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FAVISM IN A CYPRIOT CHILD
628 and putamen were shrunken. Alzheimer glial cells were common. There was no abnormal copper storage in brain or liver. Greenfield concluded that this case " may be classed as hepatolenticular degeneration, although it was atypical in several respects, but chemically it was entirely different.... Cases like this are probably not very rare, but as the biochemical changes of Wilson’s disease are recent discoveries they have not yet been reported. Their classification raises a difficult problem, since the biochemists exclude them from the category of Wilson’s disease.... Meanwhile it is important that cases such as this, which do not conform to the modern chemical criteria of Wilson’s disease, should be fully recorded ".
The position is further complicated by reported cases of " Wilson’s disease " without liver involvement. All of these, reviewed by Eicke (1957), date from before the period of biochemical definition of Wilson’s disease; hence one cannot be sure that they are indeed that condition. Only the accumulation of further cases which are biochemically documented can clarify the issue. Our case serves to underline the question raised by Greenfield (1954)-" Is hepatolenticular degeneration a clinico-
pathological entity ?
"
Summary
girl, who died at the age of 9 years 3 months, had the morphological changes of " Wilson’s disease " in the central nervous system without hepatic cirrhosis. Copper A
metabolism was not disturbed but aminoaciduria was present. She had no Kayser-Fleischer ring. This case cannot be grouped with Wilson’s disease as biochemically defined at present. Our thanks are due to Prof. Donald Court for permission to publish this case; to Prof. J. N. Cumings for the copper estimations and for permission to publish table i; to Dr. A. J. Smith for the urine chromatography; and to Mr. C. J. Duncan of the department of ohotosraohv for fig. 5. REFERENCES
Brown, I. A. (1957) Liver-Brain Relationships. Springfield, Ill. Brzezicki, E. (1937) Zbl. Neurol. 86, 119. Cumings, J. N. (1959) Heavy Metals and the Brain. Oxford. Eicke, W. J. (1957) in Handbuch der speziellen pathologischen Anatomie und Histologie (edited by O. Lubarsch, F. Henke, and R. Rossle); vol. XIII, part 1A. Berlin.
Greenfield, J. G. (1954) Proc. R. Soc. Med. 47, 150. Lichtenstein, B. W., Gore, I. (1955) Arch. Neurol. Psychiat. 73, Warnock, C. G., Neill, D. W. (1958) Brain, 81, 258. Wilson, A. S. K. (1912) ibid. 34, 295.
13.
FAVISM IN A CYPRIOT CHILD N. D. GOWER M.B. Lond. SENIOR REGISTRAR IN PATHOLOGY
EVA FROMMBR M.B. Lond., D.C.H. REGISTRAR IN PÆDIATRICS
EDGWARE GENERAL HOSPITAL, MIDDLESEX
FAVISM is a form of acute haemolytic anxmia which in certain sensitive subjects after eating broad beans. Most cases are said to arise in persons of Sardinian ancestry (Luisada 1941), but the disease is quite widespread throughout the Mediterranean seaboard and islands (Marcolongo 1953) and has been recognised in Hebrew children (Robinson 1941). Owing to this racial predisposition favism is rarely seen in this country. Two cases in Cypriot children in London were described by Diggle (1953) and another was recognised by Discombe and Mestitz (1956). At least one case has been seen in an English child, whose maternal uncle may have suffered from the disease (McCarthy 1955). Favism is a serious disease, especially in children, in whom the mortality-rate may reach 8% or 10% (Luisada occurs
1941, Marcolongo 1953). Renal impairment and lesions of the basal ganglia are occasional sequelx (Marcolongo 1953). For these reasons, and because favism is preventable, we have recorded the following case, which also serves as a reminder that Cypriot children may suffer from red-cell defects other than the hsemoglobinopathies. Case-report First Admission A three-year-old boy, the second child of healthy Cypriot parents, was admitted to Edgware General Hospital on July 11, 1958, with a history of rapidly increasing pallor and the passage of dark-red urine for twenty-four hours. The child had complained of pain in the neck and had vomited several times. He had previously been fit except for recurrent sore throat. There was no history of any familial disease. On examination the child was restless and obviously ill. He was very pale and slightly jaundiced. The temperature was 100°F, pulse-rate 132, and respiration-rate 28 per min. The tonsils were enlarged and injected. A few small glands were palpable in the neck and left axilla. The spleen and liver were not felt and there were no other physical findings of note. A clinical diagnosis of acute haemolytic anaemia, possibly due to streptococcal throat infection, was made.
