Intracranial Pressure Changes During Intrahospital Transports of Neurocritically Ill Patients.

BACKGROUND: Intrahospital transport is associated with a high rate of complications. Investigations of this problem using neuromonitoring remain scarce. METHODS: This is a monocentric, prospective observational study. Patients with severe brain diseases and intracranial pressure (ICP) monitoring were included. Continuous monitoring of ICP, cerebral perfusion pressure (CPP), oxygen saturation (SpO2), heart rate, and mean arterial pressure was measured during seven different periods of intrahospital transport (baseline for 30 min, I = preparation, II = transport I, III = CT scan, IV = transport II, V = postprocessing, and follow-up for another 30 min). All complications were documented. RESULTS: Between July 2013 and December 2013, a total number of 56 intrahospital transports of 43 patients were performed from ICU to CT. Data recording was incomplete in six cases. Fifty transports have been taken into account for statistical analysis. Forty-two percent were emergency transports. Mean duration of the procedure was 17' (preparation), 6' (transport I), 9' (CT scan), 6' (transport II), and 15' (postprocessing), respectively. Mean ICP at baseline was 8.53 mmHg. Comparing all periods of intrahospital transport and the follow-up period to the baseline showed a significant increase of ICP only during CT scan (15.83 mmHg, p < 0.01), not during the transport to and from the radiology department. An overall complication rate of 36 % (n = 18) was observed. In 26 % (n = 13), additional ICP therapy was necessary due to an elevation of ICP above 20 mmHg. CONCLUSION: There is a considerable rate of complications during intrahospital transport of critically ill patients with severe brain diseases, with a significant increase of ICP during transport and CT scan. In one-fifth of all patients, additional therapy was necessary. From our point of view, transport of critically ill patients should only be performed by trained staff and under monitoring of ICP and CPP.

Craniocervical manual lymphatic drainage and its impact on intracranial pressure - a pilot study.

BACKGROUND AND PURPOSE: Theoretical considerations and the results of animal studies indicate that manual lymphatic drainage (MLD) might have an impact on intracranial pressure (ICP). There is a lack of clinically qualitative investigations on patients with severe cerebral diseases. METHODS: Between April 2013 and January 2015 a prospective observational study was performed on patients who were undergoing intracranial pressure measurement and treatment with MLD. ICP, cerebral perfusion pressure, mean arterial pressure (MAP), heart rate and oxygen saturation were recorded continuously 15 min before the procedure, during MLD (22 min) and for 15 min after the procedure. For analysis the data treatment units were divided into two groups: patients with a mean baseline ICP <15 mmHg (group 1) and patients with a mean ICP ≥15 mmHg before MLD (group 2). RESULTS: A total of 133 treatment units (61 patients) were analysed (group 1 n = 99; group 2 n = 34). The mean baseline ICP was 10.4 mmHg overall, and 8.3 mmHg and 18.6 mmHg respectively in group 1 and group 2; ICP significantly decreased during therapy with MLD and this persisted during the follow-up period in group 2. MAP did not show any significant differences between the different periods. CONCLUSIONS: Our data showed a significant reduction of ICP during therapy with craniocervical MLD in patients with severe cerebral diseases.

Detection of irreversible changes in susceptibility-weighted images after whole-brain irradiation of children.

INTRODUCTION: Whole-brain irradiation is part of the therapy protocol for patients with medulloblastomas. Side effects and complications of radiation can be detected by follow-up magnetic resonance imaging (MRI). Susceptibility-weighted images (SWI) can detect even very small amounts of residual blood that cannot be shown with conventional MRI. The purpose of this study was to determine when and where SWI lesions appear after whole-brain irradiation. METHODS: MRI follow-up of seven patients with medulloblastoma who were treated with whole-brain irradiation were analyzed retrospectively. SWI were part of the initial and follow-up MRI protocol. De novo SWI lesions, localization, and development over time were documented. RESULTS: At time of irradiation, mean age of the patients was 13 years (±4 years). Earliest SWI lesions were detected 4 months after radiation treatment. In all patients, SWI lesions accumulated over time, although the individual number of SWI lesions varied. No specific dissemination of SWI lesions was observed. CONCLUSION: Whole-brain irradiation can cause relatively early dot-like SWI lesions. The lesions are irreversible and accumulate over time. Histopathological correlation and clinical impact of these SWI lesions should be investigated.

BioCARS: a synchrotron resource for time-resolved X-ray science.

