Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Transurethral collagen injection for treatment of stress urinary incontinence

Summary Minimally invasive treatment of urinary incontinence has become a subject of major interest in recent years. We examined the use of transurethral collagen injection for incontinence treatment. A total of 48 patients were selectet for this procedure from April 1993 to February 1997 – 26 male patients (19 post-RPX incontinence and 7 post-TUR incontinence) and 22 female patients (all after previous incontinence surgery) were treated by injection of collagen into the continence region. The whole group underwent an average of 1.8 sessions, and a mean collagen injection volume of 14.5 ml was delivered per session. Mean follow-up was 9.2 months. Of the female population, 68.2 % were cured or greatly improved. In the male population only 47.3 % of the post-RPX patients and 6/7 of the post-TUR patients benefited from the procedure. In males, treatment outcome depends on the degree of pretreatment incontinence, because all grade III incontinence patients did worse. Therefore we conclude: transurethral collagen injection is an interesting method in the treatment of urinary incontinence if proper patient selection is assured.      

Nonlinear excitation profiles for three-dimensional inflow MR angiography

An RF excitation pulse for three-dimensional (3D) time-of-flight (TOP) MR angiography (MRA) with a nonlinear excitation profile was numerically calculated under the condition of uniform vessel signal across the excitation volume (slab), and the superiority of the optform pulse as compared with conventional RF pulses and TONE pulses was demonstrated. For this purpose we acquired MRA of the lower leg and of the carotid and vertebral arteries in a 30-year-old healthy volunteer. Although the flow velocity ranges in these two anatomic locations are different by about a factor of 10, in both cases the corresponding optform pulse provided the best signal homogeneity at the highest level.     

Prevention of hepatitis B virus recurrence after liver transplantation

Abstract:  Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.     

Biexponential diffusion tensor analysis of human brain diffusion data.

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas.     

Mercury from gold minings in the Pantanal of Pocone (Mato Grosso,Brazil)

The Pocone gold minings are situated in the Bento Gomes River Basin, at the border of the Pantanal of Mato Grosso. Gold-bearing quartz veins are removed from the subsoils, milled with water, centrifuged and the heavier fraction is subsequently mixed with mercury for gold separation. The gold mining activities caused a very intensive landscape change, threatening many environmental processes like sediment control and storage and recycling capacity of mercury. Cold Vapor Atomic Fluorescence System (CVAFS) was used to determinate total mercury in water, suspended material and sediments from Bento Gomes River, sampled monthly for 1 year. Apart from the fact that mercury concentrations are low in water and bottom sediments, they are slightly higher in relation to background levels measured in the area. The concentration in suspended material is also lower than other rivers with gold mining activities, but the floodplains of the Bento Gomes River act as mercury sinks. Therefore, the discharge of mercury into the Pantanal floodplain should be avoided, in spite of actual contamination of the system being very low.     

Subjective work noise: A major risk factor in myocardial infarction

Summary The relationship between subjective work noise exposure and the risk of myocardial infarction (MI) was assessed in a population based casecontrol study. 395 MI patients (31–65 years) were compared to 2148 controls from a random population sample with the same age/sex distribution. The relative risk (RR) for MI—adjusted for control variables (smoking, age, social status, etc.)—was found to increase significantly and steadily with noise category. Subjective work noise exposure was the second greatest risk factor for MI after smoking. Possible bias due to overreporting of subjective noise exposure is discussed. Interdisciplinary studies on the relationship between cardiovascular diseases and workrelated stressors including subjective and objective noise assessment are needed to quantify the risk of MI due to work noise.

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Zusammenfassung In einer bevölkerungsbezogenen Fall-Kontroll-Studie wurde der Zusammenhang zwischen der subjektiven Arbeitslärmbelastung und dem Herzinfarktrisiko untersucht. 395 Herzinfarktpatienten im Alter von 31 bis 65 Jahren wurden mit 2148 Kontrollpersonen aus einer Zufallsstichprobe mit gleicher Alters- und Geschlechtsverteilung verglichen. Das relative Risiko für Herzinfarkt—adjustiert bezüglich mehrerer Einflussvariablen wie Rauchen, Alter, Sozialstatus usw.—stieg signifikant und monoton mit der Arbeitslärmbelastung an. Die subjektive Arbeitslärmbelastung erwies sich als der zweitwichtigste Risikofaktor für Herzinfarkt nach dem Rauchen. Mögliche Fehler wie z.B. Überbewertung der subjektiven Lärmbelastung werden diskutiert. Interdisziplinäre Studien zum Zusammenhang zwischen kardiovaskulären Erkrankungen und arbeitsplatzbezogenen Stressoren mit Erfassung der subjektiven und der objektiven Lärmbelastung sind notwendig, um das Herzinfarktrisiko durch Arbeitslärm zu quantifizieren.

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Résumé Le rapport entre la perception subjective de bruit gênant et le risque d'infarctus du myocarde (IM) fait l'objet d'une étude comparative portant sur 395 malades (IM) âgés de 31 à 65 ans et 2148 cas témoins sortis d'un sondage aléatoire parmi la population générale tout en assurant la même distribution d'âge et de sexe. II s'avère que—après la rectification exigée par les variables telles que consommation de tabac, âge, couche sociale, etc.—le risque relatif (RR) de IM augmente de manière significative et constante avec le gêne causé par le bruit au lieu de travail. Pour le IM, la perception subjective du bruit vécu au lieu de travail est le deuxième facteur de risque, son importance n'étant dépassée que par le tabagisme. Les auteurs discutent l'incidence possible d'une notification exagérée de bruit gênant. Afin de calculer le risque d' IM attributable au bruit perçu au lieu de travail, des études interdisciplinaires devraient être réalisées pour examiner les liens entre les maladies cardiovasculaires et les stresseurs liés au travail, y compris l'évaluation subjective et objective du bruit.