Advances in the treatment of portal hypertension in cirrhosis.

Non-selective beta-blockers and handling of esophageal varices has been key elements in the treatment of portal hypertension in recent decades. Liver vein catheterization has been essential in diagnosis and monitoring of portal hypertension, but ongoing needs for noninvasive tools has led to research in areas of both biomarkers, and transient elastography, which displays promising results in discerning clinically significant portal hypertension. Novel research into the areas of hepatic stellate cell function and the dynamic components of portal hypertension has revealed promising areas of treatment modalities, targeting intestinal decontamination, angiogenesis, inflammation and oxidative stress. Future studies may reveal if these initiatives lead to developments of new drugs for treatment of portal hypertension.

Isolation and culture of spinal cord motor neurons.

Isolated spinal motoneurons are a powerful tool for studying basic mechanisms of neurite growth and survival. Since motoneurons are a minor population of developing spinal cord cells, they need to be purified and enriched to separate them from non-neuronal cells. Therefore, the particular feature of embryonic motoneurons to express the low affinity neurotrophin receptor p75(NTR) is used to separate the motoneurons from other contaminating cells. Two ways are described to isolate embryonic motoneurons: the basic protocol taking advantage of the ability of p75(NTR) to bind lectin, and an alternative method using an antibody against p75(NTR) for a panning procedure. These protocols comprise suggestions for the cultivation of the isolated motoneurons for experiments regarding neural outgrowth and survival as well as instruction for the preparation of proteins of the cells.

Spectrophotometric assessment of the effectiveness of Opalescence PF 10%: a 14-month clinical study.

OBJECTIVES: To evaluate the effectiveness of Opalescence PF 10% just after treatment, at 6-month follow-up and at a 14-month follow-up period. METHODS: Opalescence PF 10% was applied nightly for 14 days. The color of teeth 11 and 21 of 17 subjects were measured with a spectrophotometer (L*; a*; b*) before treatment, just after treatment (14 days), after 6 months and after 14 months. Subjects were instructed to take note of any tooth sensitivity. RESULTS: For all three components (L*, a* and b*) statistical significant differences (p<0.05) in the values between base-line, after treatment (14 days later), after 6 months and after 14 months were found (Wilcoxon Signed Rank Sum Test). The decrease in L* was about 20% after 6 months and about 50% after 14 months. The a* value decreased approximately 14% after 6 months but was worse after 14 months than at the beginning. The b* value decreased the least with about 9% after 6 months and about 8% after 14 months. The decrease in DeltaE(ab)(*) was approximately 20% after 14 months. Less than 20% of the subjects experienced mild tooth sensitivity just after treatment. CONCLUSION: Significantly whiter teeth were found after treatment as well as after a 6-month follow-up period. The whiteness/brightness (L*) decreased with approximately 50% after 14 months and the a* value with approximately 50% after 7 months, while the yellowness (b* value) remained even after 14 months. CLINICAL IMPLICATIONS: The product is an effective tooth whitener resulting in only low tooth sensitivity. Re-bleaching could be done at about 14 months.

High-temperature liquid chromatography. Part II: Determination of the viscosities of binary solvent mixtures--implications for liquid chromatographic separations.

This paper is the second in a series of consecutive publications, explaining the concept of high temperature liquid chromatography under various important aspects. The second publication deals with the determination of the viscosity of binary solvent mixtures used in reversed phase liquid chromatography in a temperature range between 25 and 250 degrees C. In literature, only limited data of the temperature dependent viscosities of liquid solvents or binary solvent mixtures can be found. Therefore, the viscosities of the pure solvents as well as the binary mixtures had to be determined experimentally up to 250 degrees C. The viscosity data were used to estimate the pressure drop in a capillary connecting a high-temperature HPLC system with a mass spectrometer. The solvent perturbation could be avoided by adjusting the diameter of the transfer capillary to the viscosity and vapour pressure of the mobile phase. The viscosity data were also used to show that a significant gain in analysis speed is theoretically feasible. This factor clearly depends on the nature of the solvent system, because for mixtures with a large viscosity maximum at ambient temperature, this effect is most pronounced.

High-temperature liquid chromatography. Part III: Determination of the static permittivities of pure solvents and binary solvent mixtures--implications for liquid chromatographic separations.

