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Biomedical subjects

B G Danielson

Publications and source records attributed to B G Danielson.

At least 19 recordsLinked to original sources

Reduction of plasma fibrinogen, immunoglobulin G, and immunoglobulin M concentrations by immunoadsorption therapy with tryptophan and phenylalanine adsorbents.

Immunoadsorption (IA) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session I plasma volume (2.8 +/- 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonparametric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.

Adult

Iron absorption in patients with chronic uremia on maintenance hemodialysis and in healthy volunteers measured with a simple oral iron load test.

Gastrointestinal iron absorption was measured by an oral iron load test in patients with uremia on maintenance hemodialysis (n = 19), with iron overload (n = 9), iron deficiency (n = 10) and in healthy volunteers (n = 9). After an overnight fast, serum iron was measured before, and 1, 2, 4 and 6 h after administration of 100 mg ferrous chloride. Bone marrow iron was assessed after staining with Prussian blue. The study shows that iron absorption is impaired in uremic patients. Even uremic subjects with iron deficiency absorbed significantly less than normal subjects. Patients with iron overload and uremia absorbed even less, showing that the iron status of the patient influences absorption also in uremia.

Adult

Renal anaemia treatment with recombinant human erythropoietin increases cardiac output in patients with ischaemic heart disease.

An increase in blood pressure is common during treatment of renal anaemia with recombinant human erythropoietin (rhEPO). Concomitant findings of a decrease in cardiac output indicate that an increase in the peripheral flow resistance underlies the increase in blood pressure. The aim of this study was to elucidate the haemodynamic changes during rhEPO treatment in patients with ischaemic heart disease (IHD). Haemodynamic variables were assessed by impedance cardiography in 18 consecutive patients with renal anaemia before and after rhEPO treatment. IHD was found in eleven of these patients. The remaining seven served as controls. Before rhEPO treatment, the cardiac index was decreased in the group of patients with IHD, compared with controls and healthy subjects. Due to an increase in stroke index, the cardiac index increased during rhEPO treatment and reached values equal to those in the control group. The blood pressure increased and the increase in mean arterial pressure was correlated to the increase in cardiac index. Apparently the patients with IHD were unable to compensate for anaemia by increasing their cardiac index. Anaemia treatment increased cardiac index, which in turn caused an increase in blood pressure in these patients.

Adult

Decreased blood viscosity and serum levels of erythropoietin after anti-hypertensive treatment with amlodipine or metoprolol: results of a cross-over study.

The increased viscosity of blood of hypertensive patients can be assumed to be a risk factor for the development of cardiovascular diseases. The aim of the present study was to elucidate whether anti-hypertensive treatment has any impact on blood rheology. Twenty patients with previously untreated hypertension who consecutively attended our outpatient hypertension clinic were included in this prospective, open, cross-over study. The patients were randomly selected to treatment with amlodipine or metoprolol. The anti-hypertensive therapy was switched after 4 months. Haemorheological and haemodynamic variables were measured with rotational viscometry and impedance cardiography, respectively. Fifteen and 16 patients could be evaluated after amlodipine or metoprolol treatment respectively. The mean blood pressure (BP) decreased from 159 +/- 22/105 +/- 7 to 139 +/- 21/91 +/- 6 mm Hg on amlodipine and from 162 +/- 22/104 +/- 5 to 145 +/- 24/90 +/- 8 mm Hg on metoprolol therapy. After amlodipine treatment, the total peripheral resistance index decreased whereas metoprolol treatment was accompanied by a decrease in the cardiac index. Decreases in whole blood viscosity, haematocrit and serum erythropoietin were found after amlodipine as well as metoprolol treatment. After amlodipine the plasma viscosity decreased and the erythrocyte deformability increased in the majority of patients. Plasma fibrinogen decreased after metoprolol treatment. Despite the differences in haemodynamic mechanisms underlying the decrease in BP, amlodipine and metoprolol exert beneficial effects on blood viscosity. Haemodilution and a decrease in serum erythropoietin may be factors underlying this decrease in blood viscosity.

Adult

Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers.

