Development of a fluid-bed coating process for soil-granule-based formulations of Metarhizium brunneum, Cordyceps fumosorosea or Beauveria bassiana.

AIM: Granule-based products of solid state fermented micro-organisms are available for biocontrol. Because liquid fermentation has several advantages, we investigated fluid-bed coating with liquid fermented biomass. METHODS AND RESULTS: Biomass containing mycelium or mycelium and submerged spores of the entomopathogenic fungi Metarhizium brunneum, Cordyceps fumosorosea and Beauveria bassiana were produced in liquid culture, separated and different biomass concentrations were adjusted. Based on the examined thermo-tolerance, we defined fluid-bed coating adjustments and investigated granule colonization and sporulation on granules. Granule colonization depended on the biomass concentration and strain. For C. fumosorosea and B. bassiana, concentrations of 0·003%dry weight resulted in nearly 100% granule colonization, for M. brunneum with concentrations of 0·7%dry weight in only 50%. The conidiation on granules in sterile soil was highly influenced by the moisture content. Because the granule colonization of M. brunneum was unsatisfactory, we pre-coated nutrients followed by coating with biomass, submerged spores or conidia. Malt extract had a positive effect on the granule colonization for biomass and submerged spores. Furthermore, aerial conidia can also be coated. CONCLUSIONS: Fluid-bed coating of fungal biomass is suitable for the development of granules. SIGNIFICANCE AND IMPACT OF THIS STUDY: With this technology, cost-efficient biocontrol products can be developed.

Ferromagnetic Resonance Spin Pumping and Electrical Spin Injection in Silicon-Based Metal-Oxide-Semiconductor Heterostructures.

We present the measurement of ferromagnetic resonance (FMR-)driven spin pumping and three-terminal electrical spin injection within the same silicon-based device. Both effects manifest in a dc spin accumulation voltage V_{s} that is suppressed as an applied field is rotated to the out-of-plane direction, i.e., the oblique Hanle geometry. Comparison of V_{s} between these two spin injection mechanisms reveals an anomalously strong suppression of FMR-driven spin pumping with increasing out-of-plane field H_{app}^{z}. We propose that the presence of the large ac component to the spin current generated by the spin pumping approach, expected to exceed the dc value by 2 orders of magnitude, is the origin of this discrepancy through its influence on the spin dynamics at the oxide-silicon interface. This convolution, wherein the dynamics of both the injector and the interface play a significant role in the spin accumulation, represents a new regime for spin injection that is not well described by existing models of either FMR-driven spin pumping or electrical spin injection.

Quantification of Internal Carotid Artery Stenosis with 3D Ultrasound Angiography.

PURPOSE: The aim of this study was to evaluate a new method of three-dimensional ultrasound (3D-US) angiography of carotid vessels including 3D-US quantification of internal carotid artery (ICA) stenosis (ICAS). MATERIALS AND METHODS: Two neurologists performed native ultrasound scans of the brain-supplying carotid arteries in 73 probands (including 22 patients with 25 cases of ICAS) using a Toshiba Aplio 500 ultrasound machine equipped with the 3 D application of Curefab CS. Additionally, 25 probands underwent contrast-enhanced magnetic resonance angiography (CE-MRA) of the neck vessels. RESULTS: The mean length of the proximal ICA was 32.1 mm ±â€Š9.8 mm & 31.3 mm ±â€Š9.0 mm (each n = 97). The interrater reliability (intraclass correlation, ICC) was 0.75 ±â€Š0.23 for the common carotid artery (CCA, n = 90) and 0.78 ±â€Š0.21 (n = 92) for the ICA. The intermethod agreement between 3D-US angiography and CE-MRA was 0.67 ±â€Š0.19 (n = 45) & 0.66 ±â€Š0.19 (n = 44) for the CCA and 0.79 ±â€Š0.17 (n = 47) & 0.75 ±â€Š0.19 (n = 46) for the ICA. Quantification of ICAS applying 3D-US in comparison to 2D color-coded duplexsonography (2D-CDS) showed a moderate to good intermethod agreement both by the Bland and Altman analysis and by ICC (0.8 & 0.72; with each p < 0.001). The interrater reliability for quantification of ICAS was 0.79; p < 0.001. CONCLUSION: Native 3D-US angiography of carotid vessels shows good interrater and intermethod agreement in comparison to CE-MRA. Together with a moderate to good intermethod and interrater agreement in the quantification of ICAS, when compared to 2D-CDS, 3D-US angiography is thus a promising complementary imaging technique for carotid artery disease.