lnvestigations.-Haemoglobin 3,6 g. per 100 mI. (26%). White cells 15,300 per c.mm. Blood-film showed many fragmenting cells and occasional microspherocytes. A few myelocytes and normoblasts Direct Coombs test negative, were present. Platelets were plentiful. using Coombs serum at dilutions 1/5, 1/20, 1/80. Blood-urea 75 mg. per 100 ml. Serum-bilirubin 4 mg. per 100 ml. The urine was almost black in colour and the deposit contained a few red cells and granular casts. Spectroscopy showed the presence of oxyhasmoglobin and methxmoglobin. Three throat swabs were taken in the first two days but none yielded Streptococcus pyogenes or other pathogenic bacteria on culture. Course and Treatment The provisional diagnosis was revised to acute exacerbation of a congenital hxmolytic anxmia, but in view of the clear need for urgent blood-transfusion we decided to defer more extensive investigation until the patient was in remission. Two bottles of compatible packed cells were transfused on the same day. No difficulty was experienced with the cross-matching or transfusion of the blood. Although the Coombs test was negative 25 mg. of cortisone was given intramuscularly, followed by 5 mg. of prednisolone daily for six days. In view of the apparent tonsillitis a course of penicillin was also given. The haemoglobin level on the day following transfusion was 9,9 g. per 100 ml. and did not subsequently fall below this level. Clinical improvement was rapid, haemoglobinuria ceasing during the second day in hospital. The blood-urea and serum-bilirubin levels fell to normal by the third day. The spleen became palpable on the third day but had disappeared beyond the costal margin two days later. The patient was discharged home on the eleventh day, looking very well, with a haemoglobin level of 10-8 g. per 100 ml. and a reticulocyte-count of only 1%. One month later his blood-picture was quite normal. The child was seen again three months later. He was fit and lively, and no abnormality was found on physical examination.
Investigations.-Hxrnoglobin 12.4 g. per 100 ml. (87%). Reticulocytes less than 1%. The stained film showed no morphological abnormality of the red cells; in particular no spherocytes, target cells or macrocytes were seen. The leucocytes and platelets were normal. The osmotic fragility of the red cells was normal and incubation autohaemolysis (Selwyn and Dacie 1954) was less than 1% even without glucose. With glucose added there was no detectable haemolysis after forty-eight hours. Acid haemolysis test negative. Red-cell potassium 82 mEq. per litre. Electrophoresis showed no abnormal haemoglobin. We concluded that the child was unlikely to be suffering from even a mild congenital hsemolytic anfemia. The patient was seen again in January, 1959, as he had been unwell for a few days. No abnormality was found on examination, but his haemoglobin level was only 9-0 g. per 100 ml.
629 Second Admission He was readmitted to hospital on March 13, 1959. He had developed a sore throat several days previously and for twentyfour hours he had been passing dark-red urine. Examination revealed no physical abnormality and the child was not nearly so ill as on his first admission. Direct inquiry revealed that he had eaten broad beans, which had been purchased frozen, on the day before the onset of hxmoglobinuria. We then discovered that this little boy did not like broad beans and had eaten them only twice before. The first time was just before his serious episode of haemolysis and the second time was a few days before he was seen in January, 1959, and found to be a little anaemic. The diagnosis of favism was apparent. The child made a rapid recovery without transfusion.