The pharmacokinetics of iron were investigated after intravenous administration to 12 healthy volunteers of iron(III)-hydroxide sucrose complex (Venofer) as a single i.v. dose containing 100 mg Fe. The average predose concentration was 35.7 +/- 12.5 mumol/l. There was no statistically significant difference between the serum iron level before injection (0 h) and the level at 24 h after the injection. The compartment model used includes a Michaelis-Menten term and is in excellent agreement with the observed exchange of iron to transferrin and with the daily iron turnover by transferrin. The intravenously injected iron(III)-hydroxide sucrose complex led rapidly to high serum iron levels. Maximum measured levels averaged 538 mumol/l (30.0 mg/l) at 10 min after the injection. The terminal half-life of the injected iron was calculated to be 5.3 h. Mean total area under the curve (AUC) was 1491 mumol/l h, the mean residence time (MRT) was 5.5 h. The total body clearance was 20.5 ml/min. The volume of distribution of the central compartment (Vc) was 3.21, hence close to the volume of the serum; the volume of distribution at steady state (Vdss) was 7.31; and the volume of distribution during elimination (Vdarea) was 9.21. The calculated amount of iron transported by transferrin was 31.0 +/- 6.6 mg Fe/ 24h. In summary, the data show that the injected iron(III)-hydroxide sucrose complex is quickly cleared from the serum with a terminal half-life of approximately 5-6 h. Renal elimination of iron contributed very little to the overall elimination (in average < 5%). Renal elimination of sucrose averaged about 68 +/- 10% and 75 +/- 11% of the administered dose after 4 h and 24 h, respectively.

Adult

Treatment of erythropoietin-resistant anaemia with desferrioxamine in patients on haemofiltration.

We studied 5 anaemic patients with Hb 74 +/- 8 g/l on haemofiltration (HF) treatment. They were iron overloaded. Their serum ferritin was 2667 +/- 8 micrograms/l. All patients' haemoglobin (Hb) levels decreased after an initial response to recombinant human erythropoietin (r-HuEPO) treatment. An increase in r-HuEPO dose from 100 to 400 U/kg s.c. thrice weekly with addition of oral and intravenous iron treatment for 8 weeks arrested the fall in Hb level. However, there was no significant increase in Hb during these 8 weeks. Iron was withdrawn at week 24 and desferrioxamine (DFO) treatment (i.v. doses of 2 g thrice weekly) was added to r-HuEPO from week 26 to 36. Two weeks after DFO initiation the Hb level increased to 110 g/l. Thereafter the r-HuEPO doses were reduced from 400 to 25 U/kg within 3 months. The Hb remained stable at a level of 110 g/l during the study, i.e., 17 months after the DFO treatment. Serum ferritin levels fell at a more rapid pace during DFO treatment and continued to decrease after DFO cessation for the following 17 months. In accordance with previous observations we found a positive effect of DFO treatment on erythropoiesis in patients with anaemia and iron overload. DFO treatment should be considered in patients with iron overload and r-HuEPO-resistant anaemia.

Adult

Treatment of acute renal failure in intensive care patients by continuous arteriovenous hemofiltration (CAVH): two years' experience in two centres.

The study objective was to evaluate the outcome of continuous arteriovenous hemofiltration (CAVH) as a first choice treatment for acute renal failure (ARF) in critically ill intensive care patients in two centres with a long experience in the field of continuous renal replacement therapies. Sixty consecutive intensive-care ARF patients from Uppsala Centre and 71 consecutive ARF patients from Vicenza Centre were included during a period of two years. Their age range was 58 +/- 16 and 52 +/- 15 years in Uppsala and Vicenza, respectively. CAVH was performed in the postdilution form using different types of hemofilters. Three choices of vascular access were utilised in each centre, namely: the Buselmeier shunt, femoral vessel catheter and the Scribner shunt. The pre-treatment serum urea level (mean +/- SD) in the Uppsala patients (30 +/- 14 mmol/l) was significantly higher (p < 0.001) than that of the Vicenza patients (17 +/- 10 mmol/l). The Uppsala patients had a longer treatment duration than the Vicenza patients; 8 +/- 6 vs 5 +/- 5 days (p < 0.05) perhaps because they were much older than the Vicenza patients (p < 0.05) in addition to their multi-organ failure. However, the total outcome of CAVH in the two centers was not significantly different (52 and 58% patient's survival in Uppsala and Vicenza, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury

Treatment of renal anaemia with recombinant human erythropoietin results in decreased red cell uptake of 45Ca.

