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Friedreich ataxia is the most common hereditary ataxia. Atrophy of the spinal cord is one of the hallmarks of the disease. MRI and magnetic resonance spectroscopy are powerful and non-invasive tools to investigate pathological changes in the spinal cord. A handful of studies have reported cross-sectional alterations in Friedreich ataxia using MRI and diffusion MRI. However, to our knowledge no longitudinal MRI, diffusion MRI or MRS results have been reported in the spinal cord. Here, we investigated early-stage cross-sectional alterations and longitudinal changes in the cervical spinal cord in Friedreich ataxia, using a multimodal magnetic resonance protocol comprising morphometric (anatomical MRI), microstructural (diffusion MRI), and neurochemical (1H-MRS) assessments.We enrolled 28 early-stage individuals with Friedreich ataxia and 20 age- and gender-matched controls (cross-sectional study). Disease duration at baseline was 5.5 ± 4.0 years and Friedreich Ataxia Rating Scale total neurological score at baseline was 42.7 ± 13.6. Twenty-one Friedreich ataxia participants returned for 1-year follow-up, and 19 of those for 2-year follow-up (cohort study). Each visit consisted in clinical assessments and magnetic resonance scans. Controls were scanned at baseline only. At baseline, individuals with Friedreich ataxia had significantly lower spinal cord cross-sectional area (−31%, P = 8 × 10−17), higher eccentricity (+10%, P = 5 × 10−7), lower total N-acetyl-aspartate (tNAA) (−36%, P = 6 × 10−9) and higher myo-inositol (mIns) (+37%, P = 2 × 10−6) corresponding to a lower ratio tNAA/mIns (−52%, P = 2 × 10−13), lower fractional anisotropy (−24%, P = 10−9), as well as higher radial diffusivity (+56%, P = 2 × 10−9), mean diffusivity (+35%, P = 10−8) and axial diffusivity (+17%, P = 4 × 10−5) relative to controls. Longitudinally, spinal cord cross-sectional area decreased by 2.4% per year relative to baseline (P = 4 × 10−4), the ratio tNAA/mIns decreased by 5.8% per year (P = 0.03), and fractional anisotropy showed a trend to decrease (−3.2% per year, P = 0.08). Spinal cord cross-sectional area correlated strongly with clinical measures, with the strongest correlation coefficients found between cross-sectional area and Scale for the Assessment and Rating of Ataxia (R = −0.55, P = 7 × 10−6) and between cross-sectional area and Friedreich ataxia Rating Scale total neurological score (R = −0.60, P = 4 × 10−7). Less strong but still significant correlations were found for fractional anisotropy and tNAA/mIns. We report here the first quantitative longitudinal magnetic resonance results in the spinal cord in Friedreich ataxia. The largest longitudinal effect size was found for spinal cord cross-sectional area, followed by tNAA/mIns and fractional anisotropy. Our results provide direct evidence that abnormalities in the spinal cord result not solely from hypoplasia, but also from neurodegeneration, and show that disease progression can be monitored non-invasively in the spinal cord.

