National survey of obstetric anaesthesia clinical practices in the republic of Austria.

BACKGROUND: The aim of this study was to describe the current obstetric anaesthetic practices in Austria by performing a comprehensive questionnaire survey. METHODS: A questionnaire was sent via email to key anaesthesiologists from obstetric anaesthesia departments of 81 hospitals registered at the Austrian Ministry of Health. RESULTS: Of 81 departments contacted, 65 (80%), covering 84% of annual births in Austria, responded to the 82-question survey. Epidural analgesia was offered universally, at a rate under 30% in 56 (86%) of respondent hospitals. The caesarean section rate was under 30% in 44 (68%) respondent obstetric units. All respondents provided spinal anaesthesia as the primary anaesthetic technique for elective caesarean section. Three (5%) respondents administered long-acting intrathecal morphine and 18 (28%) respondents did not routinely administer any intrathecal opioid. Wound infiltration for acute postoperative pain control was practiced in two (3%) respondent units. A transversus abdominis plane block was offered as rescue analgesia in 14 (22%) departments. Spinal hypotension was treated using a prophylactic phenylephrine infusion in two (3%) respondent hospitals. Prophylactic antibiotics were administered prior to skin incision by 31 (48%) respondents. CONCLUSION: This survey reveals that obstetric anaesthetic practices in Austria differ in part from current European and American guidelines. Findings will direct the national workforce on obstetric anaesthesia that aims to introduce into Austria practice guidelines, based on international collaborations and guideline recommendations.

CCL4 as an adjuvant for DNA vaccination in a Her2/neu mouse tumor model.

Chemokines are key regulators of both innate and adaptive immune responses. CCL4 (macrophage inflammatory protein-1ß, MIP-1ß) is a CC chemokine that has a broad spectrum of target cells including immature dendritic cells, which express the cognate receptor CCR5. We asked whether a plasmid encoding CCL4 is able to improve tumor protection and immune responses in a Her2/neu+ mouse tumor model. Balb/c mice were immunized twice intramuscularly with plasmid DNA on days 1 and 15. On day 25, a tumor challenge was performed with 2 × 10(5) syngeneic Her2/neu+ D2F2/E2 tumor cells. Different groups of mice were vaccinated with pDNA(Her2/neu) plus pDNA(CCL4), pDNA(Her2/neu), pDNA(CCL4) or mock vector alone. Our results show that CCL4 is able to (i) improve tumor protection and (ii) augment a TH1-polarized immune response against Her2/neu. Although Her2/neu-specific humoral and T-cell immune responses were comparable with that induced in previous studies using CCL19 or CCL21 as adjuvants, tumor protection conferred by CCL4 was inferior. Whether this is due to a different spectrum of (innate) immune cells, remains to be clarified. However, combination of CCL19/21 with CCL4 might be a reasonable approach in the future, particularly for DNA vaccination in Her2/neu+ breast cancer in the situation of minimal residual disease.

A supraomohyoidal plexus block designed to avoid complications.

Interscalene blocks of the brachial plexus are used for surgery of the shoulder and are frequently associated with complications such as temporary phrenic block, Horner syndrome or hematoma. To minimize the risk of these complications, we developed an approach that avoids medially directed needle advancement and favors spread to lateral regions only: the supraomohyoidal block. We tested this procedure in 11 cadavers fixed by Thiel's method. The insertion site is at the lateral margin of the sternocleidomastoid muscle at the level of the cricoid cartilage. The needle is inserted in the axis of the plexus with an angle of approximately 35 degrees to the skin, and advanced in lateral and caudal direction. Distribution of solution was determined in ten cadavers after bilateral injection of colored solution (20 and 30 ml) and followed by dissection. In an eleventh cadaver, computerized tomography and 3D reconstruction after radio contrast injection was performed. In additional five cadavers we performed Winnie's technique with bilateral injection (20 and 30 ml). Concerning the supraomohyoidal block the injection mass reached the infraclavicular region surrounded all trunks of the brachial plexus in the supraclavicular region and the suprascapular nerve in all cases. The solution did not spread medially beyond the lateral margin of the anterior scalene muscle into the scalenovertebral triangle. Therefore, phrenic nerve, stellate ganglion, laryngeal nerve nor the vertebral artery were exposed to the injected solution. Distribution was comparable with the use of 20 and 30 ml of solution. Injections on five cadavers performing the interscalene block of Winnie resulted in an extended spread medially to the anterior scalene muscle. We conclude that our method may be a preferred approach due to its safety, because no structures out of interest were reached. Solution of 20 ml is suggested to be enough for a successful block.

Haemodynamic and catecholamine stress responses to the Laryngeal Tube-Suction Airway and the Proseal Laryngeal Mask Airway.

