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VE Torres 《Nephron. Experimental nephrology》2004,98(1):e1-e7
Advances in the understanding of cystogenesis and availability of animal models orthologous to human autosomal dominant polycystic kidney disease (ADPKD) and recessive polycystic kidney disease (ARPKD) will likely facilitate the development of treatments for these diseases. Proteins mutated in ADPKD and ARPKD, as well as in several animal models, are localized to renal primary cilia. These are thought to have a sensory function and contribute to the regulation of the intracellular calcium ([Ca2+]i). It seems likely that the maintenance of a differentiated renal epithelial phenotype, characterized by controlled fluid secretion and cell proliferation, requires precise functional coordination of cAMP and Ras/Raf/MEK/ERK signaling by [Ca2+]i. [Ca2+]i alterations, linked to genetic defects causing polycystic kidney disease, may hinder negative feedback mechanisms that control cAMP and Ras/Raf/MEK/ERK signaling, and result in increased fluid secretion and cell proliferation. cAMP levels, Raf kinase activities and ERK phosphorylation are increased in polycystic kidneys. There is also evidence of abnormal cross-talk between cAMP and MAPK pathways, that can be reproduced in wild-type cells by altering [Ca2+]i. While cAMP inhibits Ras-Raf-1-stimulated phosphorylation of ERK in normal kidney cells, it markedly increases B-Raf kinase activity and ERK phosphorylation in polycystic kidney cells. Treatment strategies should probably be aimed at increasing [Ca2+]i, inhibiting Ras/Raf/MEK/ERK signaling or lowering cAMP in the distal nephron and collecting duct. Vasopressin is the major adenylyl cyclase agonist in the collecting duct principal cells via a V2 receptor. OPC31260, a V2 receptor antagonist, lowers renal cAMP and markedly inhibits cystogenesis in four animal models of polycystic kidney disease, three of which are orthologous to human diseases (PCK rat, ARPKD; pcy mouse, adolescent nephronophthisis; Pkd2WS25/- mouse, ADPKD). The renal selectivity and safety profile of this class of drugs make it an excellent candidate for clinical trials. 相似文献
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Dipl.-Soz. A.-M. Schneider B. Klasen C. Jennerwein V.E. Amelung R. Thoma 《Schmerz (Berlin, Germany)》2013,27(2):166-173
Cross-sectoral clinical pathways for chronic pain patients in standard and routine care are a major challenge for the German healthcare system. The Algesiologikum group has developed such clinical pathways including an essential infrastructure. Cooperation partners of the Algesiologikum group are two outpatient medical care units, one neurosurgery practice and four hospitals. In the outpatient sector as well as in the inpatient sector the Algesiologikum group provides a multidisciplinary team caring for chronic pain patients. The range of treatment in the hospitals includes multimodal, invasive and surgical pain therapy. The present report illustrates possibilities and frontiers of the Algesiologikum concept based on all patients treated since 2009. 相似文献
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Alexander?K?nig Lisa?Amelung Marco?Danne Ullrich?Meier Johannes?LemckeEmail authorView authors OrcID profile 《European spine journal》2017,26(10):2565-2572
Objective
Despite the awareness and familiarity of almost every medical professional with the cauda equine compression syndrome (CES), risk factors for a poor prognosis of the disease remain elusive. Even the relationship between subsequent outcome and the time elapsed from the time of appearance of symptoms to surgery taking place remain obscure. The aim of our study, therefore, was to analyze a relatively large population of our own patients studied consecutively, to identify outcome predictors for CES and to propose a clinical score for CES symptoms (Berlin CES score).Methods
We screened the hospital’s electronic database retrospectively for patients admitted with CES between 2001 and 2010. Since our hospital is a superregional trauma center with standardized emergency room procedures, all patients included in the study underwent the same routine. Using baseline data, we analyzed the following parameters: duration of symptoms, period of time between diagnosis and imaging, respectively, surgery; pre- and postoperative pain, motor deficits, reflex changes, urinary and bowl dysfunctions, reduced anal wink, saddle anesthesia, genital or perianal sensations and residual urine. The semi-quantitative assessment of the neurological outcome was performed by application of the Berlin CES score.Results
Surprisingly, we were not able to identify any single parameters that could reliably predict the outcome of the disease. We were able to show statistically significant correlations between a high preoperatively Berlin CES score (i.e., a weighted summation of bladder dysfunction, rectal dysfunction, genital sensation, perianal sensation, rectal tone and saddle anesthesia) and a poor outcome regarding the postoperative existence of perianal (p < 0.001) and genital (p = 0.001) hypoesthesia, as well as reduced rectal tone (p = 0.0047). There was no significant interference of bladder or bowel function. Further analysis, in which we considered the time between diagnosis and surgery, revealed that both patients operated within 24 h and after 48 h could benefit from the intervention. Consequently, we were not able to show a correlation between speed of surgical treatment and outcome.Conclusion
Although we analyzed a relatively large cohort, we were not able to identify single parameters that were capable of reliably predicting the outcome of patients with CES. Nonetheless, we were able to show that consideration of multiple parameters of symptomatology would enable an improvement in making a prognosis. In conclusion, we propose establishing a simple semi-quantitative clinical score of the main symptoms of CES.67.
Experts from different areas strongly criticize the current level of palliative care in Germany, both inpatient and home care services. Apart from the experts' opinions, little is known in this context about the perspectives of hospital doctors working in different disciplines, such as surgery, internal medicine, gynaecology or anaesthesia. These doctors presumably treat many incurably ill patients with palliative care needs, but they usually have very little experience in palliative medicine. Their attitudes are particularly important because they are affected by the criticism and by future improvement strategies. To study their viewpoints, questionnaire surveys in five hospitals in the federal state of Brandenburg were performed, with 203 (69%) physicians participating. The results showed that the level of palliative care in hospitals was graded better than in the home care setting. Main needs for improvement were seen in the psychosocial support services and in the co-operation with outpatient services. In [corrected] the hospital physicians' view, palliative nursing care was of a higher standard than medical aspects [corrected] of care [corrected] The physicians showed great interest in improving their knowledge of [corrected] palliative care and in new specialist palliative care services. The conclusions were that three main strategies for improvement should be embarked on: (1) the establishment of integrated care systems to overcome financial and structural barriers between in- and outpatient care; (2) the establishment of further specialist palliative care services (eg, hospital-based palliative care teams); and (3) better education in palliative medicine. 相似文献
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Sara Y. Tartof Fagen Xie Ruchi Yadav Karen J. Wernli Emily T. Martin Edward A. Belongia Manjusha Gaglani Richard K. Zimmerman H. Keipp Talbot Natalie Thornburg Brendan Flannery US Flu VE Network Investigators 《Influenza and other respiratory viruses》2023,17(5):e13143
Background
We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI).Methods
During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status.Results
Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%–99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%–76%) against Omicron; VE against Delta could not be estimated.Conclusions
Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants. 相似文献69.
MT. Corbally P. Naughten VE. Boston RJ. Fitzgerald 《Pediatric surgery international》1990,5(5):371-374
We report two cases of sequestration of a segment of intestinal mucosa in the perineal area. In one patient this was associated with a mildly ectopic anus. No abnormalities were identified in the bladder, urethra, vagina, or rectum. The lesions were treated by excision following complete anatomical mapping. 相似文献
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