BioCARS, a NIH-supported national user facility for macromolecular time-resolved X-ray crystallography at the Advanced Photon Source (APS), has recently completed commissioning of an upgraded undulator-based beamline optimized for single-shot laser-pump X-ray-probe measurements with time resolution as short as 100 ps. The source consists of two in-line undulators with periods of 23 and 27 mm that together provide high-flux pink-beam capability at 12 keV as well as first-harmonic coverage from 6.8 to 19 keV. A high-heat-load chopper reduces the average power load on downstream components, thereby preserving the surface figure of a Kirkpatrick-Baez mirror system capable of focusing the X-ray beam to a spot size of 90 µm horizontal by 20 µm vertical. A high-speed chopper isolates single X-ray pulses at 1 kHz in both hybrid and 24-bunch modes of the APS storage ring. In hybrid mode each isolated X-ray pulse delivers up to ~4 × 10(10) photons to the sample, thereby achieving a time-averaged flux approaching that of fourth-generation X-FEL sources. A new high-power picosecond laser system delivers pulses tunable over the wavelength range 450-2000 nm. These pulses are synchronized to the storage-ring RF clock with long-term stability better than 10 ps RMS. Monochromatic experimental capability with Biosafety Level 3 certification has been retained.

X-ray diffuse scattering measurements of nucleation dynamics at femtosecond resolution.

Femtosecond time-resolved small and wide angle x-ray diffuse scattering techniques are applied to investigate the ultrafast nucleation processes that occur during the ablation process in semiconducting materials. Following intense optical excitation, a transient liquid state of high compressibility characterized by large-amplitude density fluctuations is observed and the buildup of these fluctuations is measured in real time. Small-angle scattering measurements reveal snapshots of the spontaneous nucleation of nanoscale voids within a metastable liquid and support theoretical predictions of the ablation process.

Carrier-density-dependent lattice stability in InSb.

The ultrafast decay of the x-ray diffraction intensity following laser excitation of an InSb crystal has been utilized to observe carrier dependent changes in the potential energy surface. For the first time, an abrupt carrier dependent onset for potential energy surface softening and the appearance of accelerated atomic disordering for a very high average carrier density have been observed. Inertial dynamics dominate the early stages of crystal disordering for a wide range of carrier densities between the onset of crystal softening and the appearance of accelerated atomic disordering.

Ultrafast bond softening in bismuth: mapping a solid's interatomic potential with X-rays.

Intense femtosecond laser excitation can produce transient states of matter that would otherwise be inaccessible to laboratory investigation. At high excitation densities, the interatomic forces that bind solids and determine many of their properties can be substantially altered. Here, we present the detailed mapping of the carrier density-dependent interatomic potential of bismuth approaching a solid-solid phase transition. Our experiments combine stroboscopic techniques that use a high-brightness linear electron accelerator-based x-ray source with pulse-by-pulse timing reconstruction for femtosecond resolution, allowing quantitative characterization of the interatomic potential energy surface of the highly excited solid.

Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb.

The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs. This structural anisotropy indicates that the initially generated fluid differs significantly from the equilibrium liquid.

Clocking femtosecond X rays.

Linear-accelerator-based sources will revolutionize ultrafast x-ray science due to their unprecedented brightness and short pulse duration. However, time-resolved studies at the resolution of the x-ray pulse duration are hampered by the inability to precisely synchronize an external laser to the accelerator. At the Sub-Picosecond Pulse Source at the Stanford Linear-Accelerator Center we solved this problem by measuring the arrival time of each high energy electron bunch with electro-optic sampling. This measurement indirectly determined the arrival time of each x-ray pulse relative to an external pump laser pulse with a time resolution of better than 60 fs rms.

Atomic-scale visualization of inertial dynamics.

The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.

Different lipid profiles as constituencies of liquid formula diets do not influence pain perception and the efficacy of opioids in a human model of acute pain and hyperalgesia.

Nutritional support and pain control by medication are often used concomitantly, but interactions are hardly investigated. A randomised, double-blind, cross-over study in ten right-handed volunteers was performed evaluating the influence of cholecystokinin (CCK)-excretion on the perception of pain in a standardised model. CCK-excretion was induced by a liquid formula diet with either long- or medium-chain triglycerides (LCT, MCT). Plasma samples were drawn over a 60 min period in 15-min intervals and CCK and somatostatin (SMS) were measured by radioimmunoassay (RIA). Gastric emptying was evaluated by C-13-breath testing. Transcutaneous electrical stimulation at a high current density (5 Hz, 70.1+/-5.8 mA) was used to provoke acute pain and stable areas of secondary mechanical hyperalgesia and pinprick allodynia for 2 h. Ongoing pain ratings as well as extension of pinprick-hyperalgesia and allodynia were compared between both liquid formula diets. In a second series of experiments, alfentanil (4.1+/-0.5 mg) was administered for 90 min using target-controlled infusions and measurements were performed as stated above. Oral administration of LCT as well as MCT may lead to different CCK blood levels, but we found no evidence for CCK-induced effects on pain sensation, touch-evoked allodynia, secondary hyperalgesia or morphine-induced anti-nociception in humans. In our studies, liquid formula diets did not influence acute pain perception or the efficacy of opioids in a human model of pain.

A crystal camera for ultra-small-angle x-ray scattering using synchrotron radiation.

