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Biomedical subjects

H Johnsson

Publications and source records attributed to H Johnsson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients.

The pharmacokinetics of a second-generation recombinant B-domain deleted factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to be added to stabilize the final formulation of this B-domain deleted FVIII preparation. The in vivo recovery and half-life of r-VIII SQ were similar to those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The volume of distribution and clearance were slightly, but significantly, higher for r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r = 0.94, p < 0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced after repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B-domain of FVIII does not influence its in vivo pharmacokinetics.

Adolescent↗
PubMed1997

A 6-month venographic follow-up in 164 patients with acute deep vein thrombosis.

UNLABELLED: A total of 164 patients were recruited from a randomized trial comparing a low molecular weight heparin, dalteparin, given subcutaneously once daily with a continuous intravenous infusion of unfractionated heparin in the initial treatment of acute deep vein thrombosis. The primary objective of this follow-up study was to investigate whether there were any differences between the two treatment groups with respect to Marder score changes 6 months after the initial diagnosis using repeated venography. The secondary objectives were to analyse whether certain haemostatic and acute phase parameters or patient characteristics influenced the venographic outcome. RESULTS: Complete lysis of the thrombus was observed in 38.4% of the patients and a partial lysis in another 54.3% assessed by venography 6 months after the acute event. Extension of the thrombus was seen in 7.3% of the patients. There were no significant differences in the change in mean Marder score before treatment and at the 6 month follow-up between the two treatment groups, irrespective of thrombus localisation. In a regression model, male gender, low levels of orosomucoid and increased levels of d-dimer in plasma on day 5 were independently associated (p <0.05) with an enhanced absolute resolution of the thrombus at 6 months. No differences in symptoms and signs in the thrombotic leg at follow-up, comparing the treatment given, or thrombus extension at diagnosis and 6 months later, were demonstrated. CONCLUSION: Dalteparin given once daily subcutaneously was as effective as continuous intravenous infusion of unfractionated heparin in the initial treatment of deep vein thrombosis assessed by Marder score evaluation 6 months after the acute event.

Acute Disease↗
PubMed1996

Altered properties of the fibrin gel structure in patients with IDDM.

High plasma fibrinogen levels are associated with vascular complications in the general population. Fibrin, the structural element in a clot, is derived from fibrinogen by activation of thrombin. An abnormal fibrin gel structure has been demonstrated in patients with myocardial infarction and in diabetic patients during poor metabolic control. In the present study the properties of fibrin gel structure were investigated in 20 patients with insulin-dependent diabetes mellitus (IDDM): 10 patients without (age: 30 +/- 8; diabetes duration: 7 +/- 6 years), and 10 patients (age: 44 +/- 7; diabetes duration: 27 +/- 9 years) with microangiopathy. Fifteen healthy subjects served as controls (age: 40 +/- 8 years). The glycosylated haemoglobin level (HbA1c) was elevated (p < 0.001) in the patients: 6.5 +/- 1.5% in diabetic patients without, and 7.1 +/- 1.0% in diabetic patients with microangiopathy. C-reactive protein and plasma fibrinogen were similar as compared to healthy control subjects. The properties of the fibrin gel structure; i.e. the permeability coefficient (Ks) and the fibre mass length ratio (mu) formed in recalcified plasma on addition of thrombin were investigated. Ks was decreased in the diabetic patients, with (6.5 +/- 2.0 cm2; p < 0.01) and without microangiopathy (6.5 +/- 2.7 cm2; p < 0.05), as compared to healthy subjects (10.0 +/- 3.4 cm2), while mu was not significantly (p = 0.14) altered. The results indicate a lower fibrin gel porosity in patients with IDDM, despite normal plasma fibrinogen and irrespective of microangiopathy. The abnormal fibrin gel structure may be due to an increased glycosylation of the fibrin (-ogen) molecule caused by long-term hyperglycaemia and may be of importance for the development of angiopathy in diabetic patients.

Adult↗
PubMed1996

Major surgery in haemophilic patients with inhibitors using recombinant factor VIIa.

