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Biomedical subjects

B Fellström

Publications and source records attributed to B Fellström.

At least 73 records · Page 4Linked to original sources
PubMed1992

Platelet-derived endothelial cell growth factor. Pharmacokinetics, organ distribution and degradation after intravenous administration in rats.

Platelet-derived endothelial cell growth factor (PD-ECGF) stimulates chemotaxis of endothelial cells in vitro and has angiogenic activity in vivo. Recently PD-ECGF was shown to have thymidine phosphorylase activity. In order to study possible therapeutic applications of PD-ECGF we used a rat model to determine its pharmacokinetics and tissue distribution after intravenous injection. [125I]PD-ECGF disappeared from the plasma in a biphasic manner, with estimated distribution and elimination half-lives of 17 min and 7 h, respectively. PD-ECGF was metabolized in the liver, excreted via the bile, and not accumulated in any organ system. The stability and long half-life in the circulation, together with the specificity for endothelial cells, suggest that PD-ECGF may be useful as a therapeutic agent to stimulate re-endothelialization in vivo, or, in view of its thymidine phosphorylase activity, in chemotherapy, by decreasing the pool of available thymidine.

Animals↗
PubMed1992

Parathyroid function in relation to intestinal function and renal calcium reabsorption in patients with nephrolithiasis.

Recently a technique to measure intact parathyroid hormone (PTH), i.e. the biologically active hormone, has been available. The aim of the present study was to apply this method to evaluate the parathyroid function in a material of recurrent renal stone formers (n = 324). Intact PTH was found to be inversely related to both urinary calcium (r = -0.15; p less than 0.01) and serum calcium (p less than 0.02) indicating that in the majority of the patients with hypercalciuria this was accounted for by intestinal hyperabsorption and not by high serum PTH. Hyperabsorption was also the likely explanation for the finding of a positive relationship between the urinary calcium and oxalate excretions (r = 0.22; p less than 0.001) in medication-free patients without intestinal disorders, i.e. without enteric hyperoxaluria. Altogether 25 patients (7%) had elevated serum PTH concentrations. They were followed up with fasting serum and urinary electrolytes and an oral calcium loading test (1 g of calcium) in order to evaluate the importance of renal and intestinal factors responsible for the elevated serum PTH concentrations. The investigation was carried out on a free diet and on low and high calcium intakes, respectively. The incidence of intestinal malfunction, which was sometimes present without clinical symptoms, was found to be approximately the same as that of impaired renal conservation of calcium. The findings in the patients with intestinal malfunction were a reduced intestinal absorption of calcium and an enhanced tubular reabsorption of calcium (TRCa), with greater reabsorption of calcium for higher PTH values. In patients with impaired renal conservation of calcium despite the raised PTH there was no correlation between PTH and TRCa. When PTH was suppressed during the oral calcium load the TRCa was found to be inappropriately low and the renal defect obvious. The intestinal calcium absorption was secondarily increased to compensate for the renal losses.

Adolescent↗
PubMed1992

Safety aspects and diagnostic findings of serial renal allograft biopsies, obtained by an automatic technique with a midsize needle.

Percutaneous biopsy is an important diagnostic procedure in evaluating the renal allograft with compromised function. Graft losses and haemorrhagic complication are major risks. To minimize these problems we used a midsize TruCut needle, controlled by an automatic firing device (Biopty-Cut), fixed to an ultrasound guidance system. Core biopsies of 1.2 x 20 mm were obtained from 1,421 kidney grafts. On 5 occasions a haemorrhagic complication that required prolonged hospitalization or intervention occurred. No grafts were lost as a consequence of the biopsy procedure. Typical histological morphological parameters found during allograft rejection has earlier been established. Using a protocol with 27 histological parameters this study confirms that recognized criteria for rejection can be relied upon even with this smaller needle. The results showed that the degree of oedema and lymphocytic infiltration of the interstitium and in the arterial wall discriminated best between rejecting grafts and non-rejection grafts.

Adult↗
PubMed1991

Calcium acetate used as phosphate binding treatment in uremic hyperphosphatemia.

