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Biomedical subjects

J D Nielsen

Publications and source records attributed to J D Nielsen.

At least 19 recordsLinked to original sources

[Acquired factor VIII deficiency treated with cyclosporine].

The treatment of acquired factor VIII inhibitors remains controversial, and no standard therapy exists. We describe a case story of successful treatment with prednisolone and cyclosporine of an 83-year old female with severe bleeding disorder due to an acquired factor VIII inhibitor. The patient had complete remission, and no side effects were observed. We recommend that treatment of acquired factor VIII inhibitor with cyclosporine is further investigated.

Aged

[Cross-sectorial cooperation regarding cancer patients in a recently started care program. Ideas and themes based on focus group interviews with general practitioners and oncologists].

This study identified ideas for an improved collaboration between general practitioners and oncologists regarding patients with cancer. A qualitative research-method with focused group interviews was chosen. The results demonstrated that both oncologists and general practitioners would like the general practitioners to take more active part in the total care programme for cancer patients. Some of the needed improvements were more detailed referral letters including description of treatment plans, information about what the patient had been told and general information about the specific cancer disease. Both parts desire bilateral information exchange and a dialogue about the distribution of tasks. Both parts are willing to collaborate but this is at present restricted due to lack of knowledge of each others' working areas and the oncologists' impression that general practitioners need more medical knowledge regarding specific aspects of cancer. A randomized intervention study using ideas from this study may clarify if it is possible to improve the collaboration and thereby the cancer patients' satisfaction with care.

Clinical Competence

Quality of reinfused drainage blood after total knee arthroplasty.

Reinfusion of postoperative wound drainage blood has become an attractive alternative in primary total knee and hip arthroplasty. Quality of the drainage blood was studied with respect to content of extracellular bioactive substances and coagulation split products. Using the HandyVac ATS autotransfusion system, drainage blood was collected and reinfused within 6 hours postoperatively from 10 patients undergoing primary total knee arthroplasty. Blood samples were collected from the patients immediately after and 1 hour after opening of the tourniquet and after reinfusion of drainage blood. Samples were also collected from the drainage blood immediately before and at the end of reinfusion. The leukocyte-derived and platelet-derived bioactive substances histamine, eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), plasminogen activator inhibitor type 1 (PAI-1), and activated complement factor C3(C3a) and various coagulation factors and split products were analyzed in patient and drainage blood samples. None of the patients received additional predonated autologous blood or allogeneic blood components during the study period. Within 6 hours postoperatively, 250 to 1,000 mL drainage blood was collected and reinfused. Histamine, ECP, EPX, MPO, PAI-1, and C3a content was significantly increased in drainage blood immediately before and at the end of reinfusion. Reinfusion did not change the concentration of these substances in samples from the patients. Coagulation factors and various split products showed that drainage blood was defibrinated. Reinfusion of drainage blood did not change the coagulative capacity of the patients. Drainage blood appears to be defibrinated and contains various extracellular leukocyte-derived and platelet-derived bioactive substances. Reinfusion does not change the coagulative capacity or the concentration of bioactive substances of patients.

Arthroplasty, Replacement, Knee

Bleeding and activation of coagulation during and after transurethral prostatectomy: importance of the acute-phase response and prostate specific antigen?

OBJECTIVE: To evaluate the importance of coagulation activation in patients with benign prostatic hyperplasia, undergoing transurethral prostatic resection (TURP) and to examine whether changes in activity are related to blood loss, the circulatory entry of prostate specific antigen (PSA), operative trauma (resected tissue weight) and the inflammatory response, as assessed by C-reactive protein (CRP). PATIENTS AND METHODS: TURP was performed in 24 men and the weight of resected tissue and blood loss determined. The activation of coagulation was followed using new sensitive and specific assays, and the changes related to blood loss, the release of PSA, operative trauma and the acute-phase response. The area under the curve (AUC) for the measured quantities was used in correlation analysis. RESULTS: TURP was followed by a marked activation in coagulation. There was no correlation between the markers of coagulation and the operative blood loss, but the latter correlated with the weight of resected tissue (P=0.001). Postoperatively, the blood loss correlated with prothrombin fragment (F1+2; P=0.010), with thrombin-antithrombin complexes (TAT; P=0.024), and with the PSA concentrations (P=0.016) but not with fibrinogen. Serum concentrations of PSA increased significantly and the AUC in the operative period correlated with F1+2 (P=0.003) and TAT (P<0. 005), but postoperatively only with F1+2 (P=0.013). The weight of resected tissue correlated operatively with PSA (P=0.012) but not with the concentrations of F1+2 or TAT. Postoperatively, there was a correlation with the acute-phase proteins, CRP (P=0.005), fibrinogen (P=0.012) and with PSA (P=0.020). CONCLUSION: The operative blood loss is caused by surgical factors and the observed postoperative hypercoagulable state can be explained as a physiological response to bleeding, i.e. to secure haemostasis. The activity of coagulation was unrelated to operative trauma, but the acute-phase proteins were. The release of PSA into the circulation probably has an effect on blood coagulation.