Supraglottic airway devices such as the ProSeal Laryngeal Mask Airway (PLMA) and Laryngeal Tube-Suction Airway (LTS) that provoke the least stress responses could be beneficial in many situations, especially in patients with cardiovascular disease. We compared the haemodynamic and catecholamine stress response of the LTS and PLMA in a randomised study of 36 patients. Mean arterial pressure, heart rate, epinephrine and norepinephrine levels were all reduced following induction of anaesthesia with no significant differences between the two groups. Following insertion of LTS, mean arterial pressure, heart rate, epinephrine and norepinephrine levels increased to pre-induction levels. However, following the insertion of the PLMA, mean arterial pressure, heart rate, epinephrine and norepinephrine levels remained significantly lower than pre-induction values. Mean arterial pressure, heart rate and epinephrine were significantly greater in the LTS group than in the PLMA group. We conclude that the LTS produces a greater and more sustained haemodynamic and catecholamine stress response than does the PLMA.

PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells.

IL-6 has been reported to play a central role in growth and survival of multiple myeloma (MM) cells. However, recently we have demonstrated that in the presence of bone marrow stromal cells, survival of MM cells becomes independent of the IL-6/gp130/STAT3 pathway questioning the singular role of IL-6 in MM. Therefore, it was the aim of this study to identify additional factors and signaling pathways that might contribute to the growth and survival of MM cells. We found that in addition to IL-6 a number of bone marrow derived cytokines such as LIF, VEGF, bFGF, MIP-1alpha, SDF-1alpha, IL-1beta, SCF and IL-3 activate the MAPK pathway and induce proliferation of MM.1S and RPMI-8226 MM cells. In addition, these cytokines independently phosphorylate the forkhead family member FKHR via PI3-K/AKT and support survival of primary human MM cells. Inhibition of these pathways induces apoptosis in MM cell lines and primary MM cells. Thus, we provide evidence that in addition to IL-6 a number of different factors trigger important growth-promoting pathways to support the proliferation and survival of MM cells. Therefore, blocking such pathways, rather than blocking a single factor, might be a promising approach for the development of novel treatment strategies in MM.

Preoperative treatment with recombinant human erythropoietin or predeposit of autologous blood in women undergoing primary hip replacement.

BACKGROUND: Controversy exists about the advantages of predeposit of autologous blood (PDAB), and whether more comfortable blood conservation regimens may yield comparable results. To test the hypothesis that preoperative treatment with recombinant human erythropoietin (rHuEPO) with or without acute concomitant normovolaemic haemodilution (ANHD) is as effective as PDAB in reducing allogeneic blood transfusions, we conducted a prospective randomised study in women undergoing primary hip replacement. METHODS: Sixty consecutive female patients scheduled for primary hip replacement and suitable for PDAB were randomly assigned to one of 3 groups. Group I (EPO) and II (ANHD) received 600 U/kg rHuEPO s.c. and 100 mg iron saccharate i.v. on day 14 and, if needed, on day 7 before surgery. Additionally, in group II acute normovolaemic haemodilution (ANHD) was implemented after induction of anaesthesia. In group III (PDAB) conventional PDAB up to 3 U, without volume replacement but with concomitant oral iron therapy, was performed starting 4 weeks before surgery. RESULTS: The blood conservation methods resulted in a comparable net gain of red cells in all 3 groups until the day of surgery. Because of the withdrawal of autologous blood, haemoglobin values before surgery were lower in the PDAB group than in the EPO and ANHD groups, and during surgery were lower in the PDAB and ANHD groups than in the rHuEPO-only group. Applying moderate ANHD in conjunction with preoperative rHuEPO treatment did not yield an incremental decrease in allogeneic transfusions. There was no difference between the groups in the number of patients who received allogeneic transfusions or in the total number of allogeneic units transfused. CONCLUSIONS: Withdrawal of autologous blood is associated with lower pre- and intraoperative haemoglobin levels when compared to preoperative augmentation of red cell mass using rHu-EPO. As a measure to reduce allogeneic transfusion requirements, preoperative treatment with rHuEPO may be as effective as standard predeposit of autologous blood in women undergoing primary hip replacement, but requires less preoperative time.

Perioperative catecholamine changes in cardiac risk patients.

BACKGROUND: It has previously been found that in cardiac risk patients undergoing non-cardiac surgery post-operative cardiac complications are correlated with high post-operative serum levels of troponin T (TNT) and troponin I (TNI). We investigated whether perioperative changes in the release of free (fCAs) and conjugated catecholamines (cCAs) correlate with the increased serum level of TN (TN upward arrow). MATERIALS AND METHODS: Plasma levels of CAs were determined in 28 patients at risk for or with definite coronary artery disease. Blood sampling was performed in the morning on the day before surgery, on the day of surgery before induction of anaesthesia and until the fifth post-operative day for measurement of CAs by high-performance liquid chromatography. RESULTS: The plasma concentrations of free and conjugated noradrenaline (fNA and cNA) as well as of free and conjugated adrenaline (fA and cA) were increased significantly in TN upward arrow patients post-operatively. The plasma levels of free as well as of conjugated NA and A in TN upward arrow patients were significantly higher than in TN0 patients over the whole post-operative period. CONCLUSION: This study demonstrates that increased post-operative release of fNA and fA as well as of cNA and cA correlates with high post-operative serum levels of troponins in cardiac risk patients undergoing non-cardiac surgery.

