Galvanic vestibular stimulation reduces the pathological rightward line bisection error in neglect-a sham stimulation-controlled study

Patients with right hemisphere lesions often show left spatial neglect and the typical rightward deviation in horizontal line bisection. Previous studies have shown that sensory stimulation modulates line bisection. A less well-known but promising sensory stimulation method is galvanic vestibular stimulation (GVS). This non-invasive technique leads to activation of the vestibular cortices and adjacent cortical areas in the temporo-parietal cortex via polarization effects of the vestibular nerves. This is accomplished by application of weak direct currents, delivered by two electrodes attached to the mastoids. Despite the relative benefits of GVS its effects on line bisection have not yet been studied in neglect patients. Thus, the present study investigated the impact of GVS on performance in a modified line bisection task in right-brain damaged patients with versus without leftsided visual neglect. In neglect patients, but not in control patients, left-cathodal and right-cathodal GVS significantly reduced the rightward line bisection error as compared to Baseline (without GVS) and sham stimulation. A larger decrease of the rightward line bisection error was observed during right-cathodal GVS. Sham stimulation showed no specific effects on line bisection. The beneficial effects of GVS might be due to activation of preserved structures of the lesioned right posterior parietal cortex which is known to be involved in line bisection.     

Surgical treatment of bile duct injuries following laparoscopic cholecystectomy. Does the concomitant hepatic arterial injury influence the long-term outcome?

BACKGROUND: Bile duct injuries are the most dreaded complication associated with laparoscopic cholecystectomy. Recent collective reviews have outlined the management of bile duct injuries, but only few have reported on the significance of concomitant injuries of the right hepatic artery. This study was conducted to compare the outcome of patients with isolated bile duct injuries and patients with additional vascular injuries. PATIENTS AND METHODS: From January 1990 to February 2002, a total of 54 patients with bile duct injuries during laparoscopic cholecystectomy were surgically treated in our institution. In 46 patients a Roux-Y hepaticojejunostomy was performed. Eight patients underwent other surgical procedures and were not included in the statistical analysis. 11 patients had a concomitant vascular injury. Multivariate analysis was performed to evaluate the impact of vascular injuries. RESULTS: The rate of postoperative biliary complications was 21.7 % for all patients. Patients with combined bile duct and hepatic arterial injuries had a higher risk for the development of a biliary complication (6 of 11 patients (54.5 %) versus 4 of 35 patients (11.4 %); p = 0.006). After a median follow-up time of 61 months (range, 2-164 months) a successful overall outcome was achieved in 42 of 46 patients (91.3 %), which included the patients who required additional endoscopic or surgical treatment after primary reconstruction. The long-term outcome was successful in 9 of 11 patients (81.8 %) with combined bile duct and hepatic arterial injuries and in 33 of 35 patients (94.3 %) with solitary bile duct injury. CONCLUSION: The outcome of patients with combined bile duct and arterial injuries is worse than in patients with isolated bile duct injuries. We therefore recommend the evaluation of patients with major bile duct injuries for additional vascular injuries. Vascular reconstruction should be performed when ever possible in early recognised injuries to prevent late complications.     

Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance.

