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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 271 records · Page 15Linked to original sources
PubMed1982

Comparative disposition of pethidine and norpethidine in old and young patients.

Pethidine was given as a single intravenous dose for premedication before minor surgery. Two groups of subjects were studied, old patients aged more than 65 years, and young patients aged 18-30 years. Blood samples were taken at fixed intervals for 30 h after the injection, and the plasma concentrations of pethidine and its major metabolite norpethidine were analyzed by gas chromatography. In comparison with the young the old patients had a lower plasma clearance for pethidine (9.13 +/- 2.50 versus 16.18 +/- 5.15 ml/min/kg), slower elimination rate beta (0.101 +/- 0.036 versus 0.211 +/- 0.146), and a larger AUC (1935 +/- 554 versus 1092 +/- 277 h . ng/ml) but a similar volume of distribution (5.69 +/- 1.54 versus 5.38 +/- 1.75 l/kg). Norpethidine appeared later and reached its peak concentration later in the old patients than in the young. In several old patients it was still present at a plateau level after 30 h. The present study emphasizes that both parent drug and active metabolite must be taken into consideration when drug therapy is evaluated. The data do not provide pharmacokinetic support for a reduction in the dose of pethidine if it is given as a single intravenous dose. However, when repeatedly administered, it is advisable to reduce the total daily dose.

Adolescent↗
PubMed1982

Pethidine binding to blood cells and plasma proteins in old and young subjects.

The distribution of 3H-pethidine in whole blood was compared in old (63-86 years; n = 11) and young (19-25 years, n = 12) subjects using equilibrium dialysis. The plasma protein binding was 52.7 +/- 3.3% (mean +/- SD) in the old subjects and 51.8 +/- 3.1% in the young: the difference was not statistically significant. Studies on isolated plasma protein fractions showed that the main pethidine-binding protein was alpha 1-acid glycoprotein. Accordingly, the degree of pethidine binding is likely to be affected by inflammatory disease rather than by age. The distribution of pethidine to blood cells showed no age-related difference; the ratio between whole blood and plasma concentrations was 0.99 in old and 0.98 in young subjects. In whole blood from old and young subjects, 43% and 41% of pethidine was present in erythrocytes, 27% and 26% in plasma water whereas 30% and 29% was bound to plasma proteins. The mean ratio between pethidine in cells and plasma water (2.01) indicates binding of the drug in or on the blood cells. These in vitro results do not support the previous theory that a decrease in intracellular pethidine distribution in old age was the reason for the reported higher plasma levels. A slower elimination rate remains the most likely explanation for the increased plasma concentration of pethidine in old patients.

Adult↗
PubMed1982

Immunoradiometric assay of inhibitors of antihaemophilic factor A.

An immunoradiometric assay (IRMA) for determination of antibodies against f. VIII:C in haemophilia A was developed. The assay was based on competitive binding of radiolabelled anti-VIII:C and antibodies in the test material to immobilized VIII:C. Fifteen haemophiliacs with known inhibitors were investigated with the new method and with a conventional neutralization test. In 3 cases the inhibitors were detected only with the IRMA and in the other 12 there was good agreement between the inhibitor levels found with the two methods. It was also possible to demonstrate the antibodies in three non-haemophilic patients with acquired inhibitors. The IRMA, which can detect the antibodies down to a concentration of 0.02 inhibitor units per ml, is more sensitive than conventional neutralization tests and is thus of practical importance in the investigation of patients with low inhibitor titres.

Antibodies↗
PubMed1982

Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).

A variant of von Willebrand's disease has been identified in which sodium dodecyl sulfate agarose electrophoresis provides evidence that the von Willebrand factor present is structurally abnormal. Rather than the repeating triplet seen in normal subjects and in patients with the IIA and IIB variants, a repeating doublet was present in the propositus. None of the bands had the same mobility as bands in normal subjects or previously described von Willebrand's disease patients. The larger multimers of von Willebrand factor were lacking both from plasma and platelets, and did not appear in the circulation after infusion of 1-deamino-[8-D-arginine]-vasopressin. There was a marked increase in the concentration of the smallest multimer in the propositus and his phenotypically normal children, indicating that this abnormality of von Willebrand factor is inherited in an autosomal-recessive manner.

Adult↗
PubMed1982

Genetic variants of haemophilia B detected by immunoradiometric assay: implications for prenatal diagnosis.

