Factor Xa-activated whole blood clotting time (Xa-ACT) for bedside monitoring of dalteparin anticoagulation during haemodialysis.

BACKGROUND: Low molecular weight heparins (LMWH) like dalteparin are increasingly used for anticoagulation during haemodialysis (HD). The available laboratory tests for monitoring LMWH anticoagulation are time-consuming and expensive, and the suitability of the conventional activated clotting time (ACT) is controversial. A simple and cheap bedside test would be useful. METHODS: We studied the factor Xa-activated whole blood clotting time (Xa-ACT) in vitro and in vivo in nine patients undergoing chronic HD with i.v. dalteparin bolus anticoagulation and compared it with the conventional ACT. Plasma anti-factor Xa (antiXa) activity was determined with a chromogenic assay. Thrombin-antithrombin complexes were measured to detect coagulation activation. RESULTS: Xa-ACT and ACT were prolonged with rising dalteparin concentration. In vitro, both clotting times were strongly correlated with the antiXa levels (r = 0.94 and 0.89, respectively). Nevertheless, compared with the ACT, the Xa-ACT was considerably more sensitive to the LMWH in vitro (healthy blood: Xa-ACT 90 s/U vs ACT 26 s/U; uraemic blood: Xa-ACT 96 s/U vs ACT 31 s/U) as well as in vivo (Xa-ACT 81 s/U vs ACT 22 s/U) and reflected different intensities of anticoagulation. An initial dalteparin bolus of 80+/-11 U/kg body weight was able to prevent coagulation activation for up to 4 h of HD. CONCLUSION: For monitoring LMWH anticoagulation the Xa-ACT was superior to the conventional ACT in vitro as well as in vivo during HD. The Xa-ACT can be useful as a LMWH bedside test. The ACT was not sensitive enough to serve as a LMWH monitoring tool.     

Freier Paraskapular-/Skapularlappen bei frakturbegleitendem Weichteildefekt an Talus oder Kalkaneus

BASIS: Fractures of the talus or calcaneus with accompanying soft tissue damage require precisely planned treatment to prevent infection of the wound over time, especially in severely injured patients. MATERIAL AND METHODS: Seven patients with fractures of the talus or calcaneus and accompanying 2nd and 3rd degree open or 3rd degree closed soft tissue injuries were followed up retrospectively. These patients were operated on between January 1999 and January 2006 with free fasciocutaneous scapular or parascapular flaps. The average age was 34 (range 16-54). Follow-up was at 6-36 months. RESULTS: Osteosynthesis was primarily in six cases, post-primarily in one, and in four cases exterior fixation was used additively. Temporary vacuum therapy was performed for a mean of 28 days (6-42). Parascapular, scapular, and Latissimus dorsi flap coverage was performed six, one, and one times, respectively. Six flaps healed without complication. One necrosis of a parascapular flap occurred and made a Latissimus dorsi flap necessary. In one case of donor-site wound dehiscense, a local rotation flap became necessary. There was no joint infection or osteomyelitis. Bony consolidation was achieved within all fractures. CONCLUSION: Traumatic soft tissue damage must be taken into account when primary or secondary internal fixation is performed and should influence the choice of implant. Free fasciocutaneous parascapular or scapular flaps are a powerful tool for preventing infection if local flaps are not sufficient to achieve stable soft tissue coverage.     

Endoscopic transthoracic sympathectomy: current indications and techniques

Zusammenfassung GRUNDLAGEN: Die endoskopische thorakale Sympathektomie (ETS) existiert seit 60 Jahren als effektive Therapie der primären Hyperhidrose. Nach wie vor gibt es in der medizinischen Welt teils Vorbehalte, teils Unwissen über die Methode selbst, ihre Erfolgs- und Komplikationsraten sowie Nebenwirkungen. METHODIK: Nach Einführung in die Symptome und Behandlung der primären Hyperhidrose (konservativ und chirurgisch) werden Operationsmethoden und Langzeitergebnisse der ETS-Operation vorwiegend anhand der Daten aus der eigenen Abteilung präsentiert. ERGEBNISSE: Von 1965–2001 wurden 734 Sympathikotomien (ETS2–4) und bis 2003 weitere 103 Sympathikusblockaden (ESB4) bei Patienten mit primärer palmarer und axillärer Hyperhidrose durchgeführt. Die Konversionsrate betrug 0,1 %. Seit Einführung der Video-Thorakoskopie 1991 trat kein postoperatives Horner-Syndrom auf (zuvor 2,2 %), Drainage-pflichtige Pneumothoraces waren in 1,1 % zu verzeichnen. Nach einem medianen Follow-up von 16 Jahren waren 93 % der Extremitäten trocken, 5 % fast trocken und 2 % feucht. Nebenwirkungen traten in Form von kompensatorischem Schwitzen am Stamm (55 % insgesamt, davon 5 % stark) und gustatorischem Schwitzen (33 %) auf. Seit Einführung der limitierten Sympathikusblockade auf Höhe T4 (ESB4) konnte (bei naturgemäß kurzer Nachbeobachtungszeit) das kompensatorische Schwitzen auf 8,5 % und das gustatorische Schwitzen auf 2,1 % gesenkt werden. Mit dem postoperativen Ergebnis waren 100 % der Patienten nach ESB4 zufrieden, nach ETS2–4 waren 80 % zufrieden, 14 % teilweise zufrieden und 6 % unzufrieden (meist wegen starken kompensatorischen Schwitzens). SCHLUSSFOLGERUNGEN: Die ETS-Operation bietet hohe langfristige Erfolgsraten bei niedrigen Komplikationsraten. Patienten sollten über die zu erwartenden Nebenwirkungen genau aufgeklärt werden, für unzufriedene Patienten mit starkem kompensatorischem Schwitzen besteht nun die Möglichkeit der thorakoskopischen Klip-Entfernung.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