In the haemophilic patient, development of antibodies that inhibit the function of the missing coagulation factor causes several delicate problems. Most importantly, antibodies will block the function of the specific coagulation factor, and often the antibody activity is so fierce that effective substitution therapy is outruled. In consequence, alternative measures must be adopted to control bleeding. Amongst those most commonly employed, like factor IX concentrates, activated prothrombin complex concentrates, and factor VIII of porcine origin, a new recombinant activated factor VII molecule has been evaluated clinically for some years with promising results. The aim of the present paper was to present a series of patients suffering from haemophilia A or B in whom inhibitors have complicated the clinical picture, and in whom a surgical procedure was indicated. As part of a compassionate use program devised by the producer of this genetically engineered factor VIIa, 12 patients underwent life-saving or essential surgery where the recombinant factor VIIa product was used to promote haemostasis in 13 surgical procedures. Due to a short in vivo half-life of activated factor VIIa, frequent administration was scheduled, injecting factor VIIa every 2-3 h for up to 2 days after which dosage intervals were prolonged. In one case, a global evaluation of the end treatment result was not reported, but in all of the other 12 cases the end result were considered excellent (n = 11) or efficient (n = 1). In none of the cases was other types of coagulation factor treatment modalities necessary. In conclusion, recombinant factor VIIa seems a tempting alternative to traditional treatment of the haemophilic patient with inhibitors, in whom surgery is called for. With other types of haemostatic agents, surgery in haemophilic inhibitor patients has only been studied rarely, and operations have generally been restricted to life-threatening situations.

Adolescent↗
PubMed1996

In vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway.

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.

Adult↗
PubMed1995

Influence of changes in lifestyle on fibrinolytic parameters and recurrence rate in patients with venous thromboembolism.

A prospective, non-randomized, interventional study was carried out to evaluate the effect of changes in lifestyle on abnormal fibrinolytic parameters, and the influence of those, in turn, on the risk of recurrence among patients with venous thromboembolism. Patients with elevated plasminogen activator inhibitor 1 (PAI-1) levels or decreased release of tissue plasminogen activator (t-PA) antigen were given information and advice about improved diet, increased physical activity, weight loss and/or cessation of smoking. Totally 144 patients (119 with elevated PAI-1 and 25 with deficient t-PA release) were followed with repeated analyses of the fibrinolytic parameters for a median of 8 months after the initial advice, and 65% of the patients managed to execute at least one change in their lifestyle. The reduction of PAI-1 activity after one, two and three changes in lifestyle were -2.4, -10.0 and -14.0 AU/ml (-10, -30 and -48% of baseline activity), respectively. Those who accomplished two or three changes in their lifestyle had a greater chance of normalizing the PAI-1 level than those with no or only one change (P = 0.009). The effects of improved diet, weight loss and increased physical activity on the PAI-1 level were of a similar magnitude, -7.0 to -10.4 AU/ml (24-32% reduction). The effect on t-PA release was more difficult to evaluate due to the limited number of those patients. After a follow-up of 6 years (mean) after the first visit the patients were inquired about recurrent events, with a response rate of 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Intracranial traumatic and non-traumatic haemorrhagic complications of warfarin treatment.

An increased referral of patients with anticoagulation related haemorrhages necessitated an analysis of causes and outcome of these complications in a patient group that reflected Swedish therapeutic traditions of anticoagulation treatment. Prospectively, all patients from Stockholm evaluated for warfarin related intracranial haemorrhage occurring during 1987 were analysed and their 6 month outcome recorded. Sixty-eight patients were included. The results of intracranial haemorrhagic complications were catastrophic with a 77% mortality rate. Their incidence was much higher than expected. Forty-one patients had non-traumatic intracerebral haematomas, 1 had a non-traumatic subarachnoid haemorrhage and 26 had traumatic injuries. In the 42 patients with non-traumatic haemorrhages, the indications for anticoagulation were cerebral ischaemic events in a majority (27/42). The remaining 15 patients had different indications for anticoagulation. They also had an increased frequency of hypertension (p < 0.05). In the 26 patients with traumatic haematomas, only 6/26 patients had previous cerebral ischaemic injuries (p < 0.01). Valvular heart prosthesis was their most common indication (11/26) for anticoagulation. Caution in instituting anticoagulation therapy in patients with hypertension or cerebrovascular disease, which is an important indication for anticoagulation in Sweden, is mandatory. Adherence to strict treatment regimens and their continuous reevaluation may help to avoid complications. The finding of more patients than expected with haemorrhagic complications is not compatible with the risk evaluations used to justify anticoagulation therapy in the patient groups studied. Clinical practice must have changed with time, showing that risk evaluations from controlled trials or retrospectively collected clinical data from selected patients are not necessarily applicable for long-term clinical practice.

