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Biomedical subjects

S Halvorsen

Publications and source records attributed to S Halvorsen.

At least 55 records · Page 3Linked to original sources

Does Lp(a) lipoprotein inhibit the fibrinolytic system?

Lp(a) lipoprotein contains a unique apolipoprotein, apolipoprotein (a), that has a striking homology with plasminogen. This homology has brought forward speculations as to an inhibitory effect of Lp(a) lipoproteins on fibrinolysis. The present investigation was undertaken to study the influence of Lp(a) lipoprotein on the fibrinolytic system. In an in vitro model, we have studied the influence of purified Lp(a) lipoprotein on plasminogen activation by tissue plasminogen activator (t-PA) in the presence of soluble fibrin. Increasing concentrations of Lp(a) lipoprotein (0-32 mg/dl) did not inhibit plasminogen activation by t-PA in the presence of thrombin or bathroxobin digested fibrinogen. When purified Lp(a) lipoprotein was added to whole blood, the degree of fibrin degradation obtained following standardized coagulation, as evaluated by the generation of D-dimer, was not reduced. D-dimer levels in plasma and in serum after standardized coagulation, as well as conventional parameters for evaluation of the fibrinolytic system, were determined in 10 individuals with high and 10 individuals with low levels of Lp(a) lipoprotein. No differences in the fibrinolytic parameters were observed between the groups. Thus, we found no evidence that Lp(a) lipoprotein interferes with the fibrinolytic process in the present experiments.

Amino Acid Sequence↗

Long term morbidity and mortality after kidney transplantation.

A cohort of 69 patients received a kidney transplant in the period 1963-1977. The mean observation time was 9.5 years. Accumulated follow-up time was 661.4 patients year. The mean (SE) 10-year survival was 55(5.9)%. Univariate analysis showed that female patients had poorer survival than male. Patients with a cadaveric donor had lower survival than those with a living donor. Also survival with different HLA-A,B match differed significantly. A multivariate analysis pinpointed nature of donor, cadaveric vs. living, as the sole independent predictor of mortality. Patients receiving a cadaveric kidney were on double (2.2) relative risk of mortality as compared to patients with a living donor. The major causes of death were infections during rejection treatment, and cardiovascular disease. Patients had low rates of morbidity. Our results showed satisfactory outcome of kidney transplantation.

Adolescent↗

Leukaemia and anaemia in AKR/O mice. II. Role of the spleen as an erythropoietic organ during leukaemia development.

In order to study the role of the spleen in erythropoiesis during AKR/O leukaemogenesis, we have cultured bone marrow and spleen erythroid colony-forming units (CFU-E) and burst-forming units (BFU-E) from AKR/O mice (n = 40) with leukemia of varying severity and type of manifestation. Mice with leukaemia/lymphoma had reduced concentrations of bone marrow CFU-E and BFU-E as compared to healthy, age-matched AKR/O mice. The spleen content of CFU-E was increased, and highest in mice with a spleen size between 500 and 1000 mg. The largest spleens had a somewhat lower CFU-E content. Mice with the highest spleen CFU-E content most often had a normal PCV; however, 4/7 had a normal bone marrow CFU-E concentration. During AKR/O leukaemogenesis with development of spleen enlargement, the spleen may act as an erythropoietic organ, and contribute to maintaining a normal PCV. This may be a temporary ability which is reduced or lost with further progress of the disease.

Anemia↗

Pregnancy outcome in renal allograft recipients: influence of ciclosporin A.

The outcome of 35 pregnancies in 26 renal allograft recipients is reported. Twenty-four pregnancies in patients treated with prednisolone and azathioprine resulted in 22 live-born infants (one twin pregnancy) and 3 induced abortions on medical indications. Three of the deliveries were preterm, and one of the infants had a birth weight below the 2.5th percentile. Ten patients (11 pregnancies) were treated with ciclosporin A (CsA). These women delivered 5 infants (3 preterm deliveries of whom the birth weight of one infant was below the 5th percentile) and underwent 3 induced (medical indications) and 3 spontaneous abortions. Mean birth weight in the CsA treated group was 2464 g (range 1790-2930 g), and their gestational age varied from 232 to 271 days. No foetal malformations were observed in the two groups. The results may indicate a harmful effect of CsA on pregnancy outcome.

