Factors associated with keel bone damage - a longitudinal study of commercial layer flocks during the laying period.

1. Keel bone damage, such as deformations and fractures, is a severe problem regarding animal welfare in layers. To identify risk factors under commercial conditions, 33 layer flocks (22 barn, 11 free range) with white (n = 18), brown (n = 11) and mixed (n = 4) genotypes were examined.2. Keel bone status was frequently scored by palpation throughout the laying period. Data on housing and management conditions were collected. Multiple regression and Generalized Estimating Equations procedure were used for analysis.3. At 65-74 weeks of age, the prevalence of keel bone damage ranged between 26% and 74%. White genotypes and those kept in multi-tier systems developed significantly (p < 0.05) more keel bone damage than brown genotypes or those kept in single-tier systems. Wing feather condition was associated with keel bone damage (p < 0.05), while other investigated variables regarding health, housing and management were not associated.4. In conclusion, housing and management should be adapted to meet the birds' specific needs in multi-tier systems, which may vary for brown and white genotypes. Whether those differences result from genotype associated predispositions or other individual traits remains to be determined.

Plumage damage and back skin lesions in laying hens with untrimmed beak depend on rearing of pullets and genetics.

1. Within a triennial project, 34 layer flocks with untrimmed beaks were examined regularly throughout the laying period to broaden knowledge on the occurrence and development of severe feather pecking and cannibalism, as well as on factors influencing this non-desirable behaviour.2. Flocks involved 850 to 27,183 hens of seven different genetics, kept in a barn or on free-range systems. Damage to the plumage and skin was assessed in individual hens during each visit and their body weights recorded. Correlations smaller than 0.8 between different body areas for damage indicated the necessity to consider them separately. Accounting for the risk of bias due to unevenly distributed factors, regression functions were used to assess associations between pecking damage, losses and performance, housing and management conditions. In addition, temporal pattern of pecking damage for flocks with severe, medium and little damage was modelled using these functions.3. As expected, plumage damage increased with age, whereas the development of skin lesions was less consistent. From 30 weeks of age, pecking damage on the back increased remarkably in flocks with the most severe scores compared to those with medium and little damage, especially during the later laying period. Associations were found between pecking damage on the back of hens with plumage quality of pullets when entering the layer house (point of lay). Damage to the vent/cloacal region was more pronounced in white compared to brown layers. However, this did not deny the importance of factors not significant in this study.4. The study identified factors related to genetics and status of hens when entering the layer house, particularly the influence of the rearing phase.

A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493), a folate receptor targeted chemotherapeutic agent in humans with advanced solid tumors.

Background The folate receptor alpha is selectively over-expressed in a number of human cancers. BMS-753493 is a folate conjugate of the epothilone analog BMS-748285 that was designed to selectively target folate receptor expressing cancer cells. Methods BMS-753493 was investigated in two parallel multi-institutional first-in-human phase I/IIa studies in patients with advanced solid tumors. In Study 1, patients were treated on a schedule of once daily dosing of BMS-753493 administered on Days 1, 4, 8 and 11 every 21 days with a starting dose of 5 mg daily and in Study 2, patients were treated once daily on Days 1-4 every 21 days, with a starting dose of 2.5 mg daily. Results A total of 65 patients were treated across the two studies. The maximum tolerated dose (MTD) was 26 mg in Study 1 and 15 mg in Study 2. Fatigue, transaminitis, gastrointestinal toxicity, and mucositis were dose-limiting toxicities. One patient in Study 2 developed Stevens-Johnson syndrome attributed to BMS-753493. Plasma exposures of both the conjugated and free epothilone increased in a dose related fashion in both studies and the half-life of the conjugated epothilone was 0.2-0.6 h across dose levels. No objective tumor responses were seen in either study. Conclusions BMS-753493 was generally tolerable and toxicities known to be associated with epothilone class of anticancer agents were common, although peripheral neuropathy and neutropenia appear to have been less frequent and less severe as compared to epothilones. Antitumor activity was not demonstrated and further development of BMS-753493 has been discontinued.

Three-dimensional high resolution OCT imaging of macular pathology.

