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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 289 records · Page 16Linked to original sources

Adverse reactions to nitrofurantoin. Analysis of 921 reports.

Reports on adverse reactions to nitrofurantoin today are common in Sweden and constitute 10 to 12 percent of all incoming reports. We present an analysis of 921 reports of adverse reactions received by the Swedish Adverse Drug Reaction Committee during the period 1966--1976. The two largest groups consist of reports of acute pulmonary reactions (43 percent) and allergic reactions (42 percent). The remaining reports fall into any of four smaller groups, chronic pulmonary reactions, liver damage, blood dyscrasias or neuropathy. Acute pulmonary and acute allergic reactions in all aspects are very similar and carry the characteristics of an acute hypersensitivity reaction. The increasing number of reports--even in relation to sales figures--would be best explained by a continuous sensitization. Chronic pulmonary reactions (interstitial pneumonitis) afflict older patients, often after prolonged treatment with relatively small doses. We suggest that these reactions are elicited by a toxic mechanism. Seventy-one percent of all reactions were severe enough to cause the patient's hospitalization; only 1 percent was fatal. The risk of an adverse reaction varies with sex and age, increases with age and is higher in women than in men. The time has come for a re-evaluation of nitrofurantoin and its role in the treatment of urinary tract infections.

Acute Disease↗

Characteristics of the factor VIII protein and Factor XIII in various factor VIII concentrates.

The in vitro properties of 5 factor VIII preparations (AHF-Kabi, Hemofil Hyland, AHF-Profilate Abbott, Kryobulin Immuno and Factorate High Purity Armour) and an ordinary cryoprecipitate were studied with reference to factor VIII clotting activity (VIII:C), factor VIII clotting antigen (VIII:CAg), factor VIII related antigen (VIIIR:Ag) (EI, IRMA, CIE), ristocetin cofactor activity (VIIIR:RCF), fibrinogen and factor XIII. All the preparations with the exception of Factorate had higher levels of VIII:CAg than VIII:C indicating inactivation of the biological activity of VIII:C during the procedure. AHF-Kabi (fraction I-0) and the cryoprecipitate, the only preparations capable of normalising the defect in patients with von Willebrand's disease, showed the same level of VIIIR:Ag determined by EI and by IRMA, while all the other preparations (i.e. cryoprecipitates purified further in different ways) had considerably lower levels of VIIIR:Ag determined by IRMA than by EI. Based on these in vitro techniques it seems to be possible to predict which preparations can be used successfully in patients with von Willebrand's disease, while no such conclusions can be made from VIIIR:RCF determinations. EI yielded similar concentrations of factor XIII a subunit in all the preparations tested. 3 functional assays showed high factor XIII activities in AHF-Kabi but low or no activities in the others. Thus, considerable differences were found on the in vitro properties of the proteins in 5 factor VIII concentrates and a cryoprecipitate. The action of proteases and the techniques used in the purification procedure are probably of crucial importance for the properties of the various factors.

Antigens↗

PPD testing as a diagnostic aid in non-tuberculous mycobacteriosis. Clinical and immunological investigations in 4 children with cervical lymphadenitis.

Four children suffering from unilateral cervical lymphadenitis with histopathological changes typical of mycobacteriosis were seen during a short time. None of the Children had been BCG vaccinated. Mycobacteria belonging to the Myobacterium aviumintracellulare complex were isolated from excised lymph nodes in two of the patients. Intracutaneous tests with PPD from M. tuberculosis were negative in all the children, whereas two children responded to each of 3 PPDs prepared from atypical mycobacteria. Two patients were unreactive in all the skin tests. Lymphocyte transformation tests in vitro with a battery of various PPDs indicated sensitization to atypical mycobacteria in two children, one of which was negative in the skin tests. All the patient had normal plasma Ig concentrations but two patients had low proportions of T lymphocytes in the peripheral blood. One of these also had reduced total numbers of T cells. Nevertheless, lymphocyte responses in vitro to phytohaemagglutinin were normal in all the children. The results show that cutaneous and in vitro tests with a battery of different PPDs have a place as diagnostic adjuncts in atypical mycobacteriosis. We suggest that immunological competence is analysed in such patients.

Child, Preschool↗

Binding of urokinase to plasma proteinase inhibitors.

125I-labelled urokinase was incubated with plasma and plasminogen free plasma, and the incubation mixtures were analyzed by agarose gel electrophoresis. Autoradiography demonstrated that non-reacted urokinase remained around the slit and that complex-formation with inhibitors altered the migration and resulted in two bands, a major one and a minor one. Crossed immunoelectrophoresis combined with autoradiography showed that the major band contained a complex between alpha 2-antiplasmin and urokinase. The minor band contained a complex between alpha 2-macroglobulin and urokinase. Also di-isopropylfluorophosphate-inactivated urokinase was bound to alpha 2-macroglobulin but not to alpha 2-antiplasmin. Thus, an intact active site of urokinase is not necessary for complex formation with alpha 2-macroglobulin.

Endopeptidases↗

Prenatal diagnosis of hemophilia B by an immunoradiometric assay of factor IX.