Adolescent↗

The stimulatory effect of soluble fibrin on plasminogen activation by tissue plasminogen activator as studied by the Coa-set Fibrin Monomer test.

The stimulatory effect of various fibrin preparations on plasminogen activation by tissue plasminogen activator, was studied by the Coa-set Fibrin Monomer test (Kabi). Fibrin obtained by complete conversion of purified fibrinogen demonstrated a greater stimulatory effect on plasminogen activation than did equal amounts of fibrin obtained by partial conversion of fibrinogen. Soluble fibrin generated by treating human plasma with minute amounts of thrombin or bathroxobin, resembled partially converted purified fibrinogen. The plasminogen activating effect of completely converted fibrinogen was similar in thrombin and bathroxobin incubated samples. In preparations of partially converted fibrinogen and in plasma samples, bathroxobin digested fibrinogen expressed a more pronounced stimulatory effect on plasminogen activation than did thrombin digested specimens. The underlying mechanism for these differences are discussed.

Batroxobin↗

Renal failure in adult patients with hereditary tyrosinaemia type I.

An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in the years preceding the transplantation. Her kidneys were contracted to 40 g. The major morphological finding was that of a tubulointerstitial nephropathy. Liver biopsies taken at the ages of 5.5 and 23 years showed cirrhotic changes. Crystalloid inclusions in the liver mitochondriae were a prominent finding on electron microscopy. Fumarylacetoacetase was deficient in liver, kidneys, fibroblasts and lymphocytes. The typical biochemical parameters of tyrosinaemia, succinylacetone, p-hydroxyphenyllactate, p-hydroxyphenylpyruvate and serum tyrosine were only slightly elevated. A brief history of a second adult tyrosinaemia patient with decreasing renal function is also given.

Adolescent↗

A comparison between haematological parameters in 'capillary' and venous blood samples from hospitalized children aged 3 months to 14 years.

In 16 hospitalized children aged 3 months to 14 years EDTA-blood samples were taken simultaneously from an anticubital vein and from a finger tip. Haematological measurements were subsequently performed in an Ortho ELT 800/WS analyzer. The thrombocyte count and the red cell indices were nearly identical in the two sets of samples. The 'capillary' erythrocyte count, haematocrit and haemoglobin values exceeded those of venous blood by 2%, and the mean 'capillary' total leukocyte count by about 20%. The relative frequency of lymphocytes, granulocytes and mononuclear cells did not alter between the two sets of samples. The significant differences demonstrated may in certain clinical settings be of medical importance. Their possible explanations are discussed.

Adolescent↗

Leukaemia and anaemia in AKR/O mice I. Leukaemia characteristics, haematological variables and erythropoiesis stimulating factor(s).

AKR/O mice were used as a model for studying the pathogenesis of the anaemia accompanying leukaemia/lymphoma. The leukaemia incidence was 87%. Median age at diagnosis was 11.3 months. At diagnosis most of the mice had normal leukocyte counts. Clinically the mice divided into subgroups depending on the relative organ involvement: 1) thymoma group (n = 98), 2) spleen group (n = 144), 3) combined group (n = 27) and 4) mice with moderate organ changes (n = 216). Mice of group 1 were younger than the others, had a rapidly progressive disease, normal to elevated packed cell volume (PCV), and plasma erythropoietin (Epo) was normal or increased. Mice of group 2 were usually anaemic with high plasma Epo estimates and often elevated reticulocyte counts. Group 4 was the oldest group. Some of these mice were severely affected haematologically. Overall there was an inverse relation between PCV and plasma Epo estimate, indicating a normal Epo response to anaemia. In all groups increasing spleen size was associated with increased severity of anaemia and increased reticulocyte counts. The association between anaemia, elevated reticulocyte counts and spleen enlargement suggests haemolysis as a mechanism for anaemia, and also raises the question of compensatory spleen erythropoiesis.

