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Biomedical subjects

S Halvorsen

Publications and source records attributed to S Halvorsen.

At least 37 records · Page 2Linked to original sources

[Critical shortage of personnel in nephrology. Assessment of causes of the crisis and suggestion for solution].

The heavier work load for qualified nephrologists in Norway over the last ten years is described and compared with the number of positions. The increase in the number of dialysis treatments, care of renal transplant patients and other tasks performed by qualified nephrologists is roughly doubled from 1985 to 1995. By contrast the number of employed qualified nephrologists to pursue the work has only increased by 20% over the same period. As of today there is a lack of capacity to educate new nephrologists to fill up forthcoming vacancies. When the actual need for nephrologists is taken into account, the discrepancy is much more serious and will become even more so over the next ten years if no immediate action is taken. We suggest the establishment of six new educational positions. Altogether, these six new positions will provide the capacity to educate a reasonable number of trained nephrologists to meet future challenges, to the benefit of patients.

Adult↗

D-dimers are degraded by human neutrophil elastase.

To see if D-dimers were degraded by human neutrophil elastase (HNE), cross-linked fibrin was obtained by adding thrombin to purified fibrinogen in the presence of calcium ions and factor XIII, and the fibrin clot subsequently degraded by plasmin. Thereafter, the supernatant containing fibrin degradation products was removed and incubated with HNE. D-dimer levels were measured by two rapid semiquantitative tests, a latex agglutination test and the Nycocard immunofiltration test, and a quantitative ELISA-method. With increasing incubation time, D-dimer levels as measured by the latex and Nycocard tests rapidly decreased and subsequently became undetectable, while the ELISA D-dimer values remained essentially unchanged. By using SDS-electrophoresis and immunoblotting, the degradation of plasmic derivatives of cross-linked fibrin by fiNE was visualised. We conclude that in a purified system, D-dimers formed during plasmin mediated lysis of cross linked fibrin are further degraded by HNE. Such HNE degradation reduces the D-dimer concentration as measured by rapid semiquantitive tests, and may be partly responsible for discrepant results when using different D-dimer assays.

Antifibrinolytic Agents↗

Parenteral iron increases serum erythropoietin concentration during the "early anaemia' of 10-20-day-old mice.

Parenteral iron abolishes the "early anaemia' in all mammals tested and increases packed cell volume (PCV) and haemoglobin concentration (Hb) significantly above adult levels. In the present study we examined the effect of parenteral iron upon serum immunoreactive erythropoietin (siEpo) concentration in young mice (age 6-24d) and in adult iron-deficient mice. Young BALB/CJ mice, from 5 to 23 d of age, and adult (60-100 d old)mice, some of which were iron deficient due to a low iron diet from the time of weaning, were given iron subcutaneously (iron sorbitol, Fe+3, 1.2 mg iron/100g body weight/injection). Iron was given as one single dose and the animals killed 20-24 h later. Control mice were similarly treated with saline. In young mice, from the age 10 d to weaning at 20 d, the siEpo level, measured 20-24 h after a single subcutaneous dose of iron, was 5 times greater than that in control mice (P < 0.0001). In contrast, there was no change in siEpo 20-24 h after a single subcutaneous dose of iron in adult mice, whether iron-deficient anaemic or normal. Thus, during the "early anaemia' in young mice over 10 d old, iron increased siEpo levels, whereas it had no such effect in iron-deficient and normal adult mice. This suggests that between ages 10 and 20 d, iron has additional effects in the regulation of erythropoiesis, which may not occur in adult or in 6-d-old mice.

Anemia, Iron-Deficiency↗

Erythropoietin (Epo), protein and iron supplementation and the prevention of anaemia of prematurity: effects on serum immunoreactive Epo, growth and protein and iron metabolism.

The effect of recombinant human (r-Hu) erythropoietin (Epo) (300 IU/Kg per week for 4 weeks) was studied in healthy preterm infants (n = 14) fed human milk with additional milk protein and high doses of iron. The controls (n = 15) were in themselves a study group and were used to follow the natural course of anaemia of prematurity on such nutrition. Serum immunoreactive Epo (SiEpo) increased significantly 24 h after r-HuEpo injections (range 36 to > 128 mU/ml) and remained at these levels throughout the treatment period. r-HuEpo in such moderate doses kept haemoglobin above 11 g/dl. Bodyweight gain, protein and iron parameters indicated adequacy of dietary protein and iron. In controls, siEpo increased during the first weeks after nutritional supplementation, with a concommitant rise in reticulocyte count. At age 3 weeks, despite low siEpo levels, reticulocyte counts indicated active erythropoiesis. Following further moderate increases in siEpo, the reticulocyte count increased to high levels (7%). The reticulocyte response suggests that erythropoiesis in preterm infants is less dependent upon Epo levels than in adults.

Anemia, Neonatal↗

Activation of coagulation and deep vein thrombosis after bone marrow harvesting and insertion of a Hickman-catheter in ABMT patients with malignant lymphoma.

