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SMALL-BOWEL CHANGES IN ICHTHYOSIS
624 for doctors, and for the local health authorities. No midwife likes to disobey the rules of the Central Midwives Board, and when the doctors with whom she is working-say that a patient may leave hospital in less than ten days they are put in a dilemma; yet from the national statistics of length of stay we know that they are not fully observing the rules. Moreover with the shortage of maternity nurses to look after the women discharged early from hospital many of the local health authorities are not obeying the law either. And if a patient leaves hospital on the eighth day is the attendance of a midwife for two further days needed ? If it really is needed then perhaps she and her baby should not have been allowed to leave hospital. I think that it is right for the Central Midwives Board to give full guidance to midwives, since many of them are in practice on their own, but that the rules of the Central Midwives Board should be given the force of a law which affects the working of hospitals and of local health authorities in the clinical field is surely now an anachronism which should be put right.
hospital midwives,
Department of Gynæcology, St. Thomas’s Hospital Medical School, London S.E.1.
PHILIP RHODES.
SECRETION OF GASTRIC INTRINSIC FACTOR SIR,-In papers from this department on radioimmunological assay of gastric intrinsic factor (I.F.) the importance has been stressed of an appropriate relationship between amounts of vitamin B12 and gastric-juice vitamin-B12-binding capacity.l The secretory patterns of Of. illustrated by Mr. Lawrie and Mr. Anderson (Jan. 14, p. 68) show post-histamine peak outputs substantially smaller than those reported by other workers.2 Mr. Lawrie and Mr. Anderson state that they used the I.F. 3 " with minor modifications ". assay of Ardeman and Chanarin Did these modifications include precautions for ensuring a proper vitamin-B12/gastric-juice ratio, so that high vitaminB12-binding capacities could be measured quantitatively ? Medical Department F,
Glostrup Hospital, Copenhagen.
*** This
letter has been shown
PAUL RØDBRO. to
Mr. Lawrie and Mr.
Anderson, who write as follows: " We used 57Covitamin-B12 in the assays. Instead of titrating3 samples of serum from patients with pernicious anaemia (P.A.), we used serum from three patients under treatment for P.A. whose serum blocked the uptake of 80-200 jjtmg. vitamin-B12. This method requires prohibitive amounts of P.A. serum, and we are currently using the method described by Herbert and his
colleagues,4 with 0-1 ml. P.A. serum instead of 1-0 ml. Our results are comparable with those from other groups who have used this method.5 "-ED. L.
GLUTEN-FREE DIET AND CŒLIAC SYNDROME SiR,ŅThe high rates of therapeutic failure and death in patients with coeliac disease treated with a gluten-free diet, reported by Dr. Pink and Dr. Creamer (Feb. 11, p. 300), are disquieting. Of 20 patients with coeliac disease treated by means of the gluten-free diet at the Jefferson Medical College Hospital over the past eight years, 4 slow responders were Rødbro, P., Christiansen, P. M., Schwartz, M. Lancet, 1965, ii, 1200; Ugeskr. Laeg. 1966, 128, 1421; Rødbro, P., Christiansen, P. M. Scand. J. clin. Lab. Invest. (in the press). 2. Irvine, W. J. Clin. exp. Immun. 1966, 1, 99; Jeffries, G. H., Sleisenger, M. H. Gastroenterology, 1965, 48, 444; Bitsch, V., Christiansen, P. M., Faber, V., Rødbro, P. Lancet, 1966, i, 1288; Weir, D. G., Temperley, I. J., Collery, D. Gastroenterology, 1967, 52, 23; Rødbro, P., Christiansen, P. M. Scand. J. Gastroent. (in the press). 3. Ardeman, S., Chanarin, I. Lancet, 1963, ii, 1350. 4. Gottlieb, C., Lau, K.-S., Wasserman, L. R., Herbert, V. Blood, 1965, 25, 875. 5. Ardeman, S., Chanarin, I., Doyle, J. C. Br. med. J. 1964, ii, 600. 1.
