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Biomedical subjects

I M Nilsson

Publications and source records attributed to I M Nilsson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Orthopaedic surgery in hemophilia. 20 Years' experience in Sweden.

At the International Hemophilia Center, Malmö, Sweden, which serves a large proportion of the Swedish hemophilia population, 98 orthopaedic surgical procedures were performed from 1970 to 1989 in 66 patients ranging in age from 6 to 71 years. The most common procedures were knee synovectomy, elbow synovectomy in combination with resection of the radial head, and total hip replacement. Comparing the 2 decades of the period, 3 differences were observed: a decreasing need of surgery, an increasing average age of the patients, and a change in the kinds of operations performed. Knee synovectomy and achillotenotomy were most frequent during the 1970s, whereas elbow synovectomy with resection of the radial head and total hip replacement were most frequent during the 1980s. Owing to the availability of regular factor replacement therapy as practiced at the Malmö Center, the situation of patients with hemophilia has improved dramatically during the last 2 decades. In the authors' opinion, it is now possible to avoid hemophilic arthropathy almost completely by giving effective continuous prophylaxis from an early age. In all likelihood, this is the explanation of the changing picture of orthopaedic surgery in patients with hemophilia today.

Adolescent↗
PubMed1995

Apheresis.

Treatment of hemophilia patients with inhibitors is most effective if circulating levels of factor VIII (F.VIII) or factor IX (F.IX) can be obtained. This is possible not only in patients with low inhibitor concentration, but also in those with high inhibitor levels after temporary removal of the inhibitors by means of apheresis methods. Extensive plasma exchange combined with huge doses of F.VIII has occasionally been tried, but the method is of limited capacity, and exposure to plasma products can initiate an anamnestic response of the inhibitor before treatment with factor concentrates can be started. A better alternative is extracorporeal immunoadsorption for removal of antibodies against F.VIII or F.IX. Two methods developed at the center in Malmö are presented. 1) Group specific elimination using protein A. This is done by computer controlled extracorporeal adsorption to protein A Sepharose columns of the antibodies in plasma transferred on-line to the plasma treatment apparatus (Citem 10, Excorim, Lund, Sweden). The plasma depleted of inhibitor is returned to the patient together with the separated blood cells. At the Malmö center, high titer inhibitors have so far been removed in 10 hemophilia patients, and 4 patients with acquired hemophilia, on a total of 25 immunoadsorption episodes. Usually between 2 and 4 plasma volumes were processed in the course of 6 to 12 hours. The inhibitor decreased to zero or very low levels, enabling conventional replacement therapy to be given for control of severe bleeding or as cover for surgery. The treatment is well tolerated and no signs of activation of the coagulation, fibrinolytic, and complement systems were seen. 2) Specific elimination using coagulation factor. A method has been developed for the removal of F.IX antibodies directly from whole blood in a continuous extracorporeal system. A F.IX preparation with a specific activity of 92 units per mg protein was covalently coupled to Macro Beaded Sepharose, which allows passage of whole blood. One ml of the absorbent was capable of binding about 2100 BU. The F.IX antibodies could be specifically adsorbed directly from citrated whole blood with a minimal extracorporeal volume. In this way, high-titer antibodies could be removed from a boy with hemophilia B, by passing four times his blood volume through the F.IX column. No side effects were noted. In the future it will be possible to use immobilized F.VIII in a similar system for the removal of F.VIII antibodies.

Adolescent↗
PubMed1994

Is haemophilia prophylaxis achievable in the context of self-sufficiency?

In Sweden prophylactic treatment in haemophilia was introduced in 1958. Patients receiving prophylactic treatment have less time off school or work, require less hospitalization, have fewer joint bleeds, and generally lead as near normal life as possible. Although prophylaxis is expensive the cost is off-set by the improvement in quality of life and in productivity. At present, Sweden is almost self-sufficient in blood products for prophylactic treatment of haemophiliacs.

