Polymorphisms of the hypoxia-inducible factor 1 gene and peripheral artery disease

Hypoxia-inducible factor 1 (HIF1) is a key regulator of angiogenesis and is involved in inflammation, which are two important features of the pathogenesis of peripheral artery disease (PAD). The gene for the HIF1-alpha subunit (HIF1A) carries two common mis-sense mutations, P582S (C>T, rs11549465) and A588T (G>A, rs11549467), which both have been related to increased trans-activation capacity of HIF1-alpha. The aim of the present study was to analyze the role of these polymorphisms in PAD. The study was designed as a case-control study including 917 patients with documented PAD and 969 control subjects. HIF1A genotypes were determined by exonuclease (TaqMan) assays. HIF1A P582S genotype frequencies were not significantly different between PAD patients (PP 82.2%; PS 16.5%; SS 1.3%) and control subjects (83.2%; 15.3%; 1.5%; p = 0.72). Similarly, HIF1A A588T genotype frequencies did not differ significantly between PAD patients (AA 95.9%; AT 4.1%) and control subjects (AA 96.8%; AT 3.2%; p = 0.28). In a multivariate logistic regression analysis including age, sex, smoking, diabetes, arterial hypertension and hypercholesterolemia, neither the HIF1A P582S polymorphism (odds ratio: 1.26; 95% confidence interval 0.92-1.74; p = 0.16) nor the A588T polymorphism (odds ratio: 1.17; 95% confidence interval 0.59-2.35; p = 0.66) was significantly associated with the presence of PAD. Both polymorphisms were furthermore not associated with age at onset of PAD, Fontaine stage of the disease or the ankle/brachial index of patients. We conclude that functional polymorphisms in the HIF1A gene do not contribute to susceptibility to PAD.     

Single Tc99m Sestamibi injection,double acquisition gated SPECT after stress and during low-dose dobutamine infusion: a new suggested protocol for evaluation of myocardial perfusion

Background The ability of low dose dobutamine (LDD) has been established in exploiting the reserved contractility of ischemic myocardium. This study was designed to assess the value of a new protocol, with an additional stress imaging during LDD infusion instead of the rest images, for evaluation of coronary artery disease (CAD) and perfusion reversibility. Methods A total of 51 patients (42 men, 9 women; 57.2 ± 11.3 years) were included in the study and underwent three sequential steps of imaging; the first step-stress gated SPECT with Tc-99m sestamibi, immediately followed by the second step-gated SPECT during constant infusion of 7.5 μg/kg/min dobutamine and finally the third step-rest phase scan following trinitroglycerine administration in the next day. The findings were interpreted using the images in three sets of display; first vs. second step-single injection-double acquisition gated SPECT before and during LDD (SIDAGS-LDD), first vs. third step-standard stress/rest protocol, and only first step-gated stress-only SPECT. In all cases, the Visual perfusion index of each protocols were calculated by summating the premeditated 5-point scale (5: normal, 4: completely reversible, 3: partially reversible, 2: nontransmural fixed and 1: transmural fixed defects) of 17 standard myocardial segments. The accuracy as well as the correlation and agreement of protocols for detecting perfusion abnormality and corresponding reversibility were statistically analyzed. Results Calculated sensitivity, specificity, positive predictive value, negative predictive value and accuracy regarding the presence of CAD in both SIDAGS-LDD and standard protocols were 90.9% (40/44), 71.4% (5/7), 95.2% (40/42), 55.6% (5/9) and 88.2% (45/51), respectively. The extent and localization of perfusion abnormality with the new protocol were correlated well with standard method. The estimation of reversibility, however, was considerably improved by SIDAGS-LDD, especially in those with history of previous myocardial infarction (MI). Conclusion Our proposed protocol demonstrates good correlation and agreement with standard method and even is superior in some cases especially for estimation of viability after MI. Regarding no need for the rest phase radiotracer injection and imaging, this protocol can be more convenient (except the need for close monitoring of the patient during LDD infusion), less time-consuming, less expensive and moreover with less radiation burden to the patients and personnel.     

Applications of virtual reality for pain management in burn-injured patients

The pain associated with burn injuries is intense, unremitting and often exacerbated by anxiety, depression and other complicating patient factors. On top of this, modern burn care involves the repetitive performance - often on a daily basis for weeks to months - of painful and anxiety-provoking procedures that create additional treatment-related pain, such as wound care, dressing changes and rehabilitation activities. Pain management in burn patients is primarily achieved by potent pharmacologic analgesics (e.g., opioids), but is necessarily complemented by nonpharmacologic techniques, including distraction or hypnosis. Immersive virtual reality provides a particularly intense form of cognitive distraction during such brief, painful procedures, and has undergone preliminary study by several research groups treating burn patients