encountered and none died. 1 patient required steroids for about a year, and another patient with concomitant pancreatic to added pancreatic enzyme in agreement with the experiences reported by Dr. Pink and Dr. Creamer. The other 2 treatment-resistant patients were of greater interest, because they failed to respond to steroids and did not manifest pancreatic insufficiency. Both these patients had severe anaemia with very low serum-iron concentrations and abnormal Schilling tests, and 1 patient also had severe hypocalcaemia (1-7 mEq. per litre) and hypomagnesaemia (0-55 mg. per 100 ml.) with tetany and a Chvostek sign. Both patients eventually responded to the gluten-free diet, but only after correction, by parenteral injections, of their deficiencies of vitamin B12, iron, calcium, magnesium, and calciferol. These clinical observations suggest that in the presence of severe secondary deficiencies of essential nutrients, including some of the metallic ions, absorptive processes presumably dependent upon enzymes containing these nutrients as cofactors remain impaired, despite removal of gluten from the diet of gluten-sensitive patients. These observations are in accord with the findings of abnormalities of intestinal function in the presence of severe iron deficiency in children reported by Naiman et aU and with the malabsorption of vitamin B12 reported by Haurani et al. in the presence of vitamin-B12 deficiency. These observations require further testing and may, if confirmed and applied to the treatment of suitable patients, lead to decreased mortality from the malabsorption syndrome. Jefferson Medical College, FRANZ GOLDSTEIN. Philadelphia, Pennsylvania 19107.
insufficiency responded partially
supplements,
SMALL-BOWEL CHANGES IN ICHTHYOSIS SIR,-The findings of Dr. Marks and her colleagues3 and of Dr. van Tongeren and his colleagues (Jan. 28, p. 218) of the association of some skin diseases with small-bowel changes prompt us to describe our own findings in a boy with ichthyosis. A nine-year-old male idiot was admitted to this department with therapy-resistant congenital ichthyosis and pronounced spasticity of his lower extremities. The clinical picture was that of the syndrome of Sjogren-Larsson.4 This syndrome was described for the first time in 1957. It consists of the following triad of symptoms: congenital oligophrenia, congenital generalised ichthyosis, and a pyramidal syndrome which is more pronounced in the lower limbs. The disease is genetically determined. The mode of inheritance is monohybrid autosomal recessive. Since birth the boy had also had chronic diarrhoea : fsecal examination showed (per day) increased excretion of lactic acid (1500-200 mg.), lipids (12 g.), and fatty acids (5 g.); there was also excessive aminoacid excretion. Peripheral-blood count showed hypochromic anaemia with distinct lymphopenia and eosinophilia; lymphocytes were also decreased in the bone-marrow. Serological tests showed constant hypoproteinsemia (5 g. per 100 ml.) with mainly decrease of albumin (1-40 g. per 100 ml.), hypocalca:mia (7-4 mg. per 100 ml.), and low values of total lipid (460 mg. per 100 ml.) and cholesterol (140 mg. per 100 ml.). This patient thus showed the clinical pattern of exudative enteropathy. The polyvinylpyrrolidone test was abnormal, and radiological examination showed flocculation of the barium and typical " puddling " Intestinal biopsy was not successful. on several X-rays. Immunoelectrophoresis revealed a dissociated disorder of the
immunoglobulins. The boy received a diet in which all normal lipids were replaced by medium-chain triglycerides. On this therapy the clinical findings of exudative enteropathy completely disappeared, with return to normal of stools, serology, and polyvinylpyrrolidone test. The boy, who was much disturbed before admission, became calmer with treatment. In addition Naiman, J. L., Oski, F. A., Diamond, L. K., Vawter, L. K., Shwachman, H. Pediatrics, Springfield, 1964, 33, 83. 2. Haurani, F. I., Sherwood, W., Goldstein, F. Metabolism, 1964, 13, 1342. 3. Marks, J., Shuster, S., Watson, A. J. Lancet, 1966, ii, 1280. 4. Sjögren, T., Larsson, T. Actapsychiat. neurol. scand. 1957, 32, suppl. 113. 1.