Acute-Phase Reaction

Safety of low-molecular-weight heparin in pregnancy: a systematic review.

Unfractionated heparin (UFH) remains the anticoagulant of choice during pregnancy. Low-molecular-weight heparins (LMWH) are an attractive alternative to UFH due to their logistic advantages and their association with a lower incidence of osteoporosis and HIT. We reviewed all published clinical reports concerning the use of LMWH during pregnancy. In addition, participants of an international interest group contributed a cohort of pregnant women treated with LMWH. Pregnancies were divided into two groups; those with and those without maternal comorbid conditions. The number of adverse fetal outcomes and the occurrence of maternal complications were evaluated in the two groups. In the group of women with comorbid conditions (n = 290), 13.4% of the pregnancies were associated with an adverse fetal outcome. In contrast, in the group of women without comorbid conditions (n = 196), 3.1% were associated with an adverse outcome, which is comparable to that seen in the normal population. We conclude that LMWH appear to be a safe alternative to unfractionated heparin as an anticoagulant during pregnancy.

Anticoagulants

[Cross-sectional therapeutic programs--an example of a cooperative health care system. A review with comments].

There is no tradition for sharing the responsibility for episodes of care between the primary and secondary sectors in the Danish health care system. Concurrently with increased international experience with shared care programmes, there is also a growing interest in Denmark in cooperation between the sectors. Based on literature research, shared care programmes are presented as a method of ensuring continuity and quality in treatment of chronic diseases. Experiences in the areas of diabetes, asthma, rheumatoid arthritis, and cancer are described. It is concluded that the Danish health care system is well prepared for the implementation of shared care programmes; there are only few sources of payment in the system, and an extensive continuing medical education system ensures that general practitioners can participate in relevant education. The implementation of shared care programmes in Denmark should be followed by scientific evaluation and documentation of the quality of the treatment programmes.

Delivery of Health Care

The effect of antithrombin on the systemic inflammatory response in disseminated intravascular coagulation.

Sepsis and major trauma are the two most common causes of disseminated intravascular coagulation (DIC) and are characterized by a sudden increase in inflammatory mediators. In general, the outcome of the patient is determined by the degree of the inflammatory response. In severe cases of sepsis and trauma, cascade systems, such as the coagulation, fibrinolytic and complement systems, are activated beyond the capacity of the autoregulatory mechanisms. During DIC, plasma levels of antithrombin (AT)--a serine protease inhibitor that acts mainly on the serine proteases of the coagulation system--decrease due to the formation and subsequent elimination of complexes between AT and activated coagulation factors. The consumption of AT may start a vicious circle by facilitating further intravascular fibrin formation, followed by ischaemic tissue injury and accelerated activation of blood coagulation. Infusion of AT has an anti-inflammatory effect through its ability to counteract microvascular thrombosis. Furthermore, AT induces the release of prostacyclin from the vessel wall by binding to glycosaminoglycans on the surface of endothelial cells. Prostacyclin has a marked anti-inflammatory effect as a result of its inhibitory effect on neutrophils, monocytes and platelets.

Animals

Lack of correlation between blood fibrinolysis and the immediate or post-operative blood loss in transurethral resection of the prostate.

