Experimental demonstration of novel beam characterization using a polarizable X-band transverse deflection structure.

The PolariX TDS (Polarizable X-Band Transverse Deflection Structure) is an innovative TDS-design operating in the X-band frequency-range. The design gives full control of the streaking plane, which can be tuned in order to characterize the projections of the beam distribution onto arbitrary transverse axes. This novel feature opens up new opportunities for detailed characterization of the electron beam. In this paper we present first measurements of the Polarix TDS at the FLASHForward beamline at DESY, including three-dimensional reconstruction of the charge-density distribution of the bunch and slice emittance measurements in both transverse directions. The experimental results open the path toward novel and more extensive beam characterization in the direction of multi-dimensional-beam-phase-space reconstruction.

Estimation of total collagen volume: a T1 mapping versus histological comparison study in healthy Landrace pigs.

Right ventricular biopsy represents the gold standard for the assessment of myocardial fibrosis and collagen content. This invasive technique, however, is accompanied by perioperative complications and poor reproducibility. Extracellular volume (ECV) measured through cardiovascular magnetic resonance (CMR) has emerged as a valid surrogate method to assess fibrosis non-invasively. Nonetheless, ECV provides an overestimation of collagen concentration since it also considers interstitial space. Our study aims to investigate the feasibility of estimating total collagen volume (TCV) through CMR by comparing it with the TCV measured at histology. Seven healthy Landrace pigs were acutely instrumented closed-chest and transported to the MRI facility for measurements. For each protocol, CMR imaging at 3T was acquired. MEDIS software was used to analyze T1 mapping and ECV for both the left ventricular myocardium (LVmyo) and left ventricular septum (LVseptum). ECV was then used to estimate TCVCMR at LVmyo and LVseptum following previously published formulas. Tissues were prepared following an established protocol and stained with picrosirius red to analyze the TCVhisto in LVmyo and LVseptum. TCV measured at LVmyo and LVseptum with both histology (8 ± 5 ml and 7 ± 3 ml, respectively) and T1-Mapping (9 ± 5 ml and 8 ± 6 ml, respectively) did not show any regional differences. TCVhisto and TCVCMR showed a good level of data agreement by Bland-Altman analysis. Estimation of TCV through CMR may be a promising way to non-invasively assess myocardial collagen content and may be useful to track disease progression or treatment response.

Tumour, but not Age-associated, Increase of Senescence Markers γH2AX and p21 in the Canine Eye.

Senescent cells display an irreversible cell cycle arrest with resistance to apoptosis. They are known to accumulate with age in mice, monkeys and man, and are suspected to drive the development and progression of neoplasia. Eyes develop age-associated changes, most commonly in the retina, cornea and lens. The aim of this study was to test whether senescent cells increase with age in the canine eye in general and in the microenvironment of ocular tumours in particular. The senescence markers γH2AX and p21 were tested in young (n = 10, age ≤2 years) versus old (n = 9, age range 9.5-12.4 years) canine eyes, as well as in the microenvironment of intraocular tumours, namely uveal melanocytomas (n = 13) and ciliary body adenomas (n = 9). To consider a potential association of senescence with biological behaviour, we compared the expression of both markers in tumour cells of benign uveal melanocytomas (n = 13) versus malignant conjunctival melanomas (n = 7). Canine eyes showed no age-dependent changes in senescent cells. However, a significant increase of the percentage of γH2AX- or p21-labelled cells was found in the retina, uvea and lens of tumour-bearing eyes. Tumour cells in conjunctival melanomas had a significantly increased percentage of p21-expressing cells compared with uveal melanocytomas. We conclude, that senescent cells do not accumulate with age in otherwise normal canine eyes and that a senescent microenvironment of intraocular tumours is unlikely to be age driven. In addition, as in man, the percentage of p21-positive cells was increased in melanomas, supporting the theory that malignant tumours may override the senescence-associated cell cycle arrest.

[Concept of an interdisciplinary emergency department at the Schwarzwald-Baar Hospital]. / Konzept einer interdisziplinären Notaufnahmeklinik am Schwarzwald-Baar Klinikum.