[Morbidity and mortality of hyperthermic intraperitoneal chemoperfusion]. / Morbidität und Letalität der hyperthermen intraperitonealen Chemoperfusion.

Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) is a treatment option for peritoneal surface malignancy. Despite the survival benefits, this treatment was previously associated with a high morbidity and mortality rates, and the perception of the poor perioperative outcomes associated with this regimen remains. Careful patient selection with an optimal level of postoperative care must be advocated to avoid undesirable complications of this treatment.However, for this treatment to be accepted as standard of care, teams undertaking this treatment strategy must aim to minimize morbidity and mortality by learning from the experience of established centers and using the "global learning curve". The HIPEC Registry and accreditation of centers will improve the quality of the treatment.

Impact of peritoneal carcinomatosis in the disease history of colorectal cancer management: a longitudinal experience of 2406 patients over two decades.

BACKGROUND: Recent therapeutic developments demand for an update of information on natural history, risk factors and prognosis of peritoneal carcinomatosis (PC) of colorectal origin. Therefore, prospective registry data should provide information about incidence, predictors and outcome. METHODS: From a prospectively expanded single-institutional database with 2406 consecutive patients with colorectal cancer (CRC), clinical, histological and survival data were analysed for independent risk factors and prognosis. Findings were then stratified to the era of treatment without chemotherapy, 5-Fluorouracil-only and contemporary systemic chemotherapy, respectively. RESULTS: Overall, 256 (10.6%) patients were diagnosed with PC thereof 141 (5.85%) with metachronous PC. Independent risk factors for the development of metachronous PC were age <62 years, N2-status, T4-status, location of the primary in the left colon or appendix. In the era of contemporary systemic chemotherapy, prognosis for PC improved only not-significantly (median survival of 17.9 months vs 7.03 months, P=0.054). CONCLUSION: Despite improvement in the overall outcome with prolonged median survival for the complete patient cohort with CRC, those patients with PC have not experienced the same benefit. In the era of contemporary systemic chemotherapy, progress in treatment resulted in only limited survival benefit. Thus, continuous efforts for further therapeutic advancements should be undertaken in these patients diagnosed with PC.

Endothelial barrier antigen-immunoreactivity is conversely associated with blood-brain barrier dysfunction after embolic stroke in rats.

While the concept of the Neurovascular Unit (NVU) is increasingly recognized for exploring mechanisms of tissue damage in ischemic stroke, immunohistochemical analyses are of interest to specifically visualize constituents like the endothelium. Changes in immunoreactivity have also been discussed to reflect functional aspects, e.g., the integrity of the blood-brain barrier (BBB). This study aimed to characterize the endothelial barrier antigen (EBA) as addressed by the antibody SMI-71 in a rat model of embolic stroke, considering FITC-albumin as BBB leakage marker and serum levels of BBB-associated matrix metalloproteinases (MMPs) to explore its functional significance. Five and 25 h after ischemia onset, regions with decreased BBB integrity exhibited a reduction in number and area of EBA-immunopositive vessels, while the stained area per vessel was not affected. Surprisingly, EBA content of remaining vessels tended to be increased in areas of BBB dysfunction. Analyses addressing this interrelation resulted in a significant and inverse correlation between the vessels' EBA content and degree of BBB permeability. In conclusion, these data provide evidence for a functional relationship between EBA-immunoreactivity and BBB dysfunction in experimental ischemic stroke. Further studies are required to explore the underlying mechanisms of altered EBA-immunoreactivity, which might help to identify novel neuroprotective strategies.