OBJECTIVE: To evaluate whether the activation of the extrinsic tissue-type plasminogen activator-related fibrinolysis is implicated in the blood loss in patients with benign prostatic hyperplasia, undergoing transurethral prostatic resection (TURP). PATIENTS AND METHODS: TURP was performed in 24 men and the operative and post-operative blood loss determined. The activation of the tissue-type plasminogen activator-related fibrinolysis was followed using new sensitive and specific assays, and the changes related to the blood loss. Measurements of the plasma concentrations of free tissue-type plasminogen activator (t-PA) activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor 1 (PAI-1) antigen, plasminogen (Plg) activity, plasminogen (Plg) antigen, alpha 2-antiplasmin (alpha 2-AP), D-dimer and fibrin degradation products (FbDP) were all determined and the area under the curve (AUC) for each of these quantities correlated with the blood loss. RESULTS: TURP was followed by a marked activation of the fibrinolytic system. There was an immediate increase in systemic t-PA activity and t-PA antigen, coinciding with a significant drop in PAI activity. Post-operatively, PAI activity and PAI-1 antigen increased. The formation of plasmin was indicated by a fall in the plasma concentration of Plg activity and Plg-antigen and alpha 2-AP but which increased significantly at the end of the study period. Increased systemic fibrinolytic activity was further confirmed by a marked increase in fibrin D-dimer and FbDP. There was no correlation between the AUC in the operative period of any of the fibrinolytic variables and the measured blood loss. In the post-operative period, t-PA antigen (P = 0.004), PAI activity (P = 0.043), PAI-1 antigen (P = 0.016) and alpha 2-AP (P = 0.047) all correlated with the post-operative blood loss, while there was no correlation between fibrin D-dimer or FbDP and blood loss. CONCLUSION: The fibrinolytic system is activated during and after TURP, but the increased activity is not of pathophysiological importance for the blood loss.

Aged

Post-operative blood loss after transurethral prostatectomy is dependent on in situ fibrinolysis.

OBJECTIVE: To evaluate whether post-operative blood loss in patients with benign prostatic hyperplasia, undergoing transurethral resection of the prostate (TURP), depends on in situ fibrinolysis in urine, and to determine the relative contributions of the urokinase and tissue-type plasminogen activator systems. PATIENTS AND METHODS: TURP was performed in 24 men (median age 68.5 years, range 52-78) and the weight of resected tissue, the operative and post-operative blood loss determined. The concentrations of the urokinase- (u-PA) and tissue-type plasminogen activator (t-PA)-related fibrinolysis in their urine was followed using sensitive and specific assays, and the changes related to post-operative blood loss. Measurements of the urinary concentrations of free t-PA activity, t-PA antigen, free u-PA activity, u-PA antigen and fibrin degradation products (FbDP) were determined and the area under the curve for each of these quantities correlated with the post-operative blood loss. RESULTS: The post-operative blood loss correlated significantly with the per-operative loss (P = 0.047) and the weight of resected tissue (P = 0.029). There was a highly significant correlation between the area under the curve of FbDP in the urine and the post-operative blood loss (P < 0.005), while there was no significant positive correlation between the PA concentration or activity in the urine and post-operative blood loss. There was a significant correlation between the urinary t-PA activity and the amount of FbDP in the urine (P = 0.047), and a significant correlation between the weight of resected tissue and the amount of FbDP in the urine (P = 0.014). CONCLUSION: The post-operative blood loss after TURP is significantly related to an increase of the urinary fibrinolytic activity and the enhanced fibrinolytic activity is probably caused by t-PA.

Aged

Internal fixation of femoral shaft fractures in children and adolescents: a ten- to twenty-one-year follow-up of 52 fractures.

In a long-term follow-up (mean 16 years) of 52 femoral shaft fractures treated by internal fixation in 50 children and adolescents, we noted a mean overgrowth of 1 mm after plating and a mean undergrowth or relative shortening of 2 and 9 mm after nailing with broad (IMN) and slender (flexible rods: IMR) intramedullary nails, respectively. The mean overgrowth was 8 mm in children, but adolescents had a mean undergrowth of 5 mm (p < 0.01). Excessive overgrowth tended to occur less frequently after intramedullary nailing than after plating (p = 0.1). Undergrowth tended to occur with increasing frequency with increasing age and attained troublesome levels in three patients with severe trauma. Three cases of moderate valgus deformity of the hip and one case of late arthrosis of the hip occurred after intramedullary nailing with IMN introduced through the greater trochanter. We conclude that this method should not be used in patients with open physes.

Adolescent

Plasminogen activator inhibitor-1, tissue-type plasminogen activator, and fibrinogen: Effect of dieting with or without exercise in overweight postmenopausal women.

