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THE HISTORY OF FILARIA
899
Annotations SUBARACHNOID HÆMORRHAGE AND CEREBRAL INFARCTION
SUBARACHNOID haemorrhage results, in more than 80% of cases, from the rupture of an intracranial aneurysm 1-3 ; bleeding from an arteriovenous angioma is another common cause. In as many as half the cases " subarachnoid hxmorrhage " is a misnomer, for the haemorrhage encroaches on the cerebral substance as well as the subarachnoid space, 24 and bleeding into the subdural space occurs in up to 5% of cases.5 When a patient presents with the typical clinical picture of subarachnoid hxmorrhage, and then develops neurological symptoms or signs such as aphasia or paralysis of one or more limbs, it is commonly assumed that these must be the direct result of bleeding into or over the surface of the brain. Comparatively little attention has been paid to the fact that cerebral infarction is a common and important complication of bleeding from an intracranial aneurysm. As Tomlinson6 points out, this omission has probably been due to the fact that the brains of patients who have died as a result of aneurysmal rupture have not often been examined carefully for the presence or absence ofischsemic lesions. Robertson4 found that infarcts were mentioned in only 2 out of 80 cases in which he reviewed the necropsy findings, while infarcts were discovered in 3 of the 10 cases which he studied personally. In 1954 Wilson et al.7 found ischaemic lesions in 45% of their cases in which death was due to bleeding intracranial aneurysm. Now Tomlinsonreporting a personal study of 32 consecutive fatal cases, has discovered massive cerebral infarction in 13 (40%). Indeed he suggests that infarction, rather than intracerebral hxmorrhage, may be the predominant cause of residual disability in patients who survive but show signs of focal brain injury. Tomlinson points out that in his cases the infarcts were sometimes multiple; sometimes they lay in the distribution of the artery on which the bleeding aneurysm lay, but this was not always so. Thrombotic occlusion of a major was observed in any case, and in the great not artery that cerebral angiography, there was no evidence majority or other form of treatment could surgical interference, any have been responsible for, or related to, the development of the infarct. From the evidence he presents, Tomlinson is not prepared to draw firm conclusions about the xtiology of the infarction in these cases. In some cases it may be due to pressure on the parent vessel by a localised collection of blood, and in others to tearing of perforating branches of the artery at the time of the haemorrhage. Localised collections of blood between the frontal lobes or in the Sylvian fissure seem to be particularly common and may compress the anterior or middle cerebral arteries. There is also, however, a deal of that arterial spasm, evidence good experimental which may follow trauma to the cerebral vessels (such as is produced by haemorrhage around them), is probably an important setiological factor. Widespread arterial constriction seems to be common in the first four or five
days
after
haemorrhage.
1. Symonds, C. P. Quart. J. Med. 1924, 18, 93. 2. Richardson, J. C., Hyland, H. H. Medicine, Baltimore, 1941, 20, 1. 3. Walton, J. N. Subarachnoid Hæmorrhage, Edinburgh, 1956. 4. Robertson, E. G. Brain, 1949, 72, 150. 5. Clarke, E. S., Walton, J. N. ibid. 1953, 76, 378. 6. Tomlinson, B. E. J. clin. Path. 1959, 12, 391. 7. Wilson, G., Riggs, H. E., Rupp, C. J. Neurosurg. 1954, 11, 128.
These findings have important therapeutic implications. Clearly hypotensive therapy designed to reduce bleeding may promote infarction by lowering the bloodflow through arteries which are already narrowed, while operative treatment carried out too soon may increase the liability to infarction by further damaging the vessels. On the other hand, it is clearly important to evacuate as early as possible a localised hxmatoma which is capable of compressing major arteries. Fortunately evidence is accumulating that hypothermia as an aid to anaesthesia will reduce the risks of operation. But it is well that the physician should be aware that cerebral infarction can account for the neurological signs he observes in a patient with subarachnoid hxmorrhage, and that the surgeon also should appreciate the importance and frequency of this complication when he plans his surgical attack. THE HISTORY OF FILARIA
THE work of great painters or poets remains with us today still fresh and enjoyed by many, but the work of great scientists is far less fortunate. It is buried under the additions of later generations of workers; and, although it serves as a foundation, it is all too often taken for granted or forgotten altogether. Yet the history of how these basic discoveries were made has still much interest and profit for the worker of today. Accordingly we should be grateful to Sir Philip Manson-Bahr for having told the story of one such discovery-that of Filaria (Wuchereria) bancrofti-in a readable and enthralling form. His story is all the more authoritative because through his family and through his own work he has been connected with this subject from its early beginnings. The tale is one of the best known in tropical medicinehow small worms (micronlariae) were found in the urine and hydrocoele fluid of men with elephantiasis in the tropics; how Patrick Manson, a medical missionary, found that they appeared in blood during the night and disappeared during the day; how this led him to conclude that their behaviour must be correlated with some biting insect such as a mosquito which sucked blood at night and which could carry them from host to host; and how this led to the discovery of insect vectors of filariasis, malaria, and many other tropical infections. Besides the name of Manson, many other names should be recalledM. Demarquay, 0. Wucherer, J. Bancroft, T. R. Lewis, T. S. Cobbold, G. C. Low, and S. P. James.