This paper is the third in a series of three publications, explaining the concept of high-temperature liquid chromatography under various important aspects. The third publication deals with the determination of the static permittivities of pure solvents and binary solvent mixtures used in reversed-phase liquid chromatography in a temperature range between 25 and 200 degrees C. Furthermore, a critical comparison is made between the polarity parameter which is generally used to define the elution strength of solvent mixtures and the experimentally determined static permittivities. Also, the necessity for using binary solvent mixtures at elevated temperatures is discussed for efficient method development.

Signalling molecules essential for neuronal survival and differentiation.

Motoneurons are made in excess throughout development. Initial analysis of the mechanisms that lead to apoptotic cell death during later stages of development and the early postnatal period led to the discovery of neurotrophic factors. These factors comprise different families acting through different tyrosine kinase receptors. Intracellular signalling cascades that lead to the survival of neurons are, on the one hand, the Ras/Raf (Ras-activated factor)/MAPK (mitogen-activated protein kinase) pathway and, on the other, the PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) pathway. The initial thought of these factors acting as single molecules in separate cascades has been converted into a model in which the dynamics of interaction of these pathways and the subcellular diverse functions of the key regulators have been taken into account. Bag1 (Bcl-2-associated athanogene 1), a molecule that was originally found to act as a co-chaperone of Hsp70 (heat-shock protein 70), also interacts with B-Raf, C-Raf and Akt to phosphorylate Bad (Bcl-2/Bcl-X(L)-antagonist, causing cell death), a pro-apoptotic member of the Bcl-2 family, and leads to specific subcellular distribution of phosphorylated Akt and B-Raf. These functions lead to survival of embryonic neural stem cells and therefore serve as a key event to regulate the viability of these cells.

A mouse model of persistent brain infection with recombinant Measles virus.

Measles virus (MV) nucleocapsids are present abundantly in brain cells of patients with subacute sclerosing panencephalitis (SSPE). This invariably lethal brain disease develops years after acute measles as result of a persistent MV infection. Various rodent models for MV infection of the central nervous system (CNS) have been described in the past, in which the detection of viral antigens is based on histological staining procedures of paraffin embedded brains. Here, the usage of a recombinant MV (MV-EGFP-CAMH) expressing the haemagglutinin (H) of the rodent-adapted MV-strain CAM/RB and the enhanced green fluorescent protein (EGFP) is described. In newborn rodents the virus infects neurons and causes an acute lethal encephalitis. From 2 weeks on, when the immune system of the genetically unmodified animal is maturating, intracerebral (i.c.) infection is overcome subclinically, however, a focal persistent infection in groups of neurons remains. The complete brain can be analysed in 50 or 100 microm slices, and infected autofluorescent cells are readily detected. Seven and 28 days post-infection (p.i.) 86 and 81% of mice are infected, respectively, and virus persists for more than 50 days p.i. Intraperitoneal immunization with MV 1 week before infection, but not after infection, protects and prevents persistence. The high percentage of persistence demonstrates that this is a reliable and useful model of a persistent CNS infection in fully immunocompetent mice, which allows the investigation of determinants of the immune system.

[Hyperbaric oxygenation: characteristics of intensive care and emergency therapy]. / Hyperbare Sauerstofftherapie: Notfall- und intensivmedizinische Besonderheiten.

Hyperbaric oxygenation (HBO) is a decisive component of a comprehensive interdisciplinary intensive care therapy for numerous disorders, such as gas embolism, severe decompression illness or carbon monoxide (CO) intoxication. However, barochambers with 24 h accessibility are often not readily available, thus, requiring an interhospital transport of critically ill patients. In order to minimise additional risks, a skilled transportation team should be involved. Furthermore, the specific physical and physiological features of HBO require that the transportation personnel must be trained adequately. Specific characteristics of the interhospital transfer of HBO patients are described as well as adverse effects and their specific therapy.

[Diving accidents. Emergency treatment of serious diving accidents]. / Der Tauchunfall. Notfallmedizinische Versorgung des schweren Tauchunfalls.

