1057 reasons for withholding a drug which has erosive and properties influences platelet function. The table shows an analysis of upper gastrointestinal tract bleeding in patients who have recently attended this renal unit; aspirin seemed to have precipitated three of these episodes. We would, therefore, endorse the recommendation that aspirin should not be given to patients with chronic renal failure either before or after transplantation.
important
Renal Unit,
C. C. DOHERTY MARY G. MCGEOWN
Belfast City Hospital, Belfast BT9 7AB
HYPERPARATHYROIDISM AFTER RENAL TRANSPLANTATION
SIR,-Your editorial (Feb. 12, p. 343) noted that Chatterjee
reported a higher frequency of aseptic necrosis of recipients with hypercalcsemia (7 of 16) after renal transplantation than among normocalcaemic long-term survivors (3 of 44). We have analysedthe clinical significance of hyperparathyroidism after renal transplantation. In 195 long-term survivors 29 (16.7%) got hypercalcaemia after transplantation. In 22 patients the hypercalcaemia was mild and resolved spontaneously or concurrently with rejection episodes. In 7 patients the hypercalcsemia was persistent, being terminated by subtotal parathyroidectomy in 5 but still persisting in 2. The hypercalcaemia was asymptomatic except in 1 patient in whom calculi in the graft and a fall in graft function developed; these problems disappeared after parathyroidectomy. 5 (17%) of the patients with hypercalcaemia got aseptic necrosis of bone, but this frequency was not significantly different from that found in patients without hypercalcaemia (10%). Further, in long-term survivors with aseptic necrosis of bone serum-parathyroid-hormone concentrations did not differ from those found in normocalc2emic patients without aseptic bone necrosis.3 Histomorphometric analysis of iliac-crest bone from 13 long-term survivors with radiologically progressive bone necrosis showed a pronounced reduction of spongy bone (osteopenia) compared with iliac-crest bone from 7 recipients without aseptic necrosis and from controls3. 4 Both groups of recipients showed similar changes in bone remodelling, indicating decreased bone formation. No signs of increased parathyroid function were found in the bone, and bone resorption et
al. had
bone in
within normal limits. These results do not support the
was
hypothesis that hyperparaafter renal transplantation plays a causative role in thyroidism aseptic osteonecrosis. The results suggest that osteopenia is an important contributory factor in the development of aseptic necrosis of bone. The osteopenia may be a consequence both of uraemic bone disease present before transplantation and immunosuppressive treatment after transplantation. Department of Medicine C, Kommunehospitalet, and Institutes of Pharmacology and Pathology, Amtssygehuset, University of Aarhus, 8000 Aarhus C, Denmark
H. E. NIELSEN* M. S. CHRISTENSEN F. MELSEN
AUTOXIDATION IN PERIPHERAL VASCULAR
DISEASE
SIR,-With reference
to
your editorial
on
prevention of
thrombosis (Jan. 15, p. 127) suggesting that autoxidative pro1. Chatterjee,
S. N., Friedler, R. M., Berne, T. V., Oldham, S. B., Singer, Massry, S. G. Nephron, 1976, 17, 1. 2. Christensen, M. S., Nielsen, H. E., Torring, S. Acta med. scand. 1977, 201, F. R.,
35. 3 Nielsen, H. E., Melsen, F., Christensen, M. S. ibid. (in the press). 4. Melsen, F., Nielsen, H. E. Acta path. microbiol. scand. A., 1977, 85,
99.