Raster scanning spectral domain optical coherence tomography (SD-OCT) enables realistic three-dimensional (3D) imaging of macular disease. This approach allows the clinician to investigate the diagnostic situation in detail before and during pharmacological or surgical intervention. This study demonstrates the clinical potential of SD-OCT in chorioretinal disease. Selected datasets are presented to visualize typical morphologic findings, which are identified in more than 2700 patients. Scans are presented as online assessable 3D-models. Clinically relevant structures are visualized in macular disease and highlight the importance of precise imaging, which clearly is a clinical necessity to plan and indicate modern therapeutic strategies for our patients.

[High-resolution optical coherence tomography to evaluate vitreomacular traction before and after membrane peeling]. / Untersuchung vitreomakulärer Traktionen vor und nach Membranpeeling mittels hochauflösendem Raster-OCT.

AIM: Morphological assessment of the vitreomacular interface and intraretinal architecture using three-dimensional high-resolution optical coherence tomography (HROCT) before and after surgical delamination of epiretinal membranes and the internal limiting membrane (ILM). METHOD: The extent and intensity of traction of the epiretinal membrane (ERM) and the morphology of the individual retinal layers were investigated preoperatively in 14 eyes of 14 patients using three-dimensional HROCT (Cirrus prototype, scanned area 6x6 mm, depth 2 mm). In addition, visual acuity and ophthalmological findings (including stratus OCT) were documented. Standardized follow-up examinations were performed prospectively adhering to a protocol on days 1, 4, and 7 as well as 1 and 3 months after surgery. RESULTS: The ERM adhered closely to the retina in 85% of cases, but in 100% it was still clearly distinguishable from the retinal surface as a separate structure when using HROCT. Vertical traction through the ERM to the deepest retinal layers could be shown on HROCT in 93% of the cases. Structural alterations of the retina were not detectable either directly after surgery or subsequently. After an average of 4 weeks, the architecture of the layers was reorganized with complete regression of the preoperative tractional aberrations. The mean preoperative Snellen visual acuity of 0.4+/-0.2 increased to an average of 0.5+/-0.2. The mean preoperative retinal thickness was 482+/-84 microm and after 3 months 328+/-80 microm (HROCT). CONCLUSIONS: Examination with high-resolution optical coherence tomography allows three-dimensional visualization of the dynamics of epiretinal tractions that had not previously been obtainable. Epiretinal membranes can be clearly distinguished and their tractional effects can be traced through all retinal layers up to the pigment epithelium. As a result of the postoperative elimination of the tractions, the morphological alterations of the individual retinal layers recede already after 1 month.

[The role of Stratus OCT in anti-VEGF therapy. Qualitative and quantitative assessment of neovascular AMD]. / Die Rolle des Stratus-OCT bei der Anti-VEGF-Therapie : Qualitative und quantitative Beurteilung bei neovaskulärer AMD.

BACKGROUND: The evaluation of OCT3 during anti-VEGF therapy. METHODS: A total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab. OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months. RESULTS: The central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%) but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal layer segmentation and inadequate CRT measurements were a significant technical limitation. CONCLUSION: During anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also for an estimation of functional improvement.

[New perspectives in diagnostic. High-resolution optical coherence tomography for age-related macular degeneration]. / Neue Perspektiven in der Diagnostik. Hochauflösende optische Kohärenztomographie bei altersbedingter Makuladegeneration.

BACKGROUND: Recent advances in optical coherence tomography (OCT) have made it possible to increase resolution and scan velocities so that even greater central areas of the retina can be scanned. The aim of this study is to describe the possibilities offered by this new technology for age-related macular degeneration. MATERIAL AND METHODS: The study included 20 patients with confirmed active choroidal neovascularization (CNV) as well as pigment epithelial detachment (PED). Three-dimensional imaging was performed with a high-definition raster scanning OCT system (HD-OCT) with an axial resolution of 6 microm and a scan velocity of up to 20,000 A-scans/s. The scanned area measured 6 x 6 mm with a depth of 2 mm. Two-dimensional imaging was carried out with a StratusOCT (Carl Zeiss Meditec). RESULTS: Comparison of the individual slices showed improved identification of intra- and subretinal structures with the HD-OCT. Demarcation of pathological changes in individual retinal layers is possible with the HD-OCT. Summation images permit accurate localization of a scan. Topographic and volumetric evaluations enable analysis of individual compartments in the entire scanned area and are suitable for monitoring treatment of CNV with anti-VEGF therapy. The raster method decreases the dependence on exploratory methods that have been necessary until now to generate retinal thickness maps. CONCLUSIONS: This report presents initial experience in using a raster scanning HD-OCT system in patients with neovascular age-related macular degeneration and describes new evaluation functions that aid in obtaining more precise assessment of treatment effect and its impact on the retinal ultrastructure. The results of this study clearly show that development of high-resolution OCT systems in conjunction with development of novel treatment options for exudative diseases offers promising perspectives.

