, and disease. Recent work on platelet agglutinins and there is much difference of opinion about the interpre. tation of results. The reduction in the platelet-count lysins shows that the search is well justified. The idea of platelet-antibodies stems from observa- of healthy people transfused with blood from patients tions on gl1.ineapigs by BEDSON,1 who prepared an with idiopathic thrombocytopenic purpura is also not specific ; thus STEFANINI et al.8 found that transantiplatelet serum which caused thrombocytopenia fusion of normal plasma causes reduction of platelets, and damaged the endothelium of the capillary bloodthe only difference with plasma from patients vessels. Interest in this aspect of purpura has been and re-awakened by two researches. Firstly, ACKROYD2 )Vith thrombocytopenic purpura is that the effect showed that the thrombocytopenic purpura caused sometimes lasts longer. ACKROYD9 concludes that the to which idiopathic thrombocytopenic purpura by’ Sedormid ’ is due to the development of an anti-3 extent to an antiplatelet factor is not easily judged, due platelet factor in the blood. Secondly, EvANs et awl. is there is evidence of such a factor in
noted that some patients with acquired hsemolytic Since the anaemia also had thrombocytopenia. h2emolytic anaemia was known to be caused by antibody destruction of red cells, they thought that the thrombocytopenia might similarly be due to an antibody ; and they detected platelet-agglutinating factors in the blood of these patients and of some with idiopathic thrombocytopenic purpura. EvANS et al. considered that the
spleen acted more as an antibodyproducer slaughterhouse of red cells and also platelets. They pointed out that children born to women who at the time had thrombocytopenic purpura often had transitory thrombocytopenia, which suggested that a platelet-destroying factor had passed across the placenta. STEFANINI and DAMESHEK,4 and others, have worked out techniques for transfusing platelets and following their fate in recipients. They found that normal platelets transfused into patients with a low platelet-count due to aplastic ansemia or leukaemia survived for two to five days ; whereas platelets transfused into patients with idiopathic thrombocytopenic purpura survived for from half an hour to twenty-four hours. HARRINGTON et awl. made the than
"
"
as a
Bedson. S. P. J. Path. Bact. 1922, 25, 94. 2. Ackroyd, J. F. Clin. Sci. 1949, 8, 269. 3. Evans, R. S., Takahashi, K., Duane, R. T., Payne, R., Liu, C.K. Arch. intern. Med. 1951, 87, 48. 4. Stefanini, M., Dameshek, W. New Engl. J. Med. 1953, 248, 797. 5. Harrington, W. J., Sprague, C. C., Minnich, V., Moore, C. V., Ahlvin, R. C., Dubach, R. Ann. intern. Med. 1953, 38, 433. 1.
or
though strong the blood of some patients with the disease. Accordingly, the clinician cannot look to information about platelet-agglutinins to help him in deciding whether splenectomy is advisable, or whether cortisone or corticotrophin should first be tried. But experience over the years has helped to clarify the division of idiopathic thrombocytopenic purpura into an acute type, which does not often call for splenectomy, and a chronic type, in which sooner or later splenectomy will probably be necessary. The acute cases, which are very alarming, were formerly treated by emergency splenectomy, but the results were often disappointing. The present practice of watchful waiting has shown that the condition often remits spontaneously after a period varying from a few weeks to three or four months ; in some instances the disorder eventually becomes chronic, but in occasional tragic cases the patient dies from uncontrollable haemorrhage that is uninfluenced even by splenectomy. Cortisone may help to tide over the waiting period ; platelet-transfusions have been given, but have severe limitations.1O In the chronic cases the platelet-count is persistently
Tullis, J. C. New Engl. J. Med. 1953, 249, 591. Stefanini, M., Pitman, G. I., Dameshek, W., Chatterjea, J. B. Mednicoff, I. B. J. Lab. clin. Med. 1953, 42, 723. 8. Stefanini, M., Dameshek, W., Chatterjea, J. B., Adelson, E., Mednicoff, I. B. Blood, 1953, 8, 26. 9. Ackroyd, J. F. Brit. med. Bull. 1955, 11, 28. 10. See Lancet, 1953, ii, 605. 6. 7.
