[Interprofessional symptom management at the end of life]. / Interprofessionelle Symptomkontrolle am Lebensende.

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated. Besides the identification of underlying causes with the possibility of causal treatment, a symptom-based therapy is often necessary. Therapeutic approaches of different professions should be equally considered and should additionally be used for the benefit of the patient.

[Potential of specialized outpatient palliative care]. / Möglichkeiten der spezialisierten ambulanten Palliativversorgung.

Palliative care patients with incurable advanced disease suffering from complex symptoms can receive specialized outpatient palliative care in addition to the existing ambulatory care system. Qualified physicians and nurses care for patients and their dependents in cooperation with other professionals. In addition to a 24/7 on-call service for emergencies or acute crises, patients and their dependents are offered regular visits.

[Interprofessional symptom management at the end of life]. / Interprofessionelle Symptomkontrolle am Lebensende.

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated. Besides the identification of underlying causes with the possibility of causal treatment, a symptom-based therapy is often necessary. Therapeutic approaches of different professions should be equally considered and should additionally be used for the benefit of the patient.

[Establishment of the new cross-sectional field of pain medicine : An application example at the medical faculty of Heidelberg]. / Etablierung des neuen Querschnittsbereichs Schmerzmedizin : Ein Anwendungsbeispiel der Medizinischen Fakultät Heidelberg.

Studies from recent years paint a picture of qualitatively deficient treatment in pain medicine. In order to improve the situation knowledge on targeted diagnostics and effective therapy should be imparted at an early stage during undergraduate studies. For this reason the cross-sectional field Q14 - pain medicine was newly created in the revision of the medical physician licencing regulations. The Q14 was then established in a longitudinal, multidisciplinary form at the medical faculty in Heidelberg, whereby the complete Kern cycle was run through. The present project report describes and discusses the establishment. The results of the first multiple choice examination and an online-based evaluation by the students are presented. The latter show that the students recognized the relevance of the teaching program for their future professional career; however, the presentation of the interdisciplinary aspect must still be improved. The students were critical of the longitudinal structure and this does indeed involve a great deal of organization for the faculty and students. On the other hand this corresponds to the basic conception of a cross-sectional field and gives a good depiction of the multidisciplinary character. The first evaluation results set the precedent for further fine adjustments of the cross-sectional field. A continuous further development is generally needed with respect to the Kern cycle.

[Cancer breakthrough pain. Indications for rapidly effective opioids]. / Tumordurchbruchschmerz. Indikation für schnell wirksame Opioide.

The pharmacotherapy of tumor pain has two main aims: to deliver an adequate basic analgesia using long-term retarded opioid medication and an effective treatment of tumor breakthrough pain using rapidly effective non-retarded opioids. Breakthrough pain is characterized by a sudden onset and rapid increase in the pain level and should be treated with correspondingly rapidly effective opioids. The pharmacological characteristics of previously available and routinely prescribed non-retarded opioids do not always correspond in oral galenics to the demands resulting from the definition of tumor breakthrough pain. As alternatives to these substances five different rapidly effective fentanyl preparations are now available for transmucosal administration.

Vertebroplasty and kyphoplasty - inefficient treatments for degenerative spine disease.

Osteoporotic vertebral fractures and pathological vertebral lesions are frequent clinical situations causing severe back pain. The pharmacological treatment of the underlying disease and the analgetic treatment of the associated back pain usually do not rid the patient's back pain completely and are insufficient to prevent the fracture-weakened vertebral body from further fracturing with long term consequences for the biomechanical competence of the entire spine. In the last 10 years the minimal invasive treatment options vertebroplasty (VP) and balloon kyphoplasty (BK) have spread quickly because these procedures appeared to be promising treatments to stop the fracture and vertebral lesion associated back pain and to internally stabilize a fractured vertebral body. Numerous published reports on VP and BK appeared to support the notion of an immediate and lasting pain reduction after VP and BK in additon to a prevention of further fracturing of the treated vertebrae. The first three randomized controlled and partly blinded trials have been published this year. Two of these trials demonstrate that VP does not result in a better pain control than a sham operation whereas BK was shown to reduce back pain due to verterbal fractures for at least 12 months. Considering that more than 1.5 million people world-wide have been treated with VP and BK until now this work discusses the recent trials and suggests clinical and academic consequences on the basis of the most recent evidence.

