Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Leichenbefund eines Erhängten 28 Wochen nach dem Tode

Ohne Zusammenfassung     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Role of amiodarone on the systemic inflammatory response induced by cardiac surgery: proinflammatory actions

PURPOSE: Amiodarone (AMIO), a widely used anti-arrhythmic drug, has been shown to reduce the incidence of atrial fibrillation after cardiac surgery and also to exert immunomodulatory actions in vitro and proinflammatory effects in vivo. The present study investigated the immunomodulatory properties of AMIO in the inflammatory response induced by cardiac surgery with cardiopulmonary bypass (CPB). METHODS: In this double-blind, placebo-controlled trial, 20 patients undergoing elective coronary artery bypass graft were randomized to receive placebo or AMIO 600 mg day(-1) orally for seven days before surgery and 45 mg hr(-1) intravenously for 48 hr postoperatively. Plasma levels of the proinflammatory markers C-reactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and the antiinflammatory marker IL-10, were compared before and after surgery. RESULTS: Ninety-six hours after start of surgery, plasma levels of FBG had more than doubled (2.2 +/- 0.5-fold increase, P < 0.0001). Overall, FBG formation was significantly increased in the AMIO group (P = 0.048). Monocyte chemoattractant protein 1 secretion transiently increased four hours after start of surgery (6.6 +/- 4.5-fold increase) but rapidly declined thereafter, (P < 0.0001). There was a trend toward higher MCP-1 plasma concentrations in the AMIO group (P = 0.13). The plasma levels of CRP, TNF-alpha, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment. CONCLUSION: In the inflammatory response induced by cardiac surgery with CPB, our data suggest that AMIO treatment is associated with a selective trend toward proinflammatory actions.     

Der ältere Rettungspatient in der Notfallaufnahme

The elderly account for an ever-increasing proportion of emergency department patients. Demographic data show that the population which is 80 years of age or older will be further increasing in coming years. Due to this fact we sought the reasons of using of the emergency department by elderly patients (≥80 years), admitted by ambulance service, and to analyse the general management of this collective according to a younger comparison group. We used the data from a prospective registry, in which all consecutive patients admitted to the emergency department by ambulance service were included, to process this retrospective analysis. In this registry, diagnosis (in the ICD-10 classification), age, sex, and inpatient/outpatient treatment were documented. In addition further management, intensive care treatment, and outcome during emergency department stay were registered. The patients were stratified by age into two groups (< 80 years; ≥80 years). The observation period lasted from January 1, 2005 to December 31, 2005. During the study 6590 patients were observed of whom 5670 patients (86.0%) were under 80 years (PG<80) and 920 (14.0%) were 80 years of age or older (PG≥80). Comparing inpatient treatment (PG<80: 40.1%; PG≥80: 39.8%) vs outpatient treatment (PG<80: 59.9%; PG≥80: 60.2%) no significant difference between both groups was registered. In comparing the ICD- 10 main diagnosis categories, no relevant difference could be ascertained. By contrast a significantly higher mortality (3.0% vs 1.6%; p≤0.01) in the emergency department was shown within the PG≥80, especially if the diagnosis was myocardial infarction or stroke. The most frequent discharge diagnosis in the PG≥80 was acute myocardial infarction (6.7%). A percutaneous coronary intervention and artificial respiration was less frequently used in the elderly group. Patients beyond 80 years of age nowadays constitute a remarkable proportion of emergency department patients admitted by ambulance service. This group does not differ substantially from younger patients, neither in questions of inpatient or outpatient treatment nor in types of diagnosis. Elderly patients in the emergency department showed a higher mortality. Invasive interventions were less frequently used in this collective in comparison to younger patients. In consideration of the fact that the proportion of elderly will further increase in our population, this analysis may give basis for development of new strategies for the treatment of old patients in emergency departments.     

Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression

Medical records of 158 patients with bipolar depression were analysed for the incidence of a switch from depression to maniform states (mania and hypomania). Relation to psychopharmacological treatment was investigated. Thirty-nine (25%) patients of the total sample had switched to a maniform state during the treatment period in the hospital. Among that group the phenomenon occurred in 23 patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with a switch were significantly more often treated with tricyclic antidepressants (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication might reduce the risk for switching, especially in patients treated with TCA; however, it seems not totally sufficient, since 59% of the switched patients received mood stabilisers. The switch phenomenon was not associated with sociodemographic or clinical data. Received: 23 September 1998 / Accepted: 28 September 1998     

Long-Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu

Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right-handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left-handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness.     

N-substituted pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. A new class of diuretics.

The synthesis and evaluation of a new class of diuretic agents derived from the pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide ring system are described. Preliminary structure-activity relationships indicate that the nature and location of the substituents at different positions of the heterocycle are crucial for activity. Thus, a novel synthetic methodology has been developed to selectively introduce the desired substituents at different positions. From the study of the pharmacological properties (dose-response curves, duration of action, and acute toxicity) of the most active compounds, 4-amino-1,7-diethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine++ + 2,2-dioxide (9) was selected for further investigation. Compound 9 (C10H15N5O2S) crystallizes in space group P21/a with unit cell dimensions a = 16.482 (1), b = 9.3484 (3), c = 8.333 (3) A, beta = 103.003 (3) degrees, Z = 4.     

Myocardial metabolic imaging by means of fluorine-18 deoxyglucose/technetium-99m sestamibi dual-isotope single-photon emission tomography

The detection of preserved glucose uptake in hypoperfused dysfunctional myocardium by fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) represents the method of choice in myocardial viability diagnostics. As the technique is not available for the majority of patients due to cost and the limited capacity of the PET centres, it was the aim of the present work to develop and test FDG single-photon emission tomography (SPET) with the means of conventional nuclear medicine. The perfusion marker sestamibi (MIBI) was used together with the metabolic tracer FDG in dual-isotope acquisition. A conventional SPET camera was equipped with a 511-keV collimator and designed to operate with simultaneous four-channel acquisition. In this way, the scatter of 18F into the technetium-99m energy window could be taken into account by a novel method of scatter correction. Thirty patients with regional wall motion abnormalities at rest were investigated. The results of visual wall motion analysis by contrast cine-ventriculography in nine segments/heart were compared with the results of quantitative scintigraphy. The scintigraphic patterns of MIBI and FDG tracer accumulation were defined as normal, matched defects and perfusion-metabolism mismatches. Spatial resolution of the system was satisfactory, with a full width at half maximum (FWHM) of 15.2 mm for ¹⁸F and 14.0 mm for ^99mTe, as measured by planar imaging in air at 5 cm distance from the collimator. Image quality allowed interpretation in all 30 patients. 88% of segments without relevant wall motion abnormalities presented normal scintigraphic results. Seventy-five akinetic segments showed mismatches in 27%, matched defects in 44% and normal perfusion in 29%. We conclude that FDG-MIBI dual-isotope SPET is technically feasible with the means of conventional nuclear medicine. Thus, the method is potentially available for widespread application in patient care and may represent an alternative to the ²⁰¹T1 reinjection technique.     

Zur Acylierung von Hydroxy- und Mercapto-carbonsäureestern nach dem Carbodiimid/Acylierungskatalysator-Verfahren

On the Acylation of Hydroxy- and Mercaptocarboxylic Acid Esters Using the Carbodiimide/Acylation Catalyst Method Acylation of esters of hydroxycarboxylic acids can be carried out easily and in good yields by using the carbodiimide/acylation catalyst method. The reaction has also been applied to dihydroxy- and mercaptocarboxylic acid esters. The compounds formed from certain esters of hydroxycarboxylic acids are unstable to heat and decompose easily to the free carboxylic acid. No racemization is observed when using enantiomeric hydroxycarboxylic acids. Use of racemic carboxylic acids leads to diastereomers, whose ¹H-NMR shifts for characteristic protons are different as expected. Five drugs are among the carboxylic acids investigated in this context.