[Three-dimensional imaging in central serous chorioretinopathy]. / Dreidimensionale Bildgebung bei Chorioretinopathia centralis serosa.

BACKGROUND: Conventional optical coherence tomography (OCT) has brought new insights to retinal diagnostics, but it is restricted due to its low scanning speed and limited resolution. In this study, high-resolution raster scanning OCT (HR-OCT) was used to identify typical changes in central serous chorioretinopathy (CSC). METHODS: Fifteen consecutive patients with acute CSC were imaged using HR-OCT with an axial image resolution of 6 mum. The scanned area measured 6x6 mm2. Three-dimensional (3D) evaluation was performed using various analysing programmes. RESULTS: Topographic changes in CSC could be visualised with 3D reconstructions in all locations. Retinal thickness was measured with the automatic segmentation mode and quantified precisely. Results were presented in 2D and 3D maps. En-face imaging as a modality to present an integrative overview showed specific alterations in CSC. CONCLUSION: HR-OCT was able to provide essential additional information about CSC when combined with appropriate analysing programmes, allowing the identification of typical differences. Aside from precise volumetric measurements, exact localisation of pathological deviations could be achieved.

Prevalence of erectile dysfunction among middle-aged men in a metropolitan area in Germany.

The comparison of results of previous studies on the prevalence of erectile dysfunction is hampered due to differences in study design and research instruments including definitions used. The aim of the study was to determine the prevalence of erectile dysfunction/erectile disorder (ED) using different definitions. An epidemiological cross-sectional study was conducted between May and November 2002 in Berlin, Germany. A total of 6000 men between 40 and 79 years of age were randomly selected by the Berlin Office of Vital Statistics and were sent a questionnaire by mail. The prevalence of ED was determined using five different methods. A total of 1915 questionnaires were eligible for analysis. The five different definitions yielded age-adjusted ED prevalence rates between 18 and 48%. Age was strongly correlated with all five definitions (P<0.001). These results indicate the need for standardized criteria when conducting future studies on ED and may aid in designing public health and clinical management strategies.

Challenges and constraints to vaccination in developing countries.

The challenges and constraints to vaccinating poultry in areas where adequate infrastructure and human resources are lacking are addressed in both a technical and a socioeconomic framework. The key issues discussed are: (1) selection of an appropriate vaccine and vaccination technique, including the advantages and disadvantages of a combined vaccine against highly pathogenic avian influenza (HPAI) and Newcastle disease and addressing the differences between endemic disease and emergency disease control; (2) vaccine conservation and distribution; (3) evaluation of the flocks to be vaccinated in terms of their disease status, immunocompetence and production systems; (4) design of effective information, education and communication materials and methods with and for veterinary and extension staff as well as commercial and smallholder producers and community vaccinators in rural areas; (5) evaluation and monitoring systems for technical and socioeconomic factors that affect vaccination; (6) support and coordination of and by relevant public and private agencies; (7) the role of simultaneous implementation of other control activities in addition to vaccination; (8) the importance of assessing the costs and cost-effectiveness of various approaches to the control of HPAI, including the prevention of other endemic killer diseases and options for cost-sharing; (9) evaluation of the incentives for poultry-holders, vaccinators and vaccine producers to contribute to and participate in effective vaccination campaigns; and (10) policy development and the organizational framework for short- and long-term implementation and communication to decision-makers.

[A discussion of the differential diagnosis of the impaired erection]. / Differentialdiagnostische Diskussion der Erektionsstörung.