Investigation on this occasion again failed to reveal any evidence of red-cell defect, but at a later date when the patient had a normal blood-picture (haemoglobin 12’0 per 100 ml., reticulocytes 1’4%), we were able to show that his red cells behaved abnormally after incubation with acetylphenylhydrazine, using the method described by Beutler et al. (1955), for the detection of primaquine-sensitive red cells. This test was unequivocally positive, 80% of the patient’s erythrocytes developing multiple small Heinz bodies, compared with 27% of the normal control. "
We are grateful to Dr. M. D. Baber for permission to publish this and to Dr. Baber and Dr. J. L. Hamilton-Paterson for advice in preparing the manuscript. case
REFERENCES
Beutler, E. (1959) Blood, 14, 103. (1957) J. Lab. clin. Med. 49, 84. Dern, R. J., Alving, A. S. (1955) ibid. 45, 40. Diggle, J. H. (1953) Arch. Dis. Childh. 28, 369. Discombe, G., Mestitz, W. (1956) Brit. Med. J. i, 1023. Larizza, P., Brunetti, P., Grignani, F., Ventura, S. (1958) Quoted by Beutler (1959). Luisada, A. (1941) Medicine, Baltimore, 20, 229. Marcolongo, F. (1953) Rec. Progr. Med. 15, 90. McCarthy, O. R. (1955) Lancet, i, 748. Robinson, P. (1941) Amer. J. Dis. Child. 62, 701. Selwyn, J. G., Dacie, J. V. (1954) Blood, 9, 414. -
-
TOXIC MARROW FAILURE TREATED BY A HOMOGRAFT OF FŒTAL HÆMOPOIETIC TISSUE
J. B. BRIDGES M.D., B.Sc. Belf.
"
LECTURER IN
QUEEN’S
J. M. BRIDGES
Discussion
Until response
M.D. Belf. "
"
recently favism was regarded as an allergic to the proteins of broad beans, but Larizza et al.
(1958) have demonstrated an intrinsic red-cell defect in patients with favism, both during the active phase of the disease and after recovery. This defect is identical with, or at least closely related to, the intrinsic abnormality found in patients in whom haemolysis develops in response to primaquine, sulphonamides, and nitrofurantoin (" primaquine sensitivity or primaquine ansemia "). Beutler (1959) and others have shown that the erythrocytes of these patients are deficient in glucose 6-phosphate dehydrogenase. These defective red cells can be most simply recognised by the characteristic pattern of Heinz-body formation produced in them by acetylphenylhydrazine treatment, or by their inability to retain glutathione (" glutathione instability ") after incubation with acetylphenylhydrazine (Beutler et al. 1955, Beutler 1957). The diagnosis of favism is not likely to present difficulty if the possibility is borne in mind, but in the absence of a history of eating broad beans it may be confused with a crisis of a congenital hxmolytic anxmia. Earlier authors have denied the presence of spherocytes in favism, but their occurrence is recognised by Marcolongo, and our case could not be differentiated on morphological grounds alone from cases of congenital spherocytosis presenting with crisis. The combination of suggestive peripheral blood findings, negative direct Coombs test and maintenance of the haemoglobin level following blood-transfusion was thought to support the latter diagnosis, but the normal result of incubation autohsemolysis excluded congenital spherocytosis and most types of congenital non-spherocytic hxmolytic anxmia. The diagnosis of favism was eventually made on the history of eating broad beans, supported by the demonstration of primaquine sensi"
ANATOMY,
UNIVERSITY OF BELFAST
"
"
tivity ". On theoretical grounds it seems possible that individuals who are subject to favism may develop haemolytic anxmia in response to certain common drugs, although little evidence to support this idea can be found in the literature apart from Luisada’s observation that quinine hxmoglobinuria is rather common in patients who have previously had favism. Nevertheless favism is an indication of enzyme-defective red cells in a person, and its diagnosis may be as important as a warning to avoid certain drugs as it is a warning to abstain from broad beans.