[From wheelchair dependency to the ability to walk: lumbar sympathectomy as a treatment for complex regional pain syndrome]. / Vom Rollstuhl zur Gehfähigkeit: Lumbale Sympathektomie zur Therapie langjähriger chronischer Schmerzen.

A 34-year-old woman developed walking disability with wheelchair dependency for more than 2 years due to chronic regional pain syndrome type II (CRPS II) in the feet. After excluding neurological and vascular disease, lumbar sympathectomy was performed on both sides. Surgical treatment was uneventful, and the patient's symptoms dramatically improved after 2 months. She is now able to walk some 500 m. This case illustrates the fact that surgical lumbar sympathectomy is an effective alternative or adjunct treatment even in fixed CRPS II.

EEG changes and serum anticholinergic activity measured in patients with delirium in the intensive care unit.

The aim of this study was to examine whether serum anticholinergic activity (SAA) is a reliable indicator of delirium in the ICU, and whether there is a significant correlation between SAA and quantitative electroencephalographic (EEG) data in delirious patients. In a prospective cohort study, we assessed ICU patients diagnosed with delirium (n = 37). EEG measurements and blood analysis including SAA were performed 48 h following ICU admission. The presence of delirium was evaluated using the Confusion Assessment Method for critically ill patients in ICU (CAM-ICU). The SAA level was measured using a competitive radioreceptor binding assay for muscarinergic receptors and quantitative EEG was measured using the CATEEM system. We found that, under comparable conditions, patients in the delirium group showed a higher relative EEG theta power and a reduced alpha power (n = 17) than did the non-delirious patients (n = 20). No difference in measured SAA levels were seen; therefore, there was no correlation between SAA and EEG measurements in delirious patients. We conclude that, in contrast to the EEG, the SAA level cannot be proposed as a tool for diagnosing delirium in ICU patients.

Adenosine A1 and A2 receptor agonists reduce endotoxin-induced cellular energy depletion and oedema formation in the lung.

BACKGROUND AND OBJECTIVE: Tissue depletion of adenosine during endotoxaemia has previously been described in the lung. Therapeutic approaches to prevent adenosine depletion and the role of A1 and A2 receptor agonists, however, have not been investigated until now. METHODS: In isolated and ventilated rabbit lungs, it was tested whether pretreatment with adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 10(-7) mol, n = 6) or A2 receptor agonist 5'-(N-cyclopropyl)-carboxyamido adenosine (CPCA; 10(-7) mol, n = 6) prior to injection of lipopolysaccharide (LPS) (500 pg mL-1) influenced pulmonary artery pressure (PAP), pulmonary energy content and oedema formation as compared with controls, solely infused with LPS (n = 6). Release rates of adenosine and uric acid were determined by high-performance liquid chromatography. Pulmonary tissue concentrations of high-energy phosphates were measured and the adenine nucleotide pool, adenosine 5'-triphosphate (ATP)/adenosine 5'-diphosphate (ADP) ratio and adenylate energy charge of the pulmonary tissue were calculated. RESULTS: Administration of LPS induced increases in PAP within 2 h up to 20.8 +/- 2.9 mmHg (P < 0.01). While pretreatment with the A1 agonist merely decelerated pressure increase (13.8 +/- 1.1 mmHg, P < 0.05), the A2 agonist completely suppressed the pulmonary pressure reaction (9.6 +/- 1.0 mmHg, P < 0.01). Emergence of lung oedema after exclusive injection of LPS up to 12.0 +/- 2.9 g was absent after A1 (0.6 +/- 0.5 g) and A2 (-0.3 +/- 0.2 g) agonists. These observations were paralleled by increased adenosine release rates compared with LPS controls (P < 0.05). Moreover, tissue concentrations of ADP, ATP, guanosine 5'-diphosphate, guanosine 5'-triphosphate, nicotinamide-adenine-dinucleotide and creatine phosphate were significantly reduced after LPS. Consequently, the calculated tissue adenine nucleotide pool and the adenylate energy charge increased after adenosine receptor stimulation (P = 0.001). CONCLUSIONS: Adenosine A1- and A2-receptor agonists reduced LPS-induced vasoconstriction and oedema formation by maintenance of tissue energy content. Thus, adenosine receptor stimulation, in particular of the A2 receptor, might be beneficial during acute lung injury.

[Drug application forms in chronic pain therapy]. / Arzneimittelanwendung in der Therapie chronischer Schmerzen.

