Biomedical subjects
Publications and source records attributed to M G McGeown.
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From 1968-1999, 868 recipients of 1,000 renal transplants were followed up for neoplasia. Altogether, 102 tumours were diagnosed in 94 patients (11.8% incidence). Eighty-seven occurred among 750 single and 15 occurred among 118 multiple graft recipients. Three of 11 patients with pre-existing tumour developed posttransplant neoplasia, either new or recurrent. The most frequently seen posttransplant neoplasms were squamous carcinoma of skin, basal cell carcinoma (BCC), posttransplant lymphoproliferative disease (PTLD) and gastro-intestinal (GI) cancer. Forty-one tumour-related deaths occurred (44% mortality). Patients on CSA (C) regimes had a greater cumulative incidence of tumour after transplantation than those on azathioprine and low-dose prednisolone alone (A regime) had--12.7% (34 of 268) vs. 4.5% (15 of 335) of those at risk up to 5 years (relative increased rate of incidence 2.4) with more early cases of PTLD. C-regime patients who developed neoplasia had been prescribed significantly higher CSA doses than tumour-free controls (4.5 vs. 3.4 mg/kg/day; p = 0.014). Patients who made a late conversion from the A to the C regime subsequently developed more neoplasms than nonconverted controls (25.7% vs. 12%), mainly due to early and often aggressive squamous carcinoma. Transplant survival figures were similar for both A- and C-regime groups. These findings suggest that current CSA doses are higher than are necessary for optimal graft survival and thus increase the risk of early neoplasia without any compensatory advantage. A dose reduction of CSA to less than 3.5 mg/kg/day in long-surviving, stable graft recipients should reduce tumour risk without imperilling function. Late conversion from the A to the C regime should be avoided where possible and CSA doses in this situation kept to a minimum.
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This paper describes the results of renal transplantation carried out in a single center from 10-26 years ago. Three hundred and eighty-six recipients received 440 grafts, 400 were cadaver grafts and 40 were from living donors, including one unrelated donor whose kidney was removed during an operation. All patients received immunosuppression with azathioprine and low-dose steroid. 1. Over the whole period, 1968-1986, 46% patients remain alive. The actual total patient survival was 65% for 1986 transplants, 51.7% for 1981 transplants, 37.1% for 1976 transplants and 31.2% for those transplanted 25 years ago. 2. Actual overall graft survival is 39.5% for the whole period. 3. Fifty-seven percent of living-related donor grafts survived over the whole period, including 48% of parental grafts and 69% of sibling grafts. 4. Ten years after transplantation, 54.2% of grafts carried out in 1986 are functioning, as are 40% of those transplanted in 1981, and 29% of those done in 1976 or before. In all 37% of first cadaver grafts continue to function, while 62% have failed. However 35 patients died with a well-functioning graft, due to either cardiovascular disease or neoplasia in 91% of cases. 5. Thirty-four percent of second cadaver grafts function over the whole period, 65.8% have failed. Only one of 9 third cadaver grafts, dating from 1975, continues to function.
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Successful renal transplantation improves fertility with 1 in 50 women of childbearing age becoming pregnant. Pregnancy following renal transplantation is associated with increased maternal and fetal complications. In Belfast 118 women of childbearing age (15-45 yrs) have received a renal allograft and of these 14 (12%) have become pregnant. Twenty-seven pregnancies have resulted in 23 live births (including one set of identical twins), 1 still birth and 4 first trimester abortions. The most frequent complications were hypertension and prematurity. In this group of patients, whose sole immunosuppressive therapy was azathioprine and prednisolone, pregnancy post transplantation was associated with frequent successful outcome and a low incidence of maternal and fetal complications.
OBJECTIVE: To determine the prevalence of advanced chronic renal failure in Northern Ireland as part of an assessment by the Renal Association of the level of service provision for treatment of such patients. DESIGN: Prospective notification of patients reaching a defined level of advanced chronic renal failure (serum creatinine concentration greater than or equal to 500 mumol/l or blood urea concentration greater than or equal to 25 mmol/l) within one year and follow up for at least three, and, at most, four years after notification. SETTING: Northern Ireland. PATIENTS: 122 Patients with a serum creatinine or blood urea concentration higher than the defined level newly detected from 1 March 1985 to 28 February 1986. MAIN OUTCOME MEASURE: Survival after notification. RESULTS: 77 Patients of all ages/million population/year had advanced chronic renal failure compared with 67/million/year between the ages of 5 and 80 found in an earlier study of the same population. 62% Of the patients were older than 50 years. Seventeen (14%) of the patients either required dialysis or died within one month of notification, 51 (42%) survived for at least three months, and 23 (19%) for one year or longer. Three patients, all of whom were attending a renal clinic, survived for periods of 43, 45, and 46 months respectively without renal replacement treatment. CONCLUSIONS: The increased number of new patients disclosed in this survey compared with the earlier survey is mainly owing to an increased number of older patients. Such patients often have disabilities other than renal failure, are less likely to be capable of self treatment, may develop complications more often and require more frequent hospital admissions, and may not be suitable for transplantation and consequently have considerable resource implications for the NHS.
