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GLYCOSURIA AND HYPERGLYCÆMIA AFTER KIDNEY TRANSPLANTATION
844
development of steroid diabetes in renal-transplant recipients as long as precautions to discover and control the
and remission tissue in organ culture. The many previously observed immunological abnormalities, which tend to improve after gluten withdrawal, would be regarded as secondary to the mucosal damage and presumed increase in permeability to antigens in the lumen. Yet another possibility would be the deletion of the second of two enzymes in a metabolic pathway, with a toxic intermediate accumulating above the blocked step. If the first enzyme were induced to higher specific activity by the presence of substrate (component of gliadin), a higher concentration of the intermediate would accumulate. These hypotheses appear compatible with data from Dr Townley’s group: duodenal mucosa from patients with coeliac sprue was shown to be defective in digesting one of ten fractions obtained by chromatography of a peptictryptic-pancreatinic digest of gliadin.The same fraction was later shown to inhibit the morphological improvement of cceliac mucosa in organ culture, and to yield the highest hsmagglutination titres with sera of coeliac patients.7 The case for an immunological abnormality as the cause of coeliac sprue is not yet proven, and the possibility of an enterocyte enzyme abnormality still warrants investigation. Gastroenterology Division, Peter Bent Brigham Hospital, Boston, Massachusetts 02115, NEVILLE D. YEOMANS. U.S.A.
the diabetes
U.S.A.
be missed. Other than these rare complications, the diabetes is almost always mild and can be managed without long-term insulin, even if insulin is necessary to initiate treatment. In order to determine the prognostic importance of the development of steroid diabetes, the 15 patients who developed steroid diabetes were each matched to transplant recipients of similar age, sex, time since transplant, and relationship to donor. Patients who developed steroid diabetes do not seem to be more prone to an increased rate or severity of infection, nor are they more likely to reject their kidneys. 14 of the 15 patients with steroid diabetes were well with normal renal function 8-46 months after renal transplantation. 8 of the 9 recipients of cadaver transplants who developed steroid diabetes were well. Thus, we cannot yet determine that there is an increased long-term morbidity associated with 6. 7. 8. 9. 10.
Cornell, H. J., Townley, R. R. W. Clinica chim. Acta, 1973, 43, 113. Townley, R. R. W., Bhathal, P. S., Cornell, H. J., Mitchell,J. D. Lancet, 1973, i, 1363. Hill, C. M., Douglas, J. F., Rajkumar, K. V., McEvoy, J., McBeown, M. Lancet, Aug. 31, 1974, p. 490. Kjellstrand, C. M., Simmons, R. L., Goetz, R. C., Buselmeier, T. J., Shideman, J. R., von Hartitzsch, B., Najarian, J. S. ibid. 1973, ii, 4. Ruiz, J. O., Simmons, R. L., Callender, C. O., Kjellstrand, C. M., Buselmeier, T. J., Najarian, J. S. Surgery, 1973, 73, 759.
R. L. SIMMONS C. M. KJELLSTRAND T. J. BUSELMEIER J. S. NAJARIAN.
LYMPHOCYTE FUNCTION AND IRONDEFICIENCY ANÆMIA
SIR,-Dr Kulapongs and his colleagues (Sept. 21, p. 689) report no significant defect in cell-mediated immunity in children with severe iron-deficiency anaemia and state that they cannot confirm our original observations showing an abnormality.In fact, a direct comparison cannot be made. We examined the lymphocyte response in vitro to tuberculin and candida antigen and found a defect both in transformation and in M.i.F. (migration inhibition factor) production. Dr Kulapongs’ group have measured the proliferative response only following P.H.A. stimulation and have found Our own findings (unpubno defect in iron deficiency. lished) agree with this. It is interesting that the failure of iron-deficient lymphocytes to produce M.i.F. in response to tuberculin in our study related well to the failure to produce a positive Mantoux reaction in vivo. Dr Kulapongs’ group note that our original paper did not document the changes in cell-mediated immunity resulting from treatment with iron. These were described at a meeting of the British Society for Hxmatology in March, 1973, and may be summarised as follows. Twelve subjects were tested.1
plants,9 we have long been interested in some of the questions Dr Hill and her colleagues ask concerning the prognostic importance of the development of steroid diabetes in non-diabetic patients.1o Of 253 non-diabetic renal-transplant recipients reviewed last May, 15 had developed steroid diabetes since transplantation as determined by fasting hyperglycasmia. The incidence was increased in women, in patients with family histories of diabetes, and among recipients of unrelated (cadaver) transplants. We agree with the observations of Hill et al. that, unless blood-glucose levels are routinely determined, the insidious appearance of ketoacidosis or hyperglycxmic coma can
taken.
Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minnesota 55455,
GLYCOSURIA AND HYPERGLYCÆMIA AFTER KIDNEY TRANSPLANTATION SiR,—The article by Dr Hill and her associateswas of some interest to us. Since we have noted an increased morbidity and mortality in patients with juvenile-onset insulin-dependent diabetes who require renal allotrans-
non-ketotic
are
These results
production °
deficiency.
were
the basis for the
statement
that M.I.F.
may return promptly after treatment of iron The return of a normal proliferative response
takes longer. We were interested to note that your leading article of Aug. 10 (p. 325) cites a paper by Fletcher et aJ. which appears to confirm our findings. The mechanism of the lymphocyte changes occurring in iron-deficiency anaemia are unknown but other disturbances have recently been described. Hoffbrand et awl. have shown that the defect in D.N.A. synthesis found in iron-deficient lymphocytes may be related to decreased activity of the iron-containing enzyme, ribonucleotide reductase. Jarvis and Jacobs3 have shown marked morphological abnormalities in the mitochondria of iron-deficient lymphocytes which suggest the existence of associated metabolic changes: While the intracellular lesions of iron deficiency are becoming clearer, their effect on immunological functions is not understood.
presumably
Department of Hæmatology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW. 1.
2. 3.
A. JACOBS D. H. M.
JOYNSON.
Joynson, D. H. M., Jacobs, A., Murray-Walker, D., Dolby, A. E. Lancet, 1972, ii, 1058. Hoffbrand, A. V., Ganeshaguru, K., Tattersall, M. H. N., Tripp, E Clin. Sci. 1974, 46, 12p. Jarvis, J., Jacobs, A. J. clin. Path. (in the press).
development of steroid diabetes in renal-transplant recipients as long as precautions to discover and control the
and remission tissue in organ culture. The many previously observed immunological abnormalities, which tend to improve after gluten withdrawal, would be regarded as secondary to the mucosal damage and presumed increase in permeability to antigens in the lumen. Yet another possibility would be the deletion of the second of two enzymes in a metabolic pathway, with a toxic intermediate accumulating above the blocked step. If the first enzyme were induced to higher specific activity by the presence of substrate (component of gliadin), a higher concentration of the intermediate would accumulate. These hypotheses appear compatible with data from Dr Townley’s group: duodenal mucosa from patients with coeliac sprue was shown to be defective in digesting one of ten fractions obtained by chromatography of a peptictryptic-pancreatinic digest of gliadin.The same fraction was later shown to inhibit the morphological improvement of cceliac mucosa in organ culture, and to yield the highest hsmagglutination titres with sera of coeliac patients.7 The case for an immunological abnormality as the cause of coeliac sprue is not yet proven, and the possibility of an enterocyte enzyme abnormality still warrants investigation. Gastroenterology Division, Peter Bent Brigham Hospital, Boston, Massachusetts 02115, NEVILLE D. YEOMANS. U.S.A.
the diabetes
U.S.A.
be missed. Other than these rare complications, the diabetes is almost always mild and can be managed without long-term insulin, even if insulin is necessary to initiate treatment. In order to determine the prognostic importance of the development of steroid diabetes, the 15 patients who developed steroid diabetes were each matched to transplant recipients of similar age, sex, time since transplant, and relationship to donor. Patients who developed steroid diabetes do not seem to be more prone to an increased rate or severity of infection, nor are they more likely to reject their kidneys. 14 of the 15 patients with steroid diabetes were well with normal renal function 8-46 months after renal transplantation. 8 of the 9 recipients of cadaver transplants who developed steroid diabetes were well. Thus, we cannot yet determine that there is an increased long-term morbidity associated with 6. 7. 8. 9. 10.