This study assessed the short- and long-term effects of an energy-restrictive diet with or without exercise on plasminogen activator inhibitor-1 antigen (PAI-1 Ag) and PAI-1 activity, tissue-type plasminogen activator antigen (TPA Ag), and fibrinogen serum levels. Healthy, overweight postmenopausal women (age, 53.8+/-2.5 years; body mass index, 25 to 42 kg/m2; n=121) were randomly assigned to one of three groups: control, 4200-kJ/d diet, or 4200-kJ/d diet with combined aerobic and anaerobic exercise. PAI-1 activity and PAI-1 Ag, TPA Ag, and fibrinogen levels were measured at baseline, after a 12-week intervention, and after a further 6-month follow-up. PAI-1 Ag and activity and TPA Ag were positively correlated with serum triglyceride levels, the abdominal-to-total-body fat ratio (as assessed by total-body dual-energy x-ray absorptiometry), fasting blood glucose, and systolic BP and negatively with HDL cholesterol and sex hormone-binding globulin. The diet led to profound decreases and normalization of PAI-1 activity (approximately 50%), PAI-1 Ag (approximately 30%) and TPA Ag (approximately (29%), but exercise conferred no additional effect. Fibrinogen did not change. At follow-up there were no longer any significant changes (P>.05). In conclusion, PAI-1 Ag and activity as well as TPA Ag seem to be part of the metabolic syndrome X. The diet made the blood less thrombogenic in the short term with no effect of the added exercise.

Exercise

Thrombogenesis.

Thrombosis occurs when there is a breakdown in the balance between thrombogenic factors and protective mechanisms. The thrombogenic factors may be exogenous (e.g. trauma, surgery), endogenous (e.g. cancer, vascular diseases) or both (e.g. atherosclerosis, complicated pregnancy). Defects in the protective mechanisms may be congenital (e.g. factor V R506Q-mutation, deficiency of protein C, protein S or antithrombin) or acquired (e.g. lupus anticoagulans, deficiency of antithrombin in nephrosis). In recent years, research in thromboembolic diseases has been overwhelmed with new observations, rendering it worthwhile to put efforts into the evaluation of thrombotic mechanisms in individuals suffering from or predisposed to thromboembolic diseases. Such efforts will pave the way for more effective prophylaxis in thrombosis-prone patients, more specific treatment of thrombotic diseases, and the mastering of recurrent thrombosis.

Animals

[Low molecular weight heparin versus unfractionated heparin in the treatment of deep venous thrombosis--a meta-analysis].

A review based on 17 randomised studies on low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) in the treatment of objectively verified deep venous thrombosis (DVT) is presented. Long-term treatment with LMWH was compared with long-term UFH in two studies and with warfarin in one study. In the rest of the studies LMWH and UFH were used during initiation of oral anticoagulant therapy, and these studies were included in a meta-analysis. The relative risk of progression of DVT during LMWH treatment compared with UFH was 0.63 (95% confidence interval: 0.39-1.00) and the relative risk of major bleeding was 0.41 (95% confidence interval: 0.24-0.70). There was no significant difference in the reduction of Marder score during treatment (LMWH 5.0 versus UFH 3.8) or in the frequency of new symptomatic, scintigraphically or angiographically verified pulmonary embolism (LMWH 0.6% versus UFH 1.1%). The frequency of complications seemed independent of whether LMWH was administered once or twice daily. Monitoring of LMWH treatment is not considered necessary but determination of anti-factor Xa in plasma is recommended if bleeding occurs during treatment with LMWH.

Heparin

Thrombosis and intrinsic fibrinolysis in percutaneous transluminal angioplasty.