BackgroundFriedreich Ataxia (FRDA) is the most common hereditary ataxia. Atrophy of the spinal cord is one of the hallmarks of the disease. Magnetic resonance imaging (MRI) and spectroscopy (MRS) are powerful and non-invasive tools to investigate pathological changes in the spinal cord. A handful of studies have reported cross-sectional alterations in FRDA using MRI and diffusion MRI (dMRI) in FRDA. However, to our knowledge no longitudinal MRI, dMRI or MRS results have been reported in the spinal cord in FRDA.ObjectiveTo investigate early-stage cross-sectional alterations and longitudinal changes in the cervical spinal cord in FRDA, using a multimodal magnetic resonance (MR) protocol comprising morphometric (anatomical MRI), microstructural (dMRI), and neurochemical (1H MRS) assessments.DesignWe enrolled 28 early-stage individuals with FRDA and 20 age- and gender-matched controls (cross-sectional study). Disease duration at baseline was 5.5±4.0 years and Friedreich Ataxia Rating Scale (FARS) total neurological score at baseline was 42.7±13.6. Twenty-one FRDA participants returned for 1-year follow-up, and 19 of those for 2-year follow-up (cohort study). Each visit consisted in clinical assessments and MR scans. Controls were scanned at baseline only.ResultsAt baseline, individuals with FRDA had significantly lower spinal cord cross-sectional area (−31%, p=4.10−17), higher eccentricity (+10%, p=5.10−7), lower total N-acetyl-aspartate (−36%, p=6.10−9) and higher myo-inositol (+37%, p=2.10−6) corresponding to a lower ratio tNAA/mIns (−52%, p=2.10−13), lower fractional anisotropy (−24%, p=10−9) as well as higher radial diffusivity (+56%, p=2.10−9), mean diffusivity (+35%, p=10−8) and axial diffusivity (+17%, p=4.10−5) relative to controls.Longitudinally, spinal cord cross-sectional area decreased by 2.4% per year relative to baseline (p=4.10−4), the ratio tNAA/mIns decreased by 5.8% per year (p=0.03), and fractional anisotropy showed a trend to decrease (−3.2% per year, p=0.08).Spinal cord cross-sectional area correlated strongly with clinical measures, with the strongest correlation coefficients found between cross-sectional area and Scale for the Assessment and Rating of Ataxia (SARA) (R=-0.55, p=7.10−6) and between cross-sectional area and FARS total neurological score (R=-0.60, p=4.10−7). Less strong but still significant correlations were found for fractional anisotropy and tNAA/mIns.ConclusionWe report here the first quantitative longitudinal MR results in the spinal cord in FRDA. The largest longitudinal effect size was found for spinal cord cross-sectional area, followed by tNAA/mIns and fractional anisotropy. Our results provide direct evidence that abnormalities in the spinal cord result not solely from hypoplasia, but also from neurodegeneration, and show that disease progression can be monitored non-invasively in the spinal cord.

This work presents a multisensor hyperspectral approach for the characterization of ultramarine blue, a valuable historical pigment, at the microscopic scale combining the information of four analytical techniques at the elemental and molecular levels. The hyperspectral images collected were combined in a single hypercube, where the pixels of the various spectral components are aligned on top of each other. Selected spectral descriptors have been defined to reduce data dimensionality before applying unsupervised chemometric data analysis approaches. Lazurite, responsible for the blue color of the pigment, was detected as the major mineral phase present in synthetic and good quality pigments. Impurities like pyrite were detected in lower quality samples, although the clear identification of other mineral phases with silicate basis was more difficult. There is no correlation between the spatial distribution of the bands arising in the Raman spectra of natural samples in the region 1200–1850 cm−1 and any of the transition metals or rare earth elements (REE). With this information, the previous hypothesis (based on bulk analysis) attributing these bands to luminescence emissions due to impurities of these elements must be revised. We propose the consideration of CO2 molecules trapped in the cages of the aluminosilicate structure of sodalite-type. Additionally, correlation between certain Raman features and the combined presence of Ca, P, and REE, in particular Nd, was detected for the lowest quality pigment. Our results highlight the usefulness of fusing chemical images obtained via different imaging techniques to obtain relevant information on chemical structure and properties.

Despite growing environmental concern, combustion engines are projected to stay the main technology of transportation for many years, so will unpopular S- and P- containing additives in lubricating oils. Therefore, it is essential to maximize efficiency and minimize the harmful impacts of these additives in the meantime. Coatings based on Mo and W hold great promise as they can chemically interact with S-bearing additives and form low friction tribofilms like MoS2 and in particular WS2. Here we highlight the reaction pathways involving first the formation of oxide intermediates, followed by the generation of a highly protective and low-shear transition metal disulfide tribofilm on a tailored WN-based coating, affording coefficients of friction as low as 0.05 combined with an extraordinary wear protection (i.e., no measurable wear on sliding surfaces even after 100 h of testing). High resolution TEM and Raman spectroscopy confirm the formation of WS2 sheets and hence the huge potential of these coatings for lubricated surfaces. Keywords: In-situ WS2, Coating-lubricant interaction, Tungsten nitride, Thin film, Tribofilm

