Dispersion-Induced Beam Instability in Circular Accelerators.

The envelope instability near the 90° phase advance in periodically focused space charge dominated beams is a well-known phenomenon in linear transport sections or linacs. The corresponding stop band is usually avoided because of the resulting strong mismatch oscillations and beam loss. We show that in circular accelerators or transport sections including bending magnets the instability is modified due to the effect of dispersion. Using the two-dimensional envelope equations extended by the dispersion equation we identify an additional stop band above 120°. For periodic focusing the stop band results from the confluence of an envelope mode with the newly identified coherent dispersion mode. Results from perturbation theory are compared with the full envelope model and particle-in-cell simulation, which all show good agreement. The newly identified mode has several implications and applications for the characterization of intense beams in circular machines.

[The role of caregivers in health care. Historical backgrounds and current conflict situations]. / Die Rolle der Pflege im Gesundheitswesen. Historische Hintergründe und heutige Konfliktkonstellationen.

As a result of recent demographic developments, there has been an increased demand for high-quality health care. Among the various health professions, caregiving represents the largest professional group, numbering approximately 820,000 caregivers. Despite its size, this group is failing to meet basic conditions in line with international standards that secure adequate care. This failing is primarily due to the special path that Germany took regarding healthcare at the end of the nineteenth century and on which it continues to this day. It manifests itself in a heteronomy to which the professional group is permanently subjected by lobbies and policies that view health care from a perspective whose primary aim is to reduce unemployment. The present lack of organization of caregivers has frustrated their political assertiveness; and not least because of this, many caregivers leave the profession early. The profession itself is grappling with its professional identity. The development of expert standards, research into care, ethical reflections, as well as the struggle for common professional training are positive signs in this ongoing debate and are reflected in the positive feedback received from patients. The interdisciplinary dialogue between caregivers and physicians is in need of improvement. The first signs of progress are evident within the framework of health care ethics committees. This dialogue would certainly benefit both the professional group as well as the patients.

[Verumontanum mucosal hyperplasia as a differential diagnosis of a local recurrence following radical prostatectomy]. / Verumontanum-Mukosahyperplasie als Differenzialdiagnose eines Lokalrezidivs nach radikaler Prostatektomie.

Verumontanum mucosal gland hyperplasia (VMGH) is a benign microacinar proliferative lesion, which occurs exclusively in the verumontanum and the posterior urethra and is one of the lesions that may be confused with a low-risk adenocarcinoma of the prostate gland.We present the case of a 72-year-old male patient who underwent radical prostatectomy due to an adenocarcinoma of the prostate gland (pT2c pN0 cM0 R0, Gleason Score: 3 + 3 = 6). Five years after the operation, we sonographically detected a 3x2 cm large tumour in the prostate bed. While our first assumption was a PSA-negative local recurrence following radical prostatectomy, a comprehensive histological examination along with the clinical evaluation led us to the diagnosis of a VMGH. VMGH is a less well-known differential diagnosis of PSA-negative local recurrence following radical prostatectomy, whose clinical manifestation should be presented.

Linkage between growth retardation and pituitary cell morphology in a dystrophin-deficient pig model of Duchenne muscular dystrophy.

OBJECTIVE: Human patients with Duchenne muscular dystrophy (DMD) commonly exhibit a short stature, but the pathogenesis of this growth retardation is not completely understood. Due to the suspected involvement of the growth hormone/insulin-like growth factor 1 (GH/IGF1) system, controversial therapeutic approaches have been developed, including both GH- administration, as well as GH-inhibition. In the present study, we examined relevant histomorphological and ultrastructural features of adenohypophyseal GH-producing somatotroph cells in a porcine DMD model. METHODS: The numbers and volumes of immunohistochemically labelled somatotroph cells were determined in consecutive semi-thin sections of plastic resin embedded adenohypophyseal tissue samples using unbiased state-of-the-art quantitative stereological analysis methods. RESULTS: DMD pigs displayed a significant growth retardation, accounting for a 55% reduction of body weight, accompanied by a significant 50% reduction of the number of somatotroph cells, as compared to controls. However, the mean volumes of somatotroph cells and the volume of GH-granules per cell were not altered. Western blot analyses of the adenohypophyseal protein samples showed no differences in the relative adenohypophyseal GH-abundance between DMD pigs and controls. CONCLUSION: The findings of this study do not provide evidence for involvement of somatotroph cells in the pathogenesis of growth retardation of DMD pigs. These results are in contrast with previous findings in other dystrophin-deficient animal models, such as the golden retriever model of Duchenne muscular dystrophy, where increased mean somatotroph cell volumes and elevated volumes of intracellular GH-granules were reported and associated with DMD-related growth retardation. Possible reasons for the differences of somatotroph morphology observed in different DMD models are discussed.

