Dose relation in the prevention of proximal vein thrombosis with a low molecular weight heparin (tinzaparin) in elective hip arthroplasty.

This is a review of a double-blind, prospective study comparing the thromboprophylactic efficacy and safety of two different prophylactic regimens of a low molecular weight heparin (tinzaparin) in 250 consecutive patients (aged < or 18) undergoing primary elective hip arthroplasty. Regimen 1: 75 U anti-Xa/kg BW (actual range 63 to 91) once daily started 12 hours before operation; and regimen 2: 50 U anti-Xa/kg BW (actual range 41 to 71) once daily started 2 hours before operation. Both regimens were administered in a weight-adjusted fashion and were continued for 7 days after operation or until full mobilization. Efficacy was evaluated by occurrence of postoperative deep vein thrombosis (DVT) diagnosed by bilateral ascending phlebography on day 7 +/- 2 after operation, and the venograms were evaluated in an assessor blind fashion by a panel of three expert radiologists. Safety was evaluated by the amount of blood lost and transfusion requirements during and after the operation; all bleeding complications, reoperations, adverse events and deaths were observed during the study. A 3-month follow-up on survival and occurrence of thromboembolism was performed on all randomized patients. The result was a significantly better protective effect against proximal DVT by regimen 1 compared with regimen 2. This was achieved with improved safety in terms of a significantly decreased need for blood transfusions during operation and fewer wound complications in the postoperative period in favor of regimen 1. Therefore, tinzaparin administered in a dosage of 75 U anti-Xa/kg BW 12 hours before surgery is significantly more protective against proximal DVT and safer than the standard regimen of 50 U anti-Xa/kg BW started 2 hours before surgery in patients undergoing primary elective hip arthroplasty.

[Many patients treated in the emergency department could be treated by a general practitioner on call]. / Mange of patienterne i en åben skadestue kunne behandles hos vagtlaegen.

Misuse of accident and emergency (A&E) departments is a problem throughout the world. Staffing A&E departments with general practitioners has been reported as successful in a few prospective studies. A medical audit of all A&E charts during one week was carried out. The audit-panel included two orthopaedic surgeons and two general practitioners. The charts were divided in two groups: 1) true A&E cases, 2) inappropriate A&E users, who should have visited the general practitioners' acute consultation instead. There was substantial agreement between audit-panel groups that 57% of attenders could visit the general practitioner instead. Ten percent of attenders received no treatment in the A&E department, but were transferred to other departments within the hospital. It is concluded that two-thirds of the A&E department attenders could have visited the general practitioners instead, for treatment or for referral to the relevant hospital department.

Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study.

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

Survival in patients undergoing total hip arthroplasty in relation to thromboprophylaxis with low molecular weight heparin: a long-term follow-up study.

The aim of the study was to determine the long-term survival in patients undergoing total hip arthroplasty in relation to type of perioperatively administered thromboprophylaxis. Patients from seven randomized controlled trials of the effect of thromboprophylaxis on development of early thromboembolic complications after total hip arthroplasty were included in a follow-up analysis with death as the end-point. There was no difference in survival between groups receiving active thromboprophylaxis, but there was a general trend towards a better survival in the 3 placebo groups compared with low molecular weight heparin (LMWH), (RR: 1.53; C.I.: 1.04-2.25). There was a significant excess of cardiovascular deaths in the LMWH groups (RR: 2.48; CI: 1.45-4.24). Long-term prospective studies should be performed to assess the long-term effect of various thromboprophylactic regimens on morbidity and mortality after total hip arthoplasty.

Perioperative thrombosis prophylaxis with low molecular weight heparins in elective hip surgery. Clinical and economic considerations.

A review and meta analysis of randomized prophylaxis studies in total hip arthroplasty (THA) surgery with the low molecular weight heparin (LMWH) compounds presently marketed in Europe. Thromboprophylaxis with recommended dosages of LMWH was significantly more effective than both placebo (no prophylaxis), dextran 70 and low-dose unfractionated heparin (UH) (5,000 IU thrice daily) in terms of protection against objectively diagnosed deep vein thrombosis (DVT), which is the main source of postoperative pulmonary embolism. The efficacy of LMWH was similar to that of adjusted-dose UH but only 2 studies have been conducted with this regimen so far. When combined with 0.5 mg dihydroergotamine (DHE), UH was as effective as LMWH, but DHE bears a definite risk of circulatory disturbances in the lower limbs. In all studies LMWH prophylaxis was safe under the clinical conditions. A cost-effectiveness analysis based on the reported efficacy and safety of LMWH in the European studies showed that, compared with no prophylaxis, dextran 70, and low-dose UH, LMWH prophylaxis used routinely in patients undergoing THA is more profitable for the health care system due to fewer expenses used on treatment of postoperative thromboembolic complications. LMWH therefore leads to better utilization of the economic resources.

Haemostatic activation in patients with head injury with and without simultaneous multiple trauma.