Adult↗
PubMed1994

The incidence of neonatal pneumococcal septicemia in Sweden 1991-92. The result of a national survey.

In a survey of the incidence of pneumococcal neonatal septicemia in Sweden 1991-92, to our knowledge the first nationwide survey of this kind, an incidence of 3.6/100,000 was found. Based on this, the relative incidence of neonatal septicemia caused by pneumococci was calculated to be 0.9-1.3%. Despite recent reports of pneumococci resistant to antibiotics, no resistant strain was found, and among the affected neonates, all treated with conventional antibiotics, there was a lower mortality as compared to prior reports. This might reflect the facts that the infants were less often born preterm, were less often born after premature rupture of membranes, and had a higher proportion with a late onset of symptoms than in earlier surveys.

Bacteremia↗
PubMed1994

Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis.

Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin, administered subcutaneously (s.c.) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i.e. an Internation Normalised Ratio, of 2.0-3.0). A second venogram was obtained after Fragmin or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT.

Adult↗
PubMed1993

Serum lipoproteins and hemostatic function in intermittent claudication.

Normoglucemic men with intermittent claudication (n = 41), mean age of 63 years, and sex-, age-, body mass index-, and smoking habit-matched controls (n = 75) were compared for plasma lipoprotein and hemostatic variables. The patients had significantly lower levels of large high-density lipoprotein (HDL) particles (HDL2b, HDL2a, and HDL3a) and elevated lipoprotein(a) [Lp(a)] concentrations than the control subjects. Of the hemostatic variables, plasminogen activator inhibitor-1 (PAI-1), plasma antiplasmin, plasma fibrinogen, and urine beta-thromboglobulin concentrations were significantly elevated in patients. In intermittent claudication patients Lp(a) correlated significantly with activation of the coagulation system, ie, with the levels of plasma fibrinogen and urine fibrinopeptide A. No correlations between the values for Lp(a) and PAI-1 or plasma alpha 2-antiplasmin were seen. The PAI-1 activity showed significant univariate correlations to the levels of HDL3b, HDL2b (inverse), and very-low-density lipoprotein triglycerides, of which the positive correlation to HDL3b persisted in multivariate analysis (r = .48, P < .001). Independent characteristics for intermittent claudication estimated by multiple regression analysis were PAI-1, plasma fibrinogen, and HDL3a, with a combined R2 of .36. The intermittent claudication subgroup that was being treated with beta-blockers/thiazides had a higher frequency of coronary heart disease compared with the other patients. In addition, the patients taking beta-blockers/thiazides had elevated triglyceride concentrations, lower HDL cholesterol with a size shift toward smaller particles, and a tendency toward raised PAI-1 and plasma alpha 2-antiplasmin levels compared with the patient group that did not take these medications.

Blood Coagulation↗
PubMed1992

Neonatal septicemia caused by pneumococci.

Pneumococci (Streptococcus pneumoniae) infrequently cause neonatal septicemia. An increased number of cases have been reported in recent years, but no increase in the relative incidence among neonatal infections has been noted. On the basis of two cases of our own and a review of 40 recently published case reports, the clinical characteristics of pneumococcal septicemia are described and the pathogenesis is discussed. The presenting clinical picture in early-onset pneumococcal septicemia is dominated by respiratory distress, frequently accompanied by leukopenia, and is indistinguishable from that seen in septicemia caused by Group B Streptococci (GBS). The onset is preceded by prelabor rupture of the fetal membranes in almost half of the instances. The mortality is 50%, twice the figure given in recent GBS reports.

Disease Outbreaks↗
PubMed1992

Two cases of neonatal pneumococcal septicemia.

Pneumococci (Streptococcus pneumoniae) infrequently cause neonatal septicemia. An increased number of cases have been reported in recent years, but no increase in the relative incidence among neonatal infections has been noted. Two recent cases that occurred within a short period of time are described. They were found to exhibit most clinical characteristics, previously described, of Group B Streptococci (GBS) septicemia with an early onset, but appear to have a graver prognosis.

Adult↗