In this paper we present a method to measure oxygen tracer diffusion coefficients in thin ion conducting films without being limited by slow oxygen incorporation kinetics. The method is based on a two step process. In the first step a substantial amount of 18O tracer is locally incorporated for example into an yttria stabilized zirconia (YSZ) layer at low temperatures with the aid of an electric current, thus overcoming slow thermal oxygen exchange while still limiting lateral diffusion to a minimum. In the second step controlled diffusion takes place at elevated temperatures in ultra high vacuum (UHV) to impede loss of tracer due to oxygen exchange at the film surface. In this second step the surface of the thin film may additionally be modified compared to the oxygen incorporation step. This allows to easily investigate effects of interfaces on ion transport. The achieved in-plane concentration profiles are then measured by secondary ion mass spectrometry (SIMS). Comparison with electrical measurements on YSZ thin films proves the applicability of the method.

The electronic system developed for the SpaCal lead/scintillating-fibre calorimeters of the H1 detector in operation at the HERA ep collider is described in detail and the performance achieved during H1 data-taking is presented. The 10 MHz bunch crossing rate of HERA puts severe constraints on the requirements of the electronics. The energy and time readout are performed respectively with a 14-bit dynamic range and with a resolution of about 0.4 ns. The trigger branch consists of a nanosecond-resolution calorimetric time-of-flight for background rejection and an electron trigger based on analog `sliding windows'. The on-line background rejection currently achieved is o(10**6). The electron trigger allows a low energy trigger threshold to be set at about 0.50 +/- 0.08 (RMS) GeV with an efficiency >99.9%. The energy and time performance of the readout and trigger electronics is based on a newly-developed low noise (sigma_noise ca. 0.4 MeV) wideband (f < 200 MHz) preamplifier located at the output of the photomultipliers which are used for the fibre light readout in the ca. 1 Tesla magnetic field of H1.

The new lead/scintillating-fibre calorimeter (“SpaCal”) for the backward region of the H1 experiment at HERA (DESY) is equipped with fine mesh phototubes which operate in a magnetic field close to 1 T. A large sample of these tubes of the types Hamamatsu R5505 and R5506, and Hamamatsu R2490-05, have been tested in fields of up to 1.2T. We have investigated the cathode homogeneity with and without magnetic field, the gain loss under the influence of the magnetic field, and stability with time. For a subsample of tubes, we have performed additional studies on stability with respect to temperature changes, variation of gain as a function of the magnetic field, high voltage discharges, single photo-electron response, and linearity. We finally summarize the experience with these tubes after one year of operation in the experiment.

A Phillips webcam (price ∼ 70 USD) was mounted on an Olympus BX60 light microscope in order to record the images produced by the lens optical system. The quality of the images is comparable to those obtained by a standard one-chip charge coupled device (CCD) camera. The handling and implementation of the whole system has proven to be very easy due to the use of a normal micro computer and standard windows compatible software. Moreover, the presented method allows to record movies of investigated samples.

The backward region of the H1 detector has been upgraded in order to provide improved measurement of the scattered electron in deep inelastic scattering events. The centerpiece of the upgrade is a high-resolution lead/scintillating-fibre calorimeter. The main design goals of the calorimeter are: good coverage of the region close to the beam pipe, high angular resolution and energy resolution of better than 2% for 30 GeV electrons. The calorimeter should be capable of providing coarse hadronic energy measurement and precise time information to suppress out-of-time background events at the first trigger level. It must be compact due to space restrictions. These requirements were fulfilled by constructing two separate calorimeter sections. The inner electromagnetic section is made of 0.5 mm scintillating plastic fibres embedded in a lead matrix. Its lead-to-fibre ratio is 2.3:1 by volume. The outer hadronic section consists of 1.0 mm diameter fibres with a lead-to-fibre ratio of 3.4:1. The mechanical construction of the new calorimeter and its assembly in the H1 detector are described.