The ability of erythrocytes to undergo deformation may be of importance to erythrocyte survival and to blood flow resistance. In a previous study a decreased deformability was demonstrated in the erythrocytes of uraemic patients treated with recombinant human erythropoietin (rhEPO). Erythrocyte deformability is, at least partly, determined by the intracellular concentration of free calcium ions. Six patients with renal anaemia (initial haemoglobin 95 +/- 11 g/l) were treated with rhEPO. They were examined with regard to certain erythrocyte characteristics before treatment and after reaching a haemoglobin concentration exceeding 120 g/l. A decrease was noted upon treatment in erythrocyte deformability and uptake of 45Ca in vitro. The blood pressure tended to increase. The individual values of the decrease in 45Ca uptake and the increase in systolic blood pressure were positively correlated to each other (r = 0.87; p < 0.05). No correlation was found between changes in erythrocyte deformability and 45Ca uptake. The decrease in 45Ca uptake may be interpreted in two different ways. It could reflect a reduced membrane permeability to calcium ions, or, which is more probable, it could be the end result of an increase in the intracellular metabolic pool of free calcium ions caused by the rhEPO treatment. We, therefore, conclude that rhEPO treatment has certain effects on calcium homeostasis in erythrocytes which may be related to blood pressure regulation.

Adult

Continuous peritoneal dialysis in children with acute renal failure.

Continuous peritoneal dialysis (CPD) was performed in 13 children with acute renal failure (ARF) in our intensive care units (ICU). The median age was 6 months (range 3 days to 77 months). Sixty-nine percent of the patients (9/13) were below the age of 12 months. CPD was performed for a median duration of 5 days (range 1-35 days). In 62% of the patients (8/13), the cause of ARF was acute tubular necrosis (ATN) due to cardiac surgery. The outcome of CPD regarding total survival was 54% (7/13). A high mortality was registered (83% of the deaths [5/6]) within the first year of life, which suggests a worse prognosis if ARF occurs at this age. Half of the total deaths (3/6) were among the cardiac surgery patients. Peritoneal equilibration tests (PET) were performed utilizing measurement of urea and glucose transport through the peritoneal membrane at short intervals during a period of 45-60 min from the start of treatment. Short dwell times of 5-20 min were found to be sufficient for adequate uremic control until a satisfactory daily urine production was noted. CPD is a useful and simple treatment modality for ARF in critically ill ICU children. Equilibration tests are useful and should be considered for optimization of CPD treatment in critically ill children with ARF in order to achieve the goal of controlling uremia and fluid overload, and giving nutritional support.

Acute Kidney Injury

Reduced oxygen affinity contributes to improved oxygen releasing capacity during erythropoietin treatment of renal anaemia.

In addition to haemoglobin concentration, haemoglobin oxygen affinity plays a major role in the oxygen releasing capacity of the blood. In this study we have measured oxygen affinity as P50 and calculated the oxygen releasing capacity of blood from 10 haemodialysis patients treated with erythropoietin (rHuEpo). The patients were examined with different assays before start of treatment, after 11 weeks, and after 27 weeks. During the first phase of treatment the oxygen releasing capacity improved because of an increase in the haemoglobin concentration and P50. During the second phase there was a further significant increase in haemoglobin concentration, but due to a decrease in the P50 value the oxygen releasing capacity remained unchanged. Despite an unchanged oxygen releasing capacity and total blood volume, the antihypertensive treatment had to be increased during that phase of treatment. An increase in whole-blood viscosity may explain the increased need of antihypertensive drugs. The increase in P50 during the first phase of rHuEpo treatment can probably be explained by decreased mean age of the erythrocyte population and implies that the beneficial effect is greater than could be concluded from the increase in haemoglobin concentration.

2,3-Diphosphoglycerate

Blood viscosity and peripheral vascular resistance in patients with untreated essential hypertension.

OBJECTIVES: The viscosity of blood is increased in patients with essential hypertension. The aim of the present study was to investigate the importance of the different variables of blood rheology to total peripheral resistance, and to elucidate whether inappropriate regulation of the formation of erythropoietin could be important. DESIGN: Nineteen consecutive patients with untreated essential hypertension were examined and compared with a group of matched healthy volunteers. METHODS: The haemorheologic variables were assessed by rotational viscometry and the haemodynamic variables by bioimpedance cardiography. The serum concentrations of erythropoietin were determined by radioimmunoassay. RESULTS: The whole blood viscosity and peripheral resistance index were elevated in the hypertensive group. The two variables were positively correlated with each other (r = 0.68, P = 0.0015). The plasma viscosity and erythrocyte aggregation tendency were increased and the erythrocyte deformability, measured as fluidity, was decreased in the hypertensive patients. In the male subpopulation (n = 12) the aggregation tendency was positively, and the deformability negatively, correlated with body mass index. The serum concentrations of erythropoietin were equal in the two groups. CONCLUSIONS: The increased total peripheral resistance in patients with essential hypertension may in part be explained by an increased blood viscosity, but the possibility of an opposite cause-effect relationship must also be taken into consideration. The haemorheological abnormalities observed in the present patients cannot be explained by high serum levels of erythropoietin.