BRITISH EMPIRE CANCER CAMPAIGN RESEARCH FELLOW, DEPARTMENT OF CLINICAL PATHOLOGY, ROYAL VICTORIA HOSPITAL, BELFAST
G. J. A. EDELSTYN M.B. Belf. REGISTRAR,
NORTHERN IRELAND RADIOTHERAPHY MONTGOMERY
HOUSE,
CENTRE,
BELFAST
A. R. LYONS M.D. Belf., M.R.C.P., D.M.R.T.E. RADIOTHERAPIST, NORTHERN IRELAND RADIOTHERAPY
CENTRE
M. G. NELSON M.D. Belf., F.R.C.P.I., M.R.C.P., D.T.M. & CLINICAL PATHOLOGIST TO THE ROYAL VICTORIA
H. HOSPITAL, BELFAST
ENCOURAGING results have recently been reported in the treatment of disseminated mammary carcinoma with thiotepa (triethylene thiophosphoramide) combined with testosterone (Watson and Turner 1959). One of the of of this form recognised complications therapy is toxic marrow damage with peripheral pancytopenia. This a metaarose in woman with complication widespread stases from a mammary carcinoma who was treated with thiotepa and testosterone at the Northern Ireland Radiotherapy Centre. Animals exposed to otherwise lethal irradiation can be saved if injected with suspensions of haemopoietic cells (Lorenz et al. 1951, Porter 1957, Ferrebee et al. 1958); under these conditions the injected cells " home to " and repopulate the depleted medullary cavities (Ford et al. 1956). Marrow infusions have also been successfully used in patients with marrow failure resulting from either irradiation (Thomas et al. 1959) or massive chemotherapy (Westbury et al. 1959). It was decided therefore to attempt marrow-replacement therapy in this patient by injecting homologous haemopoietic cells. Since experiments have shown that the interactions between host and grafted homologous material are reduced if foetal tissue is transferred (Bames et al. 1958, Uphoff 1958), suspensions of human foetal liver were used.
Early
Case-report patient, aged 43, noticed a lump in the quadrant of her left breast. When first seen, in
in 1957 the
upper outer
January, 1958, the entire breast was solid with tumour and fixed to underlying muscle, and enlarged lymph-nodes were easily felt in the left axilla and left supraclavicular region. A chest radiograph revealed some lymphangitic infiltration of
The position is further complicated by reported cases of " Wilson’s disease " without liver involvement. All of these, reviewed by Eicke (1957), date from before the period of biochemical definition of Wilson’s disease; hence one cannot be sure that they are indeed that condition. Only the accumulation of further cases which are biochemically documented can clarify the issue. Our case serves to underline the question raised by Greenfield (1954)-" Is hepatolenticular degeneration a clinico-
pathological entity ?
"
Summary
girl, who died at the age of 9 years 3 months, had the morphological changes of " Wilson’s disease " in the central nervous system without hepatic cirrhosis. Copper A
metabolism was not disturbed but aminoaciduria was present. She had no Kayser-Fleischer ring. This case cannot be grouped with Wilson’s disease as biochemically defined at present. Our thanks are due to Prof. Donald Court for permission to publish this case; to Prof. J. N. Cumings for the copper estimations and for permission to publish table i; to Dr. A. J. Smith for the urine chromatography; and to Mr. C. J. Duncan of the department of ohotosraohv for fig. 5. REFERENCES
Brown, I. A. (1957) Liver-Brain Relationships. Springfield, Ill. Brzezicki, E. (1937) Zbl. Neurol. 86, 119. Cumings, J. N. (1959) Heavy Metals and the Brain. Oxford. Eicke, W. J. (1957) in Handbuch der speziellen pathologischen Anatomie und Histologie (edited by O. Lubarsch, F. Henke, and R. Rossle); vol. XIII, part 1A. Berlin.
Greenfield, J. G. (1954) Proc. R. Soc. Med. 47, 150. Lichtenstein, B. W., Gore, I. (1955) Arch. Neurol. Psychiat. 73, Warnock, C. G., Neill, D. W. (1958) Brain, 81, 258. Wilson, A. S. K. (1912) ibid. 34, 295.