Fifty patients with haemophilia B, belonging to 29 kindreds, were investigated with a highly sensitive immunoradiometric assay based on a homologous antibody to factor IX. The assay measures factor IX antigen (f.IX:Ag) in plasma down to 0.025 U/dl. Seventeen of 18 investigated patients with severe haemophilia B had very little or no f.IX:Ag. Also four of nine patients with moderately severe disease had very low antigen levels, approximately equal to their factor IX clotting activity (f.IX:C), whereas the other 5 had antigen in excess of activity. Of the 23 investigated patients with mild haemophilia B, 20 had f.IX:Ag approximately equal to f.IX:C, whereas 3 had normal amounts of antigen. One family with mild disease was found to have a possible variant of haemophilia B Leyden, earlier described in a few families with moderately severe disease. No haemophilia BM variants, characterized by prolonged prothrombin time with bovine brain thromboplastin, were found. We have shown earlier that the immunoradiometric assay of f.IX was useful in the prenatal evaluation of one fetus at risk for haemophilia B. The present study shows that the assay can be applied for prenatal diagnostic purposes in the vast majority of carriers of severe haemophilia B and in about half of the carriers of moderately severe disease.

Antigens↗
PubMed1982

Coagulation and fibrinolysis in pregnancy complicated by intrauterine growth retardation.

In a prospective study, blood from women in the 19th and 32nd week of pregnancy was analyzed for fibrinogen, prothrombin complex (P & P), F, V, F VIII:C, F VIIIR:Ag, the VIIIR:Ag/VIII:C ratio, F IX, F XII, F XIII, antithrombin III, alpha 2-macroglobulin, alpha 1-antitrypsin, alpha 2-antiplasmin, the inhibitor of plasminogen activation and fibrinogen degradation products. In normal pregnancies all the coagulation factors except F XIII were markedly increased, as were alpha 1-antitrypsin and the inhibitor of plasminogen activation. Pregnancy did not influence the levels of antithrombin III, alpha 2-macroglobulin or alpha 2-antiplasmin. Peripheral blood from women with growth retarded fetuses differed in that the levels of P & P, F XII (in the 19th week) and the inhibitor of plasminogen activation (in the 19th and 32nd weeks) were lower. The level of F XIII was higher in the 32nd week. A low grade activation of the coagulation system is suggested as one possible factor in the pathogenesis of intrauterine growth retardation, which emphasized the value of heparin treatment in certain cases with this syndrome.

Blood Coagulation Disorders↗
PubMed1982

Immunoradiometric quantification of tissue plasminogen activator secreted by fetal organs. Comparison with urokinase.

Explants of fetal tissues were maintained in organ cultures for 2-3 weeks and the conditioned culture media analysed for the two main plasminogen activators, tissue activator and urokinase. A new immunoradiometric method was used for determining the tissue activator. The method is based on 125I-labelled antibodies to a tissue plasminogen activator which was purified from the culture medium of an established melanoma cell line. It detected tissue activator in a concentration of 1 microgram/1 or even less. Urokinase was measured with a RIA. Explants of kidney as well as thyroid gland and thymus released very substantial amounts of urokinase and smaller amounts of tissue activator. Urokinase was also detected in media conditioned by skin, spleen and pancreas. Aorta explants released only the tissue activator. The capacity of many tissues to release urokinase indicates that this is a more significant plasminogen activator in extrarenal organs that hitherto realized. The tissue activator is probably confined to vascular structures.

Animals↗
PubMed1982

Haemophilia A and B--two years experience of genetic counselling and prenatal diagnosis.

Haemophilia A. Thirty-one pregnant women, obligate or probable carriers of haemophilia A, requested prenatal diagnosis if sex determination showed the foetus to be a male. In 11 of the 31 cases the foetuses were females; in two, the genetic variant of the disease rendered prenatal diagnosis impossible; and in two, the mother aborted spontaneously. From the remaining 16 male foetuses, blood samples were obtained in utero in the 17th to 20th week of gestation. Examination of the samples showed that 11 of the foetuses were unaffected and five affected. Haemophilia B. Three carriers of haemophilia B had male foetuses. Examination of foetal blood obtained in utero showed that these three foetuses were affected. Confirmation. All women with an affected foetus requested termination of pregnancy. In one of the cases of abortion, no blood was obtained for confirmative examination. In the remaining cases, the prenatal prediction was confirmed in the abortus or in the child after birth; three women are still pregnant.

Factor IX↗
PubMed1981

Vitamin E and fatty acid composition of human milk.

The vitamin E and fatty acid composition of human milk was determined in 40 milk samples (six colostral, 10 transitional, and 24 mature) obtained at different stages of lactation. Vitamin E was determined by high performance liquid chromatography with fluorescence detection of the various tocopherols. The total tocopherol level was significantly higher in early milk than in mature milk. The difference was due to a high content of alpha-tocopherol, as the content of beta- and gamma-tocopherol was similar in the three milk types. The total tocopherol content in mature milk correlated significantly with both the total lipid and the linoleic acid content. Significantly higher tocopherol/linoleic acid ratios were found in both colostrum and transitional milk than in mature milk. The colostral milk differed from the other milk types in fatty acid composition, as it had a lower content of lauric acid and a higher content of arachidonic acid and docosahexaenoic acid. The linoleic acid levels reported here are considerably higher than those reported previously in Sweden. Still, the ratio of alpha-tocopherol equivalent/linoleic acid exceeded 0.5 mg/g in all but three milk samples.

