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Biomedical subjects

P Fauchald

Publications and source records attributed to P Fauchald.

At least 55 records · Page 3Linked 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

Accidental metabolic acidosis during hemodialysis.

Three incidents of metabolic acidosis during hemodialysis in 3 different patients are presented. Two patients became severely ill but recovered completely after treatment. In the third patient, the event was recognized before the acidosis became symptomatic. In all cases the acidosis was caused by an unbalanced supply of acidic dialysis concentrate. Two events were caused by mistaking acidic dialysis concentrate for acetate. In the third patient, the supply line from the bicarbonate concentrate jug was broken. The conductivity cell alarm was not activated during any of the incidents and in only 1 case during reconstruction of the accidents. The efficacy and safety of the conductivity cell alarm system regarding prevention of acid/base disturbances during hemodialysis are discussed.

Acidosis↗
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↗
PubMed1994

Pregnancy outcome in renal allograft recipients in Norway. The importance of immunosuppressive drug regimen and health status before pregnancy.

BACKGROUND: To study the influence of pre-conceptional health status and immunosuppressive drug regimen on pregnancy outcome in renal allograft recipients. METHODS: The study includes all pregnancies in renal allograft recipients in Norway in the period 1973-1991. The data were collected from the patient records. Serum-creatinine values, proteinuria, blood pressure, recent graft rejection, and immunosuppressive drug regimen before pregnancy as well as the interval from transplantation until pregnancy were related to the frequency of deliveries at term, preterm deliveries, and of induced and spontaneous abortions. RESULTS: 54 pregnancies in 37 renal allograft recipients resulted in 31 term deliveries, 12 preterm deliveries, four spontaneous, and seven induced abortions. One induced abortion due to psychosocial reasons was excluded from the calculations. Post-transplant intervals less than two years as compared to longer intervals were associated with an increased frequency of spontaneous and induced abortions (6/13 vs 4/40, p < 0.01) and a non-significant increase in the relation between preterm and term deliveries (3/4 vs 9/27). The few women with proteinuria, elevated serum-creatinine values, and hypertension before pregnancy had an increased number of adverse pregnancy results. The women receiving cyclosporine A experienced a larger frequency of spontaneous and induced abortions (7/18 vs 3/35, p < 0.05) and an increase in the relation between preterm and term deliveries (7/4 vs 5/27, p < 0.01) as compared to the women who received prednisolone and azathioprine only. CONCLUSIONS: The results demonstrate the importance of pre-conceptional consultation and may indicate a harmful effect of cyclosporine A on pregnancy outcome.

Abortion, Induced↗
PubMed1994

[Infection in patients with organ transplants].

The past decade has seen substantial improvements both in patient and graft survival in organ transplantation. One-year survival rates among recipients of kidney, pancreas, liver, and lung transplants now reach 80-90 per cent. The impressive survival statistics notwithstanding, any organ transplantation is still associated with a variety of possible complications. Prominent among the causes of morbidity and morality is the occurrence of infection, primarily due to the intensive immunosuppression. The diagnosis and treatment of infections are thus of paramount importance to the success of a transplantation programme.

Bacterial Infections↗
PubMed1993

[Doxazosin (Carduran)--a research survey].

4,260 patients were included in an open surveillance study simultaneously with the introduction of doxazosin for treatment of essential hypertension in Norway. The main aim of the study was to systematically collect information on side effects and events in patients being treated with a new drug. The effect on blood pressure, heart rate and lipids was also recorded. The study lasted for one year. 21 deaths were reported. 53% of the patients reported side effects and/or events. The frequency of side effects was particularly high during the first month of treatment. No new types of side effects were found. The initial higher frequency of reported side effects referred to all organ systems, and was also of the same magnitude in the different systems. A relation was found between certain cardiac side effects and/or events and cessation of previous medication upon starting treatment with doxazosin. The study shows that certain safety precautions should be observed in patients with coronary heart disease and heart failure. In three patients, doxazosin should be used only in combination with more specific treatment. Special caution should be observed when changing the specific basic treatment. Doxazosin had a very favourable antihypertensive effect. A drop in cholesterol and triglycerides was observed, as expected. The HDL-cholesterol value declined, which was unexpected. The results are difficult to interpret, owing to lack of a control group. On the other hand, the study shows how high blood pressure is being treated with drugs in ordinary practice. The authors discuss the methodology of surveillance studies.

Aged↗