Inhibition of protein kinase C (PKC) is discussed as a new approach for overcoming multidrug resistance (MDR) in cancer chemotherapy. For evaluation of this concept we applied the bisindolylmaleimide GF 109203X, which shows a highly selective inhibition of PKC isozymes alpha, beta 1, beta 2, gamma, delta and epsilon in vitro. The efficacy of this compound in modulation of MDR was examined using several P-glycoprotein (P-gp)-overexpressing cell lines including a MDR1-transfected HeLa clone, and was compared with the activities of dexniguldipine-HCI (DNIG) and dexverapamil-HC1 (DVER), both of which essentially act via binding to P-gp. As PKC alpha has been suggested to play a major role in P-gp-mediated MDR, cell lines exhibiting different expression levels of this PKC isozyme were chosen. On crude PKC preparations or in a cellular assay using a cfos(-711)CAT-transfected NIH 3T3 clone, the inhibitory qualities of the bisindolylmaleimide at submicromolar concentrations were demonstrated. At up 1 microM final concentrations of the PKC inhibitor GF 109203X, a concentration at which many PKC isozymes should be blocked substantially, no cytotoxic or MDR-reversing effects whatsoever were seen, as monitored by 72 h tetrazolium-based colorimetric MTT assays or a 90 min rhodamine 123 accumulation assay. Moreover, depletion of PKC alpha by phorbol ester in HeLa-MDR1 transfectants had no influence on rhodamine 123 accumulation after 24 or 48 h. MDR reversal activity of GF 109203X was seen at higher final drug concentrations, however. Remarkably, [3H]vinblastine-sulphate binding competition experiments using P-gp-containing crude membrane preparations demonstrated similar dose dependencies as found for MDR reversion by the three modulators, i.e. decreasing efficacy in the series dexniguldipine-HCl > dexverapamil-HCl > GF 109203X. Similar interaction with the P-gp in the micromolar concentration range was revealed by competition of GF 109203X with photoincorporation of [3H]azidopine into P-gp-containing crude membrane preparations. No significant effect of the PKC inhibitor on MDR1 expression was seen, which was examined by cDNA-PCR. Thus, the bisindolylmaleimide GF 109203X probably influences MDR mostly via direct binding to P-gp. Our work identifies the bisindolylmaleimide GF 109203X as a new type of drug interacting with P-gp directly, but does not support the concept of a major contribution of PKC to a P-gp-associated MDR, at least using the particular cellular model systems and the selective, albeit general, PKC inhibitor GF 109203X.     

Operative Interdisziplinarität. Extremitäten

From the perspective of trauma and orthopedic surgery interdisciplinary reconstructive surgery of the extremities encompasses different indications ranging from IIIB/Copen fractures with major segmental loss of bone and soft tissue, to arterial vessel in-jury necessitating vascular repair and to biological, plastic reconstructions following resections of musculoskeletal tumors. The interdisciplinary treatment concept including trauma-orthopedic surgery combined with vascular, plastic and neuro- as well as microsurgery has significantly decreased amputation rates and functional deficits thereby improving quality of life and long-term oncological outcome The multisdisciplinary management of both complex trauma and malignant bone/ soft tissue sarcoma of the extremity is an integral task of the surgical trauma or tumor center. Close interdisciplinary communication and expierence are the precondition for performance of a priority-adapted therapeutic strategy, low complication rates and improvement of overall prognosis.     

Pers?nliche Meinung?Der symptomatische Koronarpatient mit pathologischem operationsbedürftigen Koronarangiogramm

Zusammenfassung: Die Bypasschirurgie hat sich bei exzellenten Kurz- und Langzeitergebnissen als fester Bestandteil in der Therapie der koronaren Herzerkrankung etabliert. Zur Anpassung an eine veränderte Patientenstruktur mit einem hohen Anteil an Hochrisikopatienten sind zunehmend minimalinvasive chirurgische Techniken in der Herzchirurgie zum Einsatz gekommen. Ergänzend zu chirurgischen Maßnahmen werden molekularbiologische Techniken in der Primär- und Sekundärtherapie der koronaren Herzkrankheit eingesetzt. Abstract: Bypass surgery has become a routine procedure for the treatment of coronary artery disease. Due to increase numbers of high-risk patients minimally invasive techniques were introduced in cardiac surgery with excellent clinical results. In addition molecular methods have been applied for primary and secondary treatment of coronary artery disease.     