495 low for many months, and the purpura tends to vary Occasionally peptic ulceration defies all surgical is the treatstill endeavours ; PRIESTLEY et al.16 mention a patient who quite independently. Splenectomy ment of choice ; and the timing of this operation had five operations and ultimately required total depends greatly on such considerations as whether the gastrectomy. In such cases the underlying factors haemorrhages are persistent or damaging, whether can hardly be gastric, since ulceration continues to the patient is likely to become pregnant, or whether recur after most of the stomach has been removed. the central nervous system is involved. Unfortunately, WALTERS et al.14 suggest that the continual presence 11 as STEFANINI and DAMESHEK point out, it is still of free HCI in the stomach or stomach remnant is whether the disorder will important, and base their surgical approach to recurto predict impossible at respond to splenectomy, but in least two-thirds of rent ulceration on its elimination. FRENCH et al.17 In have found that in monkeys stimulation of the cases the results of operation are satisfactory. children idiopathic thrombocytopenic purpura tends hypothalamic area induces secretion of HCl. Section of the vagus nerve might have been expected to stop to be milder than in adults ; but more cases are acute, with the risk of serious complications in the first this response if their experiments had not also pointed month of the illness. KOMROWER and WATSON 12 to an extravagal pathway from the posterior hyporeport that of 28 cases in children aged 6 years or less, thalamus through the pituitary-adrenal system; stimulation caused a delayed secretion which was blocked no fewer than 24 presented as acute cases, 12 with severe and 12 with mild bleeding ; 6 of the children only by adrenalectomyJ8 If acid is a factor in with severe bleeding died, but the other 18 recovered ulceration, and if stress stimulates the hypothalamus, completely without treatment. In the chronic cases this might explain the rare recurrence of ulceration in children the onset is less dramatic, and symptoms after adequate gastric resection followed by vagotomy. tend to persist in an irregular fashion for more than FRENCH et a1.19have induced in monkeys ulceration in six months. KOMROWER and WATSON agree that in prepyloric and postpyloric areas by protracted stimuthe acute cases splenectomy is hazardous, and they lation (thirty to seventy days) of the medial prefer treatment with corticotrophin or cortisone for diencephalic axis from preoptic to postmamillary at least the first month after onset. For the chronic regions. This circumstantial evidence does not prove But that a similar mechanism operates in man. cases splenectomy should be considered after six months, but the necessity for this depends on the clinical observation caused CUSHING 20 to consider the role of stress and its impact via interbrain to midbrain disability the disease is causing. The successful management of idiopathic thrombo. and so on to the vagal centres in the medulla. His or was aroused by two cases in which acute in adults still children interest cytopenic purpura depends or duodenal perforations followed craniotomy on accurate diagnosis and on clinical assessment of the gastric condition and prognosis, as much as on information for cerebellar lesions. The several perforations were from clinical pathology. The detection of platelet- located in areas of erosion-in. the stomach in one case, agglutinins is not yet a helpful laboratory test, but and in the duodenum in the other. Ulcers that follow technical refinements may make it so. operations on the brain are apparently of two types : one is characterised by diffuse petechiæ and even gross haemorrhage, and the other by gelatinous softenPeptic Ulcer and the Brain and perforation.21 DAVIS et al.22 have erosion, ing, VAGAL section may be indicated in cases where the found that the incidence of perforation or haemorrhage anastomosis ulcerates after comprehensive gastric after 7000 neurosurgical operations was 0-7% ; but resection for duodenal ulcer ; and as a supplement to after craniotomies (943) and also after suboccipital the Billroth-i operation for duodenal ulcer it may craniectomies (350) it was about 2-5%. 8 patients in insure against recurrence.13 A report from the Mayo their series had pre-existing gastro-intestinal trouble ; Clinic 14 indicates that, though gastric resection is after all 8 were seriously ill because of operation the operation of choice for ulceration after gastroand some of these died from this cause. haematemeses, enterostomy, vagotomy, with a low mortality of 1%, In some cases gastro-intestinal haemorrhage ensued gives excellent results in 70% of patients with stomal even when the operation had not been on the central ulcer after partial gastrectomy : indeed, compared with nervous system-for example, on the autonomic the few cases submitted to gastric reresection which nerves. Moreover, as CUSHING knew, disease of the were followed up, vagotomy was apparently more effeccentral nervous system, without neurosurgical trauma, tive. WELLS 15 has reported the outcome of vagotomy may be associated with perforation or haemorrhage ; in 25 patients with ulceration after partial gastrectomy WATSON and NETSKY 23 describe 6 such cases, and and 14 after gastro-enterostomy : two-thirds of the refer to 38 previously reported, in which the patient resection group were free from trouble after three died from one of these complications. In 30 of the years; but the results in the gastro-enterostomy group total of 44 cases the neurological disorder involved were disappointing, since ulceration recurred in 10. the hypothalamus. WELLS considers that vagotomy is worth trying in the gastrectomy group, since it is safer than further 16. Priestley, J. T., Walters, W., Gray, H. K., Waugh, J. M. Proc. Mayo Clin. 1954, 29, 638. resection. There are occasions when removal of yet 17. French, J. D., Longmire, R. L., Porter, R. W., Movius, H. J. stomach is well-nigh is then a last resort. more
impossible ; vagal
section
11. 12.
Stefanini, M., Dameshek, W. Komrower, G. M., Watson, G.
13. 14.
Capper, W. M., Welbourn, R. B. Lancet, 1954, ii, 193. Walters, W., Chance, D. P., Berkson, J. Surg. Gynec. Obstet. 1955, 100, 1. Wells, B. W. Lancet, 1954, i, 599.
502.
15.
Annu. Rev. Med. 1954, 5, 87. H. Arch. Dis. Childh. 1954, 29,
Surgery, 1953, 34, 621. 18. Porter, R. W., Movius, H. J., French, J. D. Ibid, 1953, 33, 875. 19. French, J. D., Porter, R. W., Cavanaugh, E. B., Longmire, R. L. Arch. Neurol. Psychiat. 1954, 72, 267. 20. Cushing, H. Surg. Gynec. Obstet. 1932, 55, 1. 21. French, J. D., Porter, R. W., von Amerongen, F. K., Raney, R. B. Surgery, 1952, 32, 395. 22. Davis, R. A., Wetzel, N., Davis, L. Surg. Gynec. Obstet. 1955, 100, 51. 23. Watson, J. MacD.,
72, 426.
Netsky, M. G.
Arch. Neurol.
Psychiat. 1954,