In a prospective study including 16 patients with multiple trauma and head injury and 14 patients with isolated head injury we measured plasma levels of prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT) on admission and on days 1, 2, 3, and 7 after the incident. On admission, all patients had values of F1 + 2 and TAT above the reference range. Admission levels of both F1 + 2 and TAT were significantly higher compared with levels on the following days. Admission levels of F1 + 2 was significantly correlated to the Injury Severity Score. TAT was higher in patients with multiple trauma than in patients with isolated head injury and were significantly correlated to the Injury Severity Score on admission and on day 3. Levels of F1 + 2 were significantly lower on day 1 in four patients with post-traumatic pulmonary dysfunction compared with patients without pulmonary dysfunction. With respect to levels of TAT, no differences were detected between patients with and without pulmonary dysfunction.

[Low molecular heparin in prevention of thrombosis in orthopedic surgery]. / Tromboseprofylakse med lavmolekylaert heparin i ortopaedkirurgien.

The review encompasses all published clinical studies of prophylactic treatment with low molecular weight (LMW) heparins marketed in Denmark when used to prevent thrombosis in patients undergoing elective or emergency orthopaedic operations. In elective hip surgery, LMW-heparin was more effective than placebo in reducing the incidence of deep vein thrombosis. There was significantly better anti-thrombotic effect of LMW-heparin, given in recommended doses, than of Dextran 70. When compared to low-dose heparin, the incidence of deep vein thrombosis was lowest using LMW-heparin, but only one study found the difference significant. LMW-heparin compared to low-dose heparin in combination with dihydroergotamine showed no significant difference with respect to either effect of safety. The use of LMW-heparin as prophylactic treatment for patients with either trochanteric or femoral neck fractures is as yet not nearly so well-documented. The relatively few studies that have been carried out show large variation between the different LMW-heparins. There is need for a study comparing the effect of LMW-heparin with that of low-dose heparin in these patients, both with respect to thrombosis prevention and influence on total mortality.

Fibrinogen and fibrin derivatives in traumatized patients: relation to injury severity and posttraumatic pulmonary dysfunction.

In a prospective study including 30 traumatized patients, levels of fibrinogen, fibrinopeptide A (FpA), fibrin monomers (FM) and fibrin degradation products (FbDP) were measured on admission and on days 1, 2, 3 and 7 after the incident. High levels of FpA, FM and FbDP were observed immediately after the trauma. Fibrinogen levels increased during the first 7 posttraumatic days whereas FpA and FM decreased. FbDP was significantly higher on day 7 than on day 3. All variables were to some extent correlated to the injury severity score. FbDP were significantly lower on the day after admission in 4 patients who developed pulmonary dysfunction compared with patients without this complication.

Localization of the Laevigatum powdery mildew resistance gene to barley chromosome 2 by the use of RFLP markers.

The powdery mildew disease resistance gene Ml(La) was found to belong to a locus on barely chromosome 2. We suggest that this locus be designated MlLa. Linkage analysis was carried out on 72 chromosome-doubled, spring-type progeny lines from a cross between the winter var 'Vogelsanger Gold' and the spring var 'Alf'. A map of chromosome 2 spanning 119cM and flanked by two peroxidase gene loci was constructed. In addition to the Laevigatum resistance locus the map includes nine RFLP markers, the two peroxidase gene loci and the six-row locus in barley.

Femtosecond resolution of soft mode dynamics in structural phase transitions.

The microscopic pathway along which ions or molecules in a crystal move during a structural phase transition can often be described in terms of a collective vibrational mode of the lattice. In many cases, this mode, called a "soft" phonon mode because of its characteristically low frequency near the phase transition temperature, is difficult to characterize through conventional frequency-domain spectroscopies such as light or neutron scattering. A femtosecond time-domain analog of light-scattering spectroscopy called impulsive stimulated Raman scattering (ISRS) has been used to examine the soft modes of two perovskite ferroelectric crystals. The low-frequency lattice dynamics of KNbO(3) and BaTiO(3) are clarified in a manner that permits critical evaluation of microscopic models for their ferroelectric transitions. The results illustrate the advantages of ISRS over conventional Raman spectroscopy of low-frequency, heavily damped soft modes.

Markers of coagulation and fibrinolysis after fractures of the lower extremities.

The study was performed to detect activation of coagulation and fibrinolysis in terms of prothrombin fragment 1 and 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), and soluble fibrin monomers (FM) in plasma from 39 patients with fractures of the lower extremities. We found substantially elevated levels of the molecular markers at admission and on the day after admission (Day 1) compared with control levels. Admission levels of F1 + 2, TAT, FbDP and FgDP were significantly higher compared with levels on day 1, whereas levels of FM were not significantly different between the two days. Generally there were good correlations between all markers of coagulation and fibrinolysis at admission whereas correlations were weaker or absent on day 1. In conclusion we found substantial haemostatic activation as a immediate response to trauma. Increased levels of F1 + 2, TAT, FM, FbDP and FgDP appear to be a normal physiological reaction after fractures of the lower extremities.

