Cerclage performance analysis - a biomechanical comparison of different techniques and materials.

BACKGROUND: Wire cerclages play a fundamental role in fracture fixation. With an increasing variety of designs being commercially available the question arises which cerclage should be used. This study investigates the biomechanical properties of metallic and non-metallic cerclages and their different application-types. Furthermore, potential influence of muscular interposition between bone and cerclage constructs was tested. METHODS: Samples of the following four different cerclage types were tested on 3D printed models of human humeri as well as on human cadaveric humeri with and without muscular interposition: Titanium Cable Cerclage (CC), Steel Wire Cerclage (SWC), Suture Tape (ST), Suture Tape Cerclage (STC) with both single- (sSTC) and double-loop application (dSTC). A preinstalled self-locking mechanism secured by the provided tensioner in the STCs being the main difference to the STs. Cyclic loading was performed to 1 kN and then linearly to a maximum load of 3 kN. Statistical analysis was performed using either one-way ANOVA and post-hoc Tukey or Kruskal-Wallis and post-hoc Dunn test depending on normalization of data (p < 0.05). RESULTS: Whilst all cerclage options could withstand high loads during failure testing, only within the CC and dSTC group, all samples reached the maximal testing load of 3000 N without any failure. The SWC reached 2977.5 ± 63.6 N, the ST 1970.8 ± 145.9 N, and the sSTC 1617.0 ± 341.6 N on average. Neither muscular interposition nor bone quality showed to have a negative influence on the biomechanical properties of the cerclage constructs, presenting no significant differences. CONCLUSION: All tested cerclage constructs produce reliable stability but differ in their resulting compression forces, in a simplified fracture model. Therefore, non-metallic cerclage alternatives can provide similar stability with less compression and stiffness to metallic cable constructs, but they may offer several advantages and could possibly provide future benefits. Especially, by offering more elasticity without losing overall stability, may offer a biologic benefit. Installing any cerclage constructs should be performed carefully, especially if poor bone quality is present, as the tightening process leads to high forces on the construct.

High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.

Intrathecal (IT) gene transfer using adeno-associated virus (AAV) may be clinically promising as a treatment for chronic pain if it can produce sufficiently high levels of a transgene product in the cerebrospinal fluid (CSF). Although this strategy was developed in rodents, no studies investigating CSF levels of an analgesic or antiallodynic protein delivered by IT AAV have been performed in large animals. Interleukin-10 (IL-10) is an antiallodynic cytokine for which target therapeutic levels have been established in rats. The present study tested IT AAV8 encoding either human IL-10 (hIL-10) or enhanced green fluorescent protein (EGFP) in a dog model of IT drug delivery. AAV8/hIL-10 at a dose of 3.5 × 10(12) genome copies induced high hIL-10 levels in the CSF, exceeding the target concentration previously found to be antiallodynic in rodents by >1000-fold. AAV8/EGFP targeted the primary sensory and motor neurons and the meninges. hIL-10, a xenogeneic protein in dogs, induced anti-hIL-10 antibodies detectable in the CSF and serum of dogs. The high hIL-10 levels demonstrate the efficacy of AAV for delivery of secreted transgenes into the IT space of large animals, suggesting a strong case for further development toward clinical testing.

Histone and ribosomal RNA repetitive gene clusters of the boll weevil are linked in a tandem array.

Histones are the major protein component of chromatin structure. The histone family is made up of a quintet of proteins, four core histones (H2A, H2B, H3 & H4) and the linker histones (H1). Spacers are found between the coding regions. Among insects this quintet of genes is usually clustered and the clusters are tandemly repeated. Ribosomal DNA contains a cluster of the rRNA sequences 18S, 5.8S and 28S. The rRNA genes are separated by the spacers ITS1, ITS2 and IGS. This cluster is also tandemly repeated. We found that the ribosomal RNA repeat unit of at least two species of Anthonomine weevils, Anthonomus grandis and Anthonomus texanus (Coleoptera: Curculionidae), is interspersed with a block containing the histone gene quintet. The histone genes are situated between the rRNA 18S and 28S genes in what is known as the intergenic spacer region (IGS). The complete reiterated Anthonomus grandis histone-ribosomal sequence is 16,248 bp.