625 found that there was total remission of the ichthyosiform skin condition: after more than one year of therapy, the skin remains normal, except for a few small rough places. Intestinal biopsy after one year of therapy disclosed normal villi, but infiltration of neutrophils and plasmocytes in the lamina propria and slight dilatation of the mucosal capillaries. The explanation of the influence of diet on the ichthyosiform eruption is up to now unknown. We have seen the same result in another patient with ichthyosis who received the same diet.
we
Department of Pædiatrics,
University of Gent, Belgium.
C. HOOFT J. KRIEKEMANS E. DEVOS.
HEMATOLOGICAL EFFECTS OF METHYLDOPA SIR,-Following the reports 12 of haematological reactions to methyldopa, investigations were begun in our hypertension clinic. These included hsemoglobin estimations, reticulocytecounts, and direct Coombs tests (D.C.T.S) in all patients. Of 80 patients investigated, 55 were receiving methyldopa, 8 of whom (15%) had positive n.c.T.s. None of the 23 patients not on methyldopa had a positive D.c.T. The relation between dosage and duration of therapy in patients with positive D.c.T.s is shown in the accompanying figure. With the small numbers
time in 3 patients in the presence of a raised reticulocyte-count indicates that increased red-cell destruction, if present, can only be mild. Despite the development of a positive D.C.T. in a moderately high proportion of patients treated with methyldopa, the incidence of haemolytic anaemia, even in these patients, is extremely low (0-1-0-2% according to Worlledge et a1.2. In view of this low incidence of anaemia, and the value of methyldopa, we have elected, for the present, to continue treatment with this drug in these patients. However, we have decided to keep the position under review by six-monthly hsematological tests on all patients receiving methyldopa. New patients and those with a negative D.c.T. will have a D.C.T. test. Those with a positive D.c.T. will have haemoglobin determinations and
reticulocyte
counts.
Clinical Research Unit, Alfred Hospital, Melbourne.
S. CANTOR A. J. BARNETT.
GLANDULAR-FEVER CELLS SIR,-A possible relation between infective mononucleosis and acute leukxmia, and a possible viral cause has been discussed in a leader (Jan. 7, p. 33), by Professor Dameshek (Feb. 11, p. 333), and by Dr. Carter and Dr. Marsh
(Feb. 18,
p.
397).
We report here the occurrence of infective mononucleosis and lymphosarcoma (one of the leukaemias) in two siblings of an English family, and possibly lymphosarcoma in their catall having lived in close proximity to possible viral carriers from tropical Africa. The parents, both medically qualified, observed their siblings throughout the course of the illnesses.
English boy, aged 8 years, died in 1961 of lymphodiagnosis was confirmed by Dr. D. J. O. O’Brien and Dr. A. H. E. Marshall; his previous health had been good, and he had had no X-rays, but he had received a limited quantity of chloramphenicol some years before. The boy’s sister, aged 20 years, had an attack of infective mononucleosis in 1966 and, as expected, recovered; she had had a chest X-ray, but otherwise no relevant past history. Throughout most of their course the two diseases were distinct entities, but occasionally, during exacerbations of lymphosarcoma and the onset of glandular fever, the clinical features of the two illnesses were indistinguishable, as noted by Dr. Marsh. When both diseases are also characterised by high lymphocytosis and negative Paul-Bunnell tests the diagnosis can be in doubt. Two months after the start of the boy’s illness his cat fell ill. Clinically the boy’s and the cat’s illnesses appeared to Dose and duration of methyldopa treatment in 8 patients with resemble one another, since they both had fever, dysphagia, positive D.C.T.s. and swellings in the neck. After a short illness the cat died of available, no definite relation between dosage and duration of unproven ( ?) lymphosarcoma.3 Visitors from tropical Africa stayed with the family from therapy is apparent, but positive