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Biomedical subjects

B Wikström

Publications and source records attributed to B Wikström.

At least 55 records · Page 3Linked to original sources

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↗

Plasmapheresis in the treatment of primary septic shock in humans.

14 patients (mean age 25.5 yrs) with life-threatening primary septic shock were eligible for treatment with acute plasmapheresis in a prospective study. They had a short history of sepsis and had no severe underlying disease. 10/14 patients had systemic meningococcal disease. All patients were severely ill with a mean APACHE II score of 25.0. 12/14 patients were treated with plasmapheresis exchanging 1 plasma volume within hours of admission. 11/14 patients survived without major sequelae and 3 (21%) died of irreversible septic shock. This mortality is lower than that predicted from the APACHE II scores (55.2%). A subgroup of plasmapheresis-treated patients with septic shock and extensive petechiae were compared to a historical control group. The mortality in the treatment group was 1/7 (14%) versus 8/21 (38%) in the control group. We conclude that acute plasmapheresis may be a therapeutic option in the early stages of severe primary non-surgical septic shock.

Adolescent↗

Is repeated mismatching at regrafting deleterious?

We reviewed our clinical experience of allowing kidney regrafting with a repeated HLA mismatch. We also permitted a weakly positive B-cell cross-match. All patients who received a second or subsequent renal graft (n = 92) between January 1985 and June 1990 were analysed for graft survival. The overall 1-year graft survival was 70%. A repeated mismatch occurred in 29 of the patients at at least one HLA locus and their 1-year graft survival was 66%. The balance of the regrafts (63) were performed without a repeated mismatch, and their 1-year graft survival was 70%. Even a weakly positive B-cell cross-match was deleterious; when a grafting with a repeated mismatch was performed only one out of five grafts survived. Our results indicate that retransplantation of renal grafts with a repeated mismatch in the HLA A or B locus can be performed without a negative influence on transplant outcome provided that both the T- and B-cell cross-matches are negative.

Graft Survival↗

Rejection associated with early appearance of donor-reactive antibodies after kidney transplantation treated with plasmapheresis and administration of 15-deoxyspergualin. A report of two cases.

In two kidney transplant patients, one of whom had panel-reactive antibodies (PRA) before transplantation, a pretransplant negative donor-recipient crossmatch became positive within the 1st week after transplantation. Simultaneously, good graft function deteriorated to a state of anuria. One patient graft biopsy showed a vascular rejection, whilst the other patient biopsy was unrevealing. Both patients were treated with plasmapheresis and a new immunosuppressive drug, 15-deoxyspergualin (DSG). Plasmapheresis was performed for 6 and 9 days, respectively, and DSG was given for 5 days in a dosage of 6 mg/kg body weight per day. One of the patients received methylprednisolone i.v. in addition. During treatment the cross-match became negative and has since remained that way. In both patients the graft function was restored. No adverse effects were seen from the treatment, except for a slight leukocytopenia and thrombocytopenia.

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↗

DNA content in primary tumours and lymph node metastases in colorectal adenocarcinoma.

In 18 consecutive patients operated on for colorectal carcinoma of Dukes' stage C, the DNA patterns were determined in multiple samples of the primary tumours and in all detected lymph node metastases. Single-cell microspectrophotometry on Feulgen-stained smears of fine-needle aspirates was used. When the most aggressive DNA pattern was considered representative, 12 primary tumours (67%) were designated as aneuploid. The frequency of aneuploidy among the metastases was almost the same (63%). In 15 cases (83%) the DNA patterns displayed by the metastatic lymph nodes were also found in the corresponding primary tumour, while in the remaining three cases (17%) the DNA pattern in the lymph node metastases was not seen in any of the multiple samples from the primary tumour. The observed tumour DNA heterogeneity may reflect either the multicellular origin of the tumour cells or the continuous evolution and progression of a neoplasm of unicellular origin, and may partly explain the dissimilarities between the DNA patterns of the primary tumour and the lymph node metastases. Biopsy samples from a number of metastatic lymph nodes are therefore required to ensure representativeness and to permit an adequate analysis of the prognostic role of the DNA ploidy status in lymph node metastases from colorectal cancer.