Most of this work was done in the last twenty years of the 19th century, but the periodic behaviour of the microniarise has been further studied in recent years. It is now known that the disappearance of the microfilariae from the peripheral circulation during the day is due to their congregation in the capillaries and small vessels of the lungs, perhaps because the physiological conditions there favour their survival. But if they stayed there all the time they would never meet a mosquito and so have an opportunity to be transmitted to another host. Apparently, the periodicity is a compromise which enables the microniariae to make the best of both worlds. They spend the day enjoying the favourable conditions of the lungs, and they come out into the peripheral blood at night hoping to meet a mosquito. If they are disappointed, they return to the lungs the next morning in order to rest and recuperate. Two phases of the cycle can be distinguished-a passive phase (at night) when the microfilarix are evenly distributed through the blood and hence appear to be numerous 1.
J.
trop. Med. Hyg.
March, April, May, June, July,
1959.
900 in the peripheral circulation, and an active phase in which the microfilarix accumulate in the lungs. This accumulation cannot depend on opening and shutting of the capillaries of the host: it must be an active response by the microfilarix themselves to some stimulus provided by the twenty-four-hour rhythm of the host; but the exact nature of this stimulus and indeed of many other factors concerned with microfilarial periodicity are still unknown. One aspect which particularly stirs the imagination is the distribution of the two forms of W. bancrofti-the periodic and the non-periodic-among the islands and atolls scattered over the vast waters of the Pacific Ocean. When the Polynesians migrated in their canoes from one island to another, they presumably took their parasites and their mosquitoes with them. The more easterly migrants, presumably the earlier ones, carried the non-periodic filaria which is transmitted by Aedes polynesiensis and Aed. pseudoscutellaris; the less easterly (or later) migrants carried the periodic nocturnal filaria which is transmitted by Culex fatigans. The two areas are divided by a line which approximates to longitude 170°E. East of this line the people are Polynesian, malaria is absent, and the filariasis is non-periodic. West of it the people are Melanesian, malaria prevails, and filariasis is nocturnal. Thus the distribution of their parasites helps to give information about the prehistoric migration of these mysterious and romantic peoples. ACTINOMYCIN D IN THE TREATMENT OF TUMOURS
anti-tumour agents (discussed in the symposium reported on p. 907), actinomycin is of special interest. First isolated in 1940 by Waksman and Woodruff from a culture of soil actinomyces (Streptomyces antibioticus), it was found to have a strong action against gram-negative organisms, but was also selectively cytotoxic to mammalian tissues. Although too toxic as a clinical antibiotic, it was reinvestigated for its potential anti-tumour effect. Closely related compounds, designated actinomycin A, B, C, D, I, J, and X, differing only in the composition of aminoacids in the peptide side-chain of the moleculewere soon isolated. Chemically, the various actinomycins are in fact mixtures of each other, and only actinomycin D is relatively pure.3 Actinomycin D was shown to act in mice against trans-
OF the
new
planted malignant melanoma,
mammary adenocarcinoma, and leukaemia at doses of 75-100 ug. per kg. bodyweight.4 Parenteral treatment is essential,5 and even administered parenterally the drug varies in its effect, although solutions of crystalline actinomycin D in 25% ethanol have proved stable for six weeks.5 Early clinical trials failed to show any benefit in children
leukxmia, but important temporary improveproduced in rhabdomyosarcoma, Wilm’s and tumour, Hodgkin’s disease.6 Moore et al.’ studied the effect of the drug in adults with various forms of advanced malignant disease. With total doses of 50-75 {jLg. per kg. body-weight intravenously, divided into five or ten daily injections, objective temporary tumour regression was observed in only 12 of 67 patients (carcinoma of the breast 3, lymphosarcoma 3, carcinoma of stomach 1, melanoma 1, miscellaneous 4) and only 3 of these patients S. A., Woodruff, H. B. Proc. Soc. exp. Biol., N.Y. 1940, 45, 609. 1. Waksman, 2. Pugh, L. H., Katz, E., Waksman, S. A. J. Bact. 1956, 72, 660. with