Colostrum↗
PubMed1981

Inheritable molecular variants of moderate and mild hemophilia A.

Factor VIII clotting activity (VIII:C) and factor VIII clotting antigen (VIII:CAg) were investigated in 54 patients with hemophilia A of moderate or mild severity. The patients belonged to 28 kindreds. The study showed a genetically determined molecular variation within hemophilia A of both moderate and mild forms. Each form can be classified into 3 types according to the content of demonstrable VIII:CAg. Type I has no demonstrable VIII:CAg, type IIa has VIII:CAg in an amount smaller than, or approximately equal to, that of VIII:C and type IIb has a larger amount of VIII:CAg than VIII:C. Affected members of one and the same kindred always have the same type of the disease.

Antigens↗
PubMed1981

Factor VIII:C and VIII:CAg response in patients with haemophilia A and von Willebrand's disease after administration of different factor VIII concentrates or plasma.

Factor VIII procoagulant activity (VIII:C) and factor VIII procoagulant antigen (VIII:CAg) were studied in seven patients with haemophilia A after administration of three different factor VIII concentrates or plasma. The in vivo recovery of VIII:CAg was less than that of VIII:C and the disappearance rate of VIII:CAg was much higher either when concentrates or plasma were given. The half-life of VIII:C was thus about 12 h but of VIII:CAg only about 3 h or less. Six patients with von Willebrand's disease were studied after administration of AHF-Kabi. In contrast to haemophilia A the discrepancy between VIII:C and VIII:CAg disappearance rates was not present in von Willebrand's disease, since both VIII:C and VIII:CAg showed a typical progressive increase. We conclude that factor VIII:C given to haemophilia patients does not behave like native VIII:C, not even when fresh plasma is used. Patients with von Willebrand's disease are capable of forming a normal VIII:C when appropriately stimulated.

Adult↗
PubMed1981

Maternal and infantile infection with Chlamydia in a Swedish population.

Chlamydia trachomatis was isolated from 2.4% of 1 328 puerperal women. The frequency was highest in the age group below 20 years and thereafter decreased with increasing age. Chlamydial conjunctivitis was confirmed in 0.4% of the infants. Two additional cases of conjunctivitis occurred among the exposed infants but chlamydia cultures were not obtained. In a separate ophthalmological material of neonatal conjunctivitis a third of the cases developing within the first month of life was associated with chlamydia. The early and sharp incidence peak for chlamydial conjunctivitis suggested that transmission occurred at delivery. No cases of chlamydial pneumonia were noted. Peroral chemotherapy is recommended in infants for systemic eradication of C. trachomatis.

Adult↗
PubMed1981

The effect of dietary gamma-tocopherol on serum tocopherols in formulated infants.

The levels of alpha-, beta- and gamma-tocopherol were determined in two formulas (Nutramigen and Soja-semp) and in 20 infants fed either of these formulas. The gamma-tocopherol concentration in Nutramigen was 22.8 +/- 1.9 mumol/l; and that in Soja-semp 3.7 +/- 0.5 mumol/l. This difference was reflected in the serum tocopherols of the infants, since in the 10 infants fed Nutramigen, gamma-tocopherol accounted for 16.7 +/- 7.9% of the total tocopherols compared to 4.2 +/- 1.8% in the 10 infants fed Soja-semp. The study shows that gamma-tocopherol accumulates in the serum of infants fed large amounts of it. The serum gamma-tocopherol level should therefore be taken into account, when estimating the vitamin E status in humans, especially when the intake of gamma-tocopherol is high.

Female↗
PubMed1981

Pulmonary reactions to nitrofurantoin. 447 cases reported to the Swedish Adverse Drug Reaction Committee 1966-1976.

A dramatic increase in the number of adverse reactions to nitrofurantoin initiated a survey of the reports to the Swedish Adverse Drug Reaction Committee 1966-1976. Pulmonary reactions constituted about half of these reports: 398 cases with acute and 49 with chronic reactions. Three-quarters of the patients were hospitalized in connection with the reaction. Six reactions were fatal. The clinical picture and the laboratory findings differed considerably between the acute and chronic forms, although the age and sex distribution was very similar. About 85% of the patients were women. The median age was 59 years in the acute and 68 years in the chronic group. The acute pulmonary reactions carry the characteristics of an allergic reaction but we suggest that the chronic pulmonary and liver reactions may be caused by a toxic mechanism. Chronic reactions do not follow upon acute reactions, nor do acute reactions predispose to chronic ones. Early recognition of the reactions and prompt withdrawal of the drug are essential in both forms.

Adolescent↗