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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 307 records · Page 17Linked to original sources

Drug-induced blood dyscrasias. A ten-year material from the Swedish Adverse Drug Reaction Committee.

Drug-induced dyscrasias (agranulocytosis, aplastic anemia, hemolytic anemia and thrombocytopenia) in Sweden during a 10-year period (1966-75) have been analyzed. The overall occurrence is remarkably constant, although marked changes have occurred with regard to offending drugs. Drug-induced thrombocytopenia and agranulocytosis are about twice as common as hemolytic anemia, which in turn is twice as common as aplastic anemia. There is a marked increase with age in the incidence of all drug-induced cytopenias. Women predominate and make up close to 70% of the material. With regard to responsible drugs, the most remarkable finding is the high frequency with which sulfonamides appear as responsible for all types of drug-induced cytopenia.

Age Factors↗

An inhibitor from placenta specifically binds urokinase and inhibits plasminogen activator released from ovarian carcinoma in tissue culture.

An inhibitor present in placenta and released in placental tissue culture forms specific complexes with each of two molecular forms of urokinase. Autoradiography demonstrated that the inhibitor shifted the electrophoretic position of 125I-labelled urokinase. It did not change the migration of diisopropyl-fluorophosphate-inactivated 125I-labelled urokinase, thereby indicating complex formation dependent on active serine site in urokinase. The inhibitor had a strong neutralizing effect on the plasminogen activators released from human ovarian carcinoma in tissue culture. The placental inhibitor might prove useful in inhibiting the fibrinolytic process necessary for proliferation of tumour vessels.

Endopeptidases↗

Homozygous expression of haemophilia B in a heterozygote.

A case of clinically severe haemophilia B in a woman is described. In 1977 she was delivered of a healthy male child, showing that she is heterozygous for the haemophilia gene. This seems to be the first report of a proven heterozygote with the homozygous expression of severe haemophilia.

Adult↗

Type I congenital dyserythropoietic anaemia with myelopoietic abnormalities and hand malformations.

Type I dyserythropoietic anaemia was diagnosed in an infant, who presented with respiratory distress and hepatosplenomegaly soon after birth. Anaemia became manifest during the neonatal period. The case clearly proves the congenital nature of the disease. Abnormalities of the myelopoietic series indicate that it might be a stem cell disease and the presence of skeletal anomalies of the hands suggests a genetic relationship to some cases of Fanconi and Diamond anaemia. No serum lipid or vitamin E deficiency was present as in type II congenital dyserythropoietic anaemia. Serial serum ferritin determinations indicated that iron stores are increased early in type I congenital dyserythropoietic anaemia despite no transfusion load.

Anemia↗

Factor VIII activity and antigen in sick newborns with pathological proteolysis in blood.

Factor VIII clotting activity (VII:C) and factor VIII related antigen (VIII:R:AG) were determined in 12 sick newborn infants with pathological proteolysis in their circulation. A marked discrepancy was noted between VIII:R:AG and VIII:C, the ratio in sick infants being, on average, 2:1, while no discrepancy was seen in healthy newborns. The finding in the sick infants resembled a low grade plasminogen activation, which was studied experimentally. It is concluded that demonstration of a marked discrepancy between VIII:R:AG and VIII:C is a useful indication of pathologic proteolysis in sick newborns.

Antigens↗

Vitamin E requirements of preterm infants.

Differences between feeding practices in earlier investigations prompted the present study of iron and vitamin E supplementation in breast milk fed preterm infants. A new and highly sensitive technique for quantitation of alpha-tocopherol in serum was used. Studies on 34 infants with a birth weight below 2000 g or gestational age less than or equal to 35 weeks showed that supplementation with 16.5 mg tocopheryl acetate/day from 10 days of age resulted in a significantly higher haemoglobin concentration and lower reticulocyte count at 8-10 weeks than supplementation with 1.5 mg/day (p is less than 0.05). Studies on 23 infants with a birth weight of 2000-2499 g revealed subnormal alpha-tocopherol levels in 2 of the infants given 1.5 mg tocopheryl acetate/day but there was no effect on the haemoglobin concentration at 8-10 weeks. There were no untoward effects of an early iron supplementation with 2-3 mg Fe++ (as ferrous succinate)/kg/day. It is concluded that extra supplementation with vitamin E is advisable also in breast milk fed preterm infants. A low dosage iron supplementation from 3 weeks of age is safe.