Adult

Pretransplantation immunoadsorption therapy in patients immunized with human lymphocyte antigen: effect of treatment and three years' clinical follow-up of grafts.

Sensitization against human lymphocyte antigen (HLA) occurs frequently in previously transplanted patients that lose a first cadaveric graft. To shorten their time on the waiting list and reduce the incidence of early rejection in such patients, we performed immunoadsorption therapy by a tryptophan column in 10 patients as an attempt to remove circulating antibodies prior to regrafting. Resynthesis of antibodies was suppressed with cyclophosphamide and prednisolone. Following the course of immunoadsorption therapy, the panel reactive antibodies (PRA) decreased by more than 50% from the pretreatment values. In the present study, 8 patients were transplanted with cadaveric renal grafts. At the time of follow-up, graft survival was 63% in these patients (2-36 months post-transplantation, mean 23 months). There was one incidence of acute rejection, one graft was lost within 48 h owing to renal artery thrombosis, and one was lost within 2 weeks as a result of stenosis. The serum creatinine levels were down to near normal during the first 3 weeks in hospital (p < 0.0001) and remained at this level during the period of follow-up. We conclude that immunoadsorption might be a beneficial pretransplantation therapy and an alternative to plasmapheresis in HLA-immunized patients awaiting kidney transplantation.

Adult

Complement activation during tryptophan immunoadsorption treatment.

Antibodies against human lymphocyte antigens (HLA) are frequently seen among patients undergoing repeated renal transplantations. Graft survival can be improved by eliminating these antibodies by plasmapheresis before transplantation. In this study, we have tried a new extracorporeal procedure to remove the anti-HLA antibodies. An immunoadsorption column (IM-TR) with a matrix of polyvinyl alcohol (PVA) gel conjugated with a hydrophobic amino acid tryptophan was utilized. Previous results have shown that repeated IM-TR treatments are at least equally effective as plasmapheresis in reducing levels of specific immunoglobulins in treated patients. In this study, 7 HLA-immunized patients were treated before renal transplantation. Each patient was subjected to a total of 12 treatment sessions divided into 3 sessions per week. After each treatment session, the reduction of the immunoglobulins was less than what has been reported for plasmapheresis. This suggests that mechanisms other than immunoglobulin depletion are involved in the reduction of the total immunoglobulin levels. The IM-TR treatment resulted in a strong complement activation triggered by the alternative pathway. Since the adsorbed plasma was returned to the patient, exceedingly high levels of the activation fragment C3d (C3dg) were found in plasma during and after the treatment. We conclude that the extensive generation of C3dg may be one of the factors that plays a role in the reduction of the antibody levels since the C3dg fragment has been shown to down-regulate the immune response.

Adult

Continuous arteriovenous hemodialysis: outcome in intensive care acute renal failure patients.

The clinical outcome of continuous arteriovenous hemodialysis (CAVHD), an alternative to continuous arteriovenous hemofiltration (CAVH) in our intensive care units (ICU) in Uppsala, was evaluated for 2 years. Forty-three patients were included. Pretreatment serum urea and creatinine levels (mean +/- SD) were 36 +/- 13 mmol/l and 420 +/- 147 mumol/l, and during treatment, steady-state levels were 25 +/- 10 mmol/l and 333 +/- 120 mumol/l, respectively (p < 0.0001). On top of acute renal failure (ARF), some patients had multiple organ failure that made it necessary to use mechanical respiration (63%), vasopressor drugs (74%) and aortic balloon pump therapy (5%). The outcome of this treatment was 60% when overall survival was considered. Higher dialysate flow rates (i.e., 25 ml/min) were applied in some patients in whom serum urea levels were persistently rising. The result of this was a notable decrease in the urea and creatinine serum levels. From the results of this 2-year experience, we have found CAVHD a promising alternative to CAVH that can be used as a treatment of choice for ARF in critically ill ICU patients.

