Biomedical subjects
D O Oliver
Publications and source records attributed to D O Oliver.
Imaging of haemodialysis-associated amyloidosis with 123I-serum amyloid P component.
Long-term haemodialysis is frequently complicated by amyloid deposition in which the fibrils consist of beta 2-microglobulin. Dialysis-related amyloid disease causes extensive morbidity and has been associated with deaths in some cases. All amyloid deposits contain amyloid P component that is derived from the normal circulating protein, serum amyloid P component (SAP). We have used scintigraphic imaging after injection of 123I-labelled SAP to assess the distribution of amyloidosis in 38 patients receiving long-term haemodialysis for end-stage renal failure. There was focal localisation of tracer at all sites where histological examination confirmed amyloid deposition. Splenic uptake was seen in 12 patients, indicating splenic amyloidosis, but there was no evidence of other visceral involvement. 6 control subjects who had been dialysed for under 1.5 years showed no localisation of tracer, nor was there any uptake of 123I-labelled human serum albumin in 3 long-term dialysis patients with histologically confirmed amyloidosis and positive 123I-SAP images. Negative scans were also obtained in 5 patients who had been transplanted 0.8-2.4 years previously, despite past evidence of dialysis arthropathy (5) and histologically proven amyloidosis (4). 123I-SAP scintigraphy may be helpful as a non-invasive method for both the diagnosis and monitoring of dialysis-associated amyloidosis.
Stepwise correction of anaemia by subcutaneous administration of human recombinant erythropoietin in patients with chronic renal failure maintained by continuous ambulatory peritoneal dialysis.
Sixteen anaemic CAPD patients (Hb less than 9 g/dl) were treated with thrice-weekly subcutaneous recombinant erythropoietin, epoetin-alfa. The dose was adjusted to induce a stepwise increase in haemoglobin. Fourteen patients reached a first target haemoglobin of 11.0-11.5 g/dl and eight of these a second of 13.0-13.5 g/dl, but one could not be maintained at this level. Failure to reach or maintain the second target in nine subjects was accounted for by incomplete responses associated with infection in one, extreme shortening of red-cell survival in another, and was unexplained in one subject. These three received the maximum dose studied of 450 IU/kg per week. Six other subjects were withdrawn from the study for reasons unrelated to treatment with erythropoietin. The median dose required to maintain the haemoglobin at 11.0-11.5 g/dl was 75 IU/kg per week and at 13.0-13.5 g/dl was 150 IU/kg per week. Quality of life, assessed in 12 patients at haemoglobin 11.0-11.5 g/dl, showed significant improvement in energy, and at 13.0-13.5 g/dl improvements in sleep and emotional wellbeing became significant. Twelve subjects required either institution of, or an increase in, treatment for hypertension. The thrice-weekly subcutaneous doses of erythropoietin were well tolerated and were a convenient and effective treatment for anaemia in patients on CAPD.
Total parathyroidectomy alone or with autograft for renal hyperparathyroidism?
Seventy-six patients underwent parathyroidectomy for renal hyperparathyroidism. There were 10 subtotal parathyroidectomies, 49 total parathyroidectomies with implantation of part of one gland as an autograft, nine total parathyroidectomies with no autograft, and eight patients in whom only three parathyroid glands were found. In 34 dialysis patients who underwent total parathyroidectomy with an autograft there was a high rate of recurrent hyperparathyroidism after 6 years in those remaining on dialysis. Fifty per cent had asymptomatic recurrent hyperparathyroidism and 30 per cent required partial autograft excision for symptomatic hyperparathyroidism. In contrast, recurrent hyperparathyroidism was rare in renal transplant recipients with good renal function. This favourable outcome did not depend upon whether parathyroid surgery was performed before or after transplantation, or on the type of parathyroidectomy. Total parathyroidectomy without an autograft was performed in nine dialysis patients without any short-term adverse effects, and with clinical and pathological improvement in bone disease. In summary, the results of surgery for renal hyperparathyroidism were excellent in patients who received a successful renal transplant. However, there was a high incidence of recurrent hyperparathyroidism in patients who remained on long-term dialysis. Total parathyroidectomy without an autograft may be the treatment of choice in patients unlikely to receive a renal transplant.
Loss of metacarpal and iliac bone in chronic renal failure: influence of haemodialysis, parathyroid activity, type of renal disease, physical activity and heparin consumption.
Explore the source record for details and available documents.
Iron metabolism in haemodialysis patients. A study of the management of iron therapy and overload.
Explore the source record for details and available documents.
Oral versus intravenous high-dose steroid treatment of renal allograft rejection. The big shot or not?
50 episodes of renal allograft rejection were treated by oral prednisolone and 49 by intravenous methylprednisolone. Both treatments achieved reversal of rejection in approximately 60% of episodes. Morbidity-rates, as assessed by hypertension, oliguria, fluid retention, and infection, tended to be greater after oral treatment. When the results were reexamined for accelerated, acute, and chronic rejection episodes the only difference demonstrated was an increased frequency of fluid retention in patients treated by oral prednisolone for an acute rejection episode. There was no evidence that intravenous methylprednisolone was nephrotoxic.
Treatment of hyperlipidaemia in patients on chronic haemodialysis.
Explore the source record for details and available documents.
Dietary treatment of hyperlipidemia in chronic hemodialysis patients.
Explore the source record for details and available documents.
Biological activity of endogenous and exogenous calcitonin in patients with osteitis fibrosa and chronic renal failure.
