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.

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.

[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.

[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.

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.

Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism.

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Dopamine D2 receptor gene (DRD2) haplotypes in Caucasians.

The human dopamine D2 receptor gene (DRD2) is considered a candidate gene for neuro-psychiatric diseases. We typed three new DNA sequence variants in DRD2 intron 4, intron 6 and exon 8, in combination with the known TaqI A restriction fragment length polymorphism (RFLP) and exon 7 311Ser/Cys in 106 unrelated psychiatrically healthy Caucasians. Based on the genotypic data we delineated 10 distinct DRD2 haplotypes and their genetic relationship. Our data provide evidence that the Taq A1 allele and the 311Cys variant are components of different groups of haplotypes though both variants have been speculated to be associated with alcoholism or schizophrenia in recent studies. Therefore we conclude that the prior knowledge of the frequencies and genetic relationships of DRD2 haplotypes will lead to the selection of more suitable intragenic markers for future association studies.

A new observation of two cases of acrofacial dysostosis type Genée-Wiedemann in a family--remarks on the mode of inheritance: report on two sibs.

We report on a Yugoslavian sibpair with postaxial acrofacial dysostosis type Genée-Wiedemann with some novel signs which broaden the spectrum of this syndrome. The manifestations of the present cases are compared with those of the previously described patients. Life expectancy, change of symptoms over time, and the mode of inheritance are discussed.

Computer assisted diagnosis of malformation syndromes: an evaluation of three databases (LDDB, POSSUM, and SYNDROC).

Computer programs which can be used as an aid to diagnose multiple congenital anomaly syndromes have been used for many years, but up to now they have been evaluated very rarely. The diagnostic abilities of three of these systems [LDDB (London Dysmorphology Database), POSSUM (Pictures of Standard Syndromes and Undiagnosed Malformations), and SYNDROC] were analyzed. All three programs are based on an algorithm which defines a diagnosis by a set of phenotypic components all having the same weight (descriptive algorithm). A second algorithm is applied by SYNDROC to rank competing diagnoses in order of probability. This pseudo-Bayesian algorithm provides a coefficient of certitude (CC). For a test the clinical findings of 102 patients who had received a firm diagnosis were used. Two search strategies were tried: "novice's strategy" with all findings taken for a search and "expert's strategy" with a selected set of anomalies. Only those diagnoses that were suggested with the 1st rank, defined as the highest degree of agreement, or the highest CC were studied. The greatest resemblance between suggestions of the databases and the clinical diagnosis was obtained with the expert strategy. The highest number of matches were produced by SYNDROC (80 with expert strategy) and the lowest by POSSUM (54 with novice strategy). The overall agreement between the databases is about 40% for the 1st rank. This number reflects that different authors use different pivotal signs for the description of a syndrome. With the pseudo-Bayesian algorithm 59 cases obtained the highest CC value. Great difficulties exist with the subjective estimates for the calculation of these values; the absolute CC values seem to be meaningless. A small number of unusual cases with special combinations of anomalies provide serious problems for correct diagnosis.

Unilateral terminal aphalangia in father and daughter--exogenous or genetic cause?

Published cases of familial unilateral terminal transverse defects are scarce. We report on a morphologically similar defect of the hand in a father and his daughter. The hand anomaly is similar in both, but on the opposite side. Thalidomide was taken in the sensitive period of the pregnancy by the father's mother. To our knowledge this is the second description of unilateral terminal aphalangia in successive generations. In order to evaluate the possible genetic basis we analyze epidemiological studies in respect to the recurrence risk of cases with isolated limb reduction defects. We compare reports of familial occurrence concerning the degree of relationship as well as the pattern of malformation. The latter seems to be an important aspect from an evolutionary and a developmental viewpoint. For our observation an autosomal dominant transmission is the most likely although multifactorial determination cannot be excluded.

The role of exocentric reference frames in the perception of visual direction.