n.c.T.s are seen in patients on small doses of methyldopa (1 g. per day), and also in patients time to time; these possible " carriers " came from Sierra examined within one year of beginning therapy. Leone from 1955 onwards and from Ghana from 1950 3 of the 8 patients with a positive D.C.T. had reticulocyteonwards-i.e., from known geographical belts of Burkitt’s counts above 3%, the highest being 5%. Carstairs et al.11 malignant lymphoma (leukaemia).45 detected raised reticulocyte-counts of this order in 15 % of their Questions to be asked are: (1) was there a possible relation patients. Only 1 patient with a positive D.c.T. was ansemic between glandular fever and lymphosarcoma (human and (haemoglobin 10-4 g. per 100 ml.); the anamlia was explicable feline), the two diseases that occurred in this family ? ; (2) by chronic renal failure, which was present before commence- was there a possible viral aetiology in these diseases ? ; and, if ment of methyldopa. This patient had a normal reticulocyteso, (3) was the disease imported from tropical Africa ? count (1.5%). Reticulocyte-counts performed on 6 patients Viruses can cause malignant tumours in animals,5 but that with a negative D.C.T. showed values of 3% or greater in 3. leukaemia in man has a viral cause still remains unproved. These investigations confirm the findings of Carstairs et al.l The defect that makes leukaemic cells persist in proliferating that treatment of hypertensive patients with methyldopa is may be a virus plus an additional factor, and the lymphoassociated with the development of a positive D.C.T. in certain sarcoma in the boy cited above may have been a case of cases (20% in their larger series), and that this does not occur in malignant transformation by virus plus chloramphenicol. hypertensive patients treated with the other currently used A chromosomal anomaly as a possible cause is unlikely, since drugs. The precise relation of a positive D.C.T. and a raised the three other siblings of the family appear normal. The Department of Social Medicine, Oxford University, is reticulocyte count requires further investigation. The findings by Carstairs et al.1 of normal red-blood-cell survival- carrying out a nation-wide survey and reports a disturbing An
sarcoma ; the
1. 2.
Carstairs, K. C., Breckenridge, A., Dollery, C. T., Worlledge, S. M. Lancet, ii, 133, 1966. Worlledge, S. M., Carstairs, K. C., Dacie, J. V. ibid. p. 135.
3. Jarrett, W. F. H. Cited in Br. med. 4. See ibid. p. 296. 5. Burkitt, D. Triangle, 1964, 6, 222.
J. 1964, i, 1268.
hospital midwives,
Department of Gynæcology, St. Thomas’s Hospital Medical School, London S.E.1.
PHILIP RHODES.
SECRETION OF GASTRIC INTRINSIC FACTOR SIR,-In papers from this department on radioimmunological assay of gastric intrinsic factor (I.F.) the importance has been stressed of an appropriate relationship between amounts of vitamin B12 and gastric-juice vitamin-B12-binding capacity.l The secretory patterns of Of. illustrated by Mr. Lawrie and Mr. Anderson (Jan. 14, p. 68) show post-histamine peak outputs substantially smaller than those reported by other workers.2 Mr. Lawrie and Mr. Anderson state that they used the I.F. 3 " with minor modifications ". assay of Ardeman and Chanarin Did these modifications include precautions for ensuring a proper vitamin-B12/gastric-juice ratio, so that high vitaminB12-binding capacities could be measured quantitatively ? Medical Department F,
Glostrup Hospital, Copenhagen.
*** This
letter has been shown
PAUL RØDBRO. to
Mr. Lawrie and Mr.
Anderson, who write as follows: " We used 57Covitamin-B12 in the assays. Instead of titrating3 samples of serum from patients with pernicious anaemia (P.A.), we used serum from three patients under treatment for P.A. whose serum blocked the uptake of 80-200 jjtmg. vitamin-B12. This method requires prohibitive amounts of P.A. serum, and we are currently using the method described by Herbert and his
colleagues,4 with 0-1 ml. P.A. serum instead of 1-0 ml. Our results are comparable with those from other groups who have used this method.5 "-ED. L.