13.
FAVISM IN A CYPRIOT CHILD N. D. GOWER M.B. Lond. SENIOR REGISTRAR IN PATHOLOGY
EVA FROMMBR M.B. Lond., D.C.H. REGISTRAR IN PÆDIATRICS
EDGWARE GENERAL HOSPITAL, MIDDLESEX
FAVISM is a form of acute haemolytic anxmia which in certain sensitive subjects after eating broad beans. Most cases are said to arise in persons of Sardinian ancestry (Luisada 1941), but the disease is quite widespread throughout the Mediterranean seaboard and islands (Marcolongo 1953) and has been recognised in Hebrew children (Robinson 1941). Owing to this racial predisposition favism is rarely seen in this country. Two cases in Cypriot children in London were described by Diggle (1953) and another was recognised by Discombe and Mestitz (1956). At least one case has been seen in an English child, whose maternal uncle may have suffered from the disease (McCarthy 1955). Favism is a serious disease, especially in children, in whom the mortality-rate may reach 8% or 10% (Luisada occurs
1941, Marcolongo 1953). Renal impairment and lesions of the basal ganglia are occasional sequelx (Marcolongo 1953). For these reasons, and because favism is preventable, we have recorded the following case, which also serves as a reminder that Cypriot children may suffer from red-cell defects other than the hsemoglobinopathies. Case-report First Admission A three-year-old boy, the second child of healthy Cypriot parents, was admitted to Edgware General Hospital on July 11, 1958, with a history of rapidly increasing pallor and the passage of dark-red urine for twenty-four hours. The child had complained of pain in the neck and had vomited several times. He had previously been fit except for recurrent sore throat. There was no history of any familial disease. On examination the child was restless and obviously ill. He was very pale and slightly jaundiced. The temperature was 100°F, pulse-rate 132, and respiration-rate 28 per min. The tonsils were enlarged and injected. A few small glands were palpable in the neck and left axilla. The spleen and liver were not felt and there were no other physical findings of note. A clinical diagnosis of acute haemolytic anaemia, possibly due to streptococcal throat infection, was made.
lnvestigations.-Haemoglobin 3,6 g. per 100 mI. (26%). White cells 15,300 per c.mm. Blood-film showed many fragmenting cells and occasional microspherocytes. A few myelocytes and normoblasts Direct Coombs test negative, were present. Platelets were plentiful. using Coombs serum at dilutions 1/5, 1/20, 1/80. Blood-urea 75 mg. per 100 ml. Serum-bilirubin 4 mg. per 100 ml. The urine was almost black in colour and the deposit contained a few red cells and granular casts. Spectroscopy showed the presence of oxyhasmoglobin and methxmoglobin. Three throat swabs were taken in the first two days but none yielded Streptococcus pyogenes or other pathogenic bacteria on culture. Course and Treatment The provisional diagnosis was revised to acute exacerbation of a congenital hxmolytic anxmia, but in view of the clear need for urgent blood-transfusion we decided to defer more extensive investigation until the patient was in remission. Two bottles of compatible packed cells were transfused on the same day. No difficulty was experienced with the cross-matching or transfusion of the blood. Although the Coombs test was negative 25 mg. of cortisone was given intramuscularly, followed by 5 mg. of prednisolone daily for six days. In view of the apparent tonsillitis a course of penicillin was also given. The haemoglobin level on the day following transfusion was 9,9 g. per 100 ml. and did not subsequently fall below this level. Clinical improvement was rapid, haemoglobinuria ceasing during the second day in hospital. The blood-urea and serum-bilirubin levels fell to normal by the third day. The spleen became palpable on the third day but had disappeared beyond the costal margin two days later. The patient was discharged home on the eleventh day, looking very well, with a haemoglobin level of 10-8 g. per 100 ml. and a reticulocyte-count of only 1%. One month later his blood-picture was quite normal. The child was seen again three months later. He was fit and lively, and no abnormality was found on physical examination.