Hadronic response and electron identification performance of the new H1 lead-scintillating fibre calorimeter are investigated in the 1 to 7 GeV energy range using data taken at the CERN Proton Synchrotron. The energy response to minimum ionizing particles and interacting pions are studied and compared to Monte Carlo simulations. The measured energy of pions interacting either in the electromagnetic or in the hadronic section is found to scale linearly with the incident energy, providing an energy resolution σ E ∼ 38% within a depth of one interaction length and σ E ∼ 29% for a total depth of two interaction lengths. Several electron identification estimators are studied and combined as a function of energy and impact point. The probability for pions to be misidentified as electrons of any measured energy above 1 GeV ranges from 5% (for 2 GeV incident pions) to 0.4% (at 7 GeV) for an electron detection efficiency of 90%. The probability for pions of a given energy to be misidentified as electrons of the same energy falls to 0.25% at 7 GeV.

The properties of final modules of a high resolution lead/scintillating-fibre calorimeter to upgrade the backward region of the H1 detector were studied with electrons in the energy range from 2–60 GeV. The electromagnetic calorimeter consists of scintillating fibres with a diameter of 0.5 mm embedded in a lead matrix. This small fibre radius, in combination with a lead-to-fibre ratio of 2.27:1, ensures excellent energy resolution which has been measured to be δ/E=7.1%/ E/GeV ⊕ 1.0% . The spatial resolution as a function of energy for impact points at the center of a cell is given by 4.4 mm/ E/GeV + 1.0 mm . The time resolution was found to be better than 0.4 ns.

In a C. elegans embryo the third cleavages of descendants of the anterior blastomere AB of the 2-cell stage create pairs of blastomeres that develop differently. By laser ablation experiments we show that the fates of all the posterior daughters of this division depend on an induction occurring three cleavages before these blastomeres are born. The time of induction precludes a direct effect on cell fate. Alternatively, we suggest that the induction creates a heritable cell polarity which is propagated through several divisions. We suggest a model to demonstrate how a signal could be propagated through several rounds of cell division. An important implication of our observations is that this early induction acts to specify blastomere identity, not tissue type. A detailed lineage analysis revealed that altering the inductive signal alters complex lineage patterns as a whole. The induction described here, together with two inductions described previously can be used to illustrate how the anterior portion of the C. elegans embryo can be successively subdivided into blastomeres with unique developmental potential.

To update evidence-based best practice guidelines for surgical care in weight loss surgery (WLS). Systematic search of English-language literature on WLS in MEDLINE, EMBASE, and the Cochrane Library between April 2004 and May 2007. Use of key words to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. Evidence-based best practice recommendations from the most recent literature on surgical methods and technologies, risks and benefits, outcomes, and surgeon qualifications and credentialing. We identified >135 articles; the 65 most relevant were reviewed in detail. Regular updates of evidence-based recommendations for best practices in WLS are required to address rapid changes in surgical techniques and patient demographics. Key factors in patient safety include surgical risk factors, type of procedure, surgeon training, and facility certification.

150 patients with adenovirus type 8 infection where treated at random, in a prospective study. Based upon a quantifiable conjunctivitis severity score we tried to find out where there are differences in treatment. The best results were seen using polyvinylpyrrolidone-iodine (Betaisodona) although it could not prevent totally subepithelial corneal infiltrates. The combination of exogenous interferon alpha with polyvinylpyrrolidone-iodo-drops or trifluorothymidine-drops was less successful. We could not show any prophylactic effect of interferon on uninflamed fellow eyes. Treatment with vasoconstrictor did not show any therapeutic or prophylactic potency. This group of patients must be seen as a control group and the results of effective therapy should significantly differ from the results in this group. Topical corticosteroids should be reserved for severe symptomatic cases and those with iritis and pseudomembranous conjunctivitis. Giving topical corticosteroids in combination with antibiotics we did not find any influence on the incidence of subepithelial keratitis or the number of corneal infiltrates. The mean duration of acute keratoconjunctivitis using this therapy was longer than the mean duration in the control group with vasoconstrictor.