Blood Cell Count↗

Some characteristics of urokinase released in organ culture of human kidney.

Plasminogen activator produced in organ culture of human kidney, i.e. in the histotypical arrangement of the tissue, was partially purified by affinity chromatography on para-aminobenzamidine coupled to Sepharose by a 6-carbon spacer, followed by gel chromatography on Sephadex G-100. The molecular weight of 2 active peaks were 27,000 and 52,000 daltons respectively. It was inhibited by DFP and by IgG antiurokinase.

Chromatography, Affinity↗

Hemolytic uremic syndrome. Results of treatment with hemodialysis.

The characteristics of the hemolytic-uremic syndrome in 7 children living in a well defined area in the south of Sweden are described. All the patients had a severe form of the disease and were critically ill. The clinical activity could best be followed by measuring blood platelets and urinary FDP. Early institution of hemodialysis treatment, given almost daily until normalisation of platelet count and urinary output, is the most important live-saving measure. Full dosage heparin seems not to be necessary. Six patients survived and were followed-up for 1-7 years. When last seen they all had normal renal function and blood pressure.

Blood Cell Count↗

Purification of urokinase by affinity chromatography.

Commercially available urokinase (EC 3.4.99.26), though highly active, is still contaminated with unrelated proteins and degradation fragments of urokinase. Further purification of a urokinase preparation by chromatography on benzamidine-Sepharose is described. The final preparation consisted of two molecular forms of urokinase with molecular weights of respectively 31 000 and 54 000. The 54 000-dalton urokinase appears to be composed of two protein chains, one of which is the 31 000-dalton urokinase. A monospecific antiserum against urokinase was raised.

Benzamidines↗

Studies on the prolonged bleeding time in von Willebrand's disease.

Three experimental models have been employed to investigate the mechanism of the prolonged bleeding time in patients with von Willebrand's disease (vWd). 1-deamino-8-D-arginine vasopressin (DDAVP), a synthetic analogue of the antidiuretic hormone, was administered to normal volunteers and patients with vWd in order to induce a short-term, endogenous increase of factor VIII procoagulant activity (VIIIAHF), factor VIII-related antigen (VIIIAGN), and Willebrand factor (VIIIVWF); and to investigate the relationship between bleeding time and plasma variations of factor VIII-associated properties. In normal subjects DDAVP administration was followed by a marked increase of VIIIAHF, VIIIAGN, and VIIIVWF; yet the bleeding time remained unchanged. The same parameters were also raised in two groups of patients with vWd. In a third group of patients with severe recessive vWd, factor VIII-associated properties, which were not measurable before the infusion, were unmodified. The bleeding time remained unchanged in all vWd patients. To investigate the effect of the exogenous increase of factor VIII-associated properties, cryoprecipitate was given to ten vWd patients before dental surgery. Despite the marked increase of VIIAHF, VIIAGN, and VIIVWF observed after the infusion, bleeding time was not shortened. Finally, in order to evaluate the hypothesis that factor VIII may exert its effect on primary hemostasis locally in the vessel wall, VIIIAGN and its relationship with the bleeding time were studied by direct immunofluorescence in gum-biopsy specimens obtained in vWd patients before cryoprecipitate infusion. No reaction could be elicited in five patients with severe, recessive vWd, whereas venules and arterioles stained positively in five patients with a moderate form of the disease. Immunofluorescence microscopy was also carried out in specimens obtained after cryoprecipitate at a time when the plasma defects were corrected but the long bleeding time was not modified; no reaction was detectable on the vessel wall of the three patients who were negative before the infusion.

Adult↗