Investigations.-Hxrnoglobin 12.4 g. per 100 ml. (87%). Reticulocytes less than 1%. The stained film showed no morphological abnormality of the red cells; in particular no spherocytes, target cells or macrocytes were seen. The leucocytes and platelets were normal. The osmotic fragility of the red cells was normal and incubation autohaemolysis (Selwyn and Dacie 1954) was less than 1% even without glucose. With glucose added there was no detectable haemolysis after forty-eight hours. Acid haemolysis test negative. Red-cell potassium 82 mEq. per litre. Electrophoresis showed no abnormal haemoglobin. We concluded that the child was unlikely to be suffering from even a mild congenital hsemolytic anfemia. The patient was seen again in January, 1959, as he had been unwell for a few days. No abnormality was found on examination, but his haemoglobin level was only 9-0 g. per 100 ml.
629 Second Admission He was readmitted to hospital on March 13, 1959. He had developed a sore throat several days previously and for twentyfour hours he had been passing dark-red urine. Examination revealed no physical abnormality and the child was not nearly so ill as on his first admission. Direct inquiry revealed that he had eaten broad beans, which had been purchased frozen, on the day before the onset of hxmoglobinuria. We then discovered that this little boy did not like broad beans and had eaten them only twice before. The first time was just before his serious episode of haemolysis and the second time was a few days before he was seen in January, 1959, and found to be a little anaemic. The diagnosis of favism was apparent. The child made a rapid recovery without transfusion.
Investigation on this occasion again failed to reveal any evidence of red-cell defect, but at a later date when the patient had a normal blood-picture (haemoglobin 12’0 per 100 ml., reticulocytes 1’4%), we were able to show that his red cells behaved abnormally after incubation with acetylphenylhydrazine, using the method described by Beutler et al. (1955), for the detection of primaquine-sensitive red cells. This test was unequivocally positive, 80% of the patient’s erythrocytes developing multiple small Heinz bodies, compared with 27% of the normal control. "
We are grateful to Dr. M. D. Baber for permission to publish this and to Dr. Baber and Dr. J. L. Hamilton-Paterson for advice in preparing the manuscript. case
REFERENCES
Beutler, E. (1959) Blood, 14, 103. (1957) J. Lab. clin. Med. 49, 84. Dern, R. J., Alving, A. S. (1955) ibid. 45, 40. Diggle, J. H. (1953) Arch. Dis. Childh. 28, 369. Discombe, G., Mestitz, W. (1956) Brit. Med. J. i, 1023. Larizza, P., Brunetti, P., Grignani, F., Ventura, S. (1958) Quoted by Beutler (1959). Luisada, A. (1941) Medicine, Baltimore, 20, 229. Marcolongo, F. (1953) Rec. Progr. Med. 15, 90. McCarthy, O. R. (1955) Lancet, i, 748. Robinson, P. (1941) Amer. J. Dis. Child. 62, 701. Selwyn, J. G., Dacie, J. V. (1954) Blood, 9, 414. -
-
TOXIC MARROW FAILURE TREATED BY A HOMOGRAFT OF FŒTAL HÆMOPOIETIC TISSUE
J. B. BRIDGES M.D., B.Sc. Belf.
"
LECTURER IN
QUEEN’S
J. M. BRIDGES
Discussion
Until response
M.D. Belf. "
"
recently favism was regarded as an allergic to the proteins of broad beans, but Larizza et al.
