Renal transplantation in patients with lymphocytotoxic antibodies--a 5-year experience from a single centre.
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Biomedical subjects
Publications and source records attributed to G Nyberg.
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Pili prepared from Neisseria gonorrhoeae contain minor amounts of a 110 kd outer membrane protein denoted PilC. The corresponding gene exists in two copies, pilC1 and pilC2, in most strains of N.gonorrhoeae. In the piliated strain MS11(P+), only one of the genes, pilC2, was expressed. Inactivation of pilC2 by a mTnCm insertion resulted in a nonpiliated phenotype, while a mTnCm insertion in pilC1 had no effect on piliation. Expression of pilC was found to be controlled at the translational level by frameshift mutations in a run of G residues positioned in the region encoding the signal peptide. Nonpilated (P-), pilin expressing colony variants that did not express detectable levels of PilC were selected; all P+ backswitchers from these P-, PilC- clones were found to be PilC+. The structural gene for pilin, pilE, was sequenced and found to be identical in one P-, PilC- and P+, PilC+ pair. Most PilC- cells were completely bald whereas the PilC+ backswitcher had 10-40 pili per cell. Thus, a turn ON and turn OFF in the expression of PilC results in gonococcal pili phase variation. These results suggest that PilC is required for pilus assembly and/or translocation across the gonococcal outer membrane.
The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24-36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml.min-1 at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p = 0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p = 0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p = 0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types.(ABSTRACT TRUNCATED AT 250 WORDS)
During 1985 to 1990, 67 segmental pancreas transplantations with bladder drainage were performed. Fifty were combined pancreas and kidney and 17 were pancreas after kidney transplants. All patients were transplanted with the same technique. The 1-year actuarial pancreas graft survival for the combined patients with quadruple immunosuppressive therapy was 83% and the patient survival, 95%. The most important complications were infections, leakage from the pancreatico cystostoma and vascular complications.
Hyperinsulinaemia when combined with insulin resistance and hypertriglyceridaemia is a risk factor for cardiovascular disease. We have studied the serum lipid profile and glycaemic control in 27 uraemic diabetic patients, 23 Type 1 (insulin-dependent) diabetic kidney recipients, 18 non-diabetic kidney recipients, and 30 recipients of kidney and pancreas transplants at 6 months post-transplantation. Fasting serum triglycerides were increased in the uraemic diabetic patients and nondiabetic kidney transplanted patients but not in diabetic kidney transplanted patients whether or not they had received a pancreas. Total cholesterol was increased only in the uraemic diabetic patients while HDL cholesterol was normal in all groups. Within the pancreas and kidney transplanted group triglyceride values correlated with glomerular filtration rate (r = -0.55) but not with plasma insulin, glycated haemoglobin or kG-value following an intravenous glucose load. Plasma insulin was increased. Whether such isolated hyperinsulinaemia confers an increased risk of cardiovascular disease is not known. There may be adaptive feed-back mechanisms to protect target cells. Increasing the surgical risk in attempts to secure insulin delivery to the portal circulation does not seem warranted.
Echocardiography with Doppler recordings was carried out in 14 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney transplants and in 14 Type 1 diabetic kidney transplanted control patients, matched for age, sex, duration of diabetes, extent of other late complications, time since transplantation, dose of prednisolone, and renal function. HbA1c was 5.5 +/- 0.6 vs 8.7 +/- 1.4% (pancreas transplanted vs kidney only). Both groups had a slight increase in interventricular septum thickness. Left ventricular mass was equal. The ejection fraction as a measure of systolic function was normal and equal, 0.71 +/- 0.05 vs 0.69 +/- 0.07. Diastolic function was also equal in two out of three parameters, isovolumic relaxation time and deceleration time. The A/E ratio, however, tended to be lower in the pancreas transplanted group, 0.94 +/- 0.20 vs 1.06 +/- 0.18 (p = 0.04). This indicates more frequent occurrence of impaired diastolic filling in the recipients of kidney only. Follow-up will show whether diastolic dysfunction increases and may be related to the increased cardiovascular mortality in kidney transplanted Type 1 diabetic patients.
