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Biomedical subjects

P Fauchald

Publications and source records attributed to P Fauchald.

At least 19 recordsLinked to original sources
PubMed1995

Consistent absorption of cyclosporine from a microemulsion formulation assessed in stable renal transplant recipients over a one-year study period.

To evaluate the pharmacokinetic properties of the new microemulsion formulation of cyclosporine (Sandimmun Neoral), a double-blind, prospective study in stable renal transplant recipients was performed. The patients were randomized on a 4:1 basis either to receive Sandimmun Neoral (n = 45) or continue on regular Sandimmun (n = 12). Before randomization, a steady-state pharmacokinetic profile study was performed in all patients while they were still on regular Sandimmun. Pharmacokinetic assessments were then performed after 8 and 12 weeks and after 1 year. A milligram-to-milligram dose conversion was shown to be adequate to maintain the patients within a predefined target therapeutic window. Changes in pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent with an increased rate and extent of cyclosporine absorption from the Neoral formulation. This was reflected by a shorter time to reach peak concentration and also by a mean increase in peak concentration by 67%, and an overall mean increase in drug exposure (area under the curve) by 34%. These findings were also confirmed 1 year after conversion. Furthermore, significantly reduced intraindividual variability in pharmacokinetic parameters was found, as well as improvements in the correlation between trough concentrations and area under the curve after conversion to Sandimmun Neoral. In conclusion, our results indicate an improved and consistent absorption of cyclosporine from the Neoral formulation, which should make clinical management easier and safer.

Absorption↗
PubMed1995

Pretransplant plasma exchange or immunoadsorption facilitates renal transplantation in immunized patients.

Patients with preformed antibodies against HLA molecules accumulate on renal transplant waiting lists and have inferior graft survival compared with nonsensitized patients. One hundred patients were included in a program of pretransplant removal of antibodies by plasma exchange (n = 90) or immunoadsorption (n = 10) in addition to prednisolone and cyclophosphamide medication. After plasma exchange, the panel reactivity and the antibody titer were reduced in about half of the patients, and after immunoadsorption the panel reactivity fell in 6 of 10 patients. Of the 83 patients who received grafts, 17 received a graft from a living donor (LD) and 66 received a graft from a cadaver donor (CD). Patients with a positive crossmatch against their LD were included in the program and were thus grafted with a recent positive, current negative crossmatched organ. Fifteen CD graft recipients had a pretreatment positive crossmatch toward their donor. No episodes of hyperacute rejection were seen. One- and 4-year graft survival rates in LD transplants with a recent positive and current negative crossmatch were 77% and 64%, respectively. At 1 and 4 years, graft survival rates were 70% and 57% in pretreated first CD graft recipients (n = 27) and 61% and 47% in pretreated regrafted patients (n = 39), respectively. In this program, a high rate of transplantation among the sensitized patients was achieved. Graft survival was inferior to that seen in nonsensitized patients, but was comparable to graft survival in sensitized patients at other centers.

Adult↗
PubMed1995

[Pancreas transplantation. A 10-year material].

A programme for pancreas transplantation was initiated in Oslo in 1983. Of a total of 100 transplants so far, 14 were performed as pancreas transplantation alone (PTA) in non-uremic diabetics (n = 9), or as pancreas after kidney (PAK), i.e. in diabetic patients with a functioning renal transplant (n = 5). Duct occluded segmental grafts were used until 1988, when the pancreaticoduodenal technique with bladder drainage was introduced. Since 1991, owing to a low graft survival rate in PAK and PTA cases, all pancreas transplantations have been performed simultaneously with a renal transplant, giving a one-year survival of 82%, 83% and 93% for kidney, pancreas and patient respectively. The authors give a brief overview of the experience gained during ten years, with a pancreas transplant rate of ten/year.

Adult↗
PubMed1995

Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on albuminuria in insulin-dependent diabetes mellitus patients with nephropathy.

