Orthogeriatric co-management reduces incidence of delirium in hip fracture patients.

Hip fracture patients often display an acute confusional state (delirium) which is associated with worse outcomes. In this observational study, we found that co-management of hip fracture patients by a multidisciplinary team including a geriatrician and an orthopaedic surgeon could reduce the incidence of delirium. INTRODUCTION: Delirium after hip fracture is common and is associated with negative outcomes. We investigated if orthogeriatric co-management reduced the incidence of delirium in hip fracture patients. METHODS: In this single-centre, prospective observational study, we compared the incidence of delirium and subsyndromal delirium (SSD) before (usual care group, n = 94) and after (orthogeriatric group, n = 103) the introduction of orthogeriatric co-management as an integrated care model. The outcome measure 'no delirium/SSD/delirium' was treated as an ordinal variable and analysed using the chi-squared test and multivariable ordinal logistic regression. RESULTS: The groups had similar baseline characteristics except for a higher proportion of patients with pre-existing cognitive impairment in the usual care group (51% vs. 37%, p = 0.045). Fewer patients in the orthogeriatric group developed SSD or delirium (no delirium: 59% vs. 40%/SSD: 6% vs. 13%/delirium: 35% vs. 47%; p = 0.021). The number needed to treat (NNT) to avoid one case of SSD or delirium was 5.3 (95% CI: 3.1 to 19.7). In a multivariable analysis adjusted for age, sex, ASA class, pre-existing cognitive impairment, time to surgery, type of surgery, and medical or surgical complications, the odds ratio for the development of SSD/delirium was lower in the orthogeriatric group (OR = 0.46, 95% CI: 0.23-0.89, p = 0.023). CONCLUSION: Orthogeriatric co-management as an integrated care model reduced the incidence of SSD/delirium in hip fracture patients.

The MyoRobot: A novel automated biomechatronics system to assess voltage/Ca2+ biosensors and active/passive biomechanics in muscle and biomaterials.

We engineered an automated biomechatronics system, MyoRobot, for robust objective and versatile assessment of muscle or polymer materials (bio-)mechanics. It covers multiple levels of muscle biosensor assessment, e.g. membrane voltage or contractile apparatus Ca2+ ion responses (force resolution 1µN, 0-10mN for the given sensor; [Ca2+] range ~ 100nM-25µM). It replaces previously tedious manual protocols to obtain exhaustive information on active/passive biomechanical properties across various morphological tissue levels. Deciphering mechanisms of muscle weakness requires sophisticated force protocols, dissecting contributions from altered Ca2+ homeostasis, electro-chemical, chemico-mechanical biosensors or visco-elastic components. From whole organ to single fibre levels, experimental demands and hardware requirements increase, limiting biomechanics research potential, as reflected by only few commercial biomechatronics systems that can address resolution, experimental versatility and mostly, automation of force recordings. Our MyoRobot combines optical force transducer technology with high precision 3D actuation (e.g. voice coil, 1µm encoder resolution; stepper motors, 4µm feed motion), and customized control software, enabling modular experimentation packages and automated data pre-analysis. In small bundles and single muscle fibres, we demonstrate automated recordings of (i) caffeine-induced-, (ii) electrical field stimulation (EFS)-induced force, (iii) pCa-force, (iv) slack-tests and (v) passive length-tension curves. The system easily reproduces results from manual systems (two times larger stiffness in slow over fast muscle) and provides novel insights into unloaded shortening velocities (declining with increasing slack lengths). The MyoRobot enables automated complex biomechanics assessment in muscle research. Applications also extend to material sciences, exemplarily shown here for spider silk and collagen biopolymers.

Developmental disturbances associated with agenesis of the permanent maxillary lateral incisor.