The rheological changes after cesarean section: The influence of low molecular weight or unfractionated heparin on the rheological properties of blood.

Thromboembolic complications remain an important cause of maternal mortality. The present recommendations favour for prophylaxis unfractionated (UFH) and low molecular weight heparin (LMWH). We investigated 150 pregnant women before and after cesarean section in three randomized groups. Fifty women received no prophylaxis (group I), 50 women UFH two times 5000 IU/day (group III) and 50 women Dalteparin 5000 U/day (group II). We determined the blood count, the rheological parameters and cholesterol, triglycerides, D-dimer, fibrinogen and the anti-Xa-level. We found a classical hemodilution, with increase of erythrocyte aggregation and plasma viscosity postoperatively. The fibrinogen turnover and D-dimer concentration were elevated. The patients with Dalteparin prophylaxis showed lower thrombin activation, minor changes in the cholesterol and triglycerides level and an improvement of red cell deformability in low shear regions. Our results demonstrated an influence of Dalteparin on the rheological parameters post surgery. The DVT incidence was 1.33% generally and occurred only in the Control group and in women with unfractionated heparin. We observed no side effects such as major bleeding, osteopenia or allergy.

Successful treatment of life-threatening bleeding after cesarean section with recombinant activated factor VII.

Hemorrhagic shock developed in a 29-year-old nullipara without coagulopathy after emergency caesarean section. Treatment with uterotonic drugs, prostaglandins, and conservative procedures with transfusion of packed red cells and fresh-frozen plasma failed to control the diffuse vaginal and uterine bleeding. Finally an intravenous bolus injection of 90 microg/kg recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark), was given and showed success within 20 minutes after administration, without any side effects.

Fetal hemorheology in normal pregnancy and severe preeclampsia.

Hemorheological parameters were determined in 45 pairs of mothers with severe preeclampsia and their newborns in comparison with 45 women with uncomplicated pregnancies and their newborns. In both groups we investigated red cell deformability, the plasma viscosity, the red cell aggregation (during stasis and low flow), the macromolecules fibrinogen and factor VIIIR:Ag (VWF), and the blood count parameters hemoglobin, hematocrit, white cells, platelets, reticulocytes, MCV, MCHC. Cholesterol and triglycerides were correlated to the parameter of red cell deformability measured as red cell elongation. We found a significant lower plasma viscosity, red cell aggregation, fibrinogen, cholesterol, triglycerides and VWF in cord blood with a close association between plasma viscosity and fibrinogen (r = 0.56, p = 0.001). The red cell deformability measured as red cell elongation was statistically higher in the cord blood compared to the mothers and associated with a higher MCV. In contrast the MCHC values remained unchanged. Hematocrit and hemoglobin in the cord blood were higher than in the mothers. The incidence of fetal hyperviscosity-polycytemia syndrome in women with severe preeclampsia was between 4.7% and 4.9%. An elevated red cell aggregation was found in 2.8% (stasis) and 4.8% (low flow state), respectively. We conclude that in fetal blood the higher hematocrit and the presence of larger red cells do not cause impaired fetal hemorheology.

[Influence of thrombophilia in women with recurrent miscarriage: pros and cons]. / Einfluss thrombophiler Faktoren bei Patientinnen mit wiederholtem Spontanabort. Pro und Kontra.

Recurrent miscarriage is a heterogeneous condition. A large number of studies have suggested a significant role for inherited and acquired thrombophilia in the development of abortion. Preliminary case-control studies and one prospective trial suggest that low molecular weight heparin is effective in preventing pregnancy loss in women with thrombophilia and previous recurrent miscarriage.

[Hemostasis disorders in obstetrics and gynecology]. / Hamostasestorungen in Geburtshilfe und Frauenheilkunde.

A survey is given on the clinical important haemostatic facts and diseases in gynaecology and obstetrics from the viewpoint of the gynecologist and obstetrician.