Adolescent↗
PubMed1994

[Haemophilia--then and now].

Haemophilia is a bleeding disorder which has always attracted wide interest both among physicians and the laity--uncontrollable haemorrhage, blood that fails to coagulate and heredity with only males affected. The disease is probably best known to the public through its appearance in European royal families and in the Russian Imperial family. The oldest known description of haemophilia is to be found in the Talmud, the collection of ancient Judaic books from the early centuries of our era. The first clinical account of haemophilia was published by the American, Otto, in 1803. He described the disease as an inheritable bleeding disorder occurring only in males, and transmitted by female carriers who are not themselves affected. The disease manifests itself in early childhood, joint bleedings being its most characteristic feature. Otto called the male patients "bleeders". The term, haemophilia, originated with a German, Friedrich Hopff (1828), who coined the name "haemorrhaphilia" which was later abbreviated to haemophilia. ... As to future prospects, it is hoped that it will soon be possible to cure the disease by means of gene therapy, and to this end promising experimental work is already in progress.

Blood Coagulation↗
PubMed1993

Biochemical and in vivo properties of high purity factor IX concentrates.

The purified factor IX concentrates Nanotiv (Kabi Pharmacia), Immunine (Immuno), Factor IX VHP (Bio-transfusion), Alphanine (Alpha) and Mononine (Armour) have been studied in vitro and compared with the prothrombin complex concentrates (PCCs) Preconativ (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for factor IX coagulant activity (IX:C) were in good agreement with the manufacturer's label values. In contrast to the PCCs, most of the purified concentrates were virtually devoid of other vitamin K-dependent coagulation factors, the inhibitors protein C and S as well as fibrinogen, fibronectin and immunoglobulins. Indicators of thrombin generation, namely prothrombin fragments 1 and 2 (F 1 + 2) and thrombin-antithrombin complex (TAT), were present in varying amounts in all preparations. The specific activity in the purified concentrates exceeded that in the PCCs by a factor of 50-100. Some differences in purity were found between the purified concentrates. In vivo, Nanotiv was compared with Preconativ and Immunine with Prothromplex TIM4 in crossover studies in patients with severe hemophilia B, and Mononine was tested in a single drug study. Most of the preparations yielded postinfusion increases in TAT, but not in F 1 + 2. Pharmacokinetic variables were analyzed with non-linear curve-fitting combined with model-independent methods. In retrospective comparisons, there were no apparent differences between Nanotiv, Preconativ and Mononine, whereas in vivo recovery seemed lower and the apparent clearance higher for Immunine and Prothromplex. Purified factor IX concentrates were successfully used as cover for surgery or in immune tolerance induction.

Adult↗
PubMed1993

Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate.

The pharmacokinetic profile, the thrombogenicity and the virus safety of Preconativ, a PCC subjected both to virus removal procedure and dry-heat treatment were studied. Preconativ is produced from plasma pool, negative both for HBsAg and for antibodies to HIV. To further reduce the risk of virus transmission, the manufacturing process includes hydrophobic gel chromatography and dry-heat treatment at +68 degrees C for 48 hours. Nine patients with hemophilia B participated in a single dose, pharmacokinetic study. The decay curves of factor IX clotting activity were evaluated by model-independent methods. The Clearance and the Mean Residence Time were very similar to those previously reported for untreated PCC. The Volume of Distribution Area and In Vivo Recovery resulted inversely correlated and respectively larger and smaller than those of untreated PCC. A slight fall in platelet count and Antithrombin III level and an increase of Beta-Thromboglobulin and Fibrinopeptide A concentration were found, indicating a clear-cut activation of the coagulation process during the first hours following Preconativ administration. Seven patients (2 of the ones enrolled in the pharmacokinetic study) were completely fulfilling the SSC-ISTH criteria for virus safety prospective study. The follow up of these patients did not show any transaminases elevation or seroconversion against HBV, HCV or HIV. These findings did not change over a 3-5 year follow up in 3 out of 7 patients, repeatedly infused with Preconativ.