Experimental evidence of space charge driven emittance coupling in high intensity linear accelerators.

In high intensity linacs emittance exchange driven by space charge coupling may lead to the well-known "equipartitioning" phenomenon if the stop band at sigma(parallel) = sigma(perpendicular) is crossed at sufficiently slow rate. This Letter is the first experimental evidence of this phenomenon in a high intensity linear accelerator, here the UNILAC at GSI. Measurements of emittances at the entrance and exit of one drift tube linac tank comprising 15 lattice cells are taken for a set of transverse and longitudinal tunes. The onset of exchange on the stop band of previously derived "stability charts" confirms theoretical predictions. The measured transverse emittance growth also compares well with results from the beam dynamics simulation codes DYNAMION and TRACEWIN.

Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model.

Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. Vascular endothelial growth factor (VEGF) and its receptors, VEGF-receptor 1 (VEGF-R1; FLT-1) and VEGF-R2 (KDR), have been shown to play a major role in tumor angiogenesis. PTK787/ZK 222584, a specific inhibitor of both VEGF-receptor tyrosine kinases, was investigated for its antitumoral and antiangiogenic activity in a murine renal cell carcinoma model. After intrarenal application of the renal carcinoma cells, mice develop a primary tumor and metastases to the lung and to the abdominal lymph nodes. Daily oral therapy with PTK787/ZK 222584 at a dose of 50 mg/kg resulted in a significant decrease of 61 and 67% in primary tumors after 14 and 21 days, respectively. The occurrence of lung metastases was significantly inhibited at both time points (98% reduction and 78% reduction, respectively). After 14 days, no lymph node metastases developed in the PTK787/ZK 222584-treated group, whereas after 21 days of treatment, the lymph node metastases were reduced by 87%. Vessel density in tumor tissues, detected by immunohistochemistry with an anti-CD31 antibody, was significantly decreased by PTK787/ZK 222584. Using color Doppler imaging ultrasound, significant changes in blood flow in the tumor feeding renal artery were found under treatment with PTK787/ZK 222584. Blood flow changes correlated with changes in vessel density but not with tumor volume. The compound was well tolerated in all in vivo experiments and had no significant effects on body weight or general well-being of the animals. This was in contrast to the animals treated with the antiangiogenic agent TNP-470. s.c. therapy with 30 mg/kg TNP-470 every other day had to be discontinued after 13 days because of animal weight loss (>20%) and ataxia. These results demonstrate that PTK787/ZK 222584 is a potent inhibitor of tumor growth, metastases formation, and tumor vascularization in murine renal cell carcinoma. Furthermore, we have been able to demonstrate that color Doppler imaging ultrasound can be used to measure blood flow to a tumor and that flow correlates with vessel density. Thus, this may be a valuable noninvasive method for monitoring the effects of antiangiogenic agents such as PTK787/ZK 222584 on tumor vasculature.

Identification of a nonapeptide motif in the vimentin head domain involved in intermediate filament assembly.

The assembly of soluble vimentin subunits into intermediate filaments (IFs) is dependent on information located in the amino-terminal domain. Using site-directed mutagenesis of a Xenopus laevis vimentin cDNA and an Escherichia coli production system to obtain pure mutated protein, we have identified, in the head domain, a nine amino acid motif (SSYRRIFGG), evolutionarily conserved from amphibia to man, which plays an important role in the orderly formation of IFs. Exchanges in the central di-arginine and in the two aromatic residues interfere with IF assembly of vimentin in vitro: on assembly under standard assembly conditions (160 mM-NaCl) most of the protein is included in dense aggregates, with a variable and minor proportion of IFs, whereas at lower ionic concentrations short and incomplete IF-like structures are formed. The deletion of the whole motif results in a protein that under standard assembly conditions (e.g. 160 mM-NaCl) predominantly and rapidly precipitates into large aggregates of non-IF material, whereas at lower ionic strength (e.g. 50 mM-NaCl) both IFs and dense aggregates are formed simultaneously. Our results show that the mutated protein can assume different forms at the same time and under the same conditions. This motif alone is insufficient for the formation of normal IFs as demonstrated by a mutant in which the motif has been brought closer to the alpha-helical rod domain by deletion of 55 internal amino acid residues. Corresponding observations have been made, by immunofluorescence microscopy, upon transfection of cultured epithelial cells lacking vimentin IFs. The importance of the head domain motif for the assembly and higher-order arrangement of IFs is discussed.