An immunoradiometric assay of factor IX was developed based on homologous antibodies that arose in a hemophilic patient. With this assay, 11 of 12 patients with severe hemophilia B had factor IX antigen levels below 1 U/dl and 6 patients with mild hemophilia B had various levels. Factor IX antigen in 8 fetuses (16th-20th gestational week) aborted for therapeutic reasons ranged from 1.8 to 10.0 U/dl. Six amniotic fluids contained 0.28-1.2 U/dl factor IX antigen. Using the immunoradiometric assay, we could diagnose hemophilia B prenatally in one fetus at risk. No factor IX antigen (< 0.2 U/dl) was detectable in the fetoscopic sample. After termination of the pregnancy, analysis of blood from the abortus confirmed the diagnosis of severe hemophilia B. We conclude that very sensitive immunologic assays, such as the one described here, will prove useful in prenatal diagnosis of severe hemophilia B, since determination of factor IX activity in fetoscopic samples is unrealiable because of possible contamination with thromboplastic material.

Dose-Response Relationship, Immunologic↗

Purification of urokinase by a beta-naphthamidine affinity column.

Urokinase was purified by affinity chromatography using 6-amino-naththamidine-(2), a new specific ligand based on the urokinase inhibitor beta-naphthamidine. Urokinase was firmly bound at pH 7.0 and could be eluted at pH 3.0. The protein which passed the column at pH 7.0 without being bound did not contain any urokinase activity. This is an important property because it can be utilized for raising a monospecific urokinase antiserum by absorbing unspecific antibodies with only a minor loss of antiserum titre.

Amidines↗

Fanconi's anaemia associated with haemophilia A.

Fanconi's anaemia and haemophilia A are born inherited diseases creating haemostatic defects. The association of these two rare diseases in one patient is described. The patient's haemophilia was studied with a newly developed immunological technique determining the plasma antigen associated with Factor VIII activity, and was found to be a genetic variant of moderately severe haemophilia A. It was not possible to demonstrate a common bone marrow defect or a common immunological or genetical background of the two diseases. The double haemostatic defect created, i.e. Factor VIII deficiency and thrombocytopenia, resulted in only a slight increase in bleeding tendency. A favourable result was obtained with corticosteroid and androgenic treatment.

Abnormalities, Multiple↗

Measurement of antihaemophilic factor A antigen (VII:CAg) with a solid phase immunoradiometric method based on homologous non-haemophilic antibodies.

Antihaemophilic-factor-A-antibodies, which had spontaneously arisen in 2 patients, were used to develop an immunoradiometric method for measurement of antihaemophilic factor A antigen (VIII:CAg). 13 patients with severe haemophilia A had VII:CAg below the limit of detection (0.01 U/ml). Patients with moderate and mild haemophilia A either had VII:CAg roughly equal to factor VIII clotting activity (VIII:C) or a not detectable VII:CAg, suggesting 2 different molecular mechanisms in moderate and mild haemophilia A. VIII:CAg could be detected in serum but in lower amounts than in plasma. In 2 patients with von Willebrand's disease VIII:CAg equalled VII:C. The post-transfusional retarded increase of VII:C in 1 patient with von Willebrand's disease was accompanied by a slight increase in VIII:CAg. Fetal plasma contained measurable amounts of VII:CAg.

Antibodies↗

Medicinal iron to low birth weight infants.

Serum ferritin concentrations were measured during the first 6 months of life in 28 low birth weight infants (mean birth weight 1820 g range 900-2460; mean gestational age 34 weeks range 29-37) fed a standard formula fortified with ferrous sulphate. Fifteen of the infants received supplementary medicinal iron (ferrous succinate) from 3 weeks of age, and 13 only from 2 months of age. All were given vitamin E from 10 days of age. The serum ferritin values did not differ between the groups at 1-2 days, 8-10 weeks or at 6 months. Furthermore, there were no signs of hyperhaemolysis at 8-10 weeks in the group receiving medicinal iron early. The data indicate that the iron content in the formula is sufficient until 2 months of age, but also that thereis no disadvantage in starting medicinal iron at 3 weeks of age, if the diet is sufficient in vitamin E.

Breast Feeding↗

Variation of serum ferritin in low birth weight infants with maternal ferritin, birth weight and gestational age.

Serum ferritin measured at birth in 69 low birth weight infants proved to vary with gestational age as well as with weight. The increase with gestational age was even more striking when the infants small for gestational age were excluded. The relation between maternal and infant serum ferritin concentration was investigated for 2 groups of infants and their mothers (*preterm and term infants, respectively). Neither in preterm nor in term infants was the serum ferritin found to vary with that in the respective mothers.

Birth Weight↗

Infectious mononucleosis and agranulocytosis.

Infectious mononucleosis is often complicated by haematological abnormalities but agranulocytosis is so rare that a causal relationship has been questioned. We here describe 2 sisters, 3 and 5 years old, who both developed agranulocytosis or profound granulocytopenia 4-5 weeks after the acute onset of mononucleosis. No contributory cause could be found and we conclude that a constitutional disposition may be responsible for this complication.

Agranulocytosis↗

Fatal reactions to drugs. A 10-year material from the Swedish Adverse Drug Reaction Committee.

Drug-induced deaths (n = 274) in Sweden during a 10-year period have been analyzed. The incidence has been remarkably constant, with 25--30 reported cases per year. There is a marked increase with age in the incidence of fatal reactions, more so than for all drug reactions. Women consume more drugs than men and get more reactions, but not more fatal reactions. Anti-inflammatory drugs (antibiotics and sulfonamides) are responsible for 21% of the fatal reactions, followed by oral antidiabetics (9%), oral contraceptives (9%) and antiphlogistic drugs (8%). The blood and the bone marrow are the most susceptible organs, responsible for 40% of the fatal reactions, followed by thromboembolism (10%) and hepatocellular damage (9%). It is important to note that rapid changes have occurred with regard to responsible drugs as well as to the types of adverse reactions encountered.

Adolescent↗