In model-driven engineering developers work mainly or only with models, which exist in many versions. This paper presents an approach to trace single model elements or groups of elements within a version history of a model. It also offers analysis capabilities such as detection of logical coupling between model elements. The approach uses a differencing algorithm blown as SiDiff to identify similar elements in different versions of a model. SiDiff is highly configurable and thus our tracing approach can be adapted to all diagram types of the UML and to a large set of domain specific languages. The approach has been implemented as an Eclipse plug-in that visualizes all relevant information about the traces and it allows developers to interactively explore details. It has been evaluated by several groups of test persons; they considered most of the functions of the tool to be very useful.

Expression of HLA-G on the surface of malignant hematopoietic cells isolated from leukemia patients was analyzed by flow cytometry using monoclonal antibodies (mAbs) recognizing both, intact HLA-G complex (87G, 01G and MEM-G9) as well as HLA-G free heavy chain (4H84, MEM-G/1 and MEM-G/2). Prerequisite of HLA-G detection by mAbs specific to free heavy chain was mild acid treatment, which dissociates intact HLA-G complex. All mAbs, with the exception of 4H84 mAb, did not indicate the presence of HLA-G antigen in leukemia cells. Positive staining with 4H84 mAb was detected in acid-treated cells isolated from 16 out of 30 patients. Intensity of staining increased after IFN-g pre-incubation in most cases. Immunoblot analyses and RT-PCR, however, failed to detect HLA-G antigen or HLA-G transcripts in cells that bind 4H84 mAb after acid-treatment. The binding of 4H84 mAb can be explained by the acid-induced cross-reactivity of this HLA-G specific mAb with classical HLA class I molecules [15]. The results described here further demonstrate that the HLA-G molecule is not expressed in freshly isolated human leukemia cells.

The maternal tolerance to the semiallogeneic fetus is still a central theme in reproductive immunology. During placentation, fetally-derived, genetically dissimilar tissue and cells come into close contact with maternal tissue and cells, thus forming the so-called feto-maternal interface. The most extensive contact between fetally-derived and maternal blood cells is formed by the villous trophoblastic barrier, where the syncytiotrophoblast surface permanently floats in maternal blood. Further contact is made by some extravillous cytotrophoblast cells, either located at villous tips, in so-called cell islands, or the endovascular trophoblast population within the uteroplacental spiral arteries. The third contact zone is the so-called junctional zone within the decidua where the invading extravillous trophoblast cells encounter all maternal tissue leukocytes, which are mainly NK cells, macrophages and T cells; this junctional zone extends at the edge of the placenta to the amnio-chorionic membranes where the chorionic laeve trophoblast has intimate contact with decidua tissue. It is worth mentioning that evidence has shown that even in healthy pregnancies fetal and maternal lymphoid cells are able to transgress the trophoblastic barrier, which, anatomically, seems completely impermeable. Because of this intimate contact of foreign cells to the foreign immune system it is important to define the antigenic status of the placental cells, in particular with respect to antigens of the Major Histocompatibility complex. The role of the highly polymorphic classical class I molecules HLA -A, -B, -C, which are expressed on almost all somatic cells, is the induction of a specific immune response by presenting peptide antigens to T cells. In contrast, the non-classical HLA class I molecules HLA-G and HLA-E are thought to be involved in the induction of immune tolerance by acting as ligands for inhibitory receptors present on NK cells and macrophages. The non-classical HLA-E is also expressed ubiquitously, but HLA-G expression is characterized by a unique tissue expression mainly in the human placenta. A further feature of HLA-G is that its mRNA has undergone alternative splicing, resulting in at least 6 different isoforms, encoding different proteins: 4 membrane-bound and 2 soluble forms, which could simultaneously maintain different functions depending on their molecular structure. In our immunohistochemical study we investigated the expression of classical and non-classical HLA class I proteins in human placenta using various mAbs, which were kindly provided by the groups of A. Ziegler, D. Geraghty, O. Genbacev, MT. McMaster, A. King, YW. Loke and Ph. Le Bouteiller. For HLA-A,-B detection we used the antibody LA45; for detection of HLA-C,-B mAbs Tü149 and HC10. HLA-C expression alone was detected with mAb L31. HLA-G expression was studied using antibodies 4H84, G233, 87G, 16G1 and BFL.1. For HLA-E staining we used antibodies DT9 and V16. The classical HLA class I proteins are expressed in all non-trophoblastic cells including the fetal and maternal cells. Comparison of HLA-A and HLA-B staining intensities within the villous stroma indicates that during first trimester of pregnancy the fetal HLA-B proteins are expressed before HLA-A appears. Among the trophoblast populations, the syncytiotrophoblast does not show any HLA class I staining, but the extravillous cells express high amounts of HLA-G together with HLA-C. King and co-workers have shown recently, using methods other than immunohistochemistry, that first trimester extravillous trophoblast cells are also likely to express HLA-E. By contrast we did not detect HLA-E in any trophoblasts with antibodies DT9 and V16. There is still an ongoing and also controversial discussion about which kinds of cells in the placenta, other than extravillous trophoblast, express which kind of the HLA-G isoforms. Depending on the antibodies and the different immunohistochemical techniques used, different results have been described: Antibody 16G1 specific for soluble HLA-G labels syncytiotrophoblast, antibody BFL.1 endothelial cells of chorionic fetal blood vessels and antibody 87G Hofbauer cells. All these HLA-G labelings, apart from extravillous trophoblasts, are in complete contrast to the reaction pattern (merely extravillous trophoblast) given by antibody 4H84, which recognizes all HLA-G isoforms -including the soluble ones- through an epitope located on the a 1-domain of HLA-G. Future studies employing isoform-specific antibodies, which are not yet available for all of the possible isoforms, will elucidate the function and expression pattern of HLA-G in the human placenta.