Expression of chemoresistance-related genes and heat shock protein 72 in hyperthermic isolated limb perfusion of malignant melanoma: an experimental study.

Hyperthermic isolated limb perfusion (HILP) is considered an established treatment for multiple locoregional intransit metastases in malignant melanoma of the extremities. Various mechanisms such as the expression of chemoresistance genes and heat shock proteins by the tumor may be responsible for varying response rates and locoregional recurrences of the treatment. The aim of the experimental animal study was to investigate the direct impact of HILP on such mechanisms of resistance. Tissue temperature, administration of the cytostatic drug, and duration of perfusion were varied. Expression of the chemoresistance genes mdr1, mrp1, mrp2, and lrp and of heat shock protein 72 (HSP72) in the tumor tissue was analysed using RT-PCR and western blot analysis. The untreated SK-MEL-3 tumor expressed mdr1, mrp1, and lrp, but not mrp2. Neither variation of temperature, administration of the cytostatic drug, nor duration of perfusion changed the expression of this "resistance pattern". In contrast to the cytostatic drug, hyperthermia causes a persistent induction of HSP72. Both observations could offer a potential explanation for failure of HILP in malignant melanoma.

[Change in the job description of physicians. Consequences for medical education]. / Veränderung des Berufsbildes des Arztes. Konsequenzen für die ärztliche Ausbildung.

After receiving the final degree at the age of about 25 years, physicians are going to practice a minimum of 40 years. Therefore, one can assume that after graduation physicians are confronted with many occupational challenges which were not and could not be covered during their studies. This implies that medical education does not only have to provide intensive knowledge about established methods but above all about potential future techniques. Throughout the educational period and continuing during professional life, physicians have first to learn and then to be able to seek information and to conduct a critical appraisal - systematically examining research evidence, assessing its validity and the relevance of the results. The increasing velocity of innovation in the realm of medicine requires students to be prepared for life-long learning and continuous, autonomous professional development.

[Bronchial asthma and chronic obstructive pulmonary disease with acute exacerbation: preclinical differential diagnostic and emergency treatment]. / Asthma bronchiale und chronisch obstruktive Lungenerkrankung mit akuter Exazerbation: Präklinische Differenzialdiagnostik und Notfalltherapie.

Chronic obstructive pulmonary disease (COPD) and bronchial asthma are the most common causes of obstructive pulmonary diseases and acute dyspnoea. In the preclinical emergency situation a distinction between bronchial asthma and exacerbated COPD is difficult because symptoms are similar. Although the preclinical measures differ only marginally, a differential diagnosis from other causes of respiratory obstruction and acute dyspnoea, such as cardiac decompensation, anaphylaxis, aspiration of foreign bodies, tension pneumothorax and inhalation trauma is necessary because alternative treatment options are required. In the treatment of COPD and bronchial asthma inhalative bronchodilatory beta(2)-mimetics are the first choice especially for serious obstructive emergencies because there is an unfavorable relationship between effect and side-effects for the intravenous route. Dosable aerosols, nebulization and if necessary, continuous nebulization, are appropriate application forms even for serious obstructive crises with the need of a respirator. In these cases a minimal inspiratory flow in patients is not required. Theophylline only plays a minor role to beta(2)-mimetics and anticholinergics as a bronchodilator in asthma and COPD guidelines, even in serious obstructive diseases. For severe asthma attacks the administration of magnesium is a possible additional option. Systemic intravenous administration of steroids has an anti-inflammatory effect and for this reason is the second column of treatment for both diseases. Invasive ventilation remains a last resort to ensure respiratory function and indications for this are given in patients with clinical signs of impending exhaustion of breathing.

Hyperthermic intraperitoneal chemoperfusion is an option for treatment of peritoneal carcinomatosis in children.