Successful treatment of osteitis fibrosa with 1alpha-hydroxycholecalciferol (1alpha-OHD3) in 9 patients with end-stage chronic renal failure was associated with a significant increase in plasma levels of immunoreactive calcitonin (iCT) independently of changes in plasma calcium, and a decrease in levels of parathyroid hormone (iPTH). In 9 further patients whose plasma alkaline phosphatase activity failed to suppress with 1alpha-OHD3, changes in iPTH were associated with proportionate changes in iCT. This suggests that a rise in endogenous calcitonin (CT) secretion contributes to the success of treatment with 1alpha-OHD3. In 13 further patients, injections of salmon CT induced a fall in plasma calcium and phosphate which was proportional to the prevailing level of plasma alkaline phosphatase. These data provide further evidence that bone resorption can be effectively inhibited when CT levels are raised either by exogenous CT or its endogenous stimulation.
Leucocytosis is not a manifestation of rejection.
The leucocyte response to allograft rejection was retrospectively analysed in 80 rejection episodes that occurred in 50 patients. There was no significant change in leucocyte count in 32 rejection episodes. In 27 there was a fall in leucocyte count of more than 20% and in only 21 was there a rise in count of more than 20%. Thus leucocytosis seems not to be a manifestation of rejection; indeed, it is the least common response, a fall in the count being commoner. The results also suggest that the prognosis for the graft is poorer when the leucocyte count falls significantly.
Renal transplantation and a positive serological cross-match.
A renal transplant involving a recipient with a positive serological cross-match against donor lymphocytes generally results in hyperacute rejection of the graft. 13 cadaveric renal transplants were performed in recipients with a known positive serologic cross-match against donor B lymphocytes. 12 of these serological cross-matches were positive against donor blood, node, or spleen lymphocytes, but the reactivity was directed against donor B lymphocytes only. 3 transplants failed, 2 because of rejection and 1 because of renal-artery thrombosis. 10 transplants are functioning, 6 to 42 weeks after the operation. Of these 10 successful grafts, 3 had no acute rejection episodes, while 7 had an early acute rejection episode which responded to treatment. Histologically, the grafts showed a cellular rejection, similar to that in enhanced renal allografts in the rat. It is possible to transplant a kidney in a high-risk patient with a positive B lymphocyte cross-match with a low risk of failure. In addition active enhancement of the graft might sometimes occur.
Changes in histologic and biochemical indexes of bone turnover after bilateral nephrectomy in patients on hemodialysis. Evidence for a possible role of endogenous calcitonin.
We studied the effects of bilateral nephrectomy on bone metabolism in 27 patients on maintenance hemodialysis. After nephrectomy plasma alkaline phosphatase fell rapidly in 10 patients whose preoperative plasma levels had been higher than normal. This fall was associated with a transient decrease in osteoblast counts of iliac-bone biopsies. A fall in plasma phosphate and a rise in plasma immunoreactive calcitonin also occurred, but calcium and immunoreactive parathyroid hormone levels did not change. Alkaline phosphatase levels remained unchanged in a control group of 17 patients on dialysis who had undergone an operation other than nephrectomy. In 26 nonsurgical patients on dialysis, immunoreactive calcitonin was inversely related to osteoblast counts. Rises in immunoreactive calcitonin may be partly responsible for the transient decreases in bone turnover after bilateral nephrectomy. Low levels of endogenous calcitonin may allow an increase in bone turnover in chronic renal failure.
Correlation of clinical, biochemical and skeletal responses to 1alpha-hydroxyvitamin D3 in renal bone disease.
Thirty-five patients with bone disease and chronic renal failure (twenty-four on maintenance haemodialysis) were treated for 7--39 months with 1alpha-hydroxyvitamin D3, 2--2.5 microgram daily by mouth. Symptoms (bone pain and muscle weakness) and radiographic appearances improved and plasma alkaline phosphatase returned to normal in the majority of patients (87, 76 and 75% respectively). In contrast, histological appearances in bone improved in only 46% twenty-three patients from whom paired biopsies were available, and this change was not greatly different from that seen in a comparable group of untreated patients. Significant correlations were noted in individual patients between the changes in symptoms, X-rays, plasma alkaline phosphatase and immunoreactive parathyroid hormone and these, in turn, were related to histological changes in bone, although these latter changes were often small. It is concluded that 1alpha-hydroxyvitamin D3 is a useful new drug in the treatment of renal bone disease, but that the evaluation of the response depends critically on the method of assessment used.
Integration of transplantation and home dialysis.
Explore the source record for details and available documents.
The significance of vesicoureteric reflux in non-pyelonephritic patients supported by long term hemodialysis.
Vesicoureteric reflux was found unexpectedly during routine investigations before renal transplantation in 12 patients with chronic glomerulonephritis and in one with hypertensive nephrosclerosis. They had all received long term hemodialysis treatment for nine to 106 months (mean 47 months) at the time of micturating cystourethrography (MCU). Four of the patients had previously had a normal MCU indicating that reflux developed after onset of end stage renal failure. The cause of reflux is obscure. It was not related directly to defunctioning of the urinary tract as several patients had daily urine volumes in excess of 300 ml. Infection, another potential cause, was uncommon in patients with reflux. Histology of the excised ureters showed abnormality in most cases with loss of the normal mucosal folds and submucosal cellular infiltrate and fibrosis. These changes are also unexplained. In this group of patients nephroureterectomy for reflux in anticipation of renal transplantation was associated with considerable morbidity. A minimal estimate of the incidence of reflux in chronic glomerulonephritis was 11%. We suggest that in this group and in patients with renal diseases other than chronic pyelonephritis reflux alone does not constitute sufficient indication for nephroureterectomy before transplantation to warrant the risks of major surgery.