Participation of the anterior hypothalamus in the baroreceptor reflex

1. On the basis of discrete electrical stimulation in the pre-optic region and anterior hypothalamus of anaesthetized cats, a depressor area has been defined, stimulation of which elicits a fall of arterial blood pressure of 30-50 mm Hg and a bradycardia of some 25%, caused by inhibition of sympathetic vasomotor tone and by vagal activation respectively. These are accompanied by a reduction in rate and depth of respiration.2. The depressor area, from which this pattern of response is elicited, lies ventral and caudal to the anterior commissure, and extends caudally in the dorsal hypothalamus, dorsal to the fornix.3. The pattern of response elicited from identified points in the depressor area was shown to be indistinguishable from that to baroreceptor afferent stimulation.4. A lesion destroying the hypothalamic depressor area bilaterally reduced the response to baroreceptor afferent stimulation. Lesions in the medullary depressor area which spared a large part of the nucleus of the tractus solitarius also reduced, but did not abolish, the baroreceptor reflex response. The two lesions combined abolished the reflex.5. It is concluded that the whole brain-stem depressor area, from the hypothalamus through the mid-brain to the medulla, constitutes a functional unit which integrates the response to baroreceptor afferent stimulation.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Internet teleconferencing method for telepathology consultations from lung and heart transplant patients

Current Internet-based teleconferencing techniques allow a referring pathologist to transmit real-time images from a microscope to a consultant, while maintaining a verbal conversation using Internet telephony. In our study, 50 randomly selected transbronchial biopsies from lung allograft recipients and 58 randomly selected endomyocardial biopsies from heart transplant patients were diagnosed by consultant pathologists using Internet-based teleconferencing methods. The referring pathologists acquired the real-time video images from the biopsies using a light microscope equipped with a phototube adapter and a video camera. The consultant pathologists viewed the processed images on a video monitor at 800 x 600 resolution, using a standard microcomputer equipped with Netmeeting software, and directed the referring pathologist to move the slide under the microscopy and/or change image magnification. The validity of telepathology diagnoses was assessed with kappa coefficients. Consultations were completed in 5 to 15 minutes per case. Sound transmission was unreliable, and in approximately 25% of consultations the referring pathologist needed to "call back" to reestablish verbal communication. In all but 2 transbronchial biopsies there was agreement between the original diagnosis and the diagnosis by telepathology (kappa = 0.92). In 48 of 58 endomyocardial biopsies there was concordance between the 2 diagnoses (kappa = 0.692). Only 3 out of 10 of these discrepancies were clinically significant (kappa = 0.897). Internet-based teleconferencing techniques provide effective and relatively inexpensive tools for real time telepathology consultations. The technology is probably best suited for the study of small specimens from patients that require rapid diagnosis by a consultant.     

Ultimate tensile strength of dentin: Evidence for a damage mechanics approach to dentin failure

Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino-enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage-mechanics approach to studies of dentin failure.     

The pontomedullary area integrating the defence reaction in the cat and its influence on muscle blood flow

1. In anaesthetized cats the effects were investigated of electrical stimulation of regions in the caudal mesencephalon, pons and medulla on muscle blood flow, skin blood flow and arterial blood pressure.2. It was found that within the dorsal part of the well known pressor area there is a narrow strip, 2.5 mm lateral from the mid line, starting ventral to the inferior colliculus and ending in the medulla close to the floor of the IV ventricle, from which vasodilatation in skeletal muscles is selectively obtained. This strip is quite separate from the more ventral, efferent pathway for active vasodilatation running from the hypothalamic and rostral mesencephalic ;defence centre'.3. As in the case of the hypothalamic and rostral mesencephalic ;defence centre', the muscle vasodilatation obtained from the caudal strip is accompanied not only by a rise of arterial blood pressure, but also by tachycardia, vasoconstriction in the skin, pupillary dilatation and piloerection.4. Stimulation, restricted to the caudal strip, via implanted electrodes in unanaesthetized animals, produced a behavioural response resembling the defence reaction. The strip, therefore, is probably a caudal extension of the ;defence centre'.5. Unlike the vasodilatation elicited from the more rostral part of the ;defence centre' in the hypothalamus and mesencephalon, the muscle vasodilatation obtained on stimulation of the caudal strip was resistant to atropine, but was blocked by guanethidine.6. It is suggested that during naturally occurring defence reactions in the normal animal the ponto-medullary area is activated together with the hypothalamo-mesencephalic area, inhibition of vasoconstrictor tone then accompanying activation of the vasodilator nerve fibres in skeletal muscle.     

