- Email: [email protected]
FELTY'S SYNDROME
662
suggesting that peripheral decarboxylase activity is not impaired by the apparent relative vitamin-B6 deficiency. While giving rats acute hydrocortisone increases pyrrolase activity and decreased brain S-H.T. synthesis,1s-2O some data21 suggests that the brain 5-H.T. changes do not follow longerterm treatment, indicating the possible presence of other regulatory mechanisms. M.R.C. Clinical Pharmacology Unit, Radcliffe Infirmary, Oxford OX2 6HE
The effect of preoperative transfusions in lished in Transplantation.
our
series will be
pub-
R. JEFFERY A. R. DOWNS
J.
J. W. GRAHAME
A. R. GREEN
SIR,-Your editorial’ and Dr Badawy and Evans (Feb. 25,
448) discuss the possible role of increased hepatic tryptophan pyrrolase in inducing depression by diverting tryptophan away from brain 5-H.T. synthesis. We have previously reported an effect of hydrocortisone on the metabolism of a tryptophan load in the rat which is compatible with this mechanism.2 However, competition between the kynurenine and 5-H.T. pathways of tryptophan metabolism may be mediated within the brain itself since (a) rat brain contains indoleamine-2, 3-dioxygenase which metabolises tryptophan in the same way as hepatic tryptophan pyrrolase; (b) kynurenine is present in rats-’ and human7.8 brain; and (c) there is biochemical and pharmacological9 evidence that this does not merely represent kynurenine transported into brain from the plasma. This suggests the possibility of a more direct interaction between these two pathways of tryptophan metabolism within p.
the brain. Division of Psychiatry, Clinical Research Centre, Harrow, Middlesex HA1 3UJ
from any other (see table). Our results do not suggest any beneficial effect of intraoperative transfusions on grafting survival. The role of transfusions in graft survival must be subjected to critical prospective analysis.
MICHAEL H. JOSEPH
OPERATION-DAY BLOOD-TRANSFUSION AND RENAL TRANSPLANTATION
SiR,-Dr Stiller and his colleagues (Jan. 28, p. 169) survival in patients given intraoperative transfusions. We have analysed’ our own results in 90
reported improved graft
GRAFT SURVIVAL AND BLOOD-TRANSFUSION
C. LYE J. K. MCKENZIE E. RAMSEY A. E. THOMSON R. WALKER
Transplant Program, University of Manitoba Health Sciences Centre,
Winnipeg, Manitoba Canada R3E 0Z3
FELTY’S SYNDROME
SIR,-In an editorial in your issue of March 11 (p. 540) you that the leucopenia of Felty’s syndrome is due to spleno-
state
megaly.
There is
a
lot of evidence that this is
not so.
Leuco-
penia is associated with rheumatoid arthritis in 1% of cases,’ but splenomegaly has been reported in 10% of cases of rheumatoid arthritis.2 Leucopenia may exist in the absence of detectable splenomegaly.3 Splenectomy does not produce sustained neutrophil responses in at least 20% of cases.4The spleen is often abnormal in Felty’s syndrome, but such abnormalities vary. You make little of the circulating antibodies that have been demonstrated. Infusion of the plasma of patients with Felty’s syndrome into normal subjects produces neutropenia.s In 1974 I and my colleagues6 published a study on white-cell antibodies in rheumatoid arthritis. We concluded that there were two types. The first was non-specific and directed against IgG. It was present in 54% of patients without leucopenia. The second was specifically directed against white cells. This we found in patients with leucopenia with either marrow white-cell hyperplasia or maturation arrest. We drew attention to the close parallel with idiopathic thrombocytopenic purpura. In this condition antibody coating of platelets is known to occur, and splenectomy does not always produce improvement. We proposed that the diagnosis of Felty’s syndrome should be restricted to patients with leucopenia and either marrow whitecell hyperplasia or maturation arrest in whom the specific antibody could be demonstrated. Leicester Royal Infirmary, Leicester LE1 5WW
F. D. ROSENTHAL
NEBULISED SALBUTAMOL IN ADULT ASTHMA
interested in the comments of Dr Bacon and Dr Lenney (Feb. 25, p. 440) on the use of nebulised salbutamol in children. During the past 18 months we have been using this treatment for severe adult asthmatics with asthma which has been difficult to control with conventional therapy and, in some cases, has only responded to doses of oral corticosteroids which are prohibitive in the long-term. We have six such patients (16-58 years old), four with extrinsic and two with intrinsic asthma. At presentation, all were on a large number of drugs including corticosteroids, disodium cromoglycate, and a variety of bronchodilators. Two were on regular adrenaline injections.