Coagulation and fibrinolysis were investigated in 14 claudicants undergoing percutaneous transluminal angioplasty (PTA) for femoropopliteal artery lesions. Cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (t-PA) antigen, fibrinopeptide A (FPA), and plasminogen activator inhibitor-1 (PAI-1) activity were measured in peripheral blood. XL-FDP and t-PA increased, and FPA and PAI-1 decreased significantly after angioplasty. XL-FDP increased from baseline 266 +/- 72 ng/ml to 481 +/- 239 ng/ml (p < 0.0005) 30 min after PTA, indicating mural thrombus formation in spite of the significant fall in FPA influenced by heparin. A groin haematoma developed after PTA in 4/6 patients, who received more than 5600 IU heparin and in 1/8 patients receiving smaller dosages. The alterations in PAI-1 showed no correlation with those of t-PA, whereas heparin had a sparing effect on PAI-1 consumption. These findings may indicate that PAI-1 acts as a thrombin inhibitor following deep vessel wall injury by angioplasty. In two patients, who had signs of rethrombosis on the next day, residual FPA was relatively high, XL-FDP peaked at 3530 +/- 1170 ng/ml, and t-PA increased by 2.6 +/- 1.0 ng/ml. The corresponding values in patients with an uncomplicated course were 406 +/- 89 ng/ml (p < 0.0001) and 0.1 +/- 0.5 ng/ml (p < 0.02). We conclude that thrombin promotes activation of coagulation and fibrinolysis in femoropopliteal PTA. Instability between these counteracting systems resulting in thrombosis is not prevented by conventional heparin administration at dosages causing bleeding complications.

Aged

Preventive effect of levothyroxine in patients operated for non-toxic goitre: a randomized trial of one hundred patients with nine years follow-up.

OBJECTIVE: Earlier reports have shown different effects of levothyroxine in the prevention of recurrence of non-toxic goitre after operation. These studies have been either retrospective or of short-term follow-up. This study was designed to evaluate the efficacy of long-term Eltroxin treatment (levothyroxine 0.1 mg daily) in the prevention of post-operative recurrence of non-toxic goitre. DESIGN: Randomized prospective non-placebo controlled study with 9 years follow-up. Group A (n = 40) received levothyroxine and group B (n = 60) did not. PATIENTS: One hundred patients consecutively operated for non-toxic goitre. All clinically and biochemically euthyroid and none taking any thyroid and/or antithyroid medication. MEASUREMENTS: T3, T4, TSH, thyroid antibodies (microsomal/thyroglobulin), weight and neck circumference were measured and thyroid palpation were done preoperatively, 3 and 12 months after surgery and thereafter yearly up to 9 years. RESULTS: Sixty-nine patients completed 9 years follow-up. Incidence of recurrence in group A vs group B was 14.5 vs 21.8% (P < 0.05) irrespective of type of operation, pathoanatomical diagnosis, removed amount or remnant size of the thyroid gland and level of TSH. CONCLUSION: No preventive effect on incidence of recurrence of goitre by Eltroxin 0.1 mg daily in patients operated for non-toxic sporadic goitre was observed.

Adolescent

Thrombolytic therapy of acute myocardial infarction alters collagen metabolism.

The objective of the study was to monitor collagen metabolism after thrombolytic therapy. Sequential measurements of serum aminoterminal type-III procollagen propeptide (S-PIIINP) and carboxyterminal type-I procollagen propeptide (S-PICP) were made in 62 patients suspected of acute myocardial infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (p < or = 0.02), and decreased during the next 20 h with median values at 24 h still above the baseline (p < 0.02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p < 0.01), with values still elevated at 6 months. No similar biphasic pattern was found for S-PICP, but patients with acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p < 0.05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered for at least 6 months. Furthermore, fibrin-specific and nonspecific thrombolytic agents appear to affect collagen metabolism differently.

Aged

[Bacteriological urine analysis as part of check-ups on children. A retrospective study from general practice].

This paper presents a retrospective study of asymptomatic bacteriuria from general practice. The general practitioner had screened children's urine specimens for asymptomatic bacteriuria at the eight regular health examinations during preschool age. The urine was collected in special adhesive bags or as a midstream clean catch and investigated by stix and culture at the practitioner's. When significant bacteriuria was noted, a new urine sample was collected for analysis. If asymptomatic bacteriuria was again noted, the culture plates were sent to a microbiological hospital department for determination of bacterial type and antibiotic resistance. The children were subsequently treated with a relevant antibiotic. The material collected during 12 years consisted of 658 urine samples obtained from 1295 examinations of 208 children. Thirty-five samples (5.3%) were positive, and 30 of the children presented at least one positive sample (14.2%). Most of the positive samples were obtained during the first two years. However, the material is too small to obtain statistically positive results and must due to its retrospective nature be interpreted with care. Nevertheless, the high rate of infection in our study motivates the initiation of a regular prospective study.

Age Factors