Perioperative myocardial cell injury: the role of troponins.

Early recognition of minor myocardial cell injury and appropriate treatment may prevent development of myocardial infarction as one of the most severe postoperative cardiac complications. Troponins have been shown to be sensitive biochemical markers for the assessment of myocardial cell injury. We investigated prospectively 67 cardiac risk patients undergoing elective non-cardiac surgery. Troponin T (TNT) concentrations were measured during the perioperative period, and in those patients with increased TNT (cut-off 0.2 ng ml-1), troponin I (TNI) concentrations were measured additionally (cut-off 0.6 ng ml-1). Patients were allocated to one of three groups: group I, all patients with normal TNT concentrations had a good cardiac outcome (80.5%). In those patients with increased TNT concentrations (19.5%) TNI was also positive; group II, patients (8.8%) with only slightly increased TNT concentrations (0.32-0.99 ng ml-1) also had a good outcome, indicating minor myocardial cell injury, whereas patients with cardiac complications (11.9%) had higher TNT concentrations (0.47-9.8 ng ml-1) (P < 0.05) (group III). With a TNT cut-off at 0.2 ng ml-1, the positive predictive value for adverse outcome was 61.5%; the negative predictive value was 100%. With a TNT cut-off at 0.6 ng ml-1, the positive predictive value for adverse outcome increased to 87.5%, but the negative predictive value was still high (98%). Most of the patients showed an increase in TNT content from the day of surgery until the third postoperative day. We conclude that serial troponin measurements during the perioperative period identify pre-, intra- and postoperative myocardial cell injury. The concentration of troponin T may reflect the degree of injury and help categorize the subsequent risk.

Lipoprotein(a) inhibits collagen-induced aggregation of thrombocytes.

Lipoprotein(a) [Lp(a)] is known to interact with human platelets in vitro. In the present study the effect of physiological concentrations of Lp(a) on platelet aggregation was studied. Freshly prepared gel-filtered platelets from healthy donors were incubated for 30 minutes at 37 degrees C with various concentrations of Lp(a); aggregation was triggered with ADP, thrombin, and collagen. Control incubations were performed with Tyrode's solution or LDL. Thrombin- and ADP-triggered aggregations were only slightly influenced by Lp(a), but aggregation of platelets stimulated with collagen (4 micrograms/mL) was markedly inhibited. Measurable effects occurred at low concentrations (0.05 mg/mL) of total Lp(a); at 0.5 mg/mL, maximum aggregation of platelets was inhibited by 54 +/- 20%, and the aggregation rate was attenuated by 47 +/- 19% compared with platelets incubated with Tyrode's solution. Preincubation of collagen (4 micrograms/mL) with Lp(a) yielded similar results. The effect of Lp(a) on platelet aggregation was accompanied by a significant reduction of serotonin release and TXA2 formation. Higher concentrations of collagen ( > or = 10 micrograms/ mL) caused the inhibitory effect on Lp(a) on collagen-induced aggregation to disappear. In contrast, incubation of platelets with 5 mg/mL LDL led to a significant increase of aggregation rate, maximum aggregation, serotonin release, and formation of TXA2 when aggregation was induced with 4 micrograms/mL collagen. In an adhesion assay using fresh whole blood, which mimics the in vitro situation of vessel injury. Lp(a) reduced platelet adhesion at shear rates of 300 and 1600/s by 22.6% and 11.6%, respectively. In addition, Lp(a) reduced the size of platelet aggregates significantly (up to 63%); this reduction was more distant at the higher shear rate. Unlike LDL, Lp(a) is not a proaggregatory lipoprotein; rather, collagen-triggered aggregation in vitro is attenuated by Lp(a).

Magnetic DNA affinity purification of ecdysteroid receptor.

A new method for rapid purification to near homogeneity of the ecdysteroid receptor (EcdR) from Drosophila melanogaster nuclear extract is presented. In the first step of the purification procedure the EcdR molecules were radiolabelled with [3H]ponasterone A and the [3H]ponasterone A-EcdR complexes were chromatographed under very mild conditions on Fractogel EMD TMAE(s) ion-exchanger. A 23-fold purified receptor was obtained which can be stored in liquid N2 without loss of activity. The second step involved the use of a magnetic DNA affinity technique where the double stranded hsp 27 oligonucleotide containing EcdR binding sequence was biotin 5'-end labelled and bound to monodisperse superparamagnetic particles coated with streptavidin (Dynabeads M-280 Streptavidin) giving magnetic DNA affinity beads. The chromatographed EcdR-ponasterone A complexes were bound to the magnetic DNA affinity beads and by magnetic separation, wash and elution, a 29,000-fold enriched EcdR preparation was obtained within 1.5 h. This procedure can be applied for other EcdR sources with minor modifications.