Hemorheological changes in women with severe preeclampsia.

The objective of this study was to determine the differences of hemorheological parameters in association to haematological tests in patients with severe preeclampsia (blood pressure (diastolic) > 100 mm Hg, blood pressure (systolic) > 180 mm Hg and proteinuria > 3 g/24 h). Blood samples of 45 primigravidas by hospital admission were studied. The control group were 45 pregnant women--age and weight matched--with normal blood pressure and without obstetric complications. We measured red cell aggregation (stasis, low shear), red cell elongation with the ectacytometer, blood cell indices (Hct, Hbg, MCV, MCHC, reticulocytes, white cells, platelets), fibrinogen haptoglobin and factor VIIIR:Ag, cholesterol and triclycerides. In comparison between patients with severe preeclampsia and normal pregnant women we found statistically elevated values of hematocrit, hemoglobin, red cell aggregation (stasis, low shear rate), MVC and factor VIIIR:Ag. Non-significant changes were observed in values of plasma viscosity, white cells, platelets, haptoglobin, MCHC, reticulocytes, triglycerides and cholesterol. The red cell deformability measured as cell elongation was statistically reduced by high shear stress application in patients with severe preeclampsia. Our results suggest that hemorheological parameters play an important role in severe preeclampsia, especially at microcirculatory regions with high shear stress such as intervillous space of placenta.

Local and systemic tolerability of magnesium sulphate for tocolysis.

An open-label, randomised, parallel-group, study was conducted in three study centres in women with premature labor and indication for a single agent intravenous tocolysis therapy with magnesium sulphate. The aim of this study was to examine the local and general tolerability and side-effects of magnesium sulphate for tocolysis. Furthermore, we tested the tolerability of a ready-for-use magnesium solution. No measurements of efficacy were performed during this study. Initially, patients received a loading dose of 4.0 g magnesium sulphate administered over 30 min. Thereafter, a continuous intravenous infusion of 1-2 g magnesium sulphate per hour up to 21 days was given. Venous score (Maddox), vital signs, adverse events as well as general tolerability (assessed by investigator and patients) and blood parameters were assessed. We showed good local and systemic tolerability of high dose magnesium sulphate for tocolysis. Only seven patients (15%) were withdrawn from the study prematurely due to minor adverse events. Potential serious complications of MgSO(4) such as respiratory arrest or clinically relevant respiratory depression were not observed. The most frequently reported local adverse events were injection site pain, itching, erythema, swelling, induration and palpable venous cord. The most common systemic adverse events considered to be possibly related to the study drugs involved the nervous system (dizziness) followed by the digestive system (nausea, constipation). Systolic and diastolic blood pressure changed only slightly during the treatment. Respiratory rate and body temperature remained stable also. Toxic magnesium levels (>2.5 mmol/l) were not observed. The assessment of the clinical investigators with regard to tolerability was very good or good in 72.5% of the patients. The introduction of the ready-to-use solution has the advantage of eliminating the need to mix the solution prior to administration. This means a lower risk of overdose and contamination.

The influence of antiphospholipid antibodies on the pregnancy outcome of patients with recurrent spontaneous abortion.