ment
acute
was
3. Waksman, S. A., Katz, E., Vining, L. J. Path. Bact. 1958, 44, 602. 4. Farber, S. Amer. J. Path. 1955, 31, 582.
DiPaolo, J. A., Moore, G. E., Niedbala, T. F. Cancer Res. 1957, 17, 1127. Farber, S., Toch, R., Sears, E. M., Pinkel, D. Advanc. Cancer Res. 1956, 4, 49. 7. Moore, G. E., DiPaolo, J. A., Kondo, T. Cancer, 1958, 11, 1204.
5.6.
lasting more than a month. On the other cells disappeared from the blood, even masses remained unchanged. Slight depression on the fourth to twenty-fourth day
had remissions
hand, when
tumour tumour
marrow
third of the patients, but usually recovered spontaneously within ten days. Other untoward effects included anorexia, nausea, vomiting, diarrhoea, buccal ulceration, acne, alopecia, an enhanced tumour growth-rate after ineffective therapy, and thrombophlebitis at the site of injection. (Excessive skin reactions over previously irradiated areas have also been reported.8) Maintenance therapy did not appear to be of benefit. Tan et al.8 at the Sloan-Kettering Institute have now reported their experience with actinomycin D in 111 children with metastatic cancer. Striking regression of massive pulmonary metastases occurred in several patients. The drug appeared to potentiate the predicted response to radiotherapy in 28 of 50 patients treated with approximately 50% of the estimated therapeutic dose of X rays, even in some relatively radioresistant tumours. Particularly interesting are the 49 children treated with actinomycin D alone, in 16 of whom objective tumour regression was attributable solely to the drug. In a 2-year-old boy with a Wilm’s tumour a pulmonary metastasis regressed completely, and he has had no further recurrence for two years. In all, 6 of 16 children with metastatic Wilm’s tumour who received actinomycin D alone showed objective improvement; indeed, Tan et al. suggest that this should be the initial form of therapy in such cases, with additive radiotherapy only if tumour regression is incomplete. Experience with other tumours was less favourable, although temporary benefit was observed in some cases of neuroblastoma, rhabdomyoSimilar sarcoma, lymphadenoma and bone sarcoma. results were reported by Pinkel9 in a smaller series, in which objective temporary improvement in rhabdomyosarcoma and Wilm’s tumour was also recorded. A 31/2year-old girl with a recurrent rhabdomyosarcoma of the face had a particularly gratifying response, pronounced tumour shrinkage making a radical excision possible. Although tumour inhibition with oral therapy could not be shown experimentally,5 the Sloan-Kettering group, using oral doses of 3 to 10 mg. daily, estimated from the systemic effects that about 5% was absorbed. But the toxic effects on the gastrointestinal tract were more severe and commoner, preventing adequate therapy by this means. The recommended total intravenous dose is 75 (Lg. per kg. body-weight or 2-3 mg. per sq. m. body surface in three to six injections over a period of one to two weeks; but repeated courses may be needed in the absence of a suitable preparation for maintenance therapy. The evidence suggests that actinomycin D may have a useful place in the treatment of disseminated Wilm’s tumour and other metastatic sarcomas in children. Tumour shrinkage may make surgical excision possible; secondary deposits may regress following removal of the primary growth; and the effect of radiotherapy may be after the
start
of
treatment was
noted in
a
potentiated. We regret to announce the death on Nov. 14 at Bungay, of Mr. HAROLD WILSON, consulting surgeon to St. Bartholomew’s Hospital, London. Sir FRANCIS PRIDEAUX, Ministry of Pensions, died 8. 9.
formerly director-general of the on
Nov. 15
at
the age of 75.
Tan, C. T. C., Dargeon, H. W., Burchenal, J. H. Pediatrics, 1959, 24, 544. Pinkel, D. ibid. 1959 23, 342.