OBJECTIVE: The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy. DESIGN: The study consisted of a four-week run-in period, a four-week active treatment period, a four-week wash-out period and a second four-week active treatment period. SETTING: The study was performed in the out-patient clinic at a university hospital. SUBJECTS: Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 micrograms min-1), mild to moderate hypertension (diastolic blood pressure 85-115 mmHg) and serum creatinine level below 200 mumol L-1 were included in the study. MAIN OUTCOME MEASURES: The effect of the drugs on albumin and total protein excretion, beta-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. RESULTS: Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 +/- 281 micrograms min-1 to 742 +/- 246 micrograms min-1 (P < 0.01) and total protein excretion from 2.0 +/- 0.4 g per 24 h to 1.3 +/- 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of beta-2-microglobulin. However, neither the excretion of beta-2-microglobulin nor the enzyme markers were affected by either drug. CONCLUSIONS: Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.

Adult↗
PubMed1994

Contrasting short-term effects of nifedipine on glomerular and tubular functions in glomerulonephritic patients.

The short-term effects of nifedipine on glomerular hemodynamics, sieving function, and renal tubular function were assessed in 10 patients suffering from biopsy-verified chronic glomerulonephritis. Three weeks of nifedipine treatment after 2 wk of placebo significantly reduced the blood pressure from 153 +/- 6/90 +/- 3 to 139 +/- 6/84 +/- 4 mm Hg (mean +/- SE; P < 0.05). Renal vascular resistance was reduced from 0.54 +/- 0.10 to 0.46 +/- 0.08 mm Hg/mL per minute. However, GFR (44.3 +/- 7 mL/min), effective RPF (265 +/- 37 mL/min), and filtration fraction (0.17 +/- 0.01) remained unchanged. The excretion of albumin of 1,318 +/- 395 micrograms/min was not affected by nifedipine. The glomerular sieving estimated by use of the fractional dextran clearance technique revealed no significant change by nifedipine compared with placebo in the range of 30 to 60 A of hydrodynamic dextran radius. Fractional proximal reabsorption (lithium clearance method) was reduced by nifedipine from 53 +/- 5 to 46 +/- 4% (P < 0.05). Also, the excretion of beta 2-microglobulin and N-acetyl-beta-glucosaminidase increased from 10.98 +/- 4.62 to 11.86 +/- 4.74 mg/24 h (P < 0.05) and from 19.7 +/- 4.2 to 25.3 +/- 7.0 nmol/h per micromoles of creatinine (P = 0.05), respectively. It was concluded that nifedipine treatment acutely represses proximal tubular function but is without significant effect on glomerular sieving and albuminuria in these patients.

Adult↗
PubMed1993

Quality of life in Norwegian kidney donors.

The Norwegian kidney transplant programme is based on more extensive use of living donors than in other countries. Re-examination of the physical health of kidney donors has in the majority of studies revealed no long-term medical risk. The quality of life after donation has only been described in very few studies, and with a small number of donors. This report concerns a cross-sectional study of 494 donors with a mean observation time from donation of 6.7 years. A standardized questionnaire containing 19 items related to quality of life was used. The donors were compared to the general adult population in a county in mid-Norway. Out of the 19 quality of life items, the donors scored significantly better in 13. Donors who had experienced that the corresponding recipient had died have been tested separately. The results in this subgroup were equal to the population, but inferior compared to the rest of the donors. We conclude that the quality of life of Norwegian kidney donors is better than the general population. We will continue our policy of an extensive use of living kidney donors.

Adult↗
PubMed1992

[Central venous dialysis catheter. Silicone rubber dialysis catheter used for permanent vascular access].

51 dual lumen jugularis dialysis catheters (Permcath, Quinton) were placed by surgical technique in 34 patients and by percutaneous technique in eight patients. Mean catheter life-time was 4.1 months. Seven catheters were removed due to complications (infection three catheters, clotting four catheters). Minor flow problems occurred in 8.8% of all procedures. Seven occluded catheters were successfully reopened by use of locally applied streptokinase. A strict aseptic technique is essential to avoid infection. Permcath is an acceptable vascular access device for patients in whom it is impossible to create an arterio-venous fistula.

Adolescent↗
PubMed1992

Fifteen years' experience with renal transplantation in systemic amyloidosis.