Heterotypic interactions and filament assembly of type I and type II cytokeratins in vitro: viscometry and determinations of relative affinities.

We have determined relative affinities of type I and type II human non-epidermal cytokeratin (CK) polypeptides synthesized in Escherichia coli from cDNA, using the method of surface plasmon resonance, and have compared the influence of ionic strength and ion quality on the assembly to intermediate filaments (IFs) by viscometry and electron microscopy. By surface plasmon resonance (total internal reflection) we determined the real-time relative binding of various type I CKs to the type II CK8. Surprisingly, the various type I CKs examined (i.e., CKs 13, 18, 19 and 20) differed markedly in their relative binding rate: For example, CK18 and CK13 displayed much higher resonance signals than CK19 and CK20. In addition, soluble complexes of type II CK8 with various type I cytokeratins were reconstituted at slightly alkaline pH and low ionic strength. Subsequent IF assembly was induced by simultaneous shifting to neutral pH and increasing the ionic strength. Both mono- and divalent ions as well as tris (hydroxymethyl)-aminomethane (Tris) alone were able to induce IF assembly. When we compared the time course of viscosity increase of CK8 in combination with either CK13, CK18, CK19 or CK20, we found that the cytokeratin pairs 8:18 and 8:20 attained the highest viscosity values, whereas the cytokeratin pair 8:19 displayed a relatively low value. Significantly lower values of specific viscosity were also observed in competition experiments when CK18 was gradually replaced by CK19. The observed differences in relative affinities and assembly kinetics of certain CK combinations allow quantitations of the interactions between different CKs and are discussed in relation to IF stability and cell differentiation.

Assembly and structure of calcium-induced thick vimentin filaments.

Using a viscometric assay and various electron microscopic procedures (negative staining, rotary shadowing, ultrathin sectioning) we have determined the influences of different kinds of ions and of ionic strength on the structures formed by assembly of soluble subunits of vimentin from bovine lens tissue or from Escherichia coli transformed with Xenopus vimentin cDNA. In contrast to the assembly of typical, i.e., 8 to 14-nm, intermediate-sized filaments (IFs) at elevated (e.g., 160 mM) concentrations of monovalent cations and at millimolar Mg2+ concentrations, filaments formed in the presence of Ca2+ ions (e.g., 5 mM) appeared at a lower rate, attained lower viscosity and were considerably thicker and shorter. The largest diameter measured was that for the recombinant amphibian protein: 24.2 +/- 8.5 nm in negative staining, 28.7 +/- 5.6 nm in sections. These thick Ca(2+)-induced filaments, however, revealed the same approximately 2 nm protofilament composition and approximately 20 nm cross-striation pattern as typical IFs, indicative of a similar molecular arrangement. The significance of this unusual structural IF protein assembly is discussed.

Drebrin particles: components in the ensemble of proteins regulating actin dynamics of lamellipodia and filopodia.

Drebrin, an actin-binding 70-kDa protein with an unusually slow SDS-PAGE mobility corresponding to approximately 120 kDa, containing a proline-rich, profilin-binding motif, had originally been reported from neuronal cells, but recently has also been found in diverse other kinds of tissues and cell lines. In biochemical analyses of various cells and tissues, employing gel filtration, sucrose gradient centrifugation, immunoprecipitation and -blotting, we have identified distinct states of soluble drebrin: a approximately 4S monomer, an 8S, ca. 217-kDa putative trimer, a 13S and a > 20S oligomer. In the 8S particles only [35S]methionine-labelled drebrin but no other actin-binding protein has been detected in stoichiometric amounts. By immunofluorescence and immunoelectron microscopy, drebrin-positive material often appeared as "granules" up to 400 nm in diameter, in some cell types clustered near the Golgi apparatus or in lamellipodia, particularly at leading edges, or in dense-packed submembranous masses at tips (acropodia) or ruffles of leading edges, in filopodia and at plaques of adhering junctions. We conclude that these drebrin complexes and drebrin-rich structures allow the build-up and maintenance of high local drebrin concentrations in strategic positions for the regulation of actin filament assembly, thereby contributing to cell motility and morphology, in particular local changes of plasticity and the formation of protrusions.