AMPK调节骨骼肌细胞GLUT4基因表达的机制研究

腺苷酸活化蛋白激酶(AMPK)能调节运动/肌肉收缩所引起的骨骼肌细胞葡萄糖转运蛋白4(GLUT4)基因的表达,但至今它的调节机制不清.研究显示在非运动刺激引起的细胞信号事件中由组蛋白去乙酰化酶(HDACs)以及组蛋白乙酰化酶(HATs)控制的组蛋白乙酰化状态是调节基因表达的重要机制,所以我们假设AMPK信号途径是通过征用HDACs中的HDAC5(在骨骼肌细胞内高表达)来实现对运动/肌肉收缩引起的GLUT4基因表达控制.细胞分为正常浓度葡萄糖对照组(NGLU组)、正常浓度AICAR组(NGLU AICAR组)、高浓度对照组(HGLU组)、高浓度AICAR组(HGLU AICAR组).用5 mmol/L和20 mmol/L葡萄糖浓度培养骨骼肌细胞后,NGLU AICAR组和HGLU AICAR组与肌肉收缩模拟信号刺激5-氨基-4-甲酰胺咪唑核糖核苷酸(AICAR)孵育.AICAR能激活NGLU组骨骼肌细胞AMPKα2、减少骨骼肌细胞核HDAC5蛋白、促使HDAC5与骨骼肌细胞加强因子(MEF2)蛋白分离和上调GLUT4基因的表达;相反,高浓度葡萄糖延迟由AICAR引起的AMPKα2磷酸化、AMPKα2向细胞核转入、HDAC5向细胞核转出和GLUT4基因的表达.实验结果说明在不同葡萄糖浓度下的骨骼肌细胞GLUT4基因表达变化都对应着上游AMPK蛋白和下游HDAC5蛋白的变化,AMPK可能是征用转录抑制子HDAC5来调节MEF2的活性而达到控制肌肉收缩所引起的GLUT4基因表达.     

The impact of decentralisation on the performance of health care systems: a non-linear relationship

The European Journal of Health Economics - This paper examines the role of institutions—notably the degree of administrative decentralisation across levels of government—in health care...     

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer

ContextMolecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.ObjectiveTo perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).Evidence acquisitionThe review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446–52) and American Urology Association (AUA) criteria.Evidence synthesisIn total, 42 studies and 30 407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n = 12 141), prospective registries (n = 17 053), and prospective and post hoc randomized trial analyses (n = 1213). In 32 studies (n = 12 600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n = 8543). GC use changed the management in active surveillance (number needed to test [NNT] = 9) and postprostatectomy (NNT = 1.5–4) settings in five studies (n = 4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.ConclusionsConsistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.Patient summaryIn this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.     

Impact of Compensated Cirrhosis Etiology on Postoperative Outcomes Following Total Knee Arthroplasty

BackgroundCirrhotics often demonstrate worse outcomes than their non-cirrhotic counterparts following orthopedic surgery; however, there are limited arthroplasty-focused data on this occurrence. Additionally, variances in postoperative outcomes among the different etiologies of cirrhosis have not been well described. The aim of this study is to evaluate the effect compensated cirrhosis had on postoperative outcomes following elective total knee arthroplasty (TKA).MethodsIn total, 1,734,568 patients who underwent primary TKA from 2006 to 2013 were identified using the Medicare Claims Database. Patients were divided into those with a history of compensated cirrhosis and those with no history of liver disease. Subgroup analysis was performed based on the etiology of cirrhosis. Multivariate logistic regression was used to evaluate postsurgical outcomes of interest.ResultsCirrhotic patients had higher risk of developing disseminated intravascular coagulation (odds ratio [OR] 2.76, P = .003), encephalopathy (OR 3.00, P < .001), and periprosthetic infection (OR 1.79, P < .001) compared to controls. Following subgroup analysis, alcoholic cirrhotics had high risk of periprosthetic infection (OR 2.12, P < .001), fracture (OR 3.28, P < .001), transfusion (OR 2.45, P < .001), and encephalopathy (OR 7.34, P < .001) compared to controls. Viral cirrhosis was associated with an increase in 90-day charges ($14,941, P < .001) compared to controls, while cirrhosis secondary to other causes was associated with few adverse outcomes compared to controls.ConclusionLiver cirrhosis is an independent risk factor for increased perioperative morbidity and financial burden following TKA. Cirrhosis due to etiologies other than viral infections and alcoholism are associated with few adverse outcomes. Surgeons should be aware of these complications to properly optimize postoperative management.