BACKGROUND: Numerous hospitals were combined years ago into a new Central Hospital for cost reasons in the Schwarzwald-Baar region. This also suggested the idea of a large central emergency department. The concept of a central emergency department is an organizational challenge, since they are directly engaged in the organizational structure of all medical departments that are involved in emergency treatment. Such a concept can only be enforced if it is supported by hospital management and all parties are willing to accept interdisciplinary and interprofessional work. OBJECTIVE: In this paper, the concept of a central emergency department in a tertiary care hospital which was rebuilt as an organizationally independent unit is described. Collaborations with various departments, emergency services, and local physicians are highlighted. The processes of a central emergency department with an integrated admission department and personnel structures are described. CONCLUSION: The analysis of the concept after almost a year has shown that the integration into the clinic has been successful, the central emergency department has proven itself as a central hub and has been accepted as a unit within the hospital.

[Amyloidoses]. / Amyloidosen.

Amyloidoses make up a group of diseases caused by misfolded proteins. These misfolded proteins are insoluble and are deposited in various tissues and organs, ultimately resulting in severe organ dysfunction. The majority of patients with amlyoidoses suffer from chronic inflammatory, infectious or malignant diseases. Moreover, unexplained nephropathy, cardiomyopathy, neuropathy, enteropathy, arthropathy or macroglossia with or without periorbital bleeding should include an amyloidosis in the differential diagnosis. The latter is facilitated by histological examination of abdominal adipose tissue, the rectum or affected organs. Therapy focuses predominantly on reduction of activity of the underlying disease and specific organ protection. More recent therapeutic strategies include interleukin-1 inhibition, as well as inhibitors of protein misfolding.

Hematological changes during short-term tidal flow extracorporeal life support.

Various methods exist in the clinical practice of long-term venovenous (VV) extracorporeal life support (ECLS). Among the clinical techniques used are single venous access with a dual-lumen catheter, and cannulation of the jugular and femoral veins. Tidal flow VV ECLS uses a single-lumen catheter to achieve both venous drainage and arterialized reinfusion through a series of tubing occluders that are automated by a pump. A single venous occluder tidal flow system with a 15 Fr single-lumen cannula (n = 6) and passive filling M pump was compared to a conventional 14 Fr dual-lumen cannula (n = 7) and roller pump for four hours of VV ECLS. The changes in platelet count and plasma-free hemoglobin (pHgb) were compared. The results showed a decline in platelet counts typical of ECLS in both groups that were not significantly different from each other. A small elevation in pHgb did not rise above normal clinical levels of 15 mg/dL in either group after four hours of ECLS. Some recirculation was observed and needs to be addressed in future studies. Single occluder tidal flow ECLS may be feasible and efficacious for long-term application once recirculation is resolved and the system evaluated for long-term support.

[Sinus vein thrombosis. A rare complication of heparin-induced thrombocytopenia type II]. / Sinusvenenthrombose. Eine seltene Komplikation einer Heparin-induzierten Thrombozytopenie Typ II.

In the past 10 years numerous reports of cases referring to complications and their outcome with heparin-induced thrombocytopenia type II (HIT II) have been published. Clinically these symptoms are manifested as a combination of arterial and venous thromboembolisms. Mostly affected are the vessels of the limbs, the abdomen, kidneys and coronary arteries. We present the most rare initial manifestations of cerebral symptoms with headache, nausea, change of character and generalised convulsion, which have found their origin in sinus vein thrombosis and the treatment with the heparinoid danaparoid.

Development of an ambulatory artificial lung in an ovine survival model.

We are developing an artificial lung (AL) as an eventual bridge to lung transplant or recovery. The device is rigidly housed, noncompliant, and has a very low resistance to blood flow. In eight sheep, arterial cannulae were anastomosed end-to-side to the proximal and distal main pulmonary artery, and attached to the AL. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the AL. Eight of eight sheep survived the preparation. Mean pressure gradient across the AL was 8 mm Hg (3 Wood units; 8 mm Hg/2.8 L/min). Four of eight sheep tolerated immediate full diversion of blood flow and died at 24 and 40 hours (exsanguination) or 168 and 168 hours (elective sacrifice). Four of eight sheep were intolerant of full flow: two died of right heart failure at <8 hours with full flow through the device (full snare); the other two survived with partial device flow (partial snare), but the device clotted. These two then underwent successful closed-chest cannula thrombectomy and device change-out at 53 and 75 hours, and subsequently tolerated full flow. Long-term (up to 7 day) survival with complete diversion of pulmonary blood flow through a non-compliant, low-resistance AL is possible. Initial right heart failure in this model was 50% (4 of 8).

Reduced platelet activation and thrombosis in extracorporeal circuits coated with nitric oxide release polymers.