In light of the fact that internationally accepted diagnostic criteria for erectile disorder are hardly considered in prevalence studies, the Berlin Male Study (BMS) was designed to collect data both on the frequency of dysfunctional erections experienced (DSM-IV criterion A) and the concomitance of related distress (DSM-IV criterion B). As a result, the age-adjusted total prevalence for erectile disorder (17.8%) was markedly lower than in other studies with comparable samples (40-79 years of age). Likewise, the age-dependent increase in prevalence was by far less prominent than commonly reported in the literature. These findings strongly suggest the necessity to clearly differentiate between erectile disorder, indicating that the patient is experiencing some degree of distress associated with his dysfunctional erection, and erectile dysfunction, indicating that the respective individual is not too concerned about his dysfunctional erection (with respect to erectile function, there is no reason to refer to the latter as a patient). The authors suggest that the internationally used abbreviation "ED" be differentiated into "EDy" when referring to erectile dysfunction and "EDi" when referring to erectile disorder. This extended perspective on differential diagnosis would not only make future studies (more) comparable, it would also do justice to clinical experience.

Inhibitors of HIV-1 transcription.

No curative drug against HIV has yet been found, despite enormous efforts aimed at reverse transcriptase and a variety of other targets. The long terminal repeat (LTR) of HIV-1 has recently become a promising site for antiviral action. This article briefly summarizes information on the nature of this target and potential anti-LTR expression drugs.

Molecular cloning of human von Ebner's gland protein, a member of the lipocalin superfamily highly expressed in lingual salivary glands.

Von Ebner's glands (VEG) are small lingual salivary glands. Their ducts open into trenches of circumvallate and foliate papillae, thus influencing the milieu where the interaction between taste receptor cells and sapid molecules takes place. The major secretions of human VEG is a protein with a molecular mass of 18 kDa. The human VEG protein crossreacts with antibodies raised against the rat VEG protein, indicating sequence similarity between the rat and human VEG proteins. This was subsequently confirmed by N-terminal protein sequencing. A cDNA clone, isolated from a human VEG library, contained an insert of 735 bp including an open reading frame that encodes the human VEG protein of 176 amino acids. Comparison of the human and rat VEG proteins revealed an overall identity of 60%. Immunocytochemistry, in situ hybridization and in vitro translation studies demonstrated the human VEG protein to be highly and exclusively expressed in VEG. The VEG proteins are members of the lipocalin protein superfamily and, together with the rat odorant binding protein II, they constitute a new subfamily. Sequence similarity to proteins such as the retinol binding protein and the odorant binding protein which are lipophilic ligand carriers, suggests a possible function for the human VEG protein in taste perception.

Topographic angiography and optical coherence tomography: a correlation of imaging characteristics.

PURPOSE: Topographic angiography (TAG) using confocal scanning laser angiography and optical coherence tomography (OCT) are new imaging modalities that have been introduced during recent years. OCT and TAG imaging were compared to specify the characteristics of each imaging modality. METHODS: TAG using fluorescein angiography (FA) provides a three-dimensional profile of the vascular structures based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT provides cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and evaluated both modalities in 10 patients with predominantly classic choroidal neovascularization (CNV), 10 patients with serous pigment epithelial detachment (PED), and 10 patients with geographic RPE atrophy, all secondary to age-related macular degeneration (ARMD). RESULTS: In patients with classic CNV, TAG detected neovascular structures and delineated their configuration. In PEDs pooling of extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an increased depth resolution. CONCLUSIONS: TAG and OCT are useful imaging modalities in the evaluation of ARMD cases. TAG visualizes the vascular configuration and dynamic perfusion and leakage changes. OCT is able to document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. Both modalities may provide further valuable insight into ARMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

Pentoxifylline inhibits HIV-1 LTR-driven gene expression by blocking NF-kappa B action.