The aim of this study was to characterise the intra and extra-oral phenotype associated with agenesis of the permanent maxillary lateral incisor. We compared three groups: (1) subjects with agenesis of one or both permanent maxillary lateral incisors (n=80); (2) first and second degree relatives of group 1 with no agenesis of the permanent maxillary lateral incisor and (3) subjects with no agenesis of the maxillary lateral incisor or family history of it (n=49). For each of the 201 subjects detailed clinical information was reviewed and panoramic radiographs were analysed. Considering only the sample with unilateral agenesis, microdontia of the contralateral permanent maxillary lateral incisor was significantly more frequent in group 1 (82.4%) than in group 2 (25%) and the control group (2%). This supports the theory that microdontia is a variable expression of the same developmental disturbance that causes tooth agenesis. The absence of third molars occurred more often in group 1 (36.2%) than in groups 2 and 3 (18.6% and 18.9% respectively), confirming that agenesis of third molars was markedly associated with the agenesis of the permanent maxillary lateral incisor. Agenesis of teeth other than third molars was not significantly different among subjects with agenesis of the permanent maxillary lateral incisor and their relatives. The frequencies of supernumerary teeth, permanent maxillary canine impaction, general health condition and minor anomalies were not significantly different between the three groups.

[Leflunomide reduces the angiogenesis score and tumor growth of subcutaneously implanted colon carcinoma cells in the mouse model]. / Leflunomid reduziert den Angiogenesescore und das Tumorwachstum subkutan implantierter Kolonkarzinomzellen im Mausmodell.

BACKGROUND: The inhibition of tumorangiogenesis may be of importance in the additive treatment of various cancers. Leflunomide, a drug which has been approved in Germany for the therapy of rheumatoid arthritis, inhibits the activity of several growth factors in vitro. The aim of this study was to investigate the effects of the drug on tumor angiogenesis in a nude mouse model. MATERIALS AND METHODS: A total of 40 nude mice were injected with human colon carcinoma cells. Following randomization in 4 groups, therapy started on day five. Group 1 was treated daily with orally administered Leflunomide (35 mg/kg) dissolved in 1.5% Carboxymethylcellulose (CMC). Group 2 served as a control group and received 1 ml CMC orally per day. The animals of group 3 were treated daily with 35 mg Leflunomide/kg KG and 500 mg Uridine/kg dissolved in 1 ml Nacl 0.9% intraperitoneally. The 4th group again served as a control group and received only 500 mg Uridine/kg intraperitoneally each day. The main outcome criterion was the angiogenesis score (AS). In addition, the tumor volume and tumor weight were also assessed. The AS was determined by immunohistochemistry using an antibody against factor VIII related antigen. RESULTS: All animals tolerated the procedure well. In the Leflunomide and the Leflunomide/Uridine group the angiogenesis score (p < 0.01), the tumor volume (p < 0.01) and the tumor weight (p < 0.01) were lower compared to the respective control groups. CONCLUSION: The administration of Leflunomide leads to a significant reduction of tumor weight and tumor volume following subcutaneous injection of human colon carcinoma cells in a nude mouse model. This could be due to the reduction of tumor angiogenesis. Following further experimental and clinical studies, Leflunomide may come to play a role in the additive treatment of colonic carcinoma.

How anaerobic is the Wingate Anaerobic Test for humans?