Adolescent↗
PubMed1993

Determination of the distance between the oligosaccharyltransferase active site and the endoplasmic reticulum membrane.

By in vitro transcription/translation of model proteins in the presence of dog pancreas microsomes, we have measured the minimum distance of an acceptor site from the lumenal end of a transmembrane segment required for N-linked glycosylation, both when the acceptor site is placed N- and C-terminally to the membrane anchor. We observe a sharp threshold at a distance of 12-14 residues, suggesting that the oligosaccharyltransferase active site is 30-40 A above the membrane and is oriented roughly parallel to the membrane surface.

Amino Acid Sequence↗
PubMed1993

Different sec-requirements for signal peptide cleavage and protein translocation in a model E. coli protein.

We describe a secretory E. coli protein with a novel phenotype: signal peptide cleavage is largely unaffected whereas chain translocation is efficiently blocked under conditions where SecA, a central component of the secretory machinery, is rendered non-functional, and we have traced this phenotype to the presence of a mildly hydrophobic segment located approximately 30 residues downstream of the signal peptide. When this segment is deleted, normal SecA-dependent signal peptide cleavage and chain translocation is observed; when its hydrophobicity is increased, it becomes a permanent membrane anchor with cleavage of the signal peptide and membrane insertion both being SecA-independent. These findings suggest that the initial insertion of the signal peptide across the membrane can be uncoupled from the translocation process proper.

Amino Acid Sequence↗
PubMed1993

Two new candidate mutations in type IIA von Willebrand's disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor.

Recently, several von Willebrand factor gene mutations resulting in type IIA von Willebrand's disease have been reported. We examined 8 patients from Sweden and Denmark with this phenotype and found two new candidate mutations and a hitherto unknown amino acid polymorphism. One patient had a de novo occurring mutation resulting in substitution of glycine for arginine 834. Previous reports have demonstrated conversion of arginine 834 to tryptophan or glutamine in IIA patients. A 2nd patient had a G(4825)-->A transition, substituting arginine for glycine 846. The transition produces a sequence congruent with that of the pseudogene but several lines of evidence indicate that a sequencing error due to influence by the latter could be excluded. The remaining 6 patients had one of the earlier described substitution mutations: Ser743-->Leu and Ile865-->Thr. In addition, two sequence variations not linked to the phenotype were found, namely Tyr821-->Cys and Val802-->Leu.

Adolescent↗
PubMed1992

Thromboembolic disease--critical evaluation of laboratory investigation.

Previous studies of patients with thromboembolic disease have revealed an association either with hereditary anticoagulant protein deficiencies or with defects in the fibrinolytic system. To obtain a more comprehensive picture and to investigate which analyses are useful in the evaluation of such patients, we have performed an extensive laboratory investigation in 439 individuals with thromboembolic disease. Anticoagulant protein deficiencies were found in 24 patients. Deficiencies of protein C (n = 10) and protein S (n = 9) were most common followed by deficiencies of antithrombin III (n = 3) and plasminogen (n = 2). Six of the nine protein S deficient patients demonstrated a selective deficiency of free protein S with normal total protein S concentrations. To diagnose protein C and S deficiencies among the 201 patients receiving oral vitamin K antagonists, the concentrations of protein C and S were compared with the mean concentration of several other vitamin K-dependent proteins. One protein C and three protein S deficiencies were identified among the treated patients. The number of protein C deficiencies found in this group was significantly lower than the number found among untreated patients. Although fewer protein S deficiencies were also identified among the treated patients, than in the untreated group, the difference was not statistically significant. The results suggest that protein C deficiencies went undetected in the treated group and that oral anticoagulant therapy should be discontinued before efforts to diagnose protein C deficiency are made. We found no cases with heparin cofactor II deficiency. Lupus anticoagulant was present in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