GLUTEN-FREE DIET AND CŒLIAC SYNDROME SiR,ŅThe high rates of therapeutic failure and death in patients with coeliac disease treated with a gluten-free diet, reported by Dr. Pink and Dr. Creamer (Feb. 11, p. 300), are disquieting. Of 20 patients with coeliac disease treated by means of the gluten-free diet at the Jefferson Medical College Hospital over the past eight years, 4 slow responders were Rødbro, P., Christiansen, P. M., Schwartz, M. Lancet, 1965, ii, 1200; Ugeskr. Laeg. 1966, 128, 1421; Rødbro, P., Christiansen, P. M. Scand. J. clin. Lab. Invest. (in the press). 2. Irvine, W. J. Clin. exp. Immun. 1966, 1, 99; Jeffries, G. H., Sleisenger, M. H. Gastroenterology, 1965, 48, 444; Bitsch, V., Christiansen, P. M., Faber, V., Rødbro, P. Lancet, 1966, i, 1288; Weir, D. G., Temperley, I. J., Collery, D. Gastroenterology, 1967, 52, 23; Rødbro, P., Christiansen, P. M. Scand. J. Gastroent. (in the press). 3. Ardeman, S., Chanarin, I. Lancet, 1963, ii, 1350. 4. Gottlieb, C., Lau, K.-S., Wasserman, L. R., Herbert, V. Blood, 1965, 25, 875. 5. Ardeman, S., Chanarin, I., Doyle, J. C. Br. med. J. 1964, ii, 600. 1.
encountered and none died. 1 patient required steroids for about a year, and another patient with concomitant pancreatic to added pancreatic enzyme in agreement with the experiences reported by Dr. Pink and Dr. Creamer. The other 2 treatment-resistant patients were of greater interest, because they failed to respond to steroids and did not manifest pancreatic insufficiency. Both these patients had severe anaemia with very low serum-iron concentrations and abnormal Schilling tests, and 1 patient also had severe hypocalcaemia (1-7 mEq. per litre) and hypomagnesaemia (0-55 mg. per 100 ml.) with tetany and a Chvostek sign. Both patients eventually responded to the gluten-free diet, but only after correction, by parenteral injections, of their deficiencies of vitamin B12, iron, calcium, magnesium, and calciferol. These clinical observations suggest that in the presence of severe secondary deficiencies of essential nutrients, including some of the metallic ions, absorptive processes presumably dependent upon enzymes containing these nutrients as cofactors remain impaired, despite removal of gluten from the diet of gluten-sensitive patients. These observations are in accord with the findings of abnormalities of intestinal function in the presence of severe iron deficiency in children reported by Naiman et aU and with the malabsorption of vitamin B12 reported by Haurani et al. in the presence of vitamin-B12 deficiency. These observations require further testing and may, if confirmed and applied to the treatment of suitable patients, lead to decreased mortality from the malabsorption syndrome. Jefferson Medical College, FRANZ GOLDSTEIN. Philadelphia, Pennsylvania 19107.