The Wingate Anaerobic Test (WAnT) is generally used to evaluate anaerobic cycling performance, but knowledge of the metabolic profile of WAnT is limited. Therefore the energetics of WAnT was analysed with respect to working efficiency and performance. A group of 11 male subjects [mean (SD), age 21.6 (3.8) years, height 178.6 (6.6) cm, body mass 82.2 (12.1) kg] performed a maximal incremental exercise test and a WAnT. Lactic and alactic anaerobic energy outputs were calculated from net lactate production and the fast component of the kinetics of post-exercise oxygen uptake. Aerobic metabolism was determined from oxygen uptake during exercise. The WAnT mean power of 683 (96.0) W resulted from a total energy output above the value at rest of 128.1 (23.2) kJ x 30 s(-1) [mean metabolic power=4.3 (0.8) kW] corresponding to a working efficiency of 16.2 (1.6)%. The WAnT working efficiency was lower (P < 0.01) than the corresponding value of 24.1 (1.7)% at 362 (41) W at the end of an incremental exercise test. During WAnT the fractions of the energy from aerobic, anaerobic alactic and lactic acid metabolism were 18.6 (2.5)%, 31.1 (4.6)%, and 50.3 (5.1)%, respectively. Energy from metabolism of anaerobic lactic acid explained 83% and 81% of the variance of WAnT peak and mean power, respectively. The results indicate firstly that WAnT requires the use of more anaerobically derived energy than previously estimated, secondly that anaerobic metabolism is dominated by glycolysis, thirdly that WAnT mechanical efficiency is lower than that found in aerobic exercise tests, and fourthly that the latter finding partly explains discrepancies between previously published and the present data about the metabolic profile of WAnT.

[Keloid of the earlobe after ear piercing. Not only a surgical problem]. / Keloidbildung des Ohrläppchens nach Ohrlochstechen. Nicht nur ein chirurgisches Problem.

Earlobe keloids are benign, fibrous proliferations that show a high rate of recurrence of up to 80% following surgical excision. Traumas to the earlobe such as ear piercing, burns or surgical interventions are important in the pathogenesis of the disease. In addition to surgical keloid excision and reconstruction of the earlobe, several adjuvant therapeutic concepts have been described to prevent recurrence. Here we present the case of a female patient who suffered from severe bilateral keloid development after piercing of both ears. The report gives an overview of the relevant therapeutic concepts in the treatment of earlobe keloids and their possible complications. In addition, the question of written informed consent before ear piercing is discussed.

Esophageal necrosis and perforation of the left main bronchus following photodynamic therapy of esophageal carcinoma.

Photodynamic therapy is an effective palliative treatment of esophageal cancer. Minor complications associated with this therapy include pleural effusions, fever or esophageal strictures. In addition to this major complications such as respiratory-esophageal fistula and bronchus perforation have been described. We report here our experience with a patient who developed a complete esophageal necrosis and perforation of the left main bronchus following photodynamic therapy. The surgical and intensive care management of the patient is described and the literature discussed.

Long-term survival of a patient with small-cell lung cancer (SCLC) following treatment with thalidomide and combination chemotherapy.

Thalidomide, an angiogenesis inhibitor is currently used in clinical trials in the US and Europe in combination with chemotherapy for the treatment of various solid tumors. The prognosis of patients suffering from small-cell lung cancer (SCLC) is poor. A 73-year-old female with extensive disease of SCLC was given six courses of chemotherapy with adriamycine, cyclophasphamide and oncovine, which led to complete remission of the disease. Following written informed consent, the patient has been treated with thalidomide 200 mg orally on a daily basis for 2 years and 5 months. There has been no sign of tumor recurrence during the follow-up. This case underlines the possible role of additional treatment with angiogenesis inhibitors in combination with traditional chemotherapy in the therapy of SCLC. Although there is no proof that thalidomide contributed to this good outcome and no conclusions can be drawn from this treatment in a single patient, further studies may determine the role of thalidomide as an adjuvant antiangiogenic agent in the therapy of SCLC.

The constitutive photomorphogenesis 9 signalosome directs vascular endothelial growth factor production in tumor cells.

