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Biomedical subjects

K Rosenlöf

Publications and source records attributed to K Rosenlöf.

At least 19 recordsLinked to original sources
PubMed2002

Factors associated with progression of IgA nephropathy are related to renal function--a model for estimating risk of progression in mild disease.

BACKGROUND: A number of factors are linked to the outcome of IgA nephropathy (IgAN). However, it has been difficult to compare results of studies since patient populations have varied greatly. There were 3 aims in the study reported here, namely to compare factors associated with renal outcome in IgAN patients with different levels of renal function on diagnosis; to determine factors which were independently associated with progression of renal disease in initially mild IgAN; and to create a model for the estimation of the risk of progression in individual IgAN patients with normal renal function on diagnosis. METHODS: Two hundred and fifty-nine IgAN patients who had been followed on average for 9.1 (SD 4.5) after diagnosis were divided into 2 groups on the basis of renal function on diagnosis. In group 1 (98 patients), Ccr (creatinine clearance, estimated by the Cockcroft-Gault formula) was < 85 ml/min, in group 2 (161 patients) > or = 85 ml/min. Univariate analyses were used to find significant differences between progressors and non-progressors in both groups. Logistic regression analysis was used to determine factors independently associated with progression in group 2. RESULTS: Several factors were found to be associated with outcome in both groups, such as hypertension, level of Ccr, serum cholesterol, proteinuria, and also histopathological changes. Factors associated with progression in patients with initially decreased renal function (group 1), were predictable, such as male sex, absence of episodes of macroscopic hematuria, serum urate level and degree of tubular atrophy. Surprisingly, in patients with initially normal renal function (group 2), numbers of urinary erythrocytes were associated with outcome. The factors independently associated with progression in this group were number of urinary erythrocytes, existence of hypertension and in histopathology arteriolosclerosis and the level of glomerular score. A model for estimating risk of progression on the basis of various combinations of factors found to be independently associated with outcome is presented. CONCLUSIONS: We concluded that association between variable and outcome in IgAN depends partly on renal function at the time of assessment of the factor. Since there are factors which are independently associated with the outcome of early and apparently mild disease, early diagnosis of IgAN is desirable: outcome in mild IgAN can be predicted reliably on the basis of factors found to be independently associated with outcome.

Adrenal Cortex Hormones↗
PubMed2000

Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration.

BACKGROUND: I.v. iron is commonly administered to haemodialysis patients suffering from anaemia to improve their response to erythropoietin therapy. It has been unclear whether routinely used doses of i.v. iron preparations could result in iron release into plasma in amounts exceeding the iron binding capacity of transferrin. Here, we have studied the effect of 100 mg of iron saccharate given as an i.v. injection on transferrin saturation and the appearance of potentially harmful catalytically active iron. METHODS: We followed serum iron, transferrin and transferrin-saturation before and 5-210 min after administration of iron saccharate in 12 patients on chronic haemodialysis due to end-stage renal disease. We measured catalytically active iron by the bleomycin-detectable iron (BDI) assay and transferrin iron forms by urea gel electrophoresis, and studied iron-dependent growth of Staphylococcus epidermidis inoculated into the serum samples in vitro. RESULTS: The iron saccharate injection resulted in full transferrin saturation and appearance of BDI in the serum in seven out of the 12 patients. BDI appeared more often in patients with a low serum transferrin concentration, but it was not possible to identify patients at risk based on serum transferrin or ferritin level before i.v. iron. The average transferrin saturation and BDI level increased until the end of the follow-up time of 3.5 h. The appearance of BDI resulted in loss of the ability of patient serum to resist the growth of S. epidermidis, which was restored by adding iron-free apotransferrin to the serum. Iron saccharate, added to serum in vitro, released only little iron and promoted only slow bacterial growth, but caused falsely high transferrin saturation by one routinely used serum iron assay. CONCLUSIONS: The results indicate that 100 mg of iron saccharate often leads to transferrin oversaturation and the presence of catalytically active iron within 3.5 h after i.v. injection. As catalytically active iron is potentially toxic and may promote bacterial growth, it may be recommendable to use dosage regimens for i.v. iron that would not cause transferrin oversaturation.

Adult↗
PubMed1999

Ocular findings in 34 patients with Alport syndrome: correlation of the findings to mutations in COL4A5 gene.

PURPOSE: To describe the incidence and type of ocular findings of 34 patients with Alport syndrome and to analyze the association of gene defect in COL4A5 gene to ocular abnormalities found. METHODS: A nationwide search of Alport syndrome patients was performed in Finland, and patients were invited to take part in a thorough ophthalmologic investigation. RESULTS: A total of 34 Alport syndrome patients from 14 different pedigrees were examined, and ocular abnormalities were found in 32% of them. The visual acuities were normal except in 4 of the 34 patients. Six individuals had retinal flecks and 4 men had anterior lenticonus. In 57% of the pedigrees the defect in COL4A5 gene was known. CONCLUSION: Ocular abnormalities were rare in childhood and increased with age. There was no correlation between the type of mutation and the type of ocular changes. In addition, the penetrance of the ocular findings varied considerably within most families.