BACKGROUND: Gastrointestinal carcinomas in childhood are rare and frequently present at an advanced stage. Besides lymphatic and distant organ metastasis, peritoneal carcinomatosis may be detected and has a poor prognosis. In addition to surgery and intravenous chemotherapy, hyperthermic intraperitoneal chemoperfusion (HIPEC) may be an option for selected patients. Our aim was to demonstrate the feasibility of the method and to discuss possible indications. METHODS: After treating a series of adult patients, HIPEC for peritoneal carcinomatosis from a signet cell carcinoma of the colon was performed intraoperatively in a 12-year-old boy. We gave mitomycin C at a dose of 30 mg/m2 over 90 minutes at maximum temperature of 41.2 degrees C. We performed intraoperative drug level monitoring and daily postoperative liver and kidney function tests and differential blood counts. RESULTS: Hyperthermic intraperitoneal chemoperfusion was performed according to protocol without complications. Perfusate and venous drug levels were similar to those in an adult case. The patient had an uneventful recovery, and serum chemistry and blood count returned to normal after a week. The boy lived for 36 months after initial presentation. Sixteen months after HIPEC, still with excellent quality of life, an elevated carcinoembryonic antigen (CEA) indicated recurrence. Thirty months after HIPEC, he died of progressive recurrent disease. CONCLUSIONS: Hyperthermic intraperitoneal chemoperfusion as performed in adults may be beneficial to children with peritoneal carcinomatosis and merits further study.

Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model.

BACKGROUND AND AIMS: There is controversy about the effect of the influence of hyperthermia and chemotherapeutic agents on the healing of intestinal anastomosis. The effects of hyperthermic intraperitoneal chemoperfusion (HIPEC) of wound healing after colonic anastomosis were investigated in a rat model. MATERIALS AND METHODS: Thirty-six Wag/Rija rats were randomized into three groups of 12 animals each: group I: control (only colonic anastomosis was performed) (n = 12); group II: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed before HIPEC; group III: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed after HIPEC. Bursting pressure and bursting sites were recorded 4 and 10 days after intervention. Collagen deposits, inflammation and foreign body reactions were evaluated. RESULTS: Lower bursting pressure and lost of collagen were found in both HIPEC groups and compared with the control group. There was almost no difference between both HIPEC groups. They were noted overwhelmingly at the anastomosis in the HIPEC group. The degree of collagen accumulation was well-correlated with bursting pressure. CONCLUSION: These results have shown that hyperthermic intraperitoneal chemoperfusion (HIPEC) impairs wound healing in colonic anastomosis in rats.

Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C.

AIMS: Previous safety monitoring of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) did not demonstrate any detectable safety hazard to the personnel. Nevertheless, those results have been discussed controversially because of the methodological problems employed in the evaluation of potential exposure. We re-evaluated possible safety hazards of HIPEC by applying different monitoring strategies. METHODS: We monitored air samples in the operation room during HIPEC. In addition, we measured MMC in plasma of the surgeon with a newly developed analytical method. All samples were analysed by HPLC-UV at 360nm. The permeability of the gloves was tested using two in vitro techniques: diffusion cells and a glass cell chamber. In-use and worst-case exposure scenarios were imitated for in vitro experiments. RESULTS: The analysis of the air samples (n=3) could not detect any MMC. We found no drug above the limit of detection (1microg MMC/L) in the plasma samples of the surgeons (n=5). A breakthrough of latex glove material was detected in only one (worst-case exposure scenario) of 40 diffusion cell experiments. CONCLUSIONS: Established methods of safety monitoring could not reveal any detectable risk on in-use exposure conditions. The wearing of doubled latex gloves should prevent the surgeon from dermal exposure to MMC during HIPEC.

Direct measurement of quantum confinement effects at metal to quantum-well nanocontacts.

Model metal-semiconductor nanostructure Schottky nanocontacts were made on cleaved heterostructures containing GaAs quantum wells (QWs) of varying width and were locally probed by ballistic electron emission microscopy. The local Schottky barrier was found to increase by approximately 0.140 eV as the QW width was systematically decreased from 15 to 1 nm, due mostly to a large (approximately 0.200 eV) quantum-confinement increase to the QW conduction band. The measured barrier increase over the full 1 to 15 nm QW range was quantitatively explained when local "interface pinning" and image force lowering effects are also considered.