insufficiency responded partially
supplements,
SMALL-BOWEL CHANGES IN ICHTHYOSIS SIR,-The findings of Dr. Marks and her colleagues3 and of Dr. van Tongeren and his colleagues (Jan. 28, p. 218) of the association of some skin diseases with small-bowel changes prompt us to describe our own findings in a boy with ichthyosis. A nine-year-old male idiot was admitted to this department with therapy-resistant congenital ichthyosis and pronounced spasticity of his lower extremities. The clinical picture was that of the syndrome of Sjogren-Larsson.4 This syndrome was described for the first time in 1957. It consists of the following triad of symptoms: congenital oligophrenia, congenital generalised ichthyosis, and a pyramidal syndrome which is more pronounced in the lower limbs. The disease is genetically determined. The mode of inheritance is monohybrid autosomal recessive. Since birth the boy had also had chronic diarrhoea : fsecal examination showed (per day) increased excretion of lactic acid (1500-200 mg.), lipids (12 g.), and fatty acids (5 g.); there was also excessive aminoacid excretion. Peripheral-blood count showed hypochromic anaemia with distinct lymphopenia and eosinophilia; lymphocytes were also decreased in the bone-marrow. Serological tests showed constant hypoproteinsemia (5 g. per 100 ml.) with mainly decrease of albumin (1-40 g. per 100 ml.), hypocalca:mia (7-4 mg. per 100 ml.), and low values of total lipid (460 mg. per 100 ml.) and cholesterol (140 mg. per 100 ml.). This patient thus showed the clinical pattern of exudative enteropathy. The polyvinylpyrrolidone test was abnormal, and radiological examination showed flocculation of the barium and typical " puddling " Intestinal biopsy was not successful. on several X-rays. Immunoelectrophoresis revealed a dissociated disorder of the
immunoglobulins. The boy received a diet in which all normal lipids were replaced by medium-chain triglycerides. On this therapy the clinical findings of exudative enteropathy completely disappeared, with return to normal of stools, serology, and polyvinylpyrrolidone test. The boy, who was much disturbed before admission, became calmer with treatment. In addition Naiman, J. L., Oski, F. A., Diamond, L. K., Vawter, L. K., Shwachman, H. Pediatrics, Springfield, 1964, 33, 83. 2. Haurani, F. I., Sherwood, W., Goldstein, F. Metabolism, 1964, 13, 1342. 3. Marks, J., Shuster, S., Watson, A. J. Lancet, 1966, ii, 1280. 4. Sjögren, T., Larsson, T. Actapsychiat. neurol. scand. 1957, 32, suppl. 113. 1.
625 found that there was total remission of the ichthyosiform skin condition: after more than one year of therapy, the skin remains normal, except for a few small rough places. Intestinal biopsy after one year of therapy disclosed normal villi, but infiltration of neutrophils and plasmocytes in the lamina propria and slight dilatation of the mucosal capillaries. The explanation of the influence of diet on the ichthyosiform eruption is up to now unknown. We have seen the same result in another patient with ichthyosis who received the same diet.
we
Department of Pædiatrics,
University of Gent, Belgium.
C. HOOFT J. KRIEKEMANS E. DEVOS.
HEMATOLOGICAL EFFECTS OF METHYLDOPA SIR,-Following the reports 12 of haematological reactions to methyldopa, investigations were begun in our hypertension clinic. These included hsemoglobin estimations, reticulocytecounts, and direct Coombs tests (D.C.T.S) in all patients. Of 80 patients investigated, 55 were receiving methyldopa, 8 of whom (15%) had positive n.c.T.s. None of the 23 patients not on methyldopa had a positive D.c.T. The relation between dosage and duration of therapy in patients with positive D.c.T.s is shown in the accompanying figure. With the small numbers
time in 3 patients in the presence of a raised reticulocyte-count indicates that increased red-cell destruction, if present, can only be mild. Despite the development of a positive D.C.T. in a moderately high proportion of patients treated with methyldopa, the incidence of haemolytic anaemia, even in these patients, is extremely low (0-1-0-2% according to Worlledge et a1.2. In view of this low incidence of anaemia, and the value of methyldopa, we have elected, for the present, to continue treatment with this drug in these patients. However, we have decided to keep the position under review by six-monthly hsematological tests on all patients receiving methyldopa. New patients and those with a negative D.c.T. will have a D.C.T. test. Those with a positive D.c.T. will have haemoglobin determinations and
reticulocyte
counts.
Clinical Research Unit, Alfred Hospital, Melbourne.
S. CANTOR A. J. BARNETT.
GLANDULAR-FEVER CELLS SIR,-A possible relation between infective mononucleosis and acute leukxmia, and a possible viral cause has been discussed in a leader (Jan. 7, p. 33), by Professor Dameshek (Feb. 11, p. 333), and by Dr. Carter and Dr. Marsh
(Feb. 18,
p.
397).