Adolescent↗
PubMed1995

Iron availability is transiently improved by intravenous iron medication in patients on chronic hemodialysis.

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Effect of exogenous erythropoietin on haem synthesis in anaemic patients with rheumatoid arthritis.

The effect of recombinant human erythropoietin (rHuEPO) on haem biosynthesis in peripheral red blood cells was evaluated in 12 patients with RA and anaemia (mean haemoglobin concentration 102 g/l, range 90-109 g/l). Before treatment, the serum concentrations of erythropoietin (EPO) were low (mean 13 pmol/l, range 5-32 pmol/l), the activities of haem-synthesizing enzymes within the reference intervals and the erythrocyte protoporphyrin (E-PROTO) concentrations clearly higher than normal. Nine patients responded with an increase in the haemoglobin level of 15 g/l or more. rHuEPO induced a rise in the mean haem synthase (HAEM-S) activity from a baseline of 12.1 to a maximum of 26.8 pmol/h per 10(6) reticulocytes after 20 weeks of treatment (P < 0.002). The mean E-PROTO concentration also rose and reached its maximum at 8 weeks of treatment. We conclude that correction of anaemia in patients with RA using rHuEPO is associated with an activation of HAEM-S, commonly regarded as the rate-limiting enzyme of haem synthesis in erythroid cells. Functional iron deficiency probably explains the simultaneous rise in E-PROTO concentration.

Adult↗
PubMed1993

Successful treatment of the anemia of rheumatoid arthritis with subcutaneously administered recombinant human erythropoietin. Slower response in patients with more severe inflammation.

We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.

Adult↗
PubMed1990

Raised plasma endothelin-I concentration following cold pressor test.

Plasma concentration of immunoreactive endothelin-1 was measured by radioimmunoassay in 6 healthy subjects before and following cold pressor test by immersion of one fore-arm into ice-water. Mean (SEM) plasma endothelin-1 concentration rose from 1.2 (0.7) to peak value 8.4 (2.3) pg/ml in venous plasma from the immersed hand, and, reaching peak 2 minutes later, from 1.4 (0.5) to 4.6 (2.3) pg/ml in venous plasma from the contralateral hand. In 66 healthy control subjects, venous plasma concentration of endothelin-1 was 2.9 +/- 1.2 pg/ml (mean +/- SD). Exposure to cold is associated with raised blood levels of endothelin-1, which points to a relation between endothelin-1 and vasoconstriction associated with low temperature.

Cold Temperature↗
PubMed1990

Erythropoietin, aluminium, and anaemia in patients on haemodialysis.

Effects of erythropoietin treatment on haem synthesis in peripheral blood were evaluated in 11 patients on haemodialysis. After 2 weeks of erythropoietin, mean (SEM) uroporphyrinogen-l synthase activity increased significantly from 88 (10) to 116 (9) pmol/h per mg protein. Haem synthase activity, thought to be the rate-limiting step in erythroid haem synthesis, also showed a significant increase from 4.5 (0.8) to 8.4 (1.8) pmol/h per 10(6) reticulocytes. 4 patients, who showed only a partial response to erythropoietin, had significantly higher serum aluminium concentrations than the 7 who responded fully (225 [44] vs 55 [23] micrograms/l); erythrocyte protoporphyrin concentrations in partial responders were also much higher than in responders (973 [120] vs 388 [29] nmol/l). Aluminium intoxication may cause resistance to erythropoietin by interference with haem synthesis, with accumulation of protoporphyrin.

Adult↗
PubMed1989

Renin substrate in human amniotic fluid.

Purified human amniotic fluid renin substrate (RS) was compared to purified plasma RS. RS in plasma and amniotic fluid were similar in molecular weight, isoelectric point and immunological properties. Immunoreactivity of radio-iodinated amniotic fluid RS was lower than that of plasma RS. Measured by direct radioimmunoassay, RS-levels were only 10-22% of those obtained with indirect assay in 22 amniotic fluid samples. This difference suggests that amniotic fluid RS is less immunoreactive than plasma RS, possibly due to biochemical alteration or complex formation. No such difference in immunoreactivity was noticed in RS of decidual and placental cytosolic fraction.

Amniotic Fluid↗
PubMed1989

High serum erythropoietin levels are normalized during treatment of congestive heart failure with enalapril.