Determination of nodal status and treatment in early gastric cancer.

BACKGROUND: In view of its low associated risk of metastatic spread, early gastric cancer has an excellent prognosis. The basis for the choice of treatment is the risk of lymphogenous metastatic spread together with the individual surgical risk. METHODS: The data collected from 279 patients in whom, between 01/1982 and 12/2001, a gastric resection or gastrectomy was carried out for early gastric cancer at the Surgical Department of the University Hospital, Erlangen, were analysed. A number of macroscopic and histopathological factors were examined by univariate and multivariate analysis for their effect on lymphogenous metastatic spread. RESULTS: In 33 patients (11.8%), regional lymph-node metastases were confirmed histologically. The grade of malignancy (high-grade, relative risk 9.9), diameter (>20 mm, relative risk 5.0) and lymphatic invasion (relative risk 3.5) all demonstrated a significant independent influence on the occurrence of regional lymph-node metastases. Seventy-three patients were identified as a low-risk group, with a risk of lymphogenous metastatic spread of only 1%. CONCLUSIONS: Well differentiated or moderately differentiated carcinomas having a diameter of less than 2 cm can be treated by local intervention, such as local excision or endoscopic removal, without any increase in risk, provided that the tumour is reliably removed without residual tumour (histologically confirmed R0). In the presence of an elevated surgical risk, the choice of treatment must be made on an individual basis.

[Angiomyolipoma of the colon - case report and review of the literature]. / Das Angiomyolipom des Kolons - Fallbericht und Literaturübersicht.

Angiomyolipoma is one of the benign hamartomas that is found sporadically or associated with tuberous sclerosis. It is a rare soft tissue tumor involving mostly the kidneys, sometimes other visceral organs. The tumor is composed of smooth muscle cells, adipocytes and small sized hyalinized vessels. We present the case of a 74-year-old man with a bifocal angiomyolipoma of the colon. This diagnosis was confirmed at surgery, where a partial colectomy was performed. Histologic examination disclosed the tumor. The patient had no signs of family history of tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of bifocal colonic angiomyolipoma.

Oculomotor behavior and perceptual strategies in complex tasks.

While we know a great deal about the dynamics and characteristics of eye movements in relatively simple tasks performed under reduced laboratory conditions, we know less about oculomotor behavior in complex, multi-step tasks. Complex tasks are not necessarily difficult. Part of the transition from 'hard' to 'easy' in completing complex tasks is the gradual reduction in conscious effort required to complete the sub-tasks. We are interested in learning whether high-level perceptual strategies can aid that transition. In the past, subjects performed relatively simple tasks or the eye movements themselves were the instructed task. But outside the laboratory vision is a tool, not the task. To study the oculomotor system in its native mode, we developed a wearable eyetracker that allows natural eye, head and whole-body movements. Using the over-learned, common task of hand-washing, we measured the global characteristics of fixation duration, saccade amplitude, and the spatial distribution of fixation positions. An important observation was the emergence of higher-order perceptual strategies in the complex task: while most fixations were related to the immediate action, a small number of fixations were made to objects relevant only to future actions. Based on a control task that differed only in the high-level goal, we conclude that the look-ahead fixations represent a task-dependent strategy, not a general behavior elicited by the salience or conspicuity of objects in the environment. We propose that the strategy of looking ahead to objects of future relevance supports the conscious percept of an environment seamless in time as well as in space.

Enhanced terrace stability for preparation of step-free Si(001)-(2 x 1) surfaces.

We show that depositing Si while annealing patterned Si(001)-(2 x 1) substrates at sublimation temperatures enhances terrace stability, permitting larger step-free areas to be produced in a given time than possible by annealing alone. We confirm this enhanced terrace stability using real-time low-energy electron microscopy observations, and quantitative microscopic modeling of step dynamics. Our measurements can be used to estimate the lateral variation in adatom concentration across large terraces, and to estimate an adatom diffusion length lambda approximately 10-30 microm at 1000 degrees C.