Age Factors↗

Comparison of methods for detecting soluble fibrin in plasma. An in vitro study.

The ability of the COA-SET Fibrin monomer (COA-SET FM) test to detect soluble fibrin was evaluated by comparing the results of the COA-SET FM test with fibrinopeptide A (FPA) determinations following thrombin incubation of plasma or whole blood. In addition, two semiquantitative tests (erythrocytes-agglutination test (FM-test) and ethanol gelation test (EGT] were included in the study. Under the experimental conditions used, the COA-SET FM test proved less sensitive than the FPA-assay. There was a strong correlation between the results obtained by the two tests (r = 0.86, p = 0.0001). When solely regarding low levels of soluble fibrin, however, the correlation was weaker (r = 0.59, p = 0.0003). The FM-test was less sensitive than the COA-SET FM test, but more sensitive than EGT at normal and low fibrinogen concentrations. At high fibrinogen concentrations, however, EGT proved more sensitive than the FM-test. Knowing that 1-2 moles of FPA are released per mole of fibrin monomers formed, a discrepancy was observed between the FPA concentrations and the fibrin monomer concentrations as determined by the COA-SET FM test, the FPA levels being 2-25 times higher than the fibrin monomer levels. The discrepancy was greatest at incipient fibrinogen-fibrin transformation and at high plasma fibrinogen levels. This may suggest that fibrinogen in some way interfered with the stimulating effect of fibrin on the t-PA catalyzed activation of plasminogen, the principle upon which the COA-SET FM test is based.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol↗

[Treatment of chronic kidney failure with dialysis and transplantation. Development, need and organization in Norway].

Treatment of chronic renal failure by dialysis and renal transplantation has been developed over the last 20 years in Norway. 17 local nephrological units with dialysis departments cooperate with one transplantation center in Oslo. The number of new patients starting renal replacement therapy has increased only slightly during the last five years. The mean number of new patients in the period was 52 per million inhabitants per year. The proportion of elderly patients accepted for renal replacement therapy was high (39% above 60 years of age) and approximately 15% of the patients had diabetic nephropathy. Due to an active transplantation policy, the proportion of patients alive on dialysis is low (18%), compared with 82% alive with a functioning graft. The number of patients on dialysis has declined slightly the last four years. The proportion of patients on chronic ambulatory peritoneal dialysis (CAPD) is low (13%), and the number of patients on home hemodialysis has declined in the last five years. Predialytic transplantation has been performed in 18% of the patients starting renal replacement therapy during the last five years. Due to a high transplantation rate and a large number of predialytic transplantations, it has not been necessary to increase the capacity for dialysis in the last five years.

Hospital Departments↗

Variations in erythropoiesis throughout a lifetime. Studies in a high-leukaemic mouse strain, the AKR/O strain, and a non-leukaemic strain, the WLO strain.

We have studied the development of some haematological variables: erythropoiesis stimulating factor(s) (ESF), investigated with an in vitro cell culture assay; and the content of bone marrow and spleen erythroid colony forming unit(s) (CFU-E) and erythroid burst forming unit(s) (BFU-E) throughout the lifetime of 2 different mouse strains: the high-leukaemic, retrovirus infected AKR/O strain, and the non-leukaemic WLO strain. During the recovery phase of the postnatal anaemia, a peak in plasma ESF occurs in both strains. In young adult mice of both strains another peak in plasma ESF occurs at 70-110 days of age, associated with an increased number of bone marrow CFU-E, in a period when packed cell volume (PCV) remains stable. As the animals grow older PCV decreases, whereas plasma ESF and bone marrow CFU-E concentration increase. These results, together with in vitro dose-response studies, suggest reduced sensitivity to erythropoietin (Epo) of the ageing erythron. Throughout, the AKR/O strain has higher levels of plasma ESF and bone marrow CFU-E concentrations than the WLO strain, indicating both a reduced Epo responsiveness and some degree of ineffective erythropoiesis in the AKR/O strain. At all ages the AKR/O strain has a high concentration of Epo independent bone marrow CFU-E, possibly caused by the virus infection of precursor cells.