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The metabolism of recombinant human erythropoietin (rHuEpo) labelled with 125I has been investigated in five normal and nine 5/6-nephrectomised rabbits. The plasma erythropoietin half-life was significantly prolonged at 5.1 +/- 1.2 h (mean +/- SD) in the 5/6-nephrectomised rabbits, compared to 3.0 +/- 0.4 h in sham-operated controls (P less than 0.001). The disappearance of 125I-labelled rHuEpo is biphasic. Examination of serum by fast protein liquid chromatography (FPLC) following administration of 125I-labelled rHuEpo by FPLC showed a single peak of radioactivity in all rabbits except two of the nephrectomised group. In serum from both of these animals a second labelled peak was found, corresponding to material of MW 200,000-250,000 D. We conclude that the 5/6-nephrectomised rabbit provides a stable model for the study of hormonal metabolism in chronic renal failure.
The erythropoietin gene has been cloned in three mammalian species including man and recombinant erythropoietin is now used to treat the anaemia of chronic renal failure. Despite the isolation of the gene the precise cellular location of erythropoietin synthesis remains controversial. We present studies which demonstrate erythropoietin production by kidney tubular cells. Erythropoietin gene expression (messenger RNA) was detected by in situ hybridization using an oligonucleotide gene probe and the translated protein product by immunohistochemistry employing antibodies raised to pure recombinant DNA derived erythropoietin.
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Live donor renal transplants are often preferred to cadaver grafts because of better graft survival. In a retrospective study of 41 live donor transplants performed in the Belfast Renal Unit from 1971 until November 1988, actual graft survival at 2 and 5 years was 84% and 69% respectively. Corresponding patient survival rates were 87% and 81%. These results are no better than those of cadaver grafts. A subdivision of patients considered to be relatively poor risk for transplantation showed less favourable results than those who were good risk. 15% of the donors suffered post-operative complications, which occurred more often in older donors. Live donor transplantation is not necessarily preferable to cadaver organ graft, and is not recommended for poor risk recipients or donors aged over 50 years.
This paper describes the results of renal transplants carried out in a single center more than 10 years ago. One hundred fifty-five recipients received 170 grafts; 164 from cadavers and 6 from living-related donors. All patients received the same immunosuppressive therapy with azathioprine and low-dose steroid. 1. The total actual patient survival was 67.1% at 10 years; 104 patients survived and 51 died. 2. The actual first cadaver graft survival was 54.7% at 10 years; 82 grafts survived and 68 were lost. Death with a functioning graft was the commonest cause of graft loss. 3. Ninety-seven patients and 70 first cadaver grafts survived in the 12th year. Two patients survived with first cadaver grafts into the 21st year. 4. Tissue match grade was not related to cadaver graft survival at 10 years. 5. Five of the 6 recipients of living-related donor kidneys survived but only 3 of their grafts were functioning after 10 years.
Erythropoiesis has been examined in relation to kidney function in 38 patients during the 3-month period following successful renal transplantation, using serial determinations of erythropoietin, haemoglobin, and creatinine. Two peaks of serum erythropoietin were observed: an early peak that occurred within 2 days of transplantation and was observed in ten patients, and a late one between 8 and 30 days, observed in 28 patients. The early peak did not produce an increase in haemoglobin and occurred only in the presence of delayed onset of graft excretory function when serum creatinine was greater than 1000 mumols/l. The ineffectiveness of the early peak may be due to the uraemic environment, which is probably a sequel of the tubular damage associated with postoperative acute tubular necrosis. The late peak followed a decrease in serum creatinine to less than 200 mumols/l and was associated with an increase in haemoglobin of 3-4 g/dl during the next 2-6 weeks.
93 patients received 102 renal transplants between 1968 and 1977. 99 grafts were from cadavers and 3 were from live donors; 93 were first grafts, 7 were second, and 2 were third. At 10 years total actual patient survival was 66.6%. 50 (55.5%) of 90 first cadaver grafts, and 52.2% of all cadaver grafts, survived at 10 years. Cardiovascular disease was the commonest cause of death, being responsible for 18 of 31 deaths (58%).