cesses might be involved in the pathogenosis of peripheral vascular disease, and that antioxidants might have a role to play in its prevention of cure, a clinical trial at this hospital may be of interest. The substance under investigation was ’Lipostabil’-eluted phospholipids of soya bean oil (E.P.L.) (mainly linolenic acid radicles) made by Nattermann, put up in capsules with 5 mg a-tocopherol (vitamin E) as an antioxidant to prevent the oil rancidifying. A preliminary double-blind trial, lasting two months, on patients with established intermittent claudication showed considerable subjective improvement in 50% of those patients who were subsequently found to have been on the drug, but there was no improvement on those who had been on the placebo. There was also a significant decrease in the malonyldialdehyde yield on oxidation of the erythrocytes of the treated group compared with the placebo group. A three-way double-blind trial was set up. One group was given the standard lipostabil capsules; one group was given placebo capsules; and a third group were given capsules containing placebo +5 mg a-tocopherol, in case the improvement of the patients in the preliminary trial had been due to the antioxidant rather than an action of E.P.L. The patients took two capsules three times per day. Progress was assessed by a standard step-test over a period of three months. Several patients did improve in performance. However, when the results were analysed the placebo group was found to have improved more than either of the other two groups,
and the malonyldialdehyde yield showed no significant change between the three groups. Thus fx-tocopherol did not have any significant effect on intermittent claudication in this case. St. James’s Hospital, London SW12
E. M. NANSON
SEASONALITY IN DOWN SYNDROME p. 754), questioning the reality of the seasonal trend for Down syndrome to which Dr Janerich and Professor Jacobson (March 5, p. 515) referred, mentions two studies in which no such trend was found for all maternal age-groups combined 1,2 and one in which cases with mothers under 35 (but not those with older mothers) were commoner among births in May-October than in November-April.3 May I mention two series much larger than the last of these threeone (from the State of New York) with an above-average frequency reported among May-October births4 and the other (from Birmingham, England) with relatively high rates for January—June. The New York data and the Birmingham figures (see table) indicate that neither of these seasonal trends was confined to the children of women under 35. In the Birmingham series, three of the monthly rates for each of the agegroups mentioned were less than three-quarters as high as the overall rate for that group; and the low-frequency months for the two groups were either identical or adjacent and all fell during the second half of the year, when the rate for each group was lower by about one fifth than in the first half. Like the lack of consistency between the results of different studies, this within-series similarity between the findings for cases with mothers above and below 35 casts doubt on the reality of the trends reported. There are now several lines of evidence (reviewed elsewhere6) to suggest that whilst most instances of Down syndrome are produced by non-dysjunction during oocytic meiosis and are closely related to maternal age,
SIR,-Dr Sever (April 2,
A. D. Teratology, 1972, 6, 1. Haynes, S. G., Gibson, J. B., Kurland, L. T. Neurology, Minneapolis, 1974, 24, 691. 3. Goad, W. B., Robinson, A., Puck, T. T. Am. J. hum. Genet. 1976, 28, 62. 4. Hook, E. B., Porter, I. H., Keogh, M., Quickenton, P., Logrillo, V. Lancet,
1. 2.
McDonald,
1974, i, 566. 5. Leck. I. ibid. 1966, ii, 457. 6. Leck, in Handbook of Teratology (edited vol. iii. New York (in the press).
by
F. C. Fraser and
J. G. Wilson);
1058 DOWN SYNDROME CASES
(INCLUDING STILLBIRTHS) AND TOTAL
BIRTHS,
BY MONTH AND MATERNAL AGE:
BIRMINGHAM, ENGLAND,1930-
important
Renal Unit,
C. C. DOHERTY MARY G. MCGEOWN
Belfast City Hospital, Belfast BT9 7AB
HYPERPARATHYROIDISM AFTER RENAL TRANSPLANTATION
SIR,-Your editorial (Feb. 12, p. 343) noted that Chatterjee
reported a higher frequency of aseptic necrosis of recipients with hypercalcsemia (7 of 16) after renal transplantation than among normocalcaemic long-term survivors (3 of 44). We have analysedthe clinical significance of hyperparathyroidism after renal transplantation. In 195 long-term survivors 29 (16.7%) got hypercalcaemia after transplantation. In 22 patients the hypercalcaemia was mild and resolved spontaneously or concurrently with rejection episodes. In 7 patients the hypercalcsemia was persistent, being terminated by subtotal parathyroidectomy in 5 but still persisting in 2. The hypercalcaemia was asymptomatic except in 1 patient in whom calculi in the graft and a fall in graft function developed; these problems disappeared after parathyroidectomy. 5 (17%) of the patients with hypercalcaemia got aseptic necrosis of bone, but this frequency was not significantly different from that found in patients without hypercalcaemia (10%). Further, in long-term survivors with aseptic necrosis of bone serum-parathyroid-hormone concentrations did not differ from those found in normocalc2emic patients without aseptic bone necrosis.3 Histomorphometric analysis of iliac-crest bone from 13 long-term survivors with radiologically progressive bone necrosis showed a pronounced reduction of spongy bone (osteopenia) compared with iliac-crest bone from 7 recipients without aseptic necrosis and from controls3. 4 Both groups of recipients showed similar changes in bone remodelling, indicating decreased bone formation. No signs of increased parathyroid function were found in the bone, and bone resorption et
al. had
bone in
within normal limits. These results do not support the
was
hypothesis that hyperparaafter renal transplantation plays a causative role in thyroidism aseptic osteonecrosis. The results suggest that osteopenia is an important contributory factor in the development of aseptic necrosis of bone. The osteopenia may be a consequence both of uraemic bone disease present before transplantation and immunosuppressive treatment after transplantation. Department of Medicine C, Kommunehospitalet, and Institutes of Pharmacology and Pathology, Amtssygehuset, University of Aarhus, 8000 Aarhus C, Denmark
H. E. NIELSEN* M. S. CHRISTENSEN F. MELSEN
AUTOXIDATION IN PERIPHERAL VASCULAR
DISEASE
SIR,-With reference
to
your editorial
on
prevention of
thrombosis (Jan. 15, p. 127) suggesting that autoxidative pro1. Chatterjee,
S. N., Friedler, R. M., Berne, T. V., Oldham, S. B., Singer, Massry, S. G. Nephron, 1976, 17, 1. 2. Christensen, M. S., Nielsen, H. E., Torring, S. Acta med. scand. 1977, 201, F. R.,
35. 3 Nielsen, H. E., Melsen, F., Christensen, M. S. ibid. (in the press). 4. Melsen, F., Nielsen, H. E. Acta path. microbiol. scand. A., 1977, 85,
99.