Ovarian carcinoma: increase in clinical validity by simultaneous determination of SRA and CA 125.

Ovarian carcinomas are distinguished by their polyclonality, i.e., heterogeneity and polymorphism of their tissue. There is no marker available complying with the clinical demands in the case of ovarian carcinoma regarding satisfactory sensitivity and specificity. Therefore, we have simultaneously determined two entirely distinct tumor markers, serum ribonuclease activity (SRA) and cancer antigen 125 (CA 125), recommended in the literature with respect to ovarian carcinoma. After evaluation by logistic regression analysis, we found a specificity of 93% together with a sensitivity of 97% for the simultaneous determination of SRA and CA 125 (37 ovarian carcinomas, 11 cases without pathological findings after treatment, 11 benign tumors of the ovary, 61 controls). The patients are not exposed to increased stress by this simultaneous determination method compared to the determination of a single marker. The increased clinical validity justifies the recommendation of routine simultaneous determinations of SRA and CA 125 for diagnosis and monitoring of patients with ovarian carcinoma.

The effects of maternal diabetes on fetal maturation and neonatal health.

This investigation focused on the relation between metabolic control of maternal diabetes in pregnancy and the health status of the fetus and newborn in the spontaneously diabetic BB rat. The basic hypothesis tested was that "tight" control of maternal diabetes before conception and during pregnancy should result in diminished fetal and neonatal morbidity and mortality. Behavioral teratologic tests were employed to evaluate the possible long-term effects of diabetes in pregnancy on postnatal development. The results demonstrated that approximation to glucose homeostasis in diabetic BB dams was associated with increased litter and fetal size, decreased perinatal mortality, and a significant reduction in the incidence of congenital malformation. Postnatal growth and neurologic function were also enhanced. These findings are supportive of efforts to initiate diabetic control prior to conception and especially during the critical period of fetal organogenesis during the first 8 weeks of human pregnancy.

Prospective, randomized trial of Microvisc and Healon in routine phacoemulsification.

PURPOSE: To compare the safety and efficacy of the new sodium hyaluronate viscoelastic, Microvisc, with those of Healon in routine phacoemulsification. SETTING: York Finch Eye Associates and York Finch General Hospital, Toronto, Ontario, Canada. METHODS: An unmasked, prospective, randomized clinical trial of 100 eyes in 100 patients having routine phacoemulsification and intraocular lens implantation was conducted to compare the safety and efficacy of Microvisc with those of Healon. Visual acuity, corneal thickness, and intraocular pressure were assessed preoperatively and at 6 hours, 1 and 5 days, and 1 and 6 months postoperatively. RESULTS: There were no statistically significant differences between the two treatment groups at any follow-up CONCLUSION: Based on the parameters assessed, both viscoelastic products were safe and provided comparable outcomes.

Analytical calculation of the longitudinal space charge and resistive wall impedances in a smooth cylindrical pipe.

The longitudinal space charge and resistive wall impedances have been investigated in a smooth cylindrical beam pipe. At any point from the beam axis, we obtained an expression for the total impedance, which at the beam surface r=a for infinite pipe wall conductivity gives the expression for the total impedance that was derived by Zotter and Kheifets in studying the impedance of uniform beams in concentric cylindrical wall chambers, when a single cylindrical chamber is considered [B. W. Zotter and S. A. Kheifets, Impedances and Wakes in High-Energy Particle Accelerators (World Scientific, Singapore, 1998), Chap. 6]. A fitting formula for the space-charge impedance at the beam surface (r=a), which is valid for arbitrary wavelengths, is given. Rather than calculating the impedance with the field on the axis [Joseph J. Bisognano, Fifth European Particle Accelerator Conference (EPAC96), edited by S. Myers, A. Pacheco, R. Pascual, Ch. Petit-Jean-Genaz, and J. Poole (Institute of Physics, Bristol, 1996), Vol. 1, p. 328], the fitting formula is obtained by averaging over the transverse beam distribution. We also give another approach for the calculation of the resistive wall impedance using the flux of the Poynting vector at the pipe wall and then compare it with the expression obtained from the volume integral over the beam distribution.