In the nematode Caenorhabditis elegans, a well-established model organism for the analysis of nervous system development and function, nerve processes can be labelled in the intact animal with markers based on the "Green Fluorescent Protein" (GFP). The generation of GFP variants with improved brightness and modified emission spectra potentiated the use of this marker for in vivo labelling of subcellular structures. This made it possible to label different groups of neurons and their axons in the same animal with GFP variants of different spectral characteristics. Here I show with double labelling experiments that spatial relationships of axons in small axon bundles can now be resolved at the light microscopic level. In the future this will largely circumvent the need for time-consuming electron microscopic reconstructions to detect local defects in axon outgrowth. Furthermore, I demonstrate that neuronal processes can now be traced even in the head ganglia, an area of the nervous system that was previously almost inaccessible for analysis due to the compact arrangement of cell bodies and axons.

The teratocarcinoma cell line 833K and its relatively cisplatin-resistant subline 833K/63CP 10 were used to assess the cytotoxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), cisplatin, and 4-hydroxyperoxycyclophosphamide quantitatively. The results showed that paclitaxel had marked cytotoxicity against teratocarcinoma, particularly in the cells that were relatively cisplatin resistant. These studies suggested synergy in cytotoxicity for paclitaxel, cisplatin, and 4-hydroxyperoxycyclophosphamide. A phase II trial of paclitaxel was conducted in patients with previously treated germ cell tumors with restricted prior treatment. The paclitaxel dose was 250 mg/m2 given by 24-hour continuous infusion. In 31 patients treated with paclitaxel, eight (26%) achieved a major (complete or partial) response. The antitumor activity of paclitaxel in the phase II trial has led us to further study it as a part of combination therapy. Since the in vitro studies showed synergistic cytotoxicity, combination studies of paclitaxel, ifosfamide, and platinum are under way as salvage treatment for patients with germ cell tumors.