OBJECTIVE: To determine whether the use of nitric oxide (NO)-releasing polymers coated onto the inner surface of extracorporeal circuits can reduce platelet consumption and activation in the absence of systemic heparinization using a rabbit model of venovenous extracorporeal circulation. DESIGN: Prospective, controlled trial. SETTING: Research laboratory at an academic medical institution. SUBJECTS: New Zealand White Rabbits. INTERVENTIONS: Anesthetized, tracheotomized, and ventilated New Zealand White rabbits were injected with freshly prepared, 111In(oxine)3 labeled single donor platelets through the external jugular vein. After baseline measurements, these animals were placed on venovenous extracorporeal circulation through a 1-m control circuit or NO test circuit for 4 hrs at a blood flow rate of 109-118 mL/min via roller pump. Four groups were studied: systemically heparinized control circuits, systemically heparinized NO test circuits, nonheparinized control circuits, and nonheparinized NO test circuits. Platelet counts, fibrinogen levels, and plasma free indium levels were measured hourly. Circuits were rinsed and retained for gamma counting after the 4-hr run or when the circuit clotted. Four animals, one from each group, did not receive radiolabeled platelets so that the circuits could be preserved for scanning electron microscopic examination after the 4-hr study. MEASUREMENTS AND MAIN RESULTS: Platelet consumption was significantly reduced in both the heparinized and nonheparinized NO test groups when compared with the controls (p < .0001 and p < .0004, respectively). Platelet adhesion to the extracorporeal circuits was significantly reduced in the nonheparinized test circuits when compared with the controls (p < .05). Scanning electron microscopic examination of the circuits revealed that in the absence of heparin and in the presence of a NO-releasing surface, platelets retained their spherical nonactivated shape. CONCLUSIONS: The incorporation of NO into the surface of extracorporeal circuits reduces platelet consumption and eliminates the need for systemic heparinization in a rabbit model of extracorporeal circulation.

NPY Y1 antagonists: structure-activity relationships of arginine derivatives and hybrid compounds with arpromidine-like partial structures.

Previously, omega-guanidino- and omega-aminoalkanamides, structurally derived from arpromidine-like histamine H2 receptor agonists, were reported as novel neuropeptide Y Y1 antagonists. Regardless of the backbone, they resemble BIBP 3226, an argininamide with high NPY Y1 receptor affinity and selectivity, with respect to nature and arrangement of the 'terminal' diaryl, guanidine, and hydroxyphenyl groups. Hybrid compounds were synthesized combining the argininamide backbone of BIBP 3226 or partial structures derived from the C-terminal dipeptide of NPY with characteristic substructures of arpromidine- or amide-type NPY antagonists. Additionally, some analogs of BIBP 3226 with reduced flexibility were prepared. Structure-activity relationships indicate that, in contrast to alkanamides, homologs and/or isomers of BIBP 3226 with vicinal arrangement of the phenyl rings have decreased Y1 antagonistic activity (Ca2+-assay in HEL cells). Replacement of the hydroxybenzyl group by an imidazole ring further decreases activity. It is concluded that the binding sites of NPY antagonists with one and with two basic groups are not identical. Analogs with a rigid tetrahydro-2-benzazepine or an indan group in place of the benzyl moiety in BIBP 3226 are active, indicating the role of the OH group and supporting the model proposed for the interaction of BIBP 3226 with the Y1 receptor.

Effects of static pressure on red blood cells on removal of the air interface.

Previous studies investigated the effects of pressure on red blood cells, but did not address the presence of an air interface. It has been established that an air interface promotes damage to blood. This study was designed to allow for the isolation of the blood-air interface during pressurization. Fresh human blood was divided into 2 ml samples in polypropylene tubes and exposed to either negative or positive pressure for 5 min at 37 degrees C. The plasma free hemoglobin was measured and compared to controls (0 mmHg) exposed to the same environment. This procedure was duplicated with a 1 ml layer of mineral oil on each sample, to remove the air interface. The sample size for each pressure was 15. Results from this study demonstrate that blood is resistant to positive pressures (1,000 mmHg), even on removal of the air interface. However, hemolysis previously attributed to negative pressures was not seen when the air interface was removed by mineral oil. Removal of the air interface halted cavitation, which occurred at pressures equal to or below -680 mmHg in the presence of the air interface. It is the authors' belief that hemolysis is not correlated with negative pressure, but rather with the susceptibility of blood to cavitation.

Significant safety advantages gained with an improved pressure-regulated blood pump.