A knowledge based system for analysis of gated blood pool studies.

A system for obtaining a complete diagnostic description of an image sequence taken in nuclear medicine from the human heart has been developed, implemented, and tested. The knowledge about these images is represented in a semantic net, conclusions are drawn by a production rule approach, and scoring of alternative diagnoses is based on fuzzy membership functions. On the low level, image pixels are smoothed and organ contours are extracted; these are the input for the high level processing. Tests with several image sequences gave correct descriptions as compared to the diagnosis of a physician.

[Acute peripheral vestibular lesions. Monocular subjective visual vertical and cyclodeviation]. / Akute periphere vestibuläre Läsionen. Monokulare subjektive visuelle Vertikale und Zykloduktionsstellung.

BACKGROUND: A deviation of the subjective visual vertical (svv) is often found in patients with unilateral peripheral vestibular lesions and in most cases the deviation is transitory and easy to compensate. The purpose of the study was to find out if there is a correlation between deviation of the svv and objective cyclodeviation of the retina. PATIENTS AND METHODS: A total of 20 patients (10 females and 10 males aged between 16 and 78 years) with acute vestibular disease were enrolled. Only patients with a binocular deviation of the svv of more than 2 degrees and/or a difference between the monocular deviation of more than 1.5 degrees were included. The svv was examined monocular in a darkened room and after pupil dilatation, fundus photography was performed on each eye. The angle between papilla and macula was measured manually. RESULTS: We found a good qualitative correlation between svv (mean 7.9 degrees) and objective cyclodeviation (mean 10.6 degrees). CONCLUSION: In contrast to the binocular measurement of the svv, we found good correlation between the monocular svv and the objective cyclorotation measured with fundus photography. It is not yet clear which part of the vestibular system is responsible for cyclodeviation. Because of our results we recommend monocular measurement of the svv in clinical examinations.

Angle-supported refractive implantation in stable, adult accommodative esotropia.

A patient with hyperopia and accommodative esotropia was implanted bilaterally with hyperopic angle-supported refractive implants. Control of the esotropia was achieved as was some improvement in fusional ability. After three years, the endothelium remains healthy, the eye is quiet and control of the esotropia is maintained.

Does laser trabeculoplasty prevent steroid glaucoma?

OBJECTIVE: To investigate the effect of laser trabeculoplasty in the normal myopic eye on steroid intraocular pressure responsiveness in patients undergoing radial keratotomy. MATERIALS AND METHODS: Diode laser trabeculoplasty was performed on 94 patients with myopia undergoing radial keratotomy who were then started on dexamethasone drops. Intraocular pressures were measured by applanation tonometry compensated for corneal flattening. RESULTS: Twenty-eight percent of patients had an intraocular pressure increase of 6 mm Hg or more by the fourth week. CONCLUSION: Laser trabeculoplasty does not prevent steroid intraocular pressure increase in patients with myopia.

[Difficulties in interprofessional dialogue between medical and nursing colleagues]. / Schwierigkeiten im interprofessionellen Dialog zwischen ärztlichem und pflegerischem Kollegium.

A dignified care of sick, old and impaired human beings requires intensive collaborations of medical and nursing staff. In order to prevent incomplete pain management, long hospitalisations, neglect of the dying, unnecessary transfers between nursing homes and hospitals partnership and dialogue between these two disciplines is necessary. In spite of this it seems to be the exception rather than the rule. Apart from hierarchical thinking and personal preferences structural conditions play an important part. This paper tries to relate various aspects: not all these can be supported by valid data (because of lacking research) but they are based on reflective practice. This article does not pretend to be a scientific piece of work. Nevertheless, it is hoped that it contributes to the improvement of the interdisciplinary dialogue. Enhanced research interest may be an additional effect of it.

[Truth in dealing with sick people]. / Wahrheit im Umgang mit kranken Menschen.

One of the most difficult problems for many nurses and physicians is the question of truthful information, especially for seriously ill and dying people. Talking about the problem of truth from an ethical point of view there are three essential aspects to consider: First the concept of truth from an anthropological point of view has to be defined and compared to the truth in the natural sciences, second, how the concept of "Truth at the sick bed" and its effect on nurses are treated in the medical literature, third, the psychological conditions we have to consider in relating to seriously ill and dying people. It is the declared aim of this paper to describe and summarize these three theoretical aspects, which in everyday work are inseparably connected, and to show some possible solutions.