Cornell, H. J., Townley, R. R. W. Clinica chim. Acta, 1973, 43, 113. Townley, R. R. W., Bhathal, P. S., Cornell, H. J., Mitchell,J. D. Lancet, 1973, i, 1363. Hill, C. M., Douglas, J. F., Rajkumar, K. V., McEvoy, J., McBeown, M. Lancet, Aug. 31, 1974, p. 490. Kjellstrand, C. M., Simmons, R. L., Goetz, R. C., Buselmeier, T. J., Shideman, J. R., von Hartitzsch, B., Najarian, J. S. ibid. 1973, ii, 4. Ruiz, J. O., Simmons, R. L., Callender, C. O., Kjellstrand, C. M., Buselmeier, T. J., Najarian, J. S. Surgery, 1973, 73, 759.
R. L. SIMMONS C. M. KJELLSTRAND T. J. BUSELMEIER J. S. NAJARIAN.
LYMPHOCYTE FUNCTION AND IRONDEFICIENCY ANÆMIA
SIR,-Dr Kulapongs and his colleagues (Sept. 21, p. 689) report no significant defect in cell-mediated immunity in children with severe iron-deficiency anaemia and state that they cannot confirm our original observations showing an abnormality.In fact, a direct comparison cannot be made. We examined the lymphocyte response in vitro to tuberculin and candida antigen and found a defect both in transformation and in M.i.F. (migration inhibition factor) production. Dr Kulapongs’ group have measured the proliferative response only following P.H.A. stimulation and have found Our own findings (unpubno defect in iron deficiency. lished) agree with this. It is interesting that the failure of iron-deficient lymphocytes to produce M.i.F. in response to tuberculin in our study related well to the failure to produce a positive Mantoux reaction in vivo. Dr Kulapongs’ group note that our original paper did not document the changes in cell-mediated immunity resulting from treatment with iron. These were described at a meeting of the British Society for Hxmatology in March, 1973, and may be summarised as follows. Twelve subjects were tested.1
plants,9 we have long been interested in some of the questions Dr Hill and her colleagues ask concerning the prognostic importance of the development of steroid diabetes in non-diabetic patients.1o Of 253 non-diabetic renal-transplant recipients reviewed last May, 15 had developed steroid diabetes since transplantation as determined by fasting hyperglycasmia. The incidence was increased in women, in patients with family histories of diabetes, and among recipients of unrelated (cadaver) transplants. We agree with the observations of Hill et al. that, unless blood-glucose levels are routinely determined, the insidious appearance of ketoacidosis or hyperglycxmic coma can
taken.
Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minnesota 55455,
GLYCOSURIA AND HYPERGLYCÆMIA AFTER KIDNEY TRANSPLANTATION SiR,—The article by Dr Hill and her associateswas of some interest to us. Since we have noted an increased morbidity and mortality in patients with juvenile-onset insulin-dependent diabetes who require renal allotrans-
non-ketotic
are
These results
production °
deficiency.
were
the basis for the
statement
that M.I.F.
may return promptly after treatment of iron The return of a normal proliferative response
takes longer. We were interested to note that your leading article of Aug. 10 (p. 325) cites a paper by Fletcher et aJ. which appears to confirm our findings. The mechanism of the lymphocyte changes occurring in iron-deficiency anaemia are unknown but other disturbances have recently been described. Hoffbrand et awl. have shown that the defect in D.N.A. synthesis found in iron-deficient lymphocytes may be related to decreased activity of the iron-containing enzyme, ribonucleotide reductase. Jarvis and Jacobs3 have shown marked morphological abnormalities in the mitochondria of iron-deficient lymphocytes which suggest the existence of associated metabolic changes: While the intracellular lesions of iron deficiency are becoming clearer, their effect on immunological functions is not understood.
presumably
Department of Hæmatology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW. 1.
2. 3.
A. JACOBS D. H. M.
JOYNSON.
Joynson, D. H. M., Jacobs, A., Murray-Walker, D., Dolby, A. E. Lancet, 1972, ii, 1058. Hoffbrand, A. V., Ganeshaguru, K., Tattersall, M. H. N., Tripp, E Clin. Sci. 1974, 46, 12p. Jarvis, J., Jacobs, A. J. clin. Path. (in the press).