We report here the occurrence of infective mononucleosis and lymphosarcoma (one of the leukaemias) in two siblings of an English family, and possibly lymphosarcoma in their catall having lived in close proximity to possible viral carriers from tropical Africa. The parents, both medically qualified, observed their siblings throughout the course of the illnesses.
English boy, aged 8 years, died in 1961 of lymphodiagnosis was confirmed by Dr. D. J. O. O’Brien and Dr. A. H. E. Marshall; his previous health had been good, and he had had no X-rays, but he had received a limited quantity of chloramphenicol some years before. The boy’s sister, aged 20 years, had an attack of infective mononucleosis in 1966 and, as expected, recovered; she had had a chest X-ray, but otherwise no relevant past history. Throughout most of their course the two diseases were distinct entities, but occasionally, during exacerbations of lymphosarcoma and the onset of glandular fever, the clinical features of the two illnesses were indistinguishable, as noted by Dr. Marsh. When both diseases are also characterised by high lymphocytosis and negative Paul-Bunnell tests the diagnosis can be in doubt. Two months after the start of the boy’s illness his cat fell ill. Clinically the boy’s and the cat’s illnesses appeared to Dose and duration of methyldopa treatment in 8 patients with resemble one another, since they both had fever, dysphagia, positive D.C.T.s. and swellings in the neck. After a short illness the cat died of available, no definite relation between dosage and duration of unproven ( ?) lymphosarcoma.3 Visitors from tropical Africa stayed with the family from therapy is apparent, but positive n.c.T.s are seen in patients on small doses of methyldopa (1 g. per day), and also in patients time to time; these possible " carriers " came from Sierra examined within one year of beginning therapy. Leone from 1955 onwards and from Ghana from 1950 3 of the 8 patients with a positive D.C.T. had reticulocyteonwards-i.e., from known geographical belts of Burkitt’s counts above 3%, the highest being 5%. Carstairs et al.11 malignant lymphoma (leukaemia).45 detected raised reticulocyte-counts of this order in 15 % of their Questions to be asked are: (1) was there a possible relation patients. Only 1 patient with a positive D.c.T. was ansemic between glandular fever and lymphosarcoma (human and (haemoglobin 10-4 g. per 100 ml.); the anamlia was explicable feline), the two diseases that occurred in this family ? ; (2) by chronic renal failure, which was present before commence- was there a possible viral aetiology in these diseases ? ; and, if ment of methyldopa. This patient had a normal reticulocyteso, (3) was the disease imported from tropical Africa ? count (1.5%). Reticulocyte-counts performed on 6 patients Viruses can cause malignant tumours in animals,5 but that with a negative D.C.T. showed values of 3% or greater in 3. leukaemia in man has a viral cause still remains unproved. These investigations confirm the findings of Carstairs et al.l The defect that makes leukaemic cells persist in proliferating that treatment of hypertensive patients with methyldopa is may be a virus plus an additional factor, and the lymphoassociated with the development of a positive D.C.T. in certain sarcoma in the boy cited above may have been a case of cases (20% in their larger series), and that this does not occur in malignant transformation by virus plus chloramphenicol. hypertensive patients treated with the other currently used A chromosomal anomaly as a possible cause is unlikely, since drugs. The precise relation of a positive D.C.T. and a raised the three other siblings of the family appear normal. The Department of Social Medicine, Oxford University, is reticulocyte count requires further investigation. The findings by Carstairs et al.1 of normal red-blood-cell survival- carrying out a nation-wide survey and reports a disturbing An
sarcoma ; the
1. 2.
Carstairs, K. C., Breckenridge, A., Dollery, C. T., Worlledge, S. M. Lancet, ii, 133, 1966. Worlledge, S. M., Carstairs, K. C., Dacie, J. V. ibid. p. 135.
3. Jarrett, W. F. H. Cited in Br. med. 4. See ibid. p. 296. 5. Burkitt, D. Triangle, 1964, 6, 222.
J. 1964, i, 1268.