Reduction of plasma levels of prothrombin fragments 1 and 2 during thromboprophylaxis with a low-molecular-weight heparin.

In a randomized double-blind placebo-controlled study, plasma levels of prothrombin fragment 1 and 2 and total fibrin/fibrinogen degradation products were measured preoperatively and on days 1, 3, 5 and 7 postoperatively in 131 patients undergoing total hip replacement. Patients received a subcutaneous injection of either a low molecular weight heparin (Logiparin) or placebo once daily. Postoperative deep vein thrombosis was diagnosed by bilateral phlebography 7 to 10 days after operation. In the placebo group postoperative levels of prothrombin fragments 1 and 2 and total fibrin/fibrinogen degradation products were significantly higher in patients with postoperative thromboembolic complications, whereas in the low-molecular-weight heparin group no statistical differences were observed. Compared with placebo the administration of a low-molecular-weight heparin was associated with a significant reduction in the levels of prothrombin fragments 1 and 2 and total degradation products. Our observations suggest that the postoperative thrombin generation is moderated by thromboprophylaxis with Logiparin.

Neurogenic pulmonary edema: treatment with dobutamine.

In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema.

Slipped capital femoral epiphysis: long-term results of an abandoned technique.

Sixty-two (11 women and 51 men) of 76 consecutive patients treated between January 1960 and December 1979 with percutaneous pinning, traction, and ambulation in Thomas splints for slipped capital femoral epiphyses (physiolysis colli femoris; PCF) were re-examined radiologically and clinically to evaluate long-term results of an abandoned technique. Median follow-up time was 21 years (range: 8 to 28). The average age at symptom start was 14 years (range: 9 to 17). Fourteen patients were operated bilaterally, while 15 were operated on the right side only and 33 on the left side only. No additional hip surgery for coxarthrosis as adults had been performed. At the clinical examination the mean hip-movement-sum was 220 degrees (range: 30 degrees to 300 degrees). Pain occurred in 31 hips. A limp was found in 23 patients, and 56 had no impairment of working ability. At radiologic examination, 30 patients showed sequelae of PCF, and 30 (48%) had bilateral signs of PCF at follow up.

Clinical trials with low molecular weight heparins in the prevention of postoperative thromboembolic complications: a meta-analysis.

Several clinical studies have evaluated the efficacy and safety of LMWH in the prevention of postoperative thromboembolic complications. We subjected 42 studies to a statistical meta-analysis in order to evaluate the efficacy of different prophylactic regimens compared with LMWH prophylaxis. In general surgery LMWH was more effective than LDH three times daily and placebo, but comparable with LDH twice daily. In elective hip surgery, thromboprophylaxis with LMWH was more effective than placebo, LDH, and dextran 70, but comparable with LDH in combination with dihydroergotamine. In patients undergoing surgery for hip fractures LMWH was more effective than placebo, but the studies comparing LMWH with LDH were too small to show any clinically relevant difference, although there was a trend toward a better efficacy of LMWH. This study demonstrated that LMWH is clinically effective and safe to use in the prevention of thromboembolic complications after general and orthopedic surgery.

Hip physiolysis. Bilaterality in 62 cases followed for 20 years.

The frequency of bilateral physiolysis colli femoris was evaluated in 62 patients. At first admission, 5 patients had a bilateral slipping. Further, 9 patients had slipping diagnosed in the contralateral hip during adolescence 1-3 years after the primary operation. At the follow-up examination 22 years after the primary operation, radiographs showed bilateral sequelae of slipping in 30 of 62 patients. Of the nine slips diagnosed later during adolescence, one showed mild and two severe arthrosis. Among the 16 slips diagnosed at follow-up, mild arthrosis was found in four hips. We recommend bilateral pinning at first admission in all patients with a slipped capital femoral epiphysis.

Extrachromosomal plasmid-like DNA in the obligate parasitic fungus Erysiphe graminis f. sp. hordei.

The obligate parasitic fungus, Erysiphe graminis f. sp. hordei, was found to harbour plasmid-like extrachromosomal DNA. A 1.35-kb fragment of this 9kb plasmid was cloned into the pUC12 vector. No homology was detected to nuclear or mitochondrial DNA. As only about half of the 27 isolates examined contained plasmid-like DNA, this appears to be inessential for fungal survival. The plasmid is frequent in European isolates and is found in both newly collected isolates and in isolates kept under laboratory conditions for many years. No correlation between presence of plasmid and specific avirulence/virulence genes was found. The plasmid appear to be located in the mitochondria.

[New aspects of the diagnosis and therapy of microangioma]. / Neue Gesichtspunkte zur Diagnostik und Therapie von Mikroangiomen.

Microangioma means a clinical entity of different arterio-venous vascular malformations. Often so called atypical intracerebral hemorrhage or a symptomatic epilepsy are caused by these malformations. Nowerdays diagnosis is much more easier by the new imaging devices like CT and MRI. Especially MRI allows to interpretate the dignity and exact localisation of these malformations. Therefore microsurgical extirpation without postoperative morbidity becomes possible.