Alterations of the hepatocytic intermediate filament (IF) cytoskeleton, i.e., derangement and diminution of the keratin network and appearance of cytoplasmic aggregates of keratin-containing material, termed Mallory bodies, are characteristic features of human alcoholic hepatitis. Mallory bodies can be experimentally produced in mouse liver by chronic griseofulvin (GF) administration. GF intoxication of mice is, therefore, a suitable model to study the mechanisms of Mallory body formation and related cytoskeletal changes.To investigate the correlation between morphologic alterations of the keratin cytoskeletal network and the mRNA levels for liver keratins A (8) and D (18) in this pathologic situation immunohistochemical studies and northern blot analyses were performed. The amount of mRNA for both keratins was also analyzed by nuclease S1 protection assay.In GF-treated livers (4 months of treatment) an increase of mRNA for both liver keratins was found. This increase of mRNA was unexpected under these conditions, since in longterm GF-fed animals, the amount of keratin IFs was reduced as revealed by immunofluorescence and electron microscopy and by biochemical analysis of keratin proteins. In livers treated for 2 months with GF the IF meshwork seemed to be still intact, but the increase of RNA was already detectable indicating that alterations of keratin mRNA precede detectable morphologic alterations. When using this mRNA for in vitro translation experiments, strong keratin polypeptide spots could be detected by autoradiography of 2-dimensional gels.These results strongly suggest that in vivo under the conditions of GF intoxication posttranslational modifications, like phosphorylation, proteolysis and covalent cross-linking, could influence IF homeostasis and interfere with IF assembly. Increase of mRNA for liver keratins despite IF protein reduction might be due to negative feedback regulation.

Chronic griseofulvin (GF) intoxication of mice leads to severe alterations of the hepatocytic intermediate filament cytoskeleton similar to that found in alcoholic hepatitis in humans (i.e., derangement and diminution of the keratin filament network and appearance of cytoplasmic aggregates of keratin-containing material, termed Mallory bodies). To investigate eventual alterations of nuclear lamins under these pathologic situations monoclonal antibodies were produced. One of these, GL-35, was directed to lamin B1 and lamin B2. Immunofluorescence microscopy revealed in GF-treated livers, in comparison to normal mouse livers, a highly reduced immunoreaction for lamins B1 and B2, whereas the staining for lamins A and C was unchanged. This reduction of both B-type lamins occurred before detectable alterations of keratin filaments and was reversible after cessation of GF intoxication. A diminished content of both B-type lamins in relation to lamins A and C in GF-intoxicated livers was also revealed by analysis of isolated nuclear envelopes on two-dimensional gels. Moreover, there was a clear predominance of more acidic isoelectric variants of lamins B1 and B2. In contrast to the reduced amount of B-type lamin proteins no reduction in the concentration of the mRNA for lamin B1 was found. For lamin B2 even an increase of mRNA was detected in GF-treated livers. These results indicate that GF not only interferes with expression of the keratin intermediate filament skeleton of hepatocytes but also leads to selective alterations of the nuclear lamins, most likely by posttranslational modifications of intermediate filament proteins.

150 patients with adenovirus type 8 infection where treated at random, in a prospective study. Based upon a quantifiable conjunctivitis severity score we tried to find out where there are differences in treatment. The best results were seen using polyvinylpyrrolidone-iodine (Betaisodona) although it could not prevent totally subepithelial corneal infiltrates. The combination of exogenous interferon alpha with polyvinylpyrrolidone-iodo-drops or trifluorothymidine-drops was less successful. We could not show any prophylactic effect of interferon on uninflamed fellow eyes. Treatment with vasoconstrictor did not show any therapeutic or prophylactic potency. This group of patients must be seen as a control group and the results of effective therapy should significantly differ from the results in this group. Topical corticosteroids should be reserved for severe symptomatic cases and those with iritis and pseudomembranous conjunctivitis. Giving topical corticosteroids in combination with antibiotics we did not find any influence on the incidence of subepithelial keratitis or the number of corneal infiltrates. The mean duration of acute keratoconjunctivitis using this therapy was longer than the mean duration in the control group with vasoconstrictor.