The choice of the appropriate application form is a critical prerequisite to ensure therapeutic success in pain therapy. Tablets, capsules, and oral liquids are the classical application forms. Slow release formulas have optimized the therapy of chronic pain and offer the possibility of an oral basic medication with only two applications a day. Transdermal delivery systems of highly effective opioids offer particular advantages in chronic and stable pain conditions. Oromucosal delivery systems are an option for a rapidly effective rescue medication, while suppositories are not an application form of first choice because of their low acceptance by the patients and poorly reproducible bioavailability. PCA (patient controlled analgesia) needs to be reserved for patients lacking other therapeutic options. For many of those application forms specific information about prescription and application is needed to ensure good therapeutic results.

Targeted-HASTE imaging with automated device tracking for MR-guided needle interventions in closed-bore MR systems.

Percutaneous MR-guided interventions with needles require fast pulse sequences to image the needle trajectory with minimal susceptibility artifacts. Spin-echo pulse sequences are well suited for reducing artifact size; however, even with single-shot turbo spin-echo techniques, such as rapid acquisition with relaxation enhancement (RARE) or half-Fourier acquisition single-shot turbo spin-echo (HASTE), fast imaging remains challenging. In this work we present a HASTE pulse sequence that is combined with inner-volume excitation to reduce the scan time and limit the imaging field of view (FOV) to a small strip close to the needle trajectory (targeted-HASTE). To compensate for signal saturation from fast repeated acquisitions, a magnetization restore pulse (driven equilibrium Fourier transform (DEFT)) is used. The sequence is combined with dedicated active marker coils to measure the position and orientation of the needle so that the targeted-HASTE image slice is automatically repositioned. In an animal experiment the coils were attached to an MR-compatible robotic assistance system for MR-guided interventions. Needle insertion and infusion via the needle could be visualized with a temporal resolution of 1 s, and the needle tip could be localized even in the presence of a stainless steel mandrel.

[Postoperative pulmonary complications: prophylaxis after noncardiac surgery]. / Postoperative pulmonale Komplikationen : Prophylaxe nach nichtkardiochirurgischen Eingriffen.

Postoperative pulmonary complications are a major problem after upper abdominal or thoracoabdominal surgery. They lead to a prolonged ICU stay as well as increased costs and are one of the main causes of early postoperative mortality. Even after uncomplicated operations, postoperative hypoxemia occurs in 30-50% of patients. Acute respiratory failure involves a disturbance in gas exchange. The mortality ranges from 10 to 60% according to the severity of respiratory failure. The most important complications are interstitial and alveolar pulmonary edema, atelectasis, postoperative pneumonia, hypoventilation, and aspiration. Preoperative optimization, postoperative prophylaxis according to a stepwise approach, and early mobilization decrease the rate of complications.

Adenosine-induced cardiac arrest and EEG changes in patients with thoracic aorta endovascular repair.

BACKGROUND: We studied haemodynamic and metabolic variables, and cerebral function after cardiac arrest induced by high dose of adenosine in patients undergoing thoracic aorta endovascular repair. METHODS: Arterial blood pressure, blood gas values and EEG were recorded continuously in 15 patients undergoing anaesthesia (isoflurane) for endovascular thoracic aorta repair. Cardiac arrest was induced by different doses of adenosine (Adrekar, Sanofi-Synthelabo, Berlin, Germany; 0.4-1.8 mg kg(-1) body weight). Serum concentrations of neurone-specific enolase (NSE) were determined before and after stent graft implantation. Neurological function was assessed before and after surgery. RESULTS: After adenosine, the heart beat stopped immediately for 18-58 s in close relation to the adenosine dose. EEG power was significantly reduced to -57%, but reached normal values within 5 min after cardiac arrest. In particular, the fast alpha- and beta-EEG-frequencies sensitively reflected patients' EEG activity during the procedure. No intraoperative increases in NSE concentrations, and no neurological dysfunctions after surgery, were observed. CONCLUSION: After adenosine-induced cardiac arrest, changes in haemodynamic variables and EEG power spectra reversed completely within 1 and 5 min, respectively, without persistent brain dysfunction after stent graft implantation.

Amyloid precursor protein (APP) and its derivatives change after cellular energy depletion. An in vitro-study.

