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181.
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M Reincke E Fischer S Gerum K Merkle S Schulz A Pallauf M Quinkler G Hanslik K Lang S Hahner B Allolio C Meisinger R Holle F Beuschlein M Bidlingmaier S Endres;Participants of the German Conn's Registry-Else Kröner-Fresenius-Hyperaldosteronism Registry 《Hypertension》2012,60(3):618-624
In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls. 相似文献
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In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties. 相似文献
186.
Herrmann H Cerny-Reiterer S Gleixner KV Blatt K Herndlhofer S Rabitsch W Jäger E Mitterbauer-Hohendanner G Streubel B Selzer E Schwarzinger I Sperr WR Valent P 《Haematologica》2012,97(2):219-226
Background
CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias.Design and Methods
We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined.Results
As assessed by flow cytometry, stem cell-enriched CD34+/CD38−/CD123+ leukemic cells expressed significantly higher levels of CD33 compared to normal CD34+/CD38− stem cells. Moreover, highly enriched leukemic CD34+/CD38− cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34+/CD38− cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells.Conclusions
CD33 is expressed abundantly on immature CD34+/CD38− stem cells and may serve as a stem cell target in chronic myeloid leukemia. 相似文献187.
Udo Dannlowski Harald Kugel Franziska Huber Anja Stuhrmann Ronny Redlich Dominik Grotegerd Katharina Dohm Christina Sehlmeyer Carsten Konrad Bernhard T. Baune Volker Arolt Walter Heindel Pienie Zwitserlood Thomas Suslow 《Human brain mapping》2013,34(11):2899-2909
Major depression has been repeatedly associated with amygdala hyper‐responsiveness to negative (but not positive) facial expressions at early, automatic stages of emotion processing using subliminally presented stimuli. However, it is not clear whether this “limbic bias” is a correlate of depression or represents a vulnerability marker preceding the onset of the disease. Because childhood maltreatment is a potent risk factor for the development of major depression in later life, we explored whether childhood maltreatment is associated with amygdalar emotion processing bias in maltreated but healthy subjects. Amygdala responsiveness to subliminally presented sad and happy faces was measured by means of fMRI at 3 T in N = 150 healthy subjects carefully screened for psychiatric disorders. Childhood maltreatment was assessed by the 25‐item childhood trauma questionnaire (CTQ). A strong association of CTQ‐scores with amygdala responsiveness to sad, but not happy facial expressions emerged. This result was further qualified by an interaction of emotional valence and CTQ‐scores and was not confounded by trait anxiety, current depression level, age, gender, intelligence, education level, and more recent stressful life‐events. Childhood maltreatment is apparently associated with detectable changes in amygdala function during early stages of emotion processing which resemble findings described in major depression. Limbic hyper‐responsiveness to negative facial cues could be a consequence of the experience of maltreatment during childhood increasing the risk of depression in later life. Limitation: the present association of limbic bias and maltreatment was demonstrated in the absence of psychopathological abnormalities, thereby limiting strong conclusions. Hum Brain Mapp 34:2899–2909, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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Katharina Braun Katja Seidel Romy Holetschka Nicole Groeger Gerd Poeggel 《Brain structure & function》2013,218(4):859-872
The impact of paternal care on the development of catecholaminergic fiber innervations in the prefrontal cortex, nucleus accumbens, hippocampus and the amygdala was quantitatively investigated in the biparental Octodon degus. Two age (juvenile, adult) and rearing groups: (1) degus reared without father and (2) degus raised by both parents were compared. Juvenile father-deprived animals showed significantly elevated densities of TH-immunoreactive fibers in all analyzed regions, except in the orbitofrontal cortex, as compared to biparentally reared animals. This difference between the two rearing groups was still evident in adulthood in the prelimbic and infralimbic cortices and in the hippocampal formation. Interestingly, the elevated TH fiber density in both nucleus accumbens subregions was reversed in adulthood, i.e. adult father-deprived animals showed strongly reduced TH fiber densities as compared to biparentally reared animals. We show here that paternal care plays a critical role in the functional maturation of catecholaminergic innervation patterns in prefrontal and limbic brain circuits. 相似文献
190.
Katharina Bücher Claudia Neumann Elisabeth Thiering Reinhard Hickel Jan Kühnisch 《Clinical oral investigations》2013,17(5):1311-1318