Due to toxic side effects of aluminum-containing agents for treatment of uremic hypophosphatemia, much interest has been focused upon aluminum-free phosphate binder alternatives. From results of experimental studies with calcium acetate, this salt has been suggested as a possible effective and safe phosphate binder. In the present study, calcium acetate was used during a mean of 11 months for serum phosphate control in 30 uremic patients previously treated with aluminum and/or calcium carbonate. Satisfactory control of serum phosphate was achieved during the study (mean phosphate concentration +/- SE: 2.15 +/- 0.12 mmol/l compared to prestudy 2.23 +/- 0.19 mmol/l). Mean serum concentrations of calcium, alkaline phosphatase and parathyroid hormone did not change significantly during the study. Serum aluminum decreased significantly (p less than 0.01). Moderate hypercalcemia was observed in 6 patients. Calcium acetate treatment was withdrawn in 2 patients due to gastrointestinal discomfort. It is concluded that calcium acetate seems to be an effective phosphate binder alternative with relatively few side effects.

Acetates↗
PubMed1990

Primary haemostasis, plasmatic coagulation and fibrinolysis in renal transplantation.

The disturbed coagulation state seen in patients with uremia has been suggested to contribute to thrombotic events in kidney grafts following transplantation. Primary haemostasis, plasmatic coagulation and fibrinolysis were investigated in eight patients before and during four weeks after kidney transplantation. In spite of an improved renal function there was postoperatively still a depressed platelet aggregation and the prostacyclin concentrations in plasma were low. The plasma coagulation seemed to be activated according to short activated partial thromboplastin time, high levels of FVIII:C and prothrombin complex. The fibrinolysis was increased and the PAI-1 levels were decreased. It is concluded that the overall haemostatic balance is characterized by a high degree of activation in uremic patients and that this activation persisted four weeks after transplantation.

Blood Coagulation↗
PubMed1990

The localization of hyaluronan in normal and rejected human kidneys.

Hyaluronan (HYA) is a large glycosaminoglycan with a high capacity to immobilize water. Increased levels of HYA have previously been observed in plasma as well as in affected tissues in various inflammatory conditions. The morphological localization of HYA has, however, not been described in normal or rejected human kidneys. Using a recently developed method for localization of HYA in tissue sections by means of a biotin-labeled hyaluronan binding protein used as a probe, we have now investigated the distribution of HYA in normal and irreversibly rejected human kidneys. In the normal kidney HYA was essentially confined to the medulla. In the rejected kidneys increased amounts of HYA were observed primarily in the cortex and in sclerotic vessels. Incubating tissue sections with hyaluronidase abolished the staining for HYA, showing the specificity of the staining procedure. The increased amounts of HYA of the rejected kidney may play a role in local edema formation, and thereby alter graft function.

Connective Tissue↗
PubMed1990

Rapidly proliferative arteriopathy in cyclosporin-induced permanently surviving rat cardiac allografts simulating chronic vascular rejection.

In an attempt to create a model of chronic rejection in rat, cardiac allograft transplantation was performed of hearts from PVG rats to DA rats treated with cyclosporin, 20 mg/kg body weight per day for 14 days and thereafter no immunosuppressive therapy. Experiments were made in 83 rats fed on a normal diet and in 24 rats fed on a diet containing an additional 0.5% cholesterol. Rats on the normal diet showed moderate signs of acute rejection during the first 20-40 days and grafts were lost in acute rejection during this period of time. However, after 2-3 months no signs of acute rejection were present. On the contrary, excessive proliferative changes of the vascular intima and endocardium along with fibrosis and fibrin deposition appeared and was progressive until 6 months post-transplantation. These morphological changes are similar to those found in chronically rejected organs like heart and kidney. In rats fed on a cholesterol diet after cessation of cyclosporin, development of the vascular and endocardial proliferative changes appeared three to four times as fast and were on average fully developed within 4-6 weeks post cessation of cyclosporin treatment. The recipients' own hearts showed no signs of vascular or endocardial damage. It is thus concluded that two models of vascular and endocardial proliferative changes in cardiac allografts have been developed showing distinct similarities to chronic vascular rejections seen in the clinical transplantation and with apparent similarities to severe arteriosclerosis. The models could be useful in the investigation of pathogenesis and therapeutical means for preventing chronic vascular damage in transplanted organs and arteriosclerosis.

Animals↗
PubMed1990

Hyperoxaluria or hypercalciuria in nephrolithiasis: the importance of renal tubular functions.