Several therapeutic regimens have been proposed for women with recurrent spontaneous abortion (RSA) and antiphospholipid antibodies (APA). Conflicting results have been reported about women with history of RSA, positive APA, and failure of standard therapy. To evaluate the use of intravenous immunoglobulin in RSA patients with APA and history of treatment failure, we initiated a study with standard therapy (aspirin and low-molecular-weight heparin) and intravenous immunoglobulin. We used an enzyme-linked immunosorbent assay (ELISA) test to screen IgG and IgM anticardiolipin antibodies, and a diluted Russel viper venom time assay for the lupus anticoagulant activity. Altogether, 66 pregnant women with positive APAs at the first visit could be included. Patients with hereditable thrombophilic factors were excluded. After confirmation of the pregnancy, women received a basis immunization of 0.3 g/kg immunoglobulin in a 4-week cycle until the 28th to 32nd week of gestation. All patients received 100 mg/d aspirin and 3,000 anti-Xa U/d certoparin. Among the 66 pregnant women, 17 were persistently autoantibody positive (25.8%), of whom 11 (16.7%) were ACA positive alone, 2 (3%) were lupus anticoagulant positive, and 4 (6.4%) had both antibody types. A total of 49 patients had positive APAs at the initial test, but were negative for ACA and lupus anticoagulant at the second test administered approximately 5 weeks after the start of therapy. We described this group in our following observation as "antibody negative." Sixteen of the 17 autoantibody-positive patients (94.1%) were delivered of live infants compared with 40 patients (81.6%) in the antibody-negative group (odds ratio [OR]: 1.2; 95% CI: 0.98 to 1.4). The overall miscarriage rate was 12.1% and the fetal loss rate was 15.2%. Four patients (25%) in the antibody-positive group developed symptoms of preeclampsia and fetal growth retardation compared with four patients (9.8%) in the antibody-negative group. In conclusion, we see a reduction of the fetal loss rate in patients with RSA and positive APA (5.8%) compared with APA-negative (18.4%) women with the same therapy (OR: 0.3; 95% CI: 0.04 to 2.3).

[Effect of thrombophilic factors on thromboembolism and other pregnancy complications]. / Der Einfluss thrombophiler Faktoren auf thromboembolische und andere Schwangerschaftskomplikationen.

Pulmonary embolism and/or deep vein thrombosis are a major cause of maternal mortality. In a number of adverse pregnancy outcome including preeclampsia, recurrent spontaneous abortion, restricted fetal growth and fetal death a role for thrombophilia (acquired and hereditable) has been postulated. Monitoring of acquired factors such as antiphospholipid-antibodies and hereditable factors (factor V Leiden, prothrombin mutation) may help predict the occurrence of pregnancy complications. Low molecular weight heparins (LMWH), since their introduction well established during pregnancy, and the rate of adverse fetal outcomes are related to co-morbidity maternal conditions rather than to the treatment itself. The use of LMWH is recommended for all moderate risk and high-risk pregnant patients.

Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases.

OBJECTIVE: The present study was planned to measure preoperative levels of soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients with gynecological diseases, and to test for a relationship to clinical and biochemical patient characteristics. METHODS: Using a specific and sensitive kinetic ELISA, suPAR levels were determined in preoperative citrate plasma samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17 patients with benign ovarian tumors, and 28 patients with benign endometrial diseases. In addition, suPAR was measured in citrate samples from 31 female blood donors. RESULTS: suPAR was measurable in all samples. No significant difference was found between plasma suPAR in the blood donors and the patients with benign diseases (P = 0.58). The groups of cancer patients had suPAR levels that were significantly higher than those found in the blood donors (P < 0.0001, P < 0.0001, and P = 0.001 for patients with ovarian, endometrial, and cervical cancer, respectively). In all groups of cancer patients a trend toward increasing suPAR levels with increasing FIGO stage was noted (P = 0.0003, P = 0.02, and P = 0.01 for patients with ovarian, endometrial, and cervical cancer, respectively). Using the median suPAR level to dichotomize the ovarian cancer patients, FIGO stages I-III, a significantly increased risk of progression/relapse was found for patients with high suPAR levels (Hazard ratio (HR) = 3.1, 95% CI: 1.1-8.8, P = 0.03). A multivariate analysis was performed, including suPAR, FIGO stage, and CA-125. Only FIGO stage III compared with FIGO stage I was significant (HR = 15, 95% CI: 1.8-129, P = 0.01). Survival analyses were not performed in the endometrial or cervical cancer patients due to few progressions/relapses during the follow-up period. CONCLUSION: This study concludes that patients with gynecological cancers have elevated plasma suPAR levels as compared with healthy female blood donors and patients with benign gynecological diseases. In addition, high preoperative plasma levels of suPAR are significantly associated with poor outcome of ovarian cancer patients. However, additional studies are needed to further validate the clinical usefulness of plasma suPAR measurements in the management of ovarian cancer patients.

Neonatal platelet activation in preeclampsia.