cesses might be involved in the pathogenosis of peripheral vascular disease, and that antioxidants might have a role to play in its prevention of cure, a clinical trial at this hospital may be of interest. The substance under investigation was ’Lipostabil’-eluted phospholipids of soya bean oil (E.P.L.) (mainly linolenic acid radicles) made by Nattermann, put up in capsules with 5 mg a-tocopherol (vitamin E) as an antioxidant to prevent the oil rancidifying. A preliminary double-blind trial, lasting two months, on patients with established intermittent claudication showed considerable subjective improvement in 50% of those patients who were subsequently found to have been on the drug, but there was no improvement on those who had been on the placebo. There was also a significant decrease in the malonyldialdehyde yield on oxidation of the erythrocytes of the treated group compared with the placebo group. A three-way double-blind trial was set up. One group was given the standard lipostabil capsules; one group was given placebo capsules; and a third group were given capsules containing placebo +5 mg a-tocopherol, in case the improvement of the patients in the preliminary trial had been due to the antioxidant rather than an action of E.P.L. The patients took two capsules three times per day. Progress was assessed by a standard step-test over a period of three months. Several patients did improve in performance. However, when the results were analysed the placebo group was found to have improved more than either of the other two groups,
and the malonyldialdehyde yield showed no significant change between the three groups. Thus fx-tocopherol did not have any significant effect on intermittent claudication in this case. St. James’s Hospital, London SW12
E. M. NANSON
SEASONALITY IN DOWN SYNDROME p. 754), questioning the reality of the seasonal trend for Down syndrome to which Dr Janerich and Professor Jacobson (March 5, p. 515) referred, mentions two studies in which no such trend was found for all maternal age-groups combined 1,2 and one in which cases with mothers under 35 (but not those with older mothers) were commoner among births in May-October than in November-April.3 May I mention two series much larger than the last of these threeone (from the State of New York) with an above-average frequency reported among May-October births4 and the other (from Birmingham, England) with relatively high rates for January—June. The New York data and the Birmingham figures (see table) indicate that neither of these seasonal trends was confined to the children of women under 35. In the Birmingham series, three of the monthly rates for each of the agegroups mentioned were less than three-quarters as high as the overall rate for that group; and the low-frequency months for the two groups were either identical or adjacent and all fell during the second half of the year, when the rate for each group was lower by about one fifth than in the first half. Like the lack of consistency between the results of different studies, this within-series similarity between the findings for cases with mothers above and below 35 casts doubt on the reality of the trends reported. There are now several lines of evidence (reviewed elsewhere6) to suggest that whilst most instances of Down syndrome are produced by non-dysjunction during oocytic meiosis and are closely related to maternal age,
SIR,-Dr Sever (April 2,
A. D. Teratology, 1972, 6, 1. Haynes, S. G., Gibson, J. B., Kurland, L. T. Neurology, Minneapolis, 1974, 24, 691. 3. Goad, W. B., Robinson, A., Puck, T. T. Am. J. hum. Genet. 1976, 28, 62. 4. Hook, E. B., Porter, I. H., Keogh, M., Quickenton, P., Logrillo, V. Lancet,
1. 2.
McDonald,
1974, i, 566. 5. Leck. I. ibid. 1966, ii, 457. 6. Leck, in Handbook of Teratology (edited vol. iii. New York (in the press).
by
F. C. Fraser and
J. G. Wilson);
1058 DOWN SYNDROME CASES
(INCLUDING STILLBIRTHS) AND TOTAL
BIRTHS,
BY MONTH AND MATERNAL AGE:
BIRMINGHAM, ENGLAND,1930-