SiR,—We
(Jan. 21,
who have been followed up for at least three months. No combination of preoperative or operation-day transfusion is significantly different
first-transplant cadaveric-graft recipients
18. Green, A. R., Curzon, G. Nature, 1968, 220, 1095. 19. Green, A. R., Sourkes, T. L., Young, S. N. Br. J. Pharmac. 1975, 53, 287. 20. Green, A. R., Woods, H. F., Knott, P. J., Curzon, G. Nature, 1975, 255, 170. 21. Curzon, G., Green, A. R. Life Sci. 1968, 7, 657. 1. Lancet,1977, ii, 1333. 2. Joseph, M. H., Young, S. N., Curzon, G. Biochem. Pharmac. 1976, 25, 2599. 3. Gal, E. M.J. Neurochem. 1974, 22, 861. 4. Hayaishi, O.J. Biochem. 1976, 79, 13p. 5. Joseph, M. H. Br.J. Pharmac. 1977, 59, 525p. 6. Gal, E. M., Young, R. B., Sherman, A. D. Trans. Am. Soc. Neurochem. 1977, 8, 211. 7. Joseph, M. H., Baker, H. F., Lawson, A. M. Biochem. Soc. Trans. 1978, 6, 123. 8. Joseph, M. H.J. Chromatog. (in the press). 9. Joseph, M. H., Hall-Tipping, D. L. C., Waddington, J. L. Unpublished.
p.
were
158)
Green, R. A., Fromke, V. L. Ann. intern. Med. 1966, 64. 1265. Short, G. L., Bauer, W., Reynolds, W. E. Rheumatoid Arthritis. Cambridge, Massachusetts, 1957. 3. Hutchinson, H. E., Alexander, W. D. Blood, 1954,9,986. 4. Mason, D. T., Morris, J. J., Jr. Am.J. Med. 1964, 36, 463. 5. Calabresi, P., Edwards, E. E., Schilling, R. F.J. clin. Invest. 1959, 36, 2091. 6. Rosenthal, F. D., Beeley, J. M., Gelsthorpe, K., Doughty, R. W. Q. Jl Med. 1974, 43, 187. 1. 2.
suggesting that peripheral decarboxylase activity is not impaired by the apparent relative vitamin-B6 deficiency. While giving rats acute hydrocortisone increases pyrrolase activity and decreased brain S-H.T. synthesis,1s-2O some data21 suggests that the brain 5-H.T. changes do not follow longerterm treatment, indicating the possible presence of other regulatory mechanisms. M.R.C. Clinical Pharmacology Unit, Radcliffe Infirmary, Oxford OX2 6HE
The effect of preoperative transfusions in lished in Transplantation.
our
series will be
pub-
R. JEFFERY A. R. DOWNS
J.
J. W. GRAHAME
A. R. GREEN
SIR,-Your editorial’ and Dr Badawy and Evans (Feb. 25,
448) discuss the possible role of increased hepatic tryptophan pyrrolase in inducing depression by diverting tryptophan away from brain 5-H.T. synthesis. We have previously reported an effect of hydrocortisone on the metabolism of a tryptophan load in the rat which is compatible with this mechanism.2 However, competition between the kynurenine and 5-H.T. pathways of tryptophan metabolism may be mediated within the brain itself since (a) rat brain contains indoleamine-2, 3-dioxygenase which metabolises tryptophan in the same way as hepatic tryptophan pyrrolase; (b) kynurenine is present in rats-’ and human7.8 brain; and (c) there is biochemical and pharmacological9 evidence that this does not merely represent kynurenine transported into brain from the plasma. This suggests the possibility of a more direct interaction between these two pathways of tryptophan metabolism within p.
the brain. Division of Psychiatry, Clinical Research Centre, Harrow, Middlesex HA1 3UJ
from any other (see table). Our results do not suggest any beneficial effect of intraoperative transfusions on grafting survival. The role of transfusions in graft survival must be subjected to critical prospective analysis.
MICHAEL H. JOSEPH
OPERATION-DAY BLOOD-TRANSFUSION AND RENAL TRANSPLANTATION
SiR,-Dr Stiller and his colleagues (Jan. 28, p. 169) survival in patients given intraoperative transfusions. We have analysed’ our own results in 90
reported improved graft
GRAFT SURVIVAL AND BLOOD-TRANSFUSION
C. LYE J. K. MCKENZIE E. RAMSEY A. E. THOMSON R. WALKER
Transplant Program, University of Manitoba Health Sciences Centre,
Winnipeg, Manitoba Canada R3E 0Z3
FELTY’S SYNDROME
SIR,-In an editorial in your issue of March 11 (p. 540) you that the leucopenia of Felty’s syndrome is due to spleno-
state
megaly.