To study the relationship between the metabolism of amyloid precursor protein (APP) and cellular energy failure, HEK 293 cells stably transfected with betaAPP 695 underwent graded energy failure induced either by i) hypoxia (pO(2) 25 mm Hg), ii) inhibition of the respiratory chain by sodium azide (NaN(3)), or iii) by combined glucose deprivation/hypoxia of different duration and severity. Secreted APP (APPs) and the derivative betaA4 were quantified autoradiographically by immunoprecipitation, and [(35)S] methionine labeling. APP holoprotein (APPh) was determined by Western blot analysis. The concentrations of the energy-rich metabolites ATP, ADP, creatine phosphate (CrP), and adenosine were measured by high performance liquid chromatography. Mild to moderate energy failure after NaN(3) treatment (2h, 4h) and hypoxia (2h, 8h) was characterized by normal ATP concentration but also by a high reduction in CrP. A stress condition indicated by an increased ATP turnover and adenosine increase was obtained. Intracellular APPh increased but its metabolites APPs and betaA4 as measured in the extracellular compartment decreased. These changes may point to a compensatory response of APP but also to a initial disturbance in intracellular APP metabolism. Severe abnormalities in both energy formation and utilization after 8h NaN(3) and hypoxia glucose deprivation were found to be accompanied by a drastic fall in intracellular APPh concentration by at least 50%, paralleled by an accelerating reduction in the extracellular concentrations of both APPs and betaA4.A significant linear correlation between APPh and ATP and between CrP and betaA4 became obvious. The data of the present study indicate that abnormalities in APP metabolism were generated in an energy-dependent manner. The obvious similarities to sporadic Alzheimer s disease are discussed.

Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting prophylaxis: a randomised placebo-controlled patient and observer blind trial.

This randomised, placebo-controlled, patient and observer blinded trial was conducted to determine whether acupuncture at the acupuncture point P6 is effective in preventing postoperative nausea and vomiting (PONV) compared to placebo acupuncture. Female patients (n = 220) scheduled for gynaecological or breast surgery were randomly assigned to two groups receiving either acupuncture (n = 109) or placebo acupuncture (n = 111). Each group was stratified for type of surgery and included two subgroups receiving intervention either before or after induction of anaesthesia. The incidence of PONV and/or antiemetic rescue medication within 24 h after surgery was the main outcome measure which showed no statistically significant difference between groups (43.7% acupuncture, 50.9% placebo, p = 0.27). The differences were more pronounced for patients having gynaecological surgery (48.9% acupuncture, 67.6% placebo, p = 0.07) than for those having breast surgery (38.7% acupuncture, 40.3% placebo, p = 0.86). The secondary outcome, vomiting, was significantly reduced by acupuncture from 39.6% to 24.8% (p = 0.03). Subgroup analysis showed no difference between applications of acupuncture before compared to after induction of anaesthesia.

[Role of the innate immune response in sepsis]. / Bedeutung der angeborenen Immunantwort in der Sepsis.

The innate immune system succeeds against the majority of infections before the adaptive immune system is activated. New findings contribute to a better understanding of the pathophysiology of sepsis and lead to the development of new therapeutic strategies. The innate immune system, being responsible for the first response to infections, can trigger adaptive immune responses in case the initial response is ineffective. Both arms of the immune system interact with each other, mainly via cell-cell-interactions but also by soluble factors, such as cytokines and chemokines. Two sub-populations of helper T-cells direct both balanced activation and inhibition of the two arms of the immune systems using specific patterns of cytokine release. Results obtained in new animal models of sepsis, taking a progressive growth of bacteria into account, have implied that existing knowledge has to be reanalyzed. The idea of sepsis as a mere "over-reaction to inflammation" has to be abandoned. Various so-called pattern recognition receptors (e.g. toll-like receptors, TLRs, NOD proteins) are located intracellularly or in the plasma membrane of innate immune cells and recognize certain patterns expressed exclusively by extracellular pathogens. Upon receptor engagement, intracellular signaling pathways lead to cellular activation, followed by release of various cytokines and anti-microbial substances. During the course of sepsis a cytokine shift towards increasing immune suppression occurs. The innate immune system also contributes to the migration of leukocytes in inflammed tissue, involving chemokines and adhesion molecules. Leukocytes also secrete the tissue factor leading to formation of thrombin. The environment in sepsis can cause disseminated intravascular coagulation (DIC), but at the same time thrombin triggers the release of chemokines and adhesion molecules through endothelial cells, which represents a positive feedback mechanism for innate immune responses. New therapeutic strategies for sepsis try to establish a well-balanced immune response. Intervention is accomplished through inhibition of inflammatory cytokines, their receptors or through activation of immunostimulatory responses.