The drug pentoxifylline (PTX) (1-(5'-oxohexyl) 3,7-dimethylxanthine) down-regulates human immunodeficiency virus (HIV-1) long terminal repeat (LTR)-directed gene expression in the human monocytic cell line U38. This effect of PTX has been tested in clinical trials. In this investigation, a similar inhibitory effect of PTX on HIV-1 LTR-driven gene expression was observed (a) in a stable transfectant of the human embryo kidney cell line 293-27-2 carrying an expression plasmid construct with the HIV-1 LTR fused to the bacterial lac Z gene, and also (b) by transient transfection of human embryo kidney cells 293 S with fusion plasmid constructs with wild-type [pHIV-LTR-chloramphenicol acetyltransferase (CAT)] or mutated (pHIV-LTR-mut-CAT) nuclear factor kappa B (NF-kappa B) motifs. In both stable and transient transfection studies, 4-beta-phorbol-12-beta-myristate-acetate (PMA)-induced or tumor necrosis factor-alpha (TNF-alpha)-induced activation of the HIV-1 LTR was correlated with a concomitant elevated level of NF-kappa B interaction with its motifs. The inducibility of HIV-1 LTR-driven gene expression by PMA or TNF-alpha in transiently transfected cells was completely eliminated by point mutations in the NF-kappa B motifs, suggesting that NF-kappa B plays a major role in the activation of the HIV-1 LTR by these agents in this cell system.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokine dysregulation in AIDS: in vivo overexpression of mRNA of tumor necrosis factor-alpha and its correlation with that of the inflammatory cytokine GRO.

The human immunodeficiency virus establishes an intimate interaction with the immune system. The virus can use cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (Il-1), to regulate its own expression by modifying the normal immunoregulatory network. We demonstrate that mRNA of the cytokine TNF-alpha from peripheral blood mononuclear cells is overexpressed in virtually all patients with AIDS who do not have active opportunistic infections compared with uninfected volunteers (p < 0.0001). This overexpression correlates with elevated mRNA levels of the recently discovered GRO (p < 0.05), a cytokine involved in the inflammatory response.

Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. NIAID AIDS Clinical Trials Group.

Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV long terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group study (ACTG #160), the goal of which was to investigate the ability of the drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicity. Data were analyzed on the 17 patients who completed the 8-week study treatment with pentoxifylline, 400 mg, thrice daily. The median pretreatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglycerides, which have previously been shown to correlate with levels of interferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TNF mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 patients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group as a whole. This study demonstrates the safety of pentoxifylline in AIDS patients and its ability to decrease triglycerides and TNF mRNA levels.

Structural brain correlates of anterograde memory deficits in multiple sclerosis.

Progressive decline of anterograde memory functions has been increasingly recognized as a frequent symptom in chronic multiple sclerosis. In order to investigate the brain structures involved, magnetic resonance imaging was performed in 20 patients. Neuropsychological assessment included the WAIS and WMS subtests information, picture completion, similarities, digit span, logical memory, and paired associate learning. All patients with severely impaired memory functions (n = 5) showed bilateral lesions in the medial temporal lobe, whereas in those patients with moderate (n = 10) or no measurable impairment of memory testing (n = 5) either no lesions were seen in the medial temporal lobes or these lesions were restricted to one side. A post hoc cluster analysis strikingly confirmed these results. The differences could not be related to the age of the patients, the disease duration, or the level of education. Extensive lesions in the white matter of the frontal lobes, thinning and lining of the corpus callosum, and bilateral involvement of the anterior cingulate gyrus had no bearing on the neuropsychological results. These findings indicate that bilateral demyelination in the hippocampal regions is the most likely explanation for the impairment of anterograde memory in such patients.

Inverse and predictive modeling of seepage into underground openings.

We discuss the development and calibration of a model for predicting seepage into underground openings. Seepage is a key factor affecting the performance of the potential nuclear-waste repository at Yucca Mountain, Nevada. Three-dimensional numerical models were developed to simulate field tests in which water was released from boreholes above excavated niches. Data from air-injection tests were geostatistically analyzed to infer the heterogeneous structure of the fracture permeability field. The heterogeneous continuum model was then calibrated against the measured amount of water that seeped into the opening. This approach resulted in the estimation of model-related, seepage-specific parameters on the scale of interest. The ability of the calibrated model to predict seepage was examined by comparing calculated with measured seepage rates from additional experiments conducted in different portions of the fracture network. We conclude that an effective capillary strength parameter is suitable to characterize seepage-related features and processes for use in a prediction model of average seepage into potential waste-emplacement drifts.