Proximaler Humerusnagel bei körpernahen Oberarmbrüchen

Zusammenfassung Frakturen des proximalen Humerus stellen beim älteren Patienten, bedingt durch Osteopenie und Verletzungsschwere, eine Herausforderung für die operative Versorgung dar. Seit wenigen Jahren stehen intramedulläre Implantate zur Verfügung, mit denen auch Mehrfragmentfrakturen mit hoher Primärstabilität versorgt werden können. Bei limitierten Weichteilschäden kann durch frühe Physiotherapie ein gutes funktionelles Ergebnis erreicht werden. Seit 2003 verwenden wir den T2-PHN (Fa. Stryker) und konnten bisher 15 Patienten nach 1-jähriger Beobachtung auswerten. Bei einem Durchschnittsalter von 64,6 Jahren lag der durchschnittliche Constant-Score nach 1 Jahr bei 68,3 (±17,3) auf der betroffenen Seite, seitenadaptiert wurden 79% erreicht. Der Anteil der 4-Segment-Frakturen lag bei 60%. Bei 4 Patienten beobachteten wir eine partielle Humeruskopfnekrose ohne Therapiekonsequenz. Implantatentfernungen waren in 5 Fällen wegen überstehender Schrauben oder vorstehendem proximalem Nagelende nötig. Mit den modernen Verriegelungsmarknägeln ist eine Gewebe schonende und sehr stabile Versorgung der proximalen Humerusfrakturen möglich.     

Pharmacotherapy of ventricular fibrillation. A prospective study in an emergency medical service

This prospective study investigated the effects of standard pharmacotherapy in out-of-hospital ventricular fibrillation (VF) after i.v. or endobronchial (e.b.) administration of epinephrine and lidocaine. METHODS. Only patients presenting with out-of-hospital VF were included in this study, whereby VF of noncardiac origin was excluded. Cardiopulmonary resuscitation (CPR) was performed according to the guidelines of the American Heart Association. Basic life support was initiated by Emergency Medical Service (EMS) technicians. The first step of advanced life support was immediate defibrillation by the EMS physician. Epinephrine was given in doses of 2.5 mg e.b. or 1.0 mg i.v. If indicated, patients received 200-500 mg lidocaine e.b. or 100 mg i.v. The course of CPR was tape-recorded and 2-3 blood samples were taken from each patient for drug monitoring. Plasma levels of epinephrine and lidocaine were measured by high-pressure liquid and gas chromatography, respectively, and then correlated to the course of CPR. RESULTS. Forty-seven patients presented VF on arrival of the EMS physician. Restoration of spontaneous circulation was achieved in 64% (Table 3), and 30% of the patients were discharged from hospital without major neurologic deficits. Immediate defibrillation before initiation of pharmacotherapy produced a success rate of 15.8%, whereas defibrillation after drug therapy was successful in 61.5% of cases. Following e.b. instillation of 2.5 mg epinephrine (Fig. 1), median peak concentrations of epinephrine (40.2, range 4.0-79.8 ng/ml) were reached after 3-4 min and plasma levels greater than or equal to 10 ng/ml were seen for 20 min. After i.v. injection of 1.0 mg epinephrine (Fig. 2) maximum concentrations (71.6, range 4.7-104.2 ng/ml) were measured after 1-2 min and plasma levels decreased below 10 ng/ml after 10 min. Following e.b. instillation of 400-500 mg lidocaine mean lidocaine concentrations within the therapeutic range (2-5 micrograms/ml) were reached after 4-5 min and remained within these limits for 20-30 min. Peak concentrations were obtained after 12 min. Doses of 200-320 mg lidocaine e.b. failed to achieve therapeutic plasma levels (Fig. 3). Regarding the pharmacodynamic aspects of drug therapy, 22.5% of the initial survivors were resuscitated from VF without therapeutic epinephrine, presenting with mean endogenous epinephrine concentrations of 7.1 ng/ml, 51.6% of patients were resuscitated after epinephrine therapy with plasma concentrations greater than 20 ng/ml. In only 1 case could a relationship be demonstrated between the administration of lidocaine and resuscitation success. CONCLUSION. In CPR, the e.b. administration of epinephrine and lidocaine is a reliable alternative to the i.v. injection route of these drugs. Recommended doses are 2.5 mg for epinephrine and 400-500 mg for lidocaine. Resuscitation from VF requires immediate epinephrine therapy if initial defibrillation is not successful. Lidocaine has no effect on resuscitation from VF and therefore should be used specifically for antiarrhythmic therapy after restoration of spontaneous circulation.     