Annotations SUBARACHNOID HÆMORRHAGE AND CEREBRAL INFARCTION
SUBARACHNOID haemorrhage results, in more than 80% of cases, from the rupture of an intracranial aneurysm 1-3 ; bleeding from an arteriovenous angioma is another common cause. In as many as half the cases " subarachnoid hxmorrhage " is a misnomer, for the haemorrhage encroaches on the cerebral substance as well as the subarachnoid space, 24 and bleeding into the subdural space occurs in up to 5% of cases.5 When a patient presents with the typical clinical picture of subarachnoid hxmorrhage, and then develops neurological symptoms or signs such as aphasia or paralysis of one or more limbs, it is commonly assumed that these must be the direct result of bleeding into or over the surface of the brain. Comparatively little attention has been paid to the fact that cerebral infarction is a common and important complication of bleeding from an intracranial aneurysm. As Tomlinson6 points out, this omission has probably been due to the fact that the brains of patients who have died as a result of aneurysmal rupture have not often been examined carefully for the presence or absence ofischsemic lesions. Robertson4 found that infarcts were mentioned in only 2 out of 80 cases in which he reviewed the necropsy findings, while infarcts were discovered in 3 of the 10 cases which he studied personally. In 1954 Wilson et al.7 found ischaemic lesions in 45% of their cases in which death was due to bleeding intracranial aneurysm. Now Tomlinsonreporting a personal study of 32 consecutive fatal cases, has discovered massive cerebral infarction in 13 (40%). Indeed he suggests that infarction, rather than intracerebral hxmorrhage, may be the predominant cause of residual disability in patients who survive but show signs of focal brain injury. Tomlinson points out that in his cases the infarcts were sometimes multiple; sometimes they lay in the distribution of the artery on which the bleeding aneurysm lay, but this was not always so. Thrombotic occlusion of a major was observed in any case, and in the great not artery that cerebral angiography, there was no evidence majority or other form of treatment could surgical interference, any have been responsible for, or related to, the development of the infarct. From the evidence he presents, Tomlinson is not prepared to draw firm conclusions about the xtiology of the infarction in these cases. In some cases it may be due to pressure on the parent vessel by a localised collection of blood, and in others to tearing of perforating branches of the artery at the time of the haemorrhage. Localised collections of blood between the frontal lobes or in the Sylvian fissure seem to be particularly common and may compress the anterior or middle cerebral arteries. There is also, however, a deal of that arterial spasm, evidence good experimental which may follow trauma to the cerebral vessels (such as is produced by haemorrhage around them), is probably an important setiological factor. Widespread arterial constriction seems to be common in the first four or five
days
after
haemorrhage.
1. Symonds, C. P. Quart. J. Med. 1924, 18, 93. 2. Richardson, J. C., Hyland, H. H. Medicine, Baltimore, 1941, 20, 1. 3. Walton, J. N. Subarachnoid Hæmorrhage, Edinburgh, 1956. 4. Robertson, E. G. Brain, 1949, 72, 150. 5. Clarke, E. S., Walton, J. N. ibid. 1953, 76, 378. 6. Tomlinson, B. E. J. clin. Path. 1959, 12, 391. 7. Wilson, G., Riggs, H. E., Rupp, C. J. Neurosurg. 1954, 11, 128.
These findings have important therapeutic implications. Clearly hypotensive therapy designed to reduce bleeding may promote infarction by lowering the bloodflow through arteries which are already narrowed, while operative treatment carried out too soon may increase the liability to infarction by further damaging the vessels. On the other hand, it is clearly important to evacuate as early as possible a localised hxmatoma which is capable of compressing major arteries. Fortunately evidence is accumulating that hypothermia as an aid to anaesthesia will reduce the risks of operation. But it is well that the physician should be aware that cerebral infarction can account for the neurological signs he observes in a patient with subarachnoid hxmorrhage, and that the surgeon also should appreciate the importance and frequency of this complication when he plans his surgical attack. THE HISTORY OF FILARIA
THE work of great painters or poets remains with us today still fresh and enjoyed by many, but the work of great scientists is far less fortunate. It is buried under the additions of later generations of workers; and, although it serves as a foundation, it is all too often taken for granted or forgotten altogether. Yet the history of how these basic discoveries were made has still much interest and profit for the worker of today. Accordingly we should be grateful to Sir Philip Manson-Bahr for having told the story of one such discovery-that of Filaria (Wuchereria) bancrofti-in a readable and enthralling form. His story is all the more authoritative because through his family and through his own work he has been connected with this subject from its early beginnings. The tale is one of the best known in tropical medicinehow small worms (micronlariae) were found in the urine and hydrocoele fluid of men with elephantiasis in the tropics; how Patrick Manson, a medical missionary, found that they appeared in blood during the night and disappeared during the day; how this led him to conclude that their behaviour must be correlated with some biting insect such as a mosquito which sucked blood at night and which could carry them from host to host; and how this led to the discovery of insect vectors of filariasis, malaria, and many other tropical infections. Besides the name of Manson, many other names should be recalledM. Demarquay, 0. Wucherer, J. Bancroft, T. R. Lewis, T. S. Cobbold, G. C. Low, and S. P. James.