There is
a
lot of evidence that this is
not so.
Leuco-
penia is associated with rheumatoid arthritis in 1% of cases,’ but splenomegaly has been reported in 10% of cases of rheumatoid arthritis.2 Leucopenia may exist in the absence of detectable splenomegaly.3 Splenectomy does not produce sustained neutrophil responses in at least 20% of cases.4The spleen is often abnormal in Felty’s syndrome, but such abnormalities vary. You make little of the circulating antibodies that have been demonstrated. Infusion of the plasma of patients with Felty’s syndrome into normal subjects produces neutropenia.s In 1974 I and my colleagues6 published a study on white-cell antibodies in rheumatoid arthritis. We concluded that there were two types. The first was non-specific and directed against IgG. It was present in 54% of patients without leucopenia. The second was specifically directed against white cells. This we found in patients with leucopenia with either marrow white-cell hyperplasia or maturation arrest. We drew attention to the close parallel with idiopathic thrombocytopenic purpura. In this condition antibody coating of platelets is known to occur, and splenectomy does not always produce improvement. We proposed that the diagnosis of Felty’s syndrome should be restricted to patients with leucopenia and either marrow whitecell hyperplasia or maturation arrest in whom the specific antibody could be demonstrated. Leicester Royal Infirmary, Leicester LE1 5WW
F. D. ROSENTHAL
NEBULISED SALBUTAMOL IN ADULT ASTHMA
interested in the comments of Dr Bacon and Dr Lenney (Feb. 25, p. 440) on the use of nebulised salbutamol in children. During the past 18 months we have been using this treatment for severe adult asthmatics with asthma which has been difficult to control with conventional therapy and, in some cases, has only responded to doses of oral corticosteroids which are prohibitive in the long-term. We have six such patients (16-58 years old), four with extrinsic and two with intrinsic asthma. At presentation, all were on a large number of drugs including corticosteroids, disodium cromoglycate, and a variety of bronchodilators. Two were on regular adrenaline injections.
SiR,—We
(Jan. 21,
who have been followed up for at least three months. No combination of preoperative or operation-day transfusion is significantly different
first-transplant cadaveric-graft recipients
18. Green, A. R., Curzon, G. Nature, 1968, 220, 1095. 19. Green, A. R., Sourkes, T. L., Young, S. N. Br. J. Pharmac. 1975, 53, 287. 20. Green, A. R., Woods, H. F., Knott, P. J., Curzon, G. Nature, 1975, 255, 170. 21. Curzon, G., Green, A. R. Life Sci. 1968, 7, 657. 1. Lancet,1977, ii, 1333. 2. Joseph, M. H., Young, S. N., Curzon, G. Biochem. Pharmac. 1976, 25, 2599. 3. Gal, E. M.J. Neurochem. 1974, 22, 861. 4. Hayaishi, O.J. Biochem. 1976, 79, 13p. 5. Joseph, M. H. Br.J. Pharmac. 1977, 59, 525p. 6. Gal, E. M., Young, R. B., Sherman, A. D. Trans. Am. Soc. Neurochem. 1977, 8, 211. 7. Joseph, M. H., Baker, H. F., Lawson, A. M. Biochem. Soc. Trans. 1978, 6, 123. 8. Joseph, M. H.J. Chromatog. (in the press). 9. Joseph, M. H., Hall-Tipping, D. L. C., Waddington, J. L. Unpublished.
p.
were
158)
Green, R. A., Fromke, V. L. Ann. intern. Med. 1966, 64. 1265. Short, G. L., Bauer, W., Reynolds, W. E. Rheumatoid Arthritis. Cambridge, Massachusetts, 1957. 3. Hutchinson, H. E., Alexander, W. D. Blood, 1954,9,986. 4. Mason, D. T., Morris, J. J., Jr. Am.J. Med. 1964, 36, 463. 5. Calabresi, P., Edwards, E. E., Schilling, R. F.J. clin. Invest. 1959, 36, 2091. 6. Rosenthal, F. D., Beeley, J. M., Gelsthorpe, K., Doughty, R. W. Q. Jl Med. 1974, 43, 187. 1. 2.