123I-amphetamine-SPECT in classical migraine and migraine accompagnée

Migraine is considered to be a functional neurological disorder. In classical migraine (headache associated with prodromal visual field disturbances) and migraine accompagnée (headache associated with transient neurological symptoms), disturbances of cerebral blood flow and amine metabolism are thought to be pathogenetic factors. However, conventional methods of neuroimaging (CAT, NMR) usually do not yield any pathological findings in patients. Since 123I-iodoamphetamine (123I-IMP) crosses the intact blood brain barrier, 123I-IMP-SPECT is used for the assessment of cerebral perfusion in various neurological diseases, including functional disorders. 123I-IMP-SPECT was performed on 5 patients with classical migraine and 18 patients with migraine accompagnée. At the time of investigation, all patients were symptom-free. Cerebral blood flow was decreased in all patients with migraine accompagnée, and often corresponded to the site of headache as well as to the topography of transient neurological symptoms. This reduction was most obvious in a patient with persisting neurological symptoms. Most patients with classical migraine, however, did not show any alteration of cerebral perfusion. It appears that migraine--and in particular migraine accompagnée--is characterized by a permanent alteration not only of cerebral blood flow but also of neuronal activity. Migraine attacks may occur in connection with exacerbations of preexisting metabolic alterations.     

Lipoprotein(a) as a strong indicator for cerebrovascular disease

To evaluate the role of lipoprotein(a) (Lp(a] in patients with cerebrovascular disease (CVD), lipid parameters were compared with a control group (CO). Additionally, the Lp(a) serum levels were investigated in a coronary artery disease (CAD) group. The CO was made up of 37 healthy persons (age: 54.5 +/- 7.7, 26 males and 11 females), the CVD group included 46 patients with sustained transient ischemic attack (TIA) prolonged reversible ischemic neurologic deficits (PRIND) and cerebral infarction (CI) (age: 53.6 +/- 9.7, 32 males and 14 females), and the CAD group was made up of 28 survivors of myocardial infarctions (age: 52.5 +/- 8.1, 18 males and 10 females). The median values of Lp(a) in CVD were significantly higher than in the CO (p less than 0.01) and did not differ significantly from the CAD. Total TC, HDL-C, TG, LDL-C and the ratio of LDL-C/HDL-C did not show any significant difference between the control and cerebrovascular disease group. For quantification of the vascular lesions of the carotid system, a Duplex Doppler score system was used. The score correlated with Lp(a) in patients between 40 to 65 years of age (r = 0.34, p less than 0.01). Thus, we conclude that Lp(a) is not only a risk factor for CAD but also for CVD.     

Characterisation of surface-modified solid lipid nanoparticles (SLN): influence of lecithin and nonionic emulsifier.

Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to polymer nanoparticles, emulsions and liposomes, are generally produced by high pressure melt-emulsification. However, the harsh production process is not applicable for formulations containing shear and temperature sensitive compounds. For that reason, subsequent adsorptive SLN loading might be a promising alternative. The aim of the present study was the development and characterisation of surface-modified SLN for adsorptive protein loading by variation of both the lipid matrix and the emulsifier concentration in the continuous phase. Variations in SLN composition resulted in particle sizes between 674 and 61 nm corresponding to specific surfaces of 4.5 m(2)/g and 48.9 m(2)/g and zeta potentials between -23.4 mV and -0.9 mV. In dependence of SLN surface properties, albumin payload ranged from 2.5 to 15%. Thermoanalysis, X-ray diffraction and electron microscopy revealed anisometrical and crystalline particles. In vitro cytotoxicity was low in terms of both haemolysis, which was between 1 and 2%, and neutral red test (NRT) showing a half lethal dose between 1.1 and 4.6%.     

Electron inelastic mean free path formula and CSDA-range calculation in biological compounds for low and intermediate energies.

In this study, for low atomic number targets and biological compounds, an inelastic mean free path (IMFP) formula and energy straggling parameter formula are presented, being valid for low and high electron energies. In addition, calculation of the continuous slowing down approximation-range (CSDA-range) from the stopping power is also made. The IMFP and the energy straggling parameter formulae are evaluated using the generalized oscillator strength (GOS) model and the exchange correction to the inelastic differential cross section (IDCS) given by Inokuti, M., [1978. Inelastic collisions of fast charged particles with atoms and molecules--the Bethe theory revisited. Rev. Mod. Phys. 50, 23-35]. The IMFP and CSDA-range for the biological compounds C5H5N5 (adenine), C5H5N5O (guanine), C4H5N3O (cytosine), C5H6N2O2 (thymine), C20H27N7O13P2 (cytosine-guanine) and C19H26N8O13P2 (thymine-adenine) have been introduced for incident electrons in the energy range 20 eV-1 MeV. The calculated results are compared with semi-empirical results and other theoretical results, good agreement being found with experimental data and Monte Carlo (PENELOPE code) predictions. All the IMFP versus energy curves exhibit minima around 80 eV.