Evidence of activation of coagulation was sought in serial plasma samples from 25 ABMT candidates with malignant lymphoma admitted for bone marrow harvesting: 10 females and 15 males, median age 41 years (range 27-58 years). Nineteen patients had non-Hodgkin's lymphoma (NHL) and six had Hodgkin's disease. Of those with NHL, 14 had high-grade and five low- grade disease. The plasma levels of markers of activation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, fibrinopeptide A and fibrinmonomers) increased significantly (P < 0.001) in association with harvesting. Except for fibrinopeptide A, the indicators of activation were still significantly elevated 24 h after marrow aspiration. Beta-thromboglobulin, a marker of the platelet release reaction, also increased significantly (P < 0.01). Four out of nine patients in whom a long-term central venous catheter was inserted just after marrow aspiration, developed catheter-related deep vein thrombosis, verified venographically, shortly after harvesting. These results suggest that patient with malignant lymphoma undergoing marrow harvesting develop a hypercoagulable state, and that insertion of a central intravenous catheter immediately after marrow harvesting should be avoided to prevent the development of symptomatic deep vein thrombosis.

Adult↗

Breast feeding and seasonal determinants of child growth in weight in east Bhutan.

In a prospective study of 113 children in rural Bhutan, morbidity, nutritional status and feeding practices were recorded monthly over a period of 32 months. This information was related to seasonal variations in rainfall. Diarrhoea had a negative impact on growth, as measured in monthly intervals, during the second and third years of life, reducing daily weight gain by 4.4 +/- 2.0 g (p<0.0001). this impact was largest during the monsoon season. For respiratory tract infections the value was 2.6 +/- 1.7 g (p<0.01). Growth in weight was lowest during the monsoon period (p<0.0001). Continued breast feeding was associated with an odds ration for diarrhoea of 0.51 (95% CI 0.34-0.78), and for respiratory tract infections of 0.63 (95% CI 0.40, 0.99). Growth in weight was less reduced during the monsoon season for children who were breast fed (2.5 +/- 1.7 g/day) than for those not breast fed (7.5 +/- 3.5 g/day) (p<0.01). We conclude that breast feeding is of particular importance throughout the warm and rainy season.

Bhutan↗

Effects of recombinant human erythropoietin on fetal and adult hemoglobin in preterm infants.

In the present study we assess the effect of recombinant human erythropoietin (r-HuEpo) upon levels of fetal Hb (HbF) and adult Hb (HbA) in preterm infants. Twenty-eight "healthy," appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 wk of age. Fourteen infants were randomized to receive r-HuEpo, and 14 infants served as controls. Four controls and six r-HuEpo treated infants had been transfused before study start, whereas four control infants were transfused in the course of the study. The untransfused infants showed a high HbF/Hb ratio during the study with only a weak tendency to decline toward the expected time of delivery. The total Hb mass increased (p < 0.05) more in the r-HuEpo-treated infants than in the untreated, whereas the rise in HbF mass was similar in the two groups. After each transfusion, the HbF/Hb ratio reverted gradually to the ratio expected at the infant's postconceptional age. There was no difference in the production rate of HbF between r-HuEpo-treated infants and controls. The present data indicate that the HbF/HbA ratio in preterm infants is subject to the same programmed mechanisms which govern intrauterine erythropoiesis until term and that exogenous r-HuEpo does not influence this pattern significantly.

Adult↗

Degradation of the alpha-chain of fibrin by human neutrophil elastase reduces the stimulating effect of fibrin on plasminogen activation.

UNLABELLED: The degradation of fibrin by human neutrophil elastase (HNE) and the interference of such degradation on the stimulating effect of fibrin on plasminogen activation by tissue plasminogen activator (t-PA) was studied. By using SDS electrophoresis and Western blotting with subsequent immunostaining with monoclonal antibodies, degradation of the fibrin molecule was monitored. This degradation was related to the stimulating effect on plasminogen activation. Degradation of the alpha-chain was seen to occur before degradation of the beta- and gamma-chains. On the alpha-chain it was found that C-terminal degradation occurred prior to visible degradation of the N-terminal end. This C-terminal degradation was associated with a fall in the stimulation of plasminogen activation, coinciding with a corresponding reduction in the polymerization of fibrin. With further degradation, including N-terminal proteolysis of the alpha-chain, the stimulating effect of fibrin was reduced to that of fibrinogen. CONCLUSIONS: Our results indicate that HNE degradation of the alpha-chain of fibrin occurs initially from the C-terminal end, affecting the polymerization of fibrin. This impaired polymerization may be important for the observed reduction in the t-PA mediated plasminogen activation.

Enzyme Activation↗

Impaired coagulation of fibrinogen due to digestion of the C-terminal end of the A alpha-chain by human neutrophil elastase.