Decompression injuries are potentially life-threatening incidents mainly due to a rapid decline in ambient pressure. Decompression illness (DCI) results from the presence of gas bubbles in the blood and tissue. DCI may be classified as decompression sickness (DCS) generated from the liberation of gas bubbles following an oversaturation of tissues with inert gas and arterial gas embolism (AGE) mainly due to pulmonary barotrauma. People working under hyperbaric pressure, e.g. in a caisson for general construction under water, and scuba divers are exposed to certain risks. Diving accidents can be fatal and are often characterized by organ dysfunction, especially neurological deficits. They have become comparatively rare among professional divers and workers. However, since recreational scuba diving is gaining more and more popularity there is an increasing likelihood of severe diving accidents. Thus, emergency staff working close to areas with a high scuba diving activity, e.g. lakes or rivers, may be called more frequently to a scuba diving accident. The correct and professional emergency treatment on site, especially the immediate and continuous administration of normobaric oxygen, is decisive for the outcome of the accident victim. The definitive treatment includes rapid recompression with hyperbaric oxygen. The value of adjunctive medication, however, remains controversial.

Signalling mechanisms for survival of lesioned motoneurons.

Mechanisms controlling neuronal survival play an important role both during development and after birth, in particular when the nervous system is lesioned. Isolated embryonic motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal cell death during development and under pathophysiological conditions after neurotrauma. These studies have led to the identification of neurotrophic factors which under physiological conditions regulate survival and functional properties, and after neurotrauma promote regeneration and plasticity. Functional analysis of these molecules, in particular by generation of gene knockout mice, has led to a more detailed understanding of complex requirements of individual types of neurons for their survival and also paved the way for a better understanding of the signalling pathways in lesioned neurons which decide on cell death or survival after axotomy and other pathophysiological conditions. These findings could ultimately lead to a rational basis for therapeutic approaches aiming at improving neuronal survival and regeneration after neurotrauma.

[Results of pars plana lensectomy for childhood cataract]. / Ergebnisse der Pars-plana-Lentektomie bei kindlicher Katarakt.

BACKGROUND: Pars plana lensectomy with subsequent fitting of contact lenses is the standard procedure for cataracts occurring within the first 2 years of life. We wanted to assess the outcome and complication rate of this procedure. METHODS: Pars plana lensectomy was performed on 29 eyes of 15 children with bilateral as well as 12 eyes with unilateral cataracts. All children were reexamined at an age of at least 3 years. RESULTS: In bilateral cases the mean age at the time of surgery was 4.0 months and mean resulting visual acuity 0.32. After exclusion of three eyes with complications or bad postoperative compliance, we found a statistically significant correlation between age at surgery and visual acuity (r(2)=0.432, p<0.05). Some form of binocular vision was achieved by 40% of the children; 17% developed ocular hypertension and 7% a secondary cataract. In the unilateral cases the mean age at surgery was 3.9 months and the mean resulting visual acuity 0.14. There was no significant correlation between age and visual acuity; 17% gained binocular function and 5% had ocular hypertension. CONCLUSION: Visual function after lensectomy is better in eyes with bilateral cataracts compared to unilateral cataracts. Early surgery as well as adequate orthoptic therapy and compliance with wearing the contact lens are necessary for good outcome.

Three-dimensional nickel ion transport through porous media using magnetic resonance imaging.

The transport of Ni2+ ions in a column, filled with porous media, was observed in three dimensions and time by magnetic resonance imaging (MRI) in a clinical scanner. For porous media we used glass beads or quartz sand in a saturated continuous flow mode. The magnetic moment of Ni2+ decreased the T1 relaxation time of 1H in aqueous solution. This concentration-dependent effect was used by a fast low angle shot (FLASH) MRI sequence for imaging the concentration of the dissolved ions. Since Ni2+ behaves as a conservative tracer under the chosen conditions, the tracer motion was representative for the water flow in the porous medium. Currently, we can achieve an isotropic spatial resolution of 1.5 mm and a temporal resolution of 170 s. The transport observation gives direct access to hydraulic flow properties of the porous media. The fluid flow velocity field was calculated by a fronttracking method and the statistical properties of the velocities were investigated. We also compared the experimental data with the three-dimensional particle tracking model PARTRACE, which uses the experimental flow field as input.

Vehicle-Mounted Optical Sensing: An Objective Means for Evaluating Turf Quality.