Preeclampsia is associated with an increased platelet activation; however, there are few studies concerning platelet activation of the newborn. The aim of our study was to compare platelet activation in newborns of preeclamptic mothers to newborns of healthy mothers by using whole blood flow cytometry. Blood samples were obtained from 20 newborns (10 healthy controls, 10 cases of preeclampsia/HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome) during cesarean section. Antibodies against the following antigens were used as markers for platelet activation: CD 41, CD62P, CD 63, and platelet-bound fibrinogen. In addition to the basal platelet activation, the ability of platelets to undergo activation as a result of in vitro incubation with a weak agonist (adenosine diphosphate) was evaluated. A significant difference between the groups concerning basal platelet activation could only be seen for platelet-bound fibrinogen; the control group showed a higher extent of platelet activation (16.6 +/- 11.3 vs. 6.1 +/- 4.9; p = 0.03). Incubation with adenosine diphosphate in the control group resulted in minor increases of platelet activation, which was significant only for platelet-bound fibrinogen (16.6 +/- 11.3 vs. 42.5 +/- 22.1; p = 0.02). However, the preeclamptic group showed significantly increased levels of platelet activation for all used markers after in vitro activation (CD 41: 115.6 +/- 18.2 vs. 163.2 +/- 29.6; p = 0.002; CD62P: 2.4 +/- 0.4 vs. 3.9 +/- 0.3; p < 0.001; CD 63: 2.7 +/- 0.5 vs. 3.7 +/- 0.6; p = 0.002; platelet-bound fibrinogen: 6.1 +/- 4.9 vs. 55.1 +/- 9.1; p < 0.001). Preeclampsia or HELLP syndrome is therefore associated with an increased susceptibility to neonatal platelets, even against weak activators such as adenosine diphosphate. Whether this results from peculiarities in the fetal vascular environment or maternal influences is yet uncertain.

The role of intravenous volume expansion in moderate pre-eclampsia.

We examined the hemodynamic and hemorheological effects of intravenous volume expansion in women with pre-eclampsia. 20 untreated women with moderate pre-eclampsia were randomized to receive a 500 ml infusion over 4 h of either hydroxyethylstarch (HAES steril 10%, HES) or NaCl 0.9% solution. After completion of the infusion trial all patients received oral antihypertensive drugs, bed rest and free sodium and water intake. The hemodynamic responses were measured by impedance cardiography. Hemorheological parameters and blood pressure were measured before and after (24 h later) infusion. The HES infusion but not NaCl leads to a significant reduction of hematocrit and erythrocyte aggregation. In addition to that there was a nonsignificant increase of the cardiac index in the HES-group but no changes in the heart rate. Intravenous volume expansion in women with pre-eclampsia with a long acting colloid like hydroxyethylstarch is associated with a significant influence on the flow properties (hematocrit and erythrocyte aggregation) of blood.

Antithrombotic therapy in high-risk pregnancy.

Venous thromboembolism remains a major cause of morbidity and mortality associated with pregnancy and puerperium. Specific risk factors for this disorder can be identified before or during pregnancy and delivery. The heritable defects believed to be associated with venous thrombosis are factor V Leiden mutation; elevated antiphospholipid antibodies; and deficiencies of antithrombin, protein C, and protein S. Women with a history of thromboembolism and thrombophilia should receive antenatal and postpartum thrombosis prophylaxis.

Antithrombotic therapy in gynecologic surgery and gynecologic oncology.

The European Consensus Conference has assessed the risk for thrombotic complications for most women undergoing gynecologic surgery and found it to be moderate. Nonetheless, it is important to analyze a patient's individual risk before surgery so that appropriate thrombosis prophylaxis can be given if increased risk is determined. Malignancy accounts for most thrombotic complications among gynecologic patients. Patients with known malignancies should receive prophylaxis during surgery, and some patients with breast cancer should receive prophylaxis during chemotherapy. Heparin, and low-molecular-weight heparin in particular, may favorably influence the outcome of cancer in some patients and treatment with these agents is currently under investigation in a number of trials as a new approach to anticancer therapy.