Bicalutamide-associated fulminant hepatotoxicity

Abstract Bicalutamide is a nonsteroidal antiandrogen used extensively during the start of androgen deprivation therapy with a luteinizing hormone-releasing hormone agonist to reduce occurrence of the symptoms of tumor flare in patients with metastatic prostate carcinoma. The most common adverse effects of bicalutamide are induced by its pharmacologic property of competitive androgen receptor blockade and include gynecomastia, hot flashes, fatigue, and decreased libido. Although not as common, increases in liver function test results are also seen with bicalutamide therapy. These elevations are typically transient, and patients remain asymptomatic. We describe a 59-year-old man with metastatic prostate carcinoma treated with bicalutamide as part of androgen deprivation therapy before starting chemotherapy. At baseline, his liver function test results and serum creatinine concentration were within normal limits, and an abdominal computed tomographic scan did not demonstrate liver metastasis. After 4 days of bicalutamide therapy, the patient came to the emergency department with complaints of abdominal pain, distension, and tenderness. His liver function tests were abnormal, and bicalutamide was discontinued. After 2 days of increasing liver function tests and symptoms of hepatotoxicity, the patient developed tachycardia and hypotension that was resistant to fluid resuscitation. Multiorgan damage was manifested by an alanine aminotransferase level greater than 40 times the upper limit of normal, serum creatinine concentration of 4.2 mg/dl, and troponin I level of 18 ng/ml. The patient died 8 days after bicalutamide therapy was begun secondary to multiorgan failure, most likely as a result of fulminant hepatotoxicity. The Naranjo adverse drug reaction probability scale showed a probable (score of 5) causal relationship between bicalutamide and fulminant hepatotoxicity. Fulminant hepatotoxicity is a rare but potentially fatal adverse effect of bicalutamide. Liver function tests should be monitored before and during bicalutamide therapy, even for patients who have previously completed a course of this therapy with no signs or symptoms of toxicity.     

Körperliche Leistungsfähigkeit und Gesundheit bei älteren Arbeitnehmern

Introduction

German executives are becoming increasingly aware of the growing significance of employee health for the future viability of their companies. For the practical implementation of health promotion in a business setting, it is imperative to identify the central determinants of health, so that targeted measures can be initiated.

Method

In the present article, results from a cross-sectional study in a German company are presented (n?=?160; mean?=?55.1 years; SD?=?3.61 years). The aim of the study was to empirically analyze whether physical fitness has a stronger association with subjective health and state of physical ailments than the determinants physical activity, BMI and smoker/non-smoker status. In order to address these questions, we calculated hierarchical regressions.

Results

The results show that fitness is the strongest determinant of subjective health perception with a Beta weight of 0.447 (T?=?5.502; p?<?0.001). The evaluation of the associational factors of the state of physical ailments also showed that the state of fitness is a highly significant predictor of physical ailments (β?=???0.498; T?=???5.838; p?<?0.001).

Conclusions

In the light of this, health promotion measures focusing on physical activity and particularly the physical fitness should be given a larger role in occupational practice.     

Solid state 13C NMR investigation of impact of annealing in lyophilized glasses

The purpose of this study was to investigate the impact of annealing on molecular mobility in lyophilized glasses, composed of a saccharide excipient and a small concentration of aspartame as a model "drug." Changes in molecular dynamics during annealing were monitored through carbon ((13)C) T(1) and T(1 rho) nuclear magnetic resonance relaxation times of the aspartame and the saccharides. Two different saccharides were studied, sucrose and trehalose. The local mobility of the aspartame guest was found to correlate closely with the overall structural relaxation monitored through calorimetric methods in the aspartame: sucrose formulation. In general terms, annealing leads to longer NMR relaxation times, indicating a slowing of the local dynamics. By contrast, annealing had only a minimal effect on the NMR relaxation times in aspartame: trehalose. Specificity of solid state NMR in detecting molecular mobility in guest and host molecules showed that sucrose provided a homogenous matrix for the guest drug as compared to the trehalose.     

MR imaging of acute intermittent porphyria mimicking reversible posterior leukoencephalopathy syndrome

Reversible posterior leukoencephalopathy syndrome (PLS) is characterized by headache, altered mental function, visual disturbances and seizures. Neuroimaging studies suggest a white-matter oedema, predominantly in the posterior parietal-temporal-occipital regions of the brain. We present the case of a 30-year-old woman who had suffered her first attack of acute intermittent porphyria (AIP). Following 1 week of abdominal pain she developed several generalized seizures, and hallucinations, and exhibited a progressive deterioration of the consciousness. T2-weighted images, especially fluid-attenuated inversion recovery (FLAIR) sequences showed bilateral lesions in the posterior frontal, parietal and occipital cortex and subcortical white matter. Following treatment with haematin and a high carbohydrate diet the patient's condition improved. Follow-up magnetic resonance imaging (MRI) revealed complete resolution of the lesions. To our knowledge, this is the first report concerning a completely reversible PLS in AIP.