(1958) have demonstrated an intrinsic red-cell defect in patients with favism, both during the active phase of the disease and after recovery. This defect is identical with, or at least closely related to, the intrinsic abnormality found in patients in whom haemolysis develops in response to primaquine, sulphonamides, and nitrofurantoin (" primaquine sensitivity or primaquine ansemia "). Beutler (1959) and others have shown that the erythrocytes of these patients are deficient in glucose 6-phosphate dehydrogenase. These defective red cells can be most simply recognised by the characteristic pattern of Heinz-body formation produced in them by acetylphenylhydrazine treatment, or by their inability to retain glutathione (" glutathione instability ") after incubation with acetylphenylhydrazine (Beutler et al. 1955, Beutler 1957). The diagnosis of favism is not likely to present difficulty if the possibility is borne in mind, but in the absence of a history of eating broad beans it may be confused with a crisis of a congenital hxmolytic anxmia. Earlier authors have denied the presence of spherocytes in favism, but their occurrence is recognised by Marcolongo, and our case could not be differentiated on morphological grounds alone from cases of congenital spherocytosis presenting with crisis. The combination of suggestive peripheral blood findings, negative direct Coombs test and maintenance of the haemoglobin level following blood-transfusion was thought to support the latter diagnosis, but the normal result of incubation autohsemolysis excluded congenital spherocytosis and most types of congenital non-spherocytic hxmolytic anxmia. The diagnosis of favism was eventually made on the history of eating broad beans, supported by the demonstration of primaquine sensi"
ANATOMY,
UNIVERSITY OF BELFAST
"
"
tivity ". On theoretical grounds it seems possible that individuals who are subject to favism may develop haemolytic anxmia in response to certain common drugs, although little evidence to support this idea can be found in the literature apart from Luisada’s observation that quinine hxmoglobinuria is rather common in patients who have previously had favism. Nevertheless favism is an indication of enzyme-defective red cells in a person, and its diagnosis may be as important as a warning to avoid certain drugs as it is a warning to abstain from broad beans.
BRITISH EMPIRE CANCER CAMPAIGN RESEARCH FELLOW, DEPARTMENT OF CLINICAL PATHOLOGY, ROYAL VICTORIA HOSPITAL, BELFAST
G. J. A. EDELSTYN M.B. Belf. REGISTRAR,
NORTHERN IRELAND RADIOTHERAPHY MONTGOMERY
HOUSE,
CENTRE,
BELFAST
A. R. LYONS M.D. Belf., M.R.C.P., D.M.R.T.E. RADIOTHERAPIST, NORTHERN IRELAND RADIOTHERAPY
CENTRE
M. G. NELSON M.D. Belf., F.R.C.P.I., M.R.C.P., D.T.M. & CLINICAL PATHOLOGIST TO THE ROYAL VICTORIA
H. HOSPITAL, BELFAST
ENCOURAGING results have recently been reported in the treatment of disseminated mammary carcinoma with thiotepa (triethylene thiophosphoramide) combined with testosterone (Watson and Turner 1959). One of the of of this form recognised complications therapy is toxic marrow damage with peripheral pancytopenia. This a metaarose in woman with complication widespread stases from a mammary carcinoma who was treated with thiotepa and testosterone at the Northern Ireland Radiotherapy Centre. Animals exposed to otherwise lethal irradiation can be saved if injected with suspensions of haemopoietic cells (Lorenz et al. 1951, Porter 1957, Ferrebee et al. 1958); under these conditions the injected cells " home to " and repopulate the depleted medullary cavities (Ford et al. 1956). Marrow infusions have also been successfully used in patients with marrow failure resulting from either irradiation (Thomas et al. 1959) or massive chemotherapy (Westbury et al. 1959). It was decided therefore to attempt marrow-replacement therapy in this patient by injecting homologous haemopoietic cells. Since experiments have shown that the interactions between host and grafted homologous material are reduced if foetal tissue is transferred (Bames et al. 1958, Uphoff 1958), suspensions of human foetal liver were used.
Early
Case-report patient, aged 43, noticed a lump in the quadrant of her left breast. When first seen, in
in 1957 the
upper outer
January, 1958, the entire breast was solid with tumour and fixed to underlying muscle, and enlarged lymph-nodes were easily felt in the left axilla and left supraclavicular region. A chest radiograph revealed some lymphangitic infiltration of