A prototype of a non-occlusive pressure-regulated blood pump (M-pump) was evaluated in-vitro for safety in a comparative study with the roller and centrifugal pumps. The M-pump consists of collapsible tubing of unique design wrapped under tension around a rotor without a stator. The prototype M-pumps were tested in vitro to evaluate performance with respect to flow/ pressure characteristics, hemolysis, bubble generation (cavitation) and durability. The M-pump and centrifugal pump did not overpressurize at any RPM when the pump outlet was occluded, but the roller pump reached pressures in excess of 1000 mmHg. The M-pump did not generate negative pressures upon occlusion of the inlet, whereas the roller and centrifugal pumps produced near-vacuum pressures. Furthermore, the M-pump was unable to empty a blood reservoir when the height of the pump inlet was placed slightly above the reservoir outlet. The levels of microbubbles in the M-pump were significantly lower than the roller and centrifugal pumps upon sudden restriction of the pump inlet as determined with an ultrasonic bubble detector. The results of our in-vitro evaluation of the M-pump have shown it to have lower hemolysis than the centrifugal pump and lower or comparable hemolysis to roller pumps at flowrates of 0.1, 0.5, 4.0 and 6 L/min. We determined that the M-pump design possesses important safety advantages over roller and centrifugal pumps for cardiopulmonary bypass applications.

Development and application of a simplified liquid ventilator.

OBJECTIVE: Perfluorocarbon liquid ventilation has been shown to have advantages over conventional gas ventilation in premature newborn and lung-injured animals. To simplify the process of liquid ventilation, we adapted an extra-corporeal life-support circuit as a time-cycled, volume-limited liquid ventilator. DESIGN: Laboratory study that involved sequential application of gas and liquid ventilation in normal cats and in lung-injured sheep. SETTING: A research laboratory at a university medical center. SUBJECTS: Eight normal cats weighing 2.7 to 3.8 kg (mean 3.1 +/- 0.5), and four lung-injured young sheep weighing 10.4 to 22.5 kg (mean 15.9 +/- 5.0). INTERVENTIONS: Normal cats were supported with traditional gas ventilation for 1 hr (respiratory rate 20 breaths/min, peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 4 cm H2O, and FIO2 1.0). The lungs were then filled with perfluorocarbon (30 mL/kg) and tidal volume liquid ventilation was instituted, utilizing a newly developed liquid ventilation device. Liquid ventilatory settings were 4 secs for inspiration time, 8 secs for expiration time, 5 breaths/min for respiratory rate, and 15 to 20 mL/kg for tidal volume. Liquid ventilation utilizing this device was also applied to sheep after induction of severe lung injury by right atrial injection of 0.07 mL/kg of oleic acid, followed by saline pulmonary lavage. Extracorporeal life support was instituted to provide a stable model of lung injury. For the first 30 mins of extracorporeal support, all animals were ventilated with gas. Animals were then ventilated with 15 mL/kg of perfluorocarbon over the ensuing 2.5 hrs. MEASUREMENTS AND MAIN RESULTS: In normal cats, mean PaO2 values after 1 hr of liquid or gas ventilation were 275 +/- 90 (SD) torr (36.7 +/- 10.4 kPa) in the liquid-ventilated animals and 332 +/- 78 torr (44.3 +/- 10.4 kPa) in the gas-ventilated animals (NS). Mean PaCO2 values were 40.5 +/- 5.7 torr (5.39 +/- 0.31 kPa) in the liquid-ventilated animals and 37.6 +/- 2.3 torr (5.01 +/- 0.31 kPa) in the gas-ventilated animals (NS). Mean arterial pH values were 7.35 +/- 0.07 in the liquid-ventilated animals and 7.34 +/- 0.04 in the gas-ventilated animals (NS). No significant changes in heart rate, mean arterial pressure, lung compliance, or right atrial venous oxygen saturation were observed during liquid ventilation when compared with gas ventilation. In the lung-injured sheep, an increase in physiologic shunt from 15 +/- 7% to 66 +/- 9% was observed with induction of lung injury during gas ventilation. Liquid ventilation resulted in a significant reduction in physiologic shunt to 31 +/- 10% (p < .001). In addition, the extracorporeal blood flow rate required to maintain the PaO2 in the 50 to 80 torr (6.7 to 10.7 kPa) range was substantially and significantly (p < .001) lower during liquid ventilation than during gas ventilation (liquid ventilation 15 +/- 5 vs. gas ventilation 87 +/- 15 mL/min/kg). CONCLUSIONS: Liquid ventilation can be performed successfully utilizing this simple adaptation of an extracorporeal life-support circuit. This modification to an existing extracorporeal circuit may allow other centers to apply this new investigational method of ventilation in the laboratory or clinical setting.