Most of this work was done in the last twenty years of the 19th century, but the periodic behaviour of the microniarise has been further studied in recent years. It is now known that the disappearance of the microfilariae from the peripheral circulation during the day is due to their congregation in the capillaries and small vessels of the lungs, perhaps because the physiological conditions there favour their survival. But if they stayed there all the time they would never meet a mosquito and so have an opportunity to be transmitted to another host. Apparently, the periodicity is a compromise which enables the microniariae to make the best of both worlds. They spend the day enjoying the favourable conditions of the lungs, and they come out into the peripheral blood at night hoping to meet a mosquito. If they are disappointed, they return to the lungs the next morning in order to rest and recuperate. Two phases of the cycle can be distinguished-a passive phase (at night) when the microfilarix are evenly distributed through the blood and hence appear to be numerous 1.
J.
trop. Med. Hyg.
March, April, May, June, July,
1959.
900 in the peripheral circulation, and an active phase in which the microfilarix accumulate in the lungs. This accumulation cannot depend on opening and shutting of the capillaries of the host: it must be an active response by the microfilarix themselves to some stimulus provided by the twenty-four-hour rhythm of the host; but the exact nature of this stimulus and indeed of many other factors concerned with microfilarial periodicity are still unknown. One aspect which particularly stirs the imagination is the distribution of the two forms of W. bancrofti-the periodic and the non-periodic-among the islands and atolls scattered over the vast waters of the Pacific Ocean. When the Polynesians migrated in their canoes from one island to another, they presumably took their parasites and their mosquitoes with them. The more easterly migrants, presumably the earlier ones, carried the non-periodic filaria which is transmitted by Aedes polynesiensis and Aed. pseudoscutellaris; the less easterly (or later) migrants carried the periodic nocturnal filaria which is transmitted by Culex fatigans. The two areas are divided by a line which approximates to longitude 170°E. East of this line the people are Polynesian, malaria is absent, and the filariasis is non-periodic. West of it the people are Melanesian, malaria prevails, and filariasis is nocturnal. Thus the distribution of their parasites helps to give information about the prehistoric migration of these mysterious and romantic peoples. ACTINOMYCIN D IN THE TREATMENT OF TUMOURS
anti-tumour agents (discussed in the symposium reported on p. 907), actinomycin is of special interest. First isolated in 1940 by Waksman and Woodruff from a culture of soil actinomyces (Streptomyces antibioticus), it was found to have a strong action against gram-negative organisms, but was also selectively cytotoxic to mammalian tissues. Although too toxic as a clinical antibiotic, it was reinvestigated for its potential anti-tumour effect. Closely related compounds, designated actinomycin A, B, C, D, I, J, and X, differing only in the composition of aminoacids in the peptide side-chain of the moleculewere soon isolated. Chemically, the various actinomycins are in fact mixtures of each other, and only actinomycin D is relatively pure.3 Actinomycin D was shown to act in mice against trans-
OF the
new
planted malignant melanoma,
mammary adenocarcinoma, and leukaemia at doses of 75-100 ug. per kg. bodyweight.4 Parenteral treatment is essential,5 and even administered parenterally the drug varies in its effect, although solutions of crystalline actinomycin D in 25% ethanol have proved stable for six weeks.5 Early clinical trials failed to show any benefit in children
leukxmia, but important temporary improveproduced in rhabdomyosarcoma, Wilm’s and tumour, Hodgkin’s disease.6 Moore et al.’ studied the effect of the drug in adults with various forms of advanced malignant disease. With total doses of 50-75 {jLg. per kg. body-weight intravenously, divided into five or ten daily injections, objective temporary tumour regression was observed in only 12 of 67 patients (carcinoma of the breast 3, lymphosarcoma 3, carcinoma of stomach 1, melanoma 1, miscellaneous 4) and only 3 of these patients S. A., Woodruff, H. B. Proc. Soc. exp. Biol., N.Y. 1940, 45, 609. 1. Waksman, 2. Pugh, L. H., Katz, E., Waksman, S. A. J. Bact. 1956, 72, 660. with