We describe a novel USAXS camera that combines the use of synchrotron radiation with collimation by perfect-crystal optics. The outstanding result is that high measuring intensities and extreme angular resolution are achieved even with a point-focusing geometry. Along the principles of the original design (U. Bonse and M. Hart, Z. Phys. 189, 151 (1966)) which had to be operated at an x-ray tube, we employ two sets of pairs of multiply reflecting channel-cut crystals diffracting in the horizontal and vertical planes. The collimation characteristics thus obtained are equivalent to the point-focusing geometry of conventional SAXS cameras based on slit collimation. We present results from samples of polystyrene spheres which were used for test measurements performed with synchrotron radiation of DORIS at HASYLAB/DESY in Hamburg. Taking into account the number of reflections within the channel-cut crystals, the theoretical resolution was calculated and found to agree well with that derived from measured scattering patterns. Structures as large as about 1.3 µm could easily be identified from the scattering curves. As expected with point-focusing geometry, desmearing of raw data was unnecessary.

X-ray Applications with Glass-Capillary Optics.

Glass capillaries have unique properties for guiding X-rays in experiments with micrometer precision. Design considerations of such optics are presented for X-ray applications involving macromolecular crystallography, tomography and high-pressure experiments at the Cornell High Energy Synchrotron Source. The authors propose that crystallography with protein crystals is feasible on a 50 mum or smaller scale using capillary optics along with a cold gas stream and precision rotation stages. For computed tomography experiments, capillary optics can produce X-ray beams on a submicrometer scale. The distribution of X-rays passing through the sample can then be blown up in size with a secondary capillary optic to match the ~10 mum pixel size of CCD detectors. For high-pressure experiments in diamond-anvil cells, mono- and polycapillary optics may provide 1-50 mum diameter beams for diffraction or X-ray absorption fine-structure applications.

Dopamine-dependent diastolic dysfunction in moderate hypothermia.

We designed an experimental animal study to study the effects of dopamine (DA) on diastolic function in hypothermia. DA was applied at five incremental infusion rates in 6 sheep during normothermia and moderate hypothermia (29 degrees C). Left ventricular end-diastolic pressure (LVEDP) was increased during hypothermia as compared with normothermia at all doses of DA. Contraction and relaxation velocity were changed only slightly during hypothermia; during normothermia, both velocities were markedly increased. The pronounced hemodynamic effect observed during hypothermia was further intensified by occurrence of aftercontractions, which disappeared at very high DA doses. These paradoxic results were considered the result of hypothermia-induced reduction in active transport mechanisms responsible for regulation of the cytoplasmic CA2+ concentration. The generally reduced inotropic effect of DA, the risk of paradoxic reactions, and the occurrence of aftercontractions must be taken into account when emergency drugs are administered clinically during hypothermia.

3D computed X-ray tomography of human cancellous bone at 8 microns spatial and 10(-4) energy resolution.

Human cancellous bone was imaged and its absorptive density accurately measured in three dimensions (3D), nondestructively and at high spatial resolution by means of computerized microtomography (microCT). Essential for achieving the resolution and accuracy was the use of monoenergetic synchrotron radiation (SR) which avoided beam hardening effects, secured excellent contrast conditions including the option of energy-modulated contrast, and yet provided high intensity. To verify the resolution, we selected objects of approximately 8 micron size that could be observed on tomograms and correlated them in a unique manner to their counter images seen in histological sections prepared from the same specimen volume. Thus we have shown that the resolution expected from the voxel size of 8 microns used in the microCT process is in effect also attained in our results. In achieving the present results no X-ray-optical magnification was used. From microCT studies of composites (Bonse et al., X-ray tomographic microscopy (XTM) applied to carbon-fibre composites. In: Materlik G, ed. HASYLAB Jahresbericht 1990. Hamburg: DESY, 1990; 567-568) we know that by including X-ray magnification a resolution below 2 microns is obtained. Therefore, with foreseeable development of our microCT method, the 3D and nondestructive investigation of structures in mineralized bone on the 2 micron level is feasible. For example, it should be possible to study tomographically the 3D distribution and amount of osteoclastic resorption in the surrounding bone structure.

Establishing a pharmacy clinic in a city-county health department.

During a one-year rotation at an urban-county health department, a pharmacy resident implemented a pharmacy clinic to serve three major purposes: (1) to provide health care to patients with selected chronic illnesses, (2) to expand the revenue base of the health department pharmacy, and (3) to make possible the clinical instruction of Doctor of Pharmacy students and pharmacy residents. The resident's activities in the clinic included conducting interviews, performing physical examinations, initiating and adjusting therapy, and counseling patients. During the first four months of operation, 36 patients were seen in the clinic a total of 98 times. Seven chronic illnesses, along with a number of minor acute disorders, were evaluated and treated by the pharmacist. The pharmacist billed $1740.00 for patient care activities. The success of this initial program indicates that similar pharmacy clinics would be of benefit to other colleges of pharmacy as well as other institutional ambulatory health care providers.