One classic piece of evidence for an efference copy signal of eye position is that a small, positive afterimage viewed in darkness is perceived to move with the eye. When a small stationary reference point is visible the afterimage appears to move relative to the reference point. However, this is true only when the afterimage is localized to a small area. We have observed that when an extended afterimage of a complex scene is generated by a brief, bright flash it does not appear to move, even with large changes in eye position. When subjects were instructed to maintain their direction of gaze, we observed small saccades (typically < 1 deg) and slow drift movements often totalling more than 10 deg over a 30 sec period. When the instructions were to simply inspect the extended afterimage, subjects made larger saccades (up to 5 deg) which were not accompanied by afterimage movement. The smaller movements observed under the first instructions are greater than those observed in the dark or with small afterimages. When a visible reference is present with these large afterimages, the afterimage appears stationary, while the reference point appears to move. Eye position was monitored following the generation of such afterimages. In general, the perceived motion of the stationary reference point was in a direction opposite to the motion of the eye. Similar drift movements of smaller magnitude were observed with localized afterimages, but the motion was attributed to the afterimage.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Frequency of trisomy 21 in Germany before and after the Chernobyl accident.

For Berlin (West) the rate of trisomy 21 among newborn and all prenatally diagnosed cases can be almost completely recorded, including the maternal age distribution. During the 9-year-period from 1980 and 1988 the average number of trisomy 21 per month was about 2, following a Poisson distribution. A significant increase (P less than 0.01) was observed in January 1987, exactly 9 months after the Chernobyl accident. In a supraregional study based on greater than 30,000 prenatal diagnoses performed in 1986, no significant effect could be observed. However, the highest rates of trisomy 21 were observed in the more heavily contaminated, southern part of Germany. The majority of these fetuses were conceived during the period of greatest radioactive exposure. The data are discussed with respect to the effect of low-dose radiation around the time of conception on the induction of non-disjunction in man.

Significant increase in trisomy 21 in Berlin nine months after the Chernobyl reactor accident: temporal correlation or causal relation?

OBJECTIVE: To assess whether the increased prevalence of trisomy 21 in West Berlin in January 1987 might have been causally related to exposure to ionising radiation as a result of the Chernobyl reactor accident or was merely a chance event. DESIGN: Analysis of monthly prevalence of trisomy 21 in West Berlin from January 1980 to December 1989. SETTING: Confines of West Berlin. RESULTS: Owing to the former "island" situation of West Berlin and its well organised health services, ascertainment of trisomy 21 was thought to be almost complete. A cluster of 12 cases occurred in January 1987 as compared with two or three expected. After exclusion of factors that might have explained the increase, including maternal age distribution, only exposure to radiation as a result of the Chernobyl reactor accident remained. In six of seven cases that could be studied cytogenetically the extra chromosome was of maternal origin, confirming that nondisjunction had occurred at about the time of conception. CONCLUSION: On the basis of two assumptions--(a) that maternal meiosis is an error prone process susceptible to exogenous factors at the time of conception; (b) that owing to the high prevalence of iodine deficiency in Berlin a large amount of iodine-131 would have been accumulated over a short period--it is concluded that the increased prevalence of trisomy 21 in West Berlin in January 1987 was causally related to a short period of exposure to ionising radiation as a result of the Chernobyl reactor accident.

[Evaluation of a patient-held medical record by patients--results from the Ried Medical Quality Network]. / Bewertung eines Patientenbuches durch Patienten--Ergebnisse aus der Arztlichen Qualitätsgemeinschaft Ried.

In the "medical-quality network Ried", an independent practice network in the south of Hessia, an A 4 format patient held record for multi-morbid chronically ill patients is used since 1997. 655 patients (response-rate 71.0%) from sixteen general practitioner (GP) practices were surveyed by written questionnaire. Respondents were in average 68.1 years of age, and for 16.3 years with their GP. 52.2% were male. Patients had their own records for 24.2 months and had in average 1.9 (women) or 2.3 (men) serious health problems. Women had in average 5.0, men had 4.8 different drugs prescribed. 96.7% of the respondents thought that the patient-held record is a good idea, 85.5% felt more secure and 98.7% have it always at hand at home. The patient-held record provides better information about ones own health (92.1%) and 96.6% want to be able to look at their own record. The patient-held record makes it easier for patients to talk to doctors (86.6%) and provides a better overview for the GP (90.8%). The more drugs patients have to take, the more important it becomes for them to have their own record. 68.6% take the record on holyday, 57% take it to other doctors than the GP. 76.4% reported that the patient-held record was used at least once by a specialist, 61.3% by a hospital. 21.8% remembered emergency situations where it was helpful. Only 4.8% thought that it is tiresome. Few proposals for improvement were made, mainly focussing on a smaller format. On the basis of these results patient-held records should be a core activity of practice networks, especially for this type of patients.