Angiogenesis is a prerequisite for solid tumor growth and metastasis. Elucidation of the signaling pathways that control tumor angiogenesis constitutes the basis for a rational antiangiogenic tumor therapy. Here we show that the production of vascular endothelial growth factor (VEGF) in HeLa and HL-60 cells is directed by the constitutive photomorphogenesis 9 signalosome (CSN). The CSN is a kinase complex that cooperates with the ubiquitin/26S proteasome system in regulating the stability of proteins involved in signal transduction. VEGF expression is controlled by the transcription factors activator protein (AP)-1, AP-2, SP-1, and hypoxia-inducible factor 1. Inhibition of CSN kinase activity by 50 microM curcumin for 2 h decreases the cellular c-Jun concentration, resulting in a reduction of the VEGF production by approximately 75%. The removal of the inhibitor from the cells led to a time-dependent recovery of endogenous c-Jun that is paralleled by increasing VEGF production. Elevated cellular CSN activity induced by CSN subunit 2 overexpression causes increased VEGF production in HeLa cells. A competitor of CSN-dependent c-Jun phosphorylation, the NH(2)-terminal c-Jun fragment Deltac-Jun(1-226), inhibits VEGF production in HeLa cells. The transcription factors AP-2 and SP-1 act independently of the CSN. They contribute less than a quarter to basal VEGF production. Under our experimental conditions, hypoxia-inducible factor 1alpha protein was not detected. Overexpression of the tumor suppressor p53 reduces VEGF production in HeLa cells. p53 competes with c-Jun for CSN-specific phosphorylation with the consequence of c-Jun destabilization. We conclude that CSN-directed c-Jun signaling mediates high VEGF production in HeLa and HL-60 cells. The data provide an explanation for the known antiangiogenic and antitumorigenic activities of curcumin. Because the CSN regulates the major part of VEGF production in the tested tumor cells, it constitutes a potentially important target for tumor therapy.

COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system.

In higher eukaryotic cells, the p53 protein is degraded by the ubiquitin-26S proteasome system mediated by Mdm2 or the human papilloma virus E6 protein. Here we show that COP9 signalosome (CSN)-specific phosphorylation targets human p53 to ubiquitin-26S proteasome-dependent degradation. As visualized by electron microscopy, p53 binds with high affinity to the native CSN complex. p53 interacts via its N-terminus with CSN subunit 5/Jab1 as shown by far-western and pull-down assays. The CSN-specific phosphorylation sites were mapped to the core domain of p53 including Thr155. A phosphorylated peptide, Deltap53(145-164), specifically inhibits CSN-mediated phosphorylation and p53 degradation. Curcumin, a CSN kinase inhibitor, blocks E6-dependent p53 degradation in reticulocyte lysates. Mutation of Thr155 to valine is sufficient to stabilize p53 against E6-dependent degradation in reticulocyte lysates and to reduce binding to Mdm2. The p53T155V mutant accumulates in both HeLa and HL 60 cells and exhibits a mutant (PAb 240+) conformation. It induces the cyclin-dependent inhibitor p21. In HeLa and MCF-7 cells, inhibition of CSN kinase by curcumin or Deltap53(145-164) results in accumulation of endogenous p53.

[Rectal formalin instillation--a practical and reliable therapy of hemorrhagic proctitis]. / Rectale Formalininstillation--eine praktikable und sichere Therapie der hämorrhagischen Proktitis.

UNLABELLED: Hemorrhagic proctitis is a rare, but severe complication of radiation therapy in the treatment of several pelvic malignancies. Administration of topical steroids, anti-inflammatory agents or laser therapy and rectal instillation of 4% formalin have been described as a method of treating this complication. A dog model was established to study the safest volume and duration of administration of formalin, the histological changes in the rectal mucosa, and rectal compliance following this treatment. METHOD: Twenty-one mongrel dogs were assigned randomly to seven groups. Three dogs received a rectal formalin bolus of 400 ml for 1 h; in the other six groups formalin was instilled in 30 ml aliquots to a total volume of 400 ml. Serum levels of formalin were obtained at designated time intervals, rectal compliance was evaluated pre- and post-formalin instillation, and rectal mucosa was analyzed for blood-vessel density and mucosal injury at different time points. RESULTS: Serum formalin in the bolus group reached toxic levels, while sequential instillation caused no serum toxicity in any dog. Rectal compliance and mucosal thickness were not affected by formalin, but there was a decrease in the angiogenesis score, and mild proctitis was seen in the acute and 1-week group.