Visual evaluation of turfgrass quality is a subjective process that requires experienced personnel. Optical sensing of plant reflectance provides objective, quantitative turf quality evaluation and requires no turf experience. This study was conducted to assess the accuracy of optical sensing for evaluating turf quality, to compare the rating consistency among human evaluators and optical sensing, and to develop a model that describes a relationship between optically sensed measurements and visual turf quality. Visual evaluations for turf color, texture, percent live cover (PLC), and optically sensed measurements were collected on the National Turfgrass Evaluation Program (NTEP) tall fescue (Festuca arundinacea Schreb) and creeping bentgrass (Agrostis palustris Huds.) trials at Stillwater, OK. Measurements were made monthly for 12 consecutive months from June 1999 through May 2000. Red (R) and near infrared (NIR) reflectance were collected with sensors and converted to normalized difference vegetative indices (NDVI). The NDVI were closely correlated with visual evaluations for turf color, moderately correlated with percent live cover (PLC), and independent of texture. Measurements of turf color and PLC were evaluated more consistently with optical sensors than by visual ratings. Normalized difference vegetation index (Y) could be reliably predicted by the following generalized model for turf color (X) and PLC (Z): Y = B(0) + B(1)log10X + B(2)Z(3). Optical sensing provided fast, reliable turf assessment and deserves consideration as a supplemental or replacement technique for evaluating turf quality.

Effect of graded hypo- and hypercapnia on fMRI contrast in visual cortex: quantification of T(*)(2) changes by multiecho EPI.

The sensitivity of functional magnetic resonance imaging (fMRI) in visual cortex to graded hypo- and hypercapnia was quantified in 10 normal subjects using single-shot multiecho echo-planar imaging (Turbo-PEPSI) with eight equidistant echo times (TEs) between 12 and 140 ms. Visual stimulation was combined with controlled hyperventilation and carbon dioxide inhalation to perform fMRI at six levels of end-expiratory pCO(2) (PETCO(2)) between 20 and 70 mm Hg. T(*)(2) in visual cortex during baseline conditions (light off) increased nonlinearly from 20 to 70 mm Hg, from 61.1 +/- 4.2 ms to 72.0 +/- 4.6 ms. Changes in T(*)(2) due to visual stimulation increased 2.1-fold, from 1.2 +/- 0.6 ms at 20 mm Hg to 2.5 +/- 0.7 ms at 50 mm Hg. An almost complete loss of functional contrast was measured at 70 mm Hg. The model of MR signal dephasing by Yablonskiy and Haacke (Mag Reson Med 1994;32:749-763) was used to predict changes in cerebral blood flow (CBF), which were found to be consistent with results from previous positron emission tomography (PET) studies. This study further emphasizes that global CBF changes (due to PETCO(2) changes even in the physiological range) strongly influence fMRI contrast and need to be controlled for.

Motoneuron cell death and neurotrophic factors: basic models for development of new therapeutic strategies in ALS.

Motoneurons are generated in excess during embryonic development of higher vertebrates. In the lumbar spinal cord of the developing rat, about 6000 motoneurons are present at embryonic day 14. These neurons grow out axons which make contact with their target tissue, the skeletal muscle. About 50% of the motoneurons are lost during a critical period from embryonic day 14 until postnatal day 3. This process, which is called physiological motoneuron cell death, has been the focus of research aiming at the identification of neurotrophic factors which regulate motoneuron survival during this developmental period. Motoneuron cell death can also be observed in vitro when the motoneurons are isolated from the embryonic avian or rodent spinal cord. These isolated motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal degeneration during development and under pathophysiological conditions in neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Accumulating evidence from such studies suggests that some specific requirements of motoneurons for survival and proper function may change during development. These findings might be relevant for understanding the pathophysiological processes underlying ALS and thus could contribute to the development of new therapeutic strategies.

A new approach to measure single-event related brain activity using real-time fMRI: feasibility of sensory, motor, and higher cognitive tasks.

Real-time fMRI is a rapidly emerging methodology that enables monitoring changes in brain activity during an ongoing experiment. In this article we demonstrate the feasibility of performing single-event sensory, motor, and higher cognitive tasks in real-time on a clinical whole-body scanner. This approach requires sensitivity optimized fMRI methods: Using statistical parametric mapping we quantified the spatial extent of BOLD contrast signal changes as a function of voxel size and demonstrate that sacrificing spatial resolution and readout bandwidth improves the detection of signal changes in real time. Further increases in BOLD contrast sensitivity were obtained by using real-time multi-echo EPI. Real-time image analysis was performed using our previously described Functional Imaging in REal time (FIRE) software package, which features real-time motion compensation, sliding window correlation analysis, and automatic reference vector optimization. This new fMRI methodology was validated using single-block design paradigms of standard visual, motor, and auditory tasks. Further, we demonstrate the sensitivity of this method for online detection of higher cognitive functions during a language task using single-block design paradigms. Finally, we used single-event fMRI to characterize the variability of the hemodynamic impulse response in primary and supplementary motor cortex in consecutive trials using single movements. Real-time fMRI can improve reliability of clinical and research studies and offers new opportunities for studying higher cognitive functions.

Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons.

Embryonic sensory and motoneurons depend on neurotrophic factors for survival. Here we show that their survival requires B-Raf, which, in this function, cannot be substituted by C-Raf. Sensory and motoneurons from b-raf-deficient mice do not respond to neurotrophic factors for their survival. However, these primary neurons can be rescued by transfection of a b-raf expression plasmid. In contrast, c-raf-deficient neurons survive in response to neurotrophic factors, similarly to neurons from wild-type mice. This points to an essential and specific function of B-Raf in mediating survival of sensory and motoneurons during development.

Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the degeneration of motor neurons in the spinal cord. The disease is caused by mutations of the survival of motor neuron 1 gene (SMN1), resulting in a reduced production of functional SMN protein. A major question unanswered thus far is why reduced amounts of ubiquitously expressed SMN protein specifically cause the degeneration of motor neurons without affecting other somatic cell types. In a first attempt to address this issue we have investigated the Smn interacting protein 1 (Sip1), with an emphasis on its developmental expression and subcellular distribution in spinal motor neurons in relation to Smn. By confocal immunofluorescence studies we provide evidence that a significant amount of Smn does not co-localize with Sip1 in neurites of motor neurons, indicating that Smn may exert motor neuron-specific functions that are not dependent on Sip1. Sip1 is highly expressed in the spinal cord during early development and expression decreases in parallel with Smn during postnatal development. Strikingly, reduced production of Smn as observed in cell lines derived from SMA patients or in a mouse model for SMA coincides with a simultaneous reduction of Sip1. The finding that expression of Sip1 and Smn is tightly co-regulated, together with the unique localization of Smn in neurites, may help in understanding the motor neuron-specific defects observed in SMA patients.

Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons.

Developing motoneurons require trophic support from their target, the skeletal muscle. Despite a large number of neurotrophic molecules with survival-promoting activity for isolated embryonic motoneurons, those factors that are required for motoneuron survival during development are still not known. Cytokines of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor (LIF) family have been shown to play a role in motoneuron (MN) survival. Importantly, in mice lacking the LIFRbeta or the CNTFRalpha there is a significant loss of MNs during embryonic development. Because genetic deletion of either (or both) CNTF or LIF fails, by contrast, to perturb MN survival before birth, it was concluded that another ligand exists that is functionally inactivated in the receptor deleted mice, resulting in MN loss during development. One possible candidate for this ligand is the CNTF-LIF family member cardiotrophin-1 (CT-1). CT-1 is highly expressed in embryonic skeletal muscle, secreted by myotubes, and promotes the survival of cultured embryonic mouse and rat MNs. Here we show that ct-1 deficiency causes increased motoneuron cell death in spinal cord and brainstem nuclei of mice during a period between embryonic day 14 and the first postnatal week. Interestingly, no further loss was detectable during the subsequent postnatal period, and nerve lesion in young adult ct-1-deficient mice did not result in significant additional loss of motoneurons, as had been previously observed in mice lacking both CNTF and LIF. CT-1 is the first bona fide muscle-derived neurotrophic factor to be identified that is required for the survival of subgroups of developing motoneurons.

Developmental motoneuron cell death and neurotrophic factors.

During the development of higher vertebrates, motoneurons are generated in excess. In the lumbar spinal cord of the developing rat, about 6000 motoneurons are present at embryonic day 14. These neurons grow out axons which make contact with their target tissue, the skeletal muscle, and about 50% of the motoneurons are lost during a critical period from embryonic day 14 until postnatal day 3. This process, which is called physiological motoneuron cell death, has been the focus of research aiming to identify neurotrophic factors which regulate motoneuron survival during this developmental period. Motoneuron cell death can also be observed in vitro when the motoneurons are isolated from the embryonic avian or rodent spinal cord. These isolated motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal degeneration during development and under pathophysiological conditions in neurodegenerative disorders. Accumulating evidence from such studies suggests that some specific requirements of motoneurons for survival and proper function may change during development. The focus of this review is a synopsis of recent data on such specific mechanisms.