The role of the kidney in states of hyperoxaluria and hypercalciuria was investigated in seven patients with hyperoxaluria after jejunoileal bypass (JIB) and six patients with idiopathic hypercalciuria (IHC). Eight apparently healthy persons formed a control group. Besides hyperoxaluria, the patients with JIB displayed an elevated plasma concentration of oxalate and the oxalate clearance was increased and higher than creatinine clearance, indicating a net tubular secretion of oxalate. The JIB patients had lower 24-h urinary excretions of calcium, phosphate, magnesium and citrate and higher serum parathyroid hormone (PTH) than controls, indicating increased secretion of PTH to compensate for calcium malabsorption. IHC patients exhibited increased fasting urinary calcium even though their serum values were similar to those in the controls. These results indicate a reduced tubular calcium reabsorption, which was most pronounced in patients with highest PTH values. We conclude that hyperoxaluria in JIB patients is associated both with intestinal hyperabsorption and with enhanced tubular secretion of oxalate, and that in some patients with IHC hypercalciuria is due to reduced tubular reabsorption of calcium.

Adult↗
PubMed1990

Characteristics of mouse to rat xenograft heart transplantation.

A simple technique for grafting a mouse heart heterotopically to rat neck vessels in experimental xenotransplantation is described. In this series, graft survival was tested with the following modes of immunomodulation: ciclosporin (Cy), athymic and nude rats, splenectomy, total lymphoid irradiation (TLI), 15-deoxyspergualin in two different doses and various combinations of these. The mean graft survival time, with Cy or athymic and nude rats as recipients, was 3 days as also seen in animals without treatment. With either irradiation, splenectomy or 15-deoxyspergualin, 10 mg/kg daily, the graft survival time was prolonged to 7.8, 4.7 and 6.8 days, respectively. In combination, TLI + splenectomy gave a graft survival of 9.7 days and Cy + splenectomy 7.2 days. With 15-deoxyspergualin at 10 mg/kg/day plus splenectomy, done 1 week prior to transplantation, graft survival was extended to 17.8 days.

Animals↗
PubMed1990

Effects on serum parathyroid hormone of intravenous treatment with alphacalcidol in patients on chronic hemodialysis.

Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidol, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1 and 4 micrograms/dialysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland's sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidol is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.

Aluminum↗
PubMed1989

Treatment of enteric hyperoxaluria with calcium-containing organic marine hydrocolloid.

An organic marine hydrocolloid (OMH) charged with calcium ('Ox-Absorb') was studied in vitro for oxalate binding and in patients with enteric hyperoxaluria to investigate oxalate excretion and the inhibitory activity on crystal formation of the urine. In-vitro experiments showed complete binding of oxalate to OMH. In clinical studies in nineteen patients with intestinal disorders and stone formation, urinary oxalate excretion was significantly lower during OMH treatment than off treatment. The activity product index of calcium oxalate was reduced on treatment. A pronounced rise in the inhibitory activity of urine was seen in two patients with very low pretreatment values. Most patients experienced virtual normalisation of bowel function, and in those with severe stone formation there was substantial clinical improvement. It is concluded that OMH has the capacity to bind oxalate in vitro and to reduce urinary oxalate excretion. These observations suggest a new promising treatment for enteric hyperoxaluria.

Administration, Oral↗
PubMed1989

Binding of glycosaminoglycan inhibitors to calcium oxalate crystals in relation to ionic strength.

Several inhibitors of calcium oxalate crystallization have been identified and shown to exhibit quantitative and qualitative differences in efficacy. Glycosaminoglycans are potent inhibitors of crystal growth and aggregation, and the efficiency seems to increase with an increasing charge density. In order to investigate the mechanism of inhibition, we performed binding experiments of radioactivity labelled heparin, chondroitin sulphate and the low-molecular mass heparin analogue pentosan polysulphate to calcium oxalate crystals and subsequent displacements by increasing the amounts of non-radioactive ligands or increasing ionic strength. Ligands with a high charge density bound more readily and with a seemingly higher affinity than ligands with a low charge density, but were also more susceptible to displacement when the ionic strength was increased. It is concluded that a higher affinity to the crystals may be the reason why highly charged glycosaminoglycans are more efficient inhibitors of calcium oxalate crystal growth.

Calcium Oxalate↗