Acute Kidney Injury

Parathyroid hormone and osteocalcin levels in plasma and ultrafiltrate during hemofiltration.

The effects of hemofiltration (HF) on serum levels of intact parathyroid hormone (PTH), as well as its mid-C regional and C-terminal fragments and bone Gla-protein (bone gamma-carboxyglutamic acid, osteocalcin), were investigated in 17 patients during one session of HF. During HF there was a significant decrease in the serum concentrations of both intact PTH (p < 0.01), mid-C regional PTH (p < 0.01) and C-terminal PTH (p < 0.01) as well as in the osteocalcin concentrations (p < 0.01). There was a significant increase in serum calcium (p < 0.05) during the procedure and this increase correlated with the reduction in PTH (r = 0.56, p < 0.05). Mid-C regional PTH and osteocalcin were found in the ultrafiltrate of all patients, while intact PTH was found in the ultrafiltrate of 8 of 17 patients and C-terminal PTH was detected only in the ultrafiltrate of one patient. The data demonstrate that the permeability of HF membranes is high enough to cause filtration of both intact PTH, PTH fragments and osteocalcin. An inhibited secretion of PTH probably played a major part in reducing intact PTH in serum during HF.

Adult

Continuous arteriovenous haemodialysis and haemofiltration in intensive care acute renal failure patients.

CAVHD and CAVH were compared regarding uraemic control in 13 critically ill intensive care patients with acute renal failure (ARF). Patients' mean age was 60 years. Pretreatment blood urea range was 17-56 mmol/l (33-56 mmol/l in 70% of the patients). All patients received vasopressor drugs, and 92% were on artificial mechanical respiration. From the results of this study both modalities gave adequate uraemic control. There was a notable decrease in the urea and creatinine levels with CAVHD more than with CAVH. There was no statistically significant difference between the two modalities in the urea clearance. However, a significant difference (P < 0.05) in creatinine was obtained with CAVHD. Our results suggest that CAVHD is a useful alternative to CAVH in ARF especially when the blood urea level is > 30 mmol/l. However, a higher dialysate flow rate (e.g. 25 ml/min) should be used if the urea level is more than 40 mmol/l. CAVH should be reserved for ARF patients in whom fluid overload is a major problem.

Acute Kidney Injury

Impaired erythrocyte fluidity during treatment of renal anaemia with erythropoietin.

Seventeen haemodialysis patients with renal anaemia were treated with recombinant human erythropoietin (rhEPO) and observed for 30 weeks. The viscosity of whole blood and plasma, the erythrocyte aggregation tendency, and the erythrocyte deformability, measured as fluidity, were analysed every second week. All patients responded with increasing haematocrit and whole-blood viscosity. The plasma viscosity and the erythrocyte aggregation tendency were already increased before the start of treatment, and remained unchanged during treatment. The basal erythrocyte fluidity tended to be impaired, although not significantly so. During treatment, significant impairment of fluidity was observed at the beginning of the treatment period. After 24 weeks the fluidity started to increase, and it later reached values observed before the start of treatment. Hence, the quality of the erythrocytes formed during the corrective phase of rhEPO treatment differs in some respects from that of cells formed at a normal production rate. The impaired fluidity might have important implications for the flow resistance in small vessels, and contribute to the development or aggravation of hypertension that is often seen during rhEPO treatment.

Anemia

Artificial renal and liver support in a severe hepatorenal syndrome of childhood.

This case report describes a special management approach in a child aged 4.5 years with a severe form of hepatorenal syndrome in which the final diagnosis was familial hemophagocytic lymphohistiocytosis (FHL). The patient presented with grade IV hepatic coma and acute renal failure (ARF). While the diagnosis was difficult at the time of admission, as well as during acute treatment, artificial liver support was established for elimination of bilirubin and other metabolic by-products by using charcoal column plasma perfusion (CCPP) and bilirubin-adsorbing resin column plasma perfusion (BRCPP). Serum levels of bilirubin showed a notable decrease after each of the four treatment sessions. Additional artificial renal function replacement by continuous arteriovenous hemofiltration and hemodialysis (CAVH, CAVHD, respectively) had a marked lowering effect on urea and creatinine serum concentrations. Both artificial liver and renal support contributed to the general clinical improvement and survival of the patient. Further experience in these therapies will be needed to establish better prognosis in such fatal or acute similar conditions.

Child, Preschool