Adenocarcinoma↗

Serum erythropoietin levels in the immediate kidney-posttransplant period.

Following successful kidney transplantation, renal anemia is gradually corrected during the first 3-4 months. Serum erythropoietin (EPO) levels are increased after the first postoperative day following grafting. In this study, the serum EPO levels in the early posttransplant phase were investigated in 8 living-donor and 7 cadaveric-kidney transplant recipients with special emphasis on the first 24 h. Despite a considerable difference in cold ischemic time of the graft in the two groups the increase in serum EPO levels was noticed at about the same time (8 h) in both groups and the first peak of serum EPO, which was observed after 24 h, reached the same level in both groups. After 9-11 days, serum EPO reached levels which usually are observed during the first months following transplantation. The EPO response seems to be blunted in relation to the degree of anemia in the early posttransplant phase.

Adult↗

Treatment of pruritus in cholestatic jaundice by bilirubin- and bile acid-adsorbing resin column plasma perfusion.

The efficacy of plasma perfusion through a new anionic resin, BR-350, for palliation of intractable pruritus secondary to intrahepatic cholestasis was studied in four patients. The treatment was given in a daily 2-h session on 3 consecutive days and was followed by repeated treatment periods each 3rd to 4th week. The patients experienced symptomatic improvement during the first treatment period, and the treatment was well tolerated. Adsorption of bile acids across the filter was efficient and resulted in a bile acid concentration gradient pre- to post-resin of 92%. Thus plasma perfusion through the ion resin BR-350 is an effective and safe treatment for symptomatic relief of intractable pruritus in cholestatic liver disease and may reduce hospitalization time and increase the quality of life.

Adult↗

Colorectal carcinoma. DNA ploidy pattern and prognosis with reference to tumor DNA heterogeneity.

Nuclear DNA content was measured in 72 colorectal carcinomas using single-cell microspectrophotometry on Feulgen-stained smears. Four samples were analyzed from each tumor. Patients were followed for 41-65 months (average, 53). DNA heterogeneity (both aneuploid and nonaneuploid patterns) was present in 44% of the cases. Sixty-eight percent of the tumors showed an aneuploid DNA pattern in at least one of the samples. Patients with nonaneuploid tumors tended to have a survival advantage over patients with homogeneously aneuploid tumors and demonstrated a significantly longer disease-free survival. The DNA ploidy pattern is of potential value in conjunction with histopathologic prognostic parameters in colorectal carcinoma. Since colorectal tumors exhibit pronounced DNA heterogeneity, multiple samples are required from each tumor to permit a proper evaluation of its DNA pattern. The DNA heterogeneity may represent tumor progression and can partly explain the conflicting results reported concerning DNA pattern and prognosis in colorectal carcinoma.

Adult↗

Prognostic importance of the DNA ploidy pattern in malignant mesothelioma of the pleura.

Malignant mesotheliomas often raise a difficult diagnostic problem: once the diagnosis is made, the possibilities of predicting the biologic activity and prognosis of the tumor are limited. DNA ploidy patterns have been used as a prognostic instrument for other tumors, and this pattern was therefore studied in 37 cases of verified mesothelioma. The measurements were made on Feulgen-stained smears from pleural effusions using a Leica Miamed computer microscope. When a highly aneuploid tumor was defined as a condition with greater than 5% of the cells within defined intervals outside the ranges of the stem-line and the peaks representing polyploidization thereof, a near-diploid/polyploid pattern was obtained in 41% of the cases, while the remaining 59% were classified as highly aneuploid. The prognosis was significantly better among the near-diploid/polyploid cases. This estimate of the outcome could not be improved by using alternative algorithms for high-grade aneuploidy.

Aneuploidy↗