At our center 62 renal transplantations (31 living donor and 31 cadaveric donor grafts) have been performed in 58 patients with amyloid renal disease since 1974. The amyloidosis was secondary to rheumatic disease in 74% of the patients. Predialytic transplantation was performed in 28% of the patients. Mean follow-up time was 5.1 years (0.3-14.5 years). One-year actuarial patient survival was 79%, decreasing to 65% after 5 years. First graft survival was 74% at 1 year and 62% at 5 years. Patient death with a functioning graft caused 16 out of 25 graft losses. Infections caused 11 out of 18 deaths (61%), more than half of them within 3 months. Renal transplant amyloid was diagnosed in about 10% of the cases (6/62); however, only about 3% of the grafts (2/62) were lost. These long-term results encourage transplantation in amyloid renal end-stage disease.

Adolescent↗
PubMed1992

Long-term clinical results of percutaneous transluminal angioplasty in transplant renal artery stenosis.

Twenty-five patients with transplant artery stenosis were identified among 1141 renal graft recipients. Impaired graft function (9 patients), hypertension (4 patients) or both (12 patients) were the indications for arteriography. All were treated by percutaneous angioplasty (PTA). The immediate technical success rate was 88% and actuarial graft survival was 88% and 80% at 2 and 5 years respectively. The long-term success rate on graft function was 67% (median observation time 24 months) and on hypertension 63% (median observation time 23 months). Six patients needed rePTA (8 procedures) and in only one patient was surgical repair performed. No case of graft loss due to PTA was recorded and in only one case did occlusion of a segmental artery lead to impairment of graft function. Minor complications were recorded in four other cases and in no case was surgical intervention necessary. Based on these results we favour PTA as a first-line interventional procedure in transplant renal artery stenosis, and the need for surgical repair has been low.

Adult↗
PubMed1992

Hormonal changes in patients with severe chronic congestive heart failure treated by ultrafiltration.

Plasma atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), plasma renin activity (PRA), and circulatory haemodynamics were studied in five patients with chronic congestive heart failure undergoing ultrafiltration on two consecutive days. The patients were in the New York Heart Association class IV, and were considered candidates for heart transplantation. A mean of 3.3 +/- 0.5 litres of fluid was removed during each ultrafiltration. Plasma ANP concentration remained unchanged during ultrafiltration: 369 +/- 151 pg/ml at start and 316 +/- 116 pg/ml at the end, while plasma ADH concentration and PRA increased from 5.1 +/- 2.1 to 7.5 +/- 3.4 pg/ml (P less than 0.02), and 5.9 +/- 3.0 to 7.7 +/- 3.2 ng/ml (P less than 0.03) respectively (n = 10). After treatment, plasma ADH and PRA declined to baseline values within 1 h. Pulmonary artery, pulmonary capillary wedge, and right atrial pressures decreased significantly, while blood pressure and heart rate remained constant during ultrafiltration. A volume of 3.3 +/- 0.5 litres of fluid was removed, and caused an increase in colloid osmotic pressure from 22.0 +/- 3.0 to 33.7 +/- 3.9 mmHg (P less than 0.02). It was unexpected that plasma ANP concentration did not decline. Due to long-standing severe heart failure the atrial wall may have lost some of its elastic properties, resulting in less ability to adapt to reduced filling pressures. Accordingly, atrial wall stretch remained unchanged, explaining the constant ANP levels. Ultrafiltration treatment caused an increased responsiveness to diuretic therapy, and four patients survived long enough to receive heart transplants.

Adult↗
PubMed1992

Results of the National Kidney Transplantation Program in Norway.

1. Of 2,003 patients starting renal replacement therapy for end-stage renal disease in Norway from 1983 through 1991, 83% were candidates for transplantation. The need for transplantations increased to 58 (50 first and 8 repeat) grafts PMP per year as the number of elderly patients increased. 2. There were 1,528 transplants performed at a rate increasing to 46 grafts PMP per year. The grafts were procured from LDs in 44% and CDs in 56%. Eighty percent of all patients in need were transplanted and 65% of all patients requiring replacement therapy for end-stage renal disease were treated by transplantation. The national waiting list and dialysis population remained almost stable. 3. Graft survival rates in recipients of first LD grafts (n = 593) were 91% and 77% at 1 and 5 years, respectively. One-year graft survival was 98% in HLA-identical grafts (n = 73), 91% in haploidentical grafts (n = 411), 89% in 2 haplotype-mismatched related grafts (n = 38), and 85% in spousal donor grafts (n = 71). Higher rates were observed in younger (< 55 yrs) patients. 4. Graft survival rates in recipients of first CD grafts (n = 688) were 78% and 59% at 1 and 5 years, respectively. The rates were 84% and 66% in younger (n = 342) versus 72% and 52% in older (> 55 years) (n = 346) patients. Death with a functioning graft caused approximately 45% and 75% of all graft losses in younger and older patients, respectively. Cardiovascular disease was the major cause of death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Pregnancy outcome in renal allograft recipients: influence of ciclosporin A.