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OBJECTIVE: To assess whether angiotensin converting enzyme inhibition reduces proteinuria in diabetic nephropathy more than blood pressure reduction with other antihypertensive treatment. DESIGN: Prospective, open randomised study lasting eight weeks in patients with diabetic nephropathy. SETTING: Outpatient nephrology clinics. PATIENTS: 40 Patients with type I diabetes and diabetic nephropathy with reduced renal function. INTERVENTION: Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURES: Arterial blood pressure and urinary excretion of albumin and protein. RESULTS: Arterial blood pressure after eight weeks was 135/82 (SD 13/7) mm Hg in the group given enalapril and 136/86 (16/12) mm Hg in the group given metoprolol. Proteinuria and albuminuria were similar in both groups before randomisation. After eight weeks' treatment, the geometric mean albumin excretion was 0.7 (95% confidence interval 0.5 to 1.2) g/24 h in the patients given enalapril and 1.6 (1.1 to 2.5) g/24 h in the patients given metoprolol (p less than 0.02). The proteinuria was 1.1 (0.7 to 1.7) and 2.4 (1.6 to 3.6) g/24 h respectively (p less than 0.02). CONCLUSIONS: Antihypertensive treatment with enalapril reduced proteinuria in patients with diabetic nephropathy more than an equally effective antihypertensive treatment with metoprolol. This points to a specific antiproteinuric effect of the angiotensin converting enzyme inhibitor independent of the effect on systemic blood pressure.
In 14 patients on hemodialysis who received kidney grafts from living related donors, plasma levels of immunoreactive atrial natriuretic factor (Ir-ANF) were determined in a sequence covering the last hemodialysis treatment, the day of transplantation, and a follow-up period of 6-12 months. The geometric mean value before dialysis was 196 pg/ml, the range 32-634. Weight loss during dialysis was 1.5 +/- 1.1 kg (mean +/- SD), but only a nonsignificant reduction in Ir-ANF levels occurred. On the day of transplantation, plasma Ir-ANF levels increased from 143 pg/ml before to 391 post-transplantation (P = 0.02, n = 12), probably in response to deliberate volume expansion. Post-transplant Ir-ANF levels correlated significantly to diuresis during the first 24 h, which ranged from 3.7 to 17.81 (mean 6.6; r = 0.65, P = 0.02). On day 2, mean 24 h diuresis decreased to 3.3 +/- 1.41. Most patients had reached their true dry weight by day 5, but Ir-ANF levels remained high, the geometric mean being 180 pg/ml. During further follow-up and preserved graft function (GFR range 34-88 ml/min per 1.73 m2 body surface area), Ir-ANF levels declined to a geometric mean of 63 pg/ml by 2-6 months and to 36 at 12 months post-transplant. We conclude that plasma Ir-ANF levels are chronically elevated in patients with chronic renal failure but may be further stimulated by acute overhydration. Transplanted kidneys initially respond to the increased levels but adapt within a day. Even with good graft function, normalization of plasma Ir-ANF requires several weeks or months.
Imdur contains isosorbide-5-mononitrate (IS-5-MN) in a controlled-release (Durules) formulation. It has a significant anti-anginal effect when taken once daily at a dose of 60 mg. This anti-anginal effect persists during long-term treatment without the development of tolerance; once-daily treatment produces a plasma nitrate profile that is high enough to give anti-anginal protection during the daytime, but low enough during the latter part of the dosage interval to avoid the development of tolerance. Evidence shows that once-daily Imdur is equivalent in efficacy to plain tablets of IS-5-MN and isosorbide dinitrate taken three times daily at the same total daily dosage (60 mg), and to the calcium antagonist diltiazem (60 mg three times daily). In addition, the anti-anginal protection provided by Imdur in combination with beta-blocker treatment is superior to that achieved with beta-blocker treatment alone. In long-term studies Imdur has been shown to be well tolerated.
Erythrocytosis after renal transplantation confers risks of thromboembolic complications and therefore necessitates repeated phlebotomies and/or anticoagulation therapy. Erythropoietin production from the retained native kidneys is one aetiological possibility for this condition. During 1982-1987, 22 patients with renal transplants underwent bilateral nephrectomy because of erythrocytosis with a median duration of 13 months. The median follow-up time was 36 months. After nephrectomy, blood counts returned to normal in all patients; these remained normal in all but two patients, who relapsed with erythrocytosis after 6 and 18 months respectively. Concomitant hypertension was cured or improved in most cases. One patient had a myocardial infarction postoperatively. No other per- or postoperative complications occurred. The mean duration of hospital stay was 7.5 days. We consider bilateral nephrectomy of the native kidneys a safe and effective alternative in the management of post-transplant erythrocytosis.