Human neutrophil elastase (HNE) possesses fibrinogenolytic capacity, with a high susceptibility towards degradation of the A alpha-chain. To study the influence of HNE digestion of the A alpha-chain on the coagulation of fibrinogen by thrombin, fibrinogen was incubated with human neutrophil elastase (HNE). At intervals, thrombin clotting time (TCT) and clottability were determined and compared with the patterns obtained with SDS electrophoresis and Western blotting with subsequent immunostaining, using monoclonal antibodies against the N-terminal end and C-terminal half of the A alpha-chain. Apparently, initial HNE digestion of the fibrinogen molecule occurred from the C-terminal end of the A alpha-chain, and was associated with prolongation of the TCT. With further C-terminal degradation TCT became indefinite and the degradation products were no longer clottable. Finally, N-terminal degradation of the A alpha-chain was observed. The present observations suggest that initial HNE-digestion of fibrinogen occurs from the C-terminal end of the A alpha-chain, and that the C-terminal end is crucial for the coagulation of fibrinogen.

Amino Acid Sequence↗

Recombinant human insulin-like growth factor 1 (rh-IGF-1) stimulates erythropoiesis in adult, but not in newborn mice.

The in vivo effect of recombinant human insulin-like growth factor (rh-IGF-1) upon erythropoiesis was studied in inbred BALB/C mice. Unweaned, rapidly growing 20 days old mice and adult female mice received subcutaneous rh-IGF-1 or control injections every 6 h for 48 h. The mice were killed either 12 or 48 h after the last injection, i.e. a study time of 60 and 96 h, respectively. Bone marrow erythroid colony forming units (CFU-E), reticulocytes, haematocrit, serum immunoreactive erythropoietin (siEPO) and body and organ weight were measured. An additional group of young mice were given iron prior to the rh-IGF-1 injections to ensure sufficient available iron. No differences in overall body or organ weights were observed. In the young mice erythropoiesis as measured by bone marrow CFU-E, reticulocytes and haematocrit did not differ between rh-IGF-1 group and controls. When iron alone was given, reticulocytes (P < 0.05) and haematocrit (P < 0.0001) increased significantly, but no further stimulation was seen when rh-IGF-1 injections were given in addition to iron. The adult female mice responded with significantly increased erythropoiesis as judged by increased reticulocyte counts following rh-IGF-1 injections (P < 0.001). No significant effect upon CFU-E and haematocrit was detected. The reticulocyte response was more pronounced at 96 than at 60 h after the first rh-IGF-1 injection. SiEPO was significantly (P < 0.01) lower in the adult 96 h rh-IGF-1 group than in the appropriate control group. In conclusion parenteral iron significantly increased haematocrit in unweaned mice. Short time rh-IGF-1 treatment did not stimulate erythropoiesis in these rapidly growing mice, whether or not iron supplementation had been given.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Thrombin treated plasma employed as a standard for determination of soluble fibrin.

The Coa-set Fibrin Monomer test (CFM-test) is a quantitative method for determination of soluble fibrin in plasma. The fibrin standard of the CFM-test is produced by bathroxobin conversion of purified fibrinogen to fibrin. Plasma treated with minute amounts of thrombin may be considered as a more physiological way of preparing fibrin monomers. Therefore, we have employed such thrombin treated plasma (TTP) as an alternative fibrin standard for the CFM-test. The fibrin concentration of the TTP was determined indirectly by quantitation of released fibrinopeptide A. The TTP was stable during freezing, thawing and storage for 3 months at -70 degrees C. The standard curve obtained using TTP as a standard was linear in the range of 0-275 nmol/l fibrin in plasma, but the slope of the line was less steep than the original standard curve. This difference was probably due to the greater plasminogen activating effect of bathroxobin digested fibrinogen compared to soluble fibrin generated in plasma by thrombin, as observed in a previous study. Because of the less steep slope of the alternative standard curve, fibrin levels in plasma samples from 20 healthy volunteers and 25 patients were found to be higher employing TTP as a standard. Preparation of a fibrin standard by incubation of plasma with minute amounts of thrombin will to some extent mimic the process of fibrin generation in vivo. Since we have found a satisfactory stability of such a standard during freezing, thawing and storage, we think the TTP standard might be useful for quantitation of soluble fibrin in plasma.

Blood Preservation↗

Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity.

The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r-HuEpo can produce significant gains in red cell production that may be clinically useful.

Anemia, Neonatal↗

The stimulatory capacity of soluble fibrin prepared from high and low molecular weight fibrinogen on plasminogen activation.

High molecular weight, low molecular weight and very low molecular weight fibrinogen were purified from human plasma, and converted partially or completely to fibrin by the action of thrombin or batroxobin. The stimulatory effects of these fibrin(ogen) preparations on plasminogen activation by tissue plasminogen activator were studied. When only 3-30% of the fibrinogen molecules were converted to fibrin, the high molecular weight fibrin had a greater stimulatory effect on plasminogen activation than equal amounts of low and very low molecular weight fibrin. In completely converted fibrin preparations, the plasminogen activating capacity of high molecular weight fibrin was either equal to (thrombin treated preparations) or greater than (batroxobin-treated preparations) that of very low molecular weight fibrin. These findings suggest that degradation of the A alpha-chain of fibrin does not per se increase its plasminogen activating capacity.

Batroxobin↗