The indication for prophylactic temporary and permanent pacing during acute myocardial infarction (MI) complicated by bundle branch block is high risk of progression via a Type II pattern to second or third degree (high degree) AV block during hospitalization or follow-up. In this study, determinants of high degree AV block during hospitalization and sudden death or recurrent high degree block during the first year of follow-up were examined in 432 patients with MI and bundle branch block. Timing of onset of bundle branch block, the involved fascicles, and the PR interval were examined as determinants of risk of progression to high degree AV block during MI. At highest risk were 186 patients with blocks involving the right bundle and at least one fascicle of the left bundle which were not documented on prior electrocardiograms. Risk was similar with (38%) or without (31%) accompanying first degree AV block. Patients with transient high degree AV block during MI had a 28% incidence of sudden death or recurrent high degree block during the first year of follow-up. Patients not continuously paced had a higher incidence of sudden death or recurrent high degree block than patients continuously paced (65% vs 10%, P less than 0.001). Sudden death during follow-up also occurred in 13% of patients without high degree block during MI. A subgroup with 1) documented prior MI, 2) anterior or indeterminant acute MI, and 3) no symptoms of cardiac failure had a 35% risk of sudden death. The role of permanent pacing in this group is unknown. Thus, patients at high risk of high degree AV block should receive prophylactic temporary pacing. Patients who survive high degree block with MI should receive temporary and then permanent pacing. Patients without high degree AV block during MI who nervertheless have a high risk of sudden death may benefit from permanent pacing.

Central areolar chorodial atrophy was first classified as a hereditary disease by Sorsby in 1935. The mode of inheritance can be both autosomal recessive and autosomal dominant. The authors present a case with autosomal dominant inheritance affecting three generations.

Die Arbeit berichtet uber die Reaktion der Kaninchenscheide in situ auf Orasthin, Tonefin, Gynergen, Ergometrin. Sie zeigt weiter, das die durch Ergotamin bewirkte Adrenalinumkehr ebenfalls an der Kaninchenscheide reproduzierbar ist.

Fatty acid composition of mature human milk from Curacao (Netherlands Antilles), Surinam and Tanzania was determined by capillary gas chromatography. In the Curacaoan samples the cholesterol and alpha- and gamma-tocopherol concentrations were also determined. Remarkable differences were found in the fatty acid composition of breastmilk fat from the three countries. The differences in the levels of medium chain fatty acids between Curacao and Tanzania, and between Curacao and Surinam were significant. The mean sum of the essential fatty acids linoleic acid and linolenic acid showed the highest values in Curacao (16.1 g per cent). Mean values for Tanzania and Surinam were 14.9 and 12.7, respectively. The mean level of the docosahexaenoic acid was higher in the Curacaoan and Surinam samples compared with that from Tanzania. In the Curacaoan breastmilk samples the concentrations of cholesterol and alpha- and gamma-tocopherol were about twice as high as those reported for Western countries.

To provide an understanding of the clinical characteristics of patients with acute myocardial infarction (MI) and bundle branch block, experience from five centers was accumulated. Patients in whom bundle branch block first appeared after the onset of cardiogenic shock were excluded. In 432 patients, the most common types of block were left (38%) and right with left anterior fascicular block (34%). In 42% of the patients, bundle branch block was new. Progression to high degree (second or third degree) atrioventricular (AV) block via a Type II pattern occurred in 22% of the patients. Hospital and first year follow-up mortality rates were 28% and 28%, respectively. Only 46% of the patients developed pulmonary edema or shock (Killip Class III or IV), and hospital mortality was related to the amount of heart failure (8%, 7%, 27%, 83% for Killip Classes I-IV, respectively). Patients with progression to second degree or third degree AV block via a Type II pattern had increased hospital mortality compared with patients without this complication (47% vs 23%, P less than 0.001). In the absence of pulmonary edema or shock, patients with Type II second degree or third degree AV block still had a higher mortality rate than patients without advanced AV block (31% vs 2%, P less than 0.005), with nearly all the deaths due to abrupt development of AV block. Thus, in many patients MI with bundle branch block is associated with severe heart failure. However, this was not true for a majority of the patients, in whom therapy aimed at preventing morbidity and mortality due to the bradyarrhythmia of advanced AV block might be beneficial.