Eighteen patients with dilated cardiomyopathy (three female, mean age 57 years), were treated for 48 weeks with enalapril added to digoxin and diuretic therapy for congestive heart failure of New York Heart Association (NYHA) functional class II (three patients). III (eight patients) and IV (seven patients), respectively. Serum levels of erythropoietin (EPO) were raised at the start (37 +/- 12.8 pmol 1(-1); mean +/- SD) and were normalized during enalapril treatment (17.5 +/- 9.9 pmol 1(-1) at 48 weeks; P less than 0.001). Serum EPO correlated at the start with NYHA functional class (r = 0.68; P less than 0.05). Normalization of elevated serum EPO concentrations during treatment with enalapril paralleled clinical and haemodynamic improvement, and probably reflected relief from renal hypoxia.

Adult↗
PubMed1989

Beneficial effects of erythropoietin on haematological parameters, aerobic capacity, and body fluid composition in patients on haemodialysis.

Eleven patients on haemodialysis were treated with erythropoietin (EPO), 50-200 U kg-1 once to three times a week, for up to 1 year. After outset of EPO all patients became transfusion-independent. Four patients did not reach the target haemoglobin (Hb) level 100 g l-1 in 5 months. These patients had higher serum concentrations of aluminium (225 +/- 87 micrograms l-1, mean +/- SD) than the responding patients (55 +/- 56 micrograms l-1). Addition of desferrioxamine to treatment with EPO resulted in a rapid rise in Hb values in these patients. Thus, aluminium may inhibit EPO responsiveness. All patients were iron overloaded. Serum ferritin levels declined in all but one patient with secondary haemochromatosis. In exercise tests the aerobic capacity and oxygen uptake increased during EPO therapy. Peak oxygen consumption (Vo2 peak), oxygen pulse, oxygen uptake at anaerobic threshold (AT) and total work output (W max) increased 19%, 36%, 26% and 24%, respectively. Lean body mass (LBM) increased by 8%. Taken together, all clinical EPO effects measured appeared clinically favourable.

Adult↗
PubMed1988

Direct radio-immunoassay of renin substrate: effect of converting enzyme inhibition.

A direct radio-immunoassay (RIA) for renin substrate (RS) was compared to the enzymatic (indirect) assay, which measures intact RS only, whereas a direct assay measures both intact RS and des-angiotensin I-RS. In normal subjects, a significant, albeit weak, correlation between the methods was noticed. In hypertensive patients with different levels of plasma renin activity (PRA), RS concentration measured by both assays increased with increasing PRA, and for patients with PRA greater than 10 micrograms AI/l/h, the direct assay gave significantly higher RS values (55%), compared to the enzymatic assay. This indicates consumption of RS by increasing plasma renin and increasing production rate of RS with increasing PRA, of potential importance in the pathogenesis of hypertension. In 11 patients with renovascular hypertension, treatment with the angiotensin-converting enzyme (ACE) inhibitor, lisinopril, resulted in a significant increase in PRA, accompanied by a decrease in RS measured by the enzymatic assay. Lowered plasma RS concentration, by reduction of the velocity of the renin-RS reaction, will distort and invalidate results of PRA determination during treatment with ACE inhibitory compounds. No change in RS measured by direct RIA was noticed, however. The results suggest that ACE inhibition may not have an effect upon RS production and that its effect on plasma RS is limited to a reduction of intact RS measured by the enzymatic assay.

Angiotensin I↗
PubMed1987

Erythropoietin in capillary hemangioblastoma. An immunohistochemical study.

Capillary hemangioblastoma is a tumor known to be associated with secondary polycythemia. Therefore, specimens from ten hemangioblastomas were studied by immunohistochemistry for the presence of erythropoietin, renin substrate, and for various endothelial, histiocytic and glial markers. In all tumors scattered cells among the stromal cells showed a positive-staining reaction with both anti-erythropoietin and anti-renin substrate. The same cells also stained positively for alpha-1-anti-trypsin. It is concluded that, in addition to the capillary endothelial cells, pericytes and stromal cells, capillary hemangioblastomas harbor cells containing and perhaps producing renin substrate and/or erythropoietin or a substance with similar antigenic determinants.

Angiotensinogen↗
PubMed1987

Receptors for recombinant erythropoietin in human bone marrow cells.

Human recombinant erythropoietin, labelled with 125I, was saturably bound to high affinity receptors, ka = 1.5 X 10(9) M-1, of bone marrow cells from 10 patients with various haematological disorders. Binding of labelled erythropoietin was specific, with less than 0.01% cross-reactivities of TSH, hCG and renin substrate (angiotensinogen). Binding capacity averaged 3 X 10(-14) moles/10(6) cells. Binding was maximal within 30 min at 37 degrees C. Low binding, less than 15% of that to bone marrow cells, was found to peripheral blood buffy coat, while erythrocytes and BALL cells did not bind labelled erythropoietin. Autoradiography showed binding of label confined to 4-5% of the bone marrow cells.

Adult↗
PubMed1987

Erythropoietin binding sites in human foetal tissues.

Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has an equilibrium association constant of 4.1-6.2 X 10(9) l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 degrees C in 1 h and at 4 degrees C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7 SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41,000 and 86,000 dalton, respectively.

Humans↗