The outcome of 35 pregnancies in 26 renal allograft recipients is reported. Twenty-four pregnancies in patients treated with prednisolone and azathioprine resulted in 22 live-born infants (one twin pregnancy) and 3 induced abortions on medical indications. Three of the deliveries were preterm, and one of the infants had a birth weight below the 2.5th percentile. Ten patients (11 pregnancies) were treated with ciclosporin A (CsA). These women delivered 5 infants (3 preterm deliveries of whom the birth weight of one infant was below the 5th percentile) and underwent 3 induced (medical indications) and 3 spontaneous abortions. Mean birth weight in the CsA treated group was 2464 g (range 1790-2930 g), and their gestational age varied from 232 to 271 days. No foetal malformations were observed in the two groups. The results may indicate a harmful effect of CsA on pregnancy outcome.

Adolescent↗
PubMed1991

The use of elderly living donors in renal transplantation.

The safety and the results of using living donors above the age of 60 years were studied. In 235 consecutive donors the complications were not different in elderly (n = 70) compared to younger donors. Graft survival and function were studied in 232 consecutive 1-HLA-haplotype mismatched grafts. Graft survival at 1 year was equivalent (87% vs. 92%), but after 2-6 years graft survival was inferior in recipients of older grafts (n = 62). The recipients of older grafts were 10 years older, and patient death with functioning graft was a more frequent cause of graft loss. Up to 4 years serum creatinine levels were significantly higher, but stable, in recipients of older grafts; at 5 years the difference was not significant. It is concluded that the use of elderly living donors is safe. Taking recipient age into consideration, graft survival is not different in the two groups. Graft function in older grafts is some what inferior, but stable.

Adult↗
PubMed1991

Long-term metabolic control in recipients of combined pancreas and kidney transplants.

Metabolic glucose control was followed in 36 patients at 12-month intervals for up to 5 years after a successful combined kidney and segmental duct-occluded pancreas transplantation. All recipients had normal blood glucose levels at each examination. HbA1 values, intravenous glucose tolerance test, C-peptide levels and C-peptide responses to glucagon stimulation were also, on average, within the normal range. Several individual patients had, however, abnormal values for these parameters. At most 46% had abnormal values for HbA1 and intravenous glucose tolerance test, up to 13% showed low C-peptide values and up to 46% of the stimulated C-peptide responses were inadequate at the different intervals. These parameters did not deteriorate with time. This was true both for the whole group of patients as well as for the 6 patients with a 5-year observation time evaluated separately. Despite these abnormalities in glucose metabolism, all patients remained normoglycaemic without need for exogenous insulin up to 5 years after transplantation. The long-term ability of duct-occluded segmental pancreatic grafts to preserve euglycaemia therefore seems to remain intact at least for 5 years.

Adult↗
PubMed1991

Rehabilitation and quality of life in diabetic patients after successful pancreas-kidney transplantation.

Twenty-seven Type I diabetic patients in end-stage renal failure were followed after combined pancreas-kidney transplantation. All patients received duct-occluded segmental pancreas grafts. Clinical progression of extrarenal diabetic complications was studied in 11 patients with long-term functioning pancreatic and renal transplants (Group 1), and in 16 patients who had lost pancreatic graft function, but retained renal graft function (Group 2). Pretransplant, extrarenal diabetic complications were equally distributed in the two groups. In the follow-up period, however, the progress of these complications was less severe in patients with functioning pancreatic transplants. No differences were found between the groups concerning rehabilitation, working capacity, need of help or hospital admittance. It is suggested that pancreas transplantation performed in an earlier stage of diabetes before serious complications have developed, would probably improve rehabilitation and quality of life in these patients.

Adult↗