Aging↗

Hereditary tyrosinemia of chronic course without rickets and renal tubular dysfunction.

Three patients with hereditary tyrosinemia type 1, two brothers and one girl, studied at the age of 5, 12 and 15 years, respectively, had neither generalized hyperaminoaciduria, glucosuria nor clinical symptoms of rickets. Untreated the elder brother had only slightly elevated plasma tyrosine level (141 mumol/l, normal less than 80), and low excretion of p-hydroxyphenyllactate. He presented with pronounced thrombocytopenia (3 X 10(9)/l). At 13 years of age he contracted hepatocellular carcinoma. The younger brother presented with serum tyrosine of 318 mumol/l and thrombocyte count 48 X 10(9)/l. Succinylacetone in urine was elevated in both, 30 and 79 mumol/mmol creatinine, respectively. The female patient was investigated for hepatomegaly in infancy, atypical tyrosinemia being considered, but afterwards developed normally without diet or any other treatment until she contracted hepatoma at the age of 15 years. Her plasma tyrosine level was 600-700 mumol/l, and she excreted large amounts of p-hydroxyphenyllactate. Succinylacetone in urine was low but elevated (8 mumol/mmol creatinine). The fumarylacetoacetase activity in fibroblasts from the brothers and in lymphocytes from the girl was less than 5% and 10% of control levels, respectively. In conclusion, the chronic form of hereditary tyrosinemia may occur without evidence of renal tubular dysfunction.

Adolescent↗

[Children with phenylketonuria (Fölling's disease). Intellectual functions and psychological adaptation].

Untreated phenylketonuria (PKU) leads to serious mental retardation. The prognosis of PKU has been dramatically improved by neonatal screening and dietary treatment. This study evaluates 25 children, ages 10 to 16 years. Children who receive early and adequate treatment have a mean IQ slightly below normal, and few psychological problems. The disease causes considerable strain on the families, however, because of the very strict diet. Recent evidence suggests that children with PKU can only rarely terminate the diet, although in many cases the diet can be relaxed. It is essential to teach the children the diet and promote autonomy in relation to phenylketonuria.

Adaptation, Psychological↗

[Metabolic diseases causing acidosis in the neonatal period].

The diagnosis of metabolic diseases during the newborn period is difficult because symptoms and findings are similar to those generally encountered in newborn babies who are ill. Moreover, metabolic diseases are often complicated by infections and cerebral hemorrhages. The article presents a short clinical review of metabolic diseases associated with metabolic acidosis in the newborn and discusses appropriate investigations and differential diagnoses. It is important to remember the possibility of metabolic diseases as the cause of metabolic acidosis in the newborn period.

Acidosis↗

Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease.

We studied prospectively the quantitative relation of circulating endotoxin (lipooligosaccharides [LOSs]) and the development of multiple organ failure and death in 45 consecutively admitted patients with bacteriologically verified systemic meningococcal disease (SMD). A plasma LOS level of greater than 700 ng/L correlated with development of severe septic shock (P less than .0001), adult respiratory distress syndrome (P = .0035), a pathologically elevated serum creatinine level (P less than .0001), or death as a consequence of multiple organ failure (P = .0002). Initial plasma LOS levels of less than 25, 25-700, 700-10,000, and greater than 10,000 ng/L were associated with 0%, 14%, 27%, and 86% fatality, respectively. The LOS half-life after initiation of antibiotic therapy was 1-3 h. Increasing plasma LOS levels were never seen. These observations suggest that LOS quantitation using the limulus amebocyte lysate assay with a chromogenic substrate gives important progsnotic information and may provide new insight concerning pathophysiological aspects of SMD.

Adolescent↗