ment
acute
was
3. Waksman, S. A., Katz, E., Vining, L. J. Path. Bact. 1958, 44, 602. 4. Farber, S. Amer. J. Path. 1955, 31, 582.
DiPaolo, J. A., Moore, G. E., Niedbala, T. F. Cancer Res. 1957, 17, 1127. Farber, S., Toch, R., Sears, E. M., Pinkel, D. Advanc. Cancer Res. 1956, 4, 49. 7. Moore, G. E., DiPaolo, J. A., Kondo, T. Cancer, 1958, 11, 1204.
5.6.
lasting more than a month. On the other cells disappeared from the blood, even masses remained unchanged. Slight depression on the fourth to twenty-fourth day
had remissions
hand, when
tumour tumour
marrow
third of the patients, but usually recovered spontaneously within ten days. Other untoward effects included anorexia, nausea, vomiting, diarrhoea, buccal ulceration, acne, alopecia, an enhanced tumour growth-rate after ineffective therapy, and thrombophlebitis at the site of injection. (Excessive skin reactions over previously irradiated areas have also been reported.8) Maintenance therapy did not appear to be of benefit. Tan et al.8 at the Sloan-Kettering Institute have now reported their experience with actinomycin D in 111 children with metastatic cancer. Striking regression of massive pulmonary metastases occurred in several patients. The drug appeared to potentiate the predicted response to radiotherapy in 28 of 50 patients treated with approximately 50% of the estimated therapeutic dose of X rays, even in some relatively radioresistant tumours. Particularly interesting are the 49 children treated with actinomycin D alone, in 16 of whom objective tumour regression was attributable solely to the drug. In a 2-year-old boy with a Wilm’s tumour a pulmonary metastasis regressed completely, and he has had no further recurrence for two years. In all, 6 of 16 children with metastatic Wilm’s tumour who received actinomycin D alone showed objective improvement; indeed, Tan et al. suggest that this should be the initial form of therapy in such cases, with additive radiotherapy only if tumour regression is incomplete. Experience with other tumours was less favourable, although temporary benefit was observed in some cases of neuroblastoma, rhabdomyoSimilar sarcoma, lymphadenoma and bone sarcoma. results were reported by Pinkel9 in a smaller series, in which objective temporary improvement in rhabdomyosarcoma and Wilm’s tumour was also recorded. A 31/2year-old girl with a recurrent rhabdomyosarcoma of the face had a particularly gratifying response, pronounced tumour shrinkage making a radical excision possible. Although tumour inhibition with oral therapy could not be shown experimentally,5 the Sloan-Kettering group, using oral doses of 3 to 10 mg. daily, estimated from the systemic effects that about 5% was absorbed. But the toxic effects on the gastrointestinal tract were more severe and commoner, preventing adequate therapy by this means. The recommended total intravenous dose is 75 (Lg. per kg. body-weight or 2-3 mg. per sq. m. body surface in three to six injections over a period of one to two weeks; but repeated courses may be needed in the absence of a suitable preparation for maintenance therapy. The evidence suggests that actinomycin D may have a useful place in the treatment of disseminated Wilm’s tumour and other metastatic sarcomas in children. Tumour shrinkage may make surgical excision possible; secondary deposits may regress following removal of the primary growth; and the effect of radiotherapy may be after the
start
of
treatment was
noted in
a
potentiated. We regret to announce the death on Nov. 14 at Bungay, of Mr. HAROLD WILSON, consulting surgeon to St. Bartholomew’s Hospital, London. Sir FRANCIS PRIDEAUX, Ministry of Pensions, died 8. 9.
formerly director-general of the on
Nov. 15
at
the age of 75.
Tan, C. T. C., Dargeon, H. W., Burchenal, J. H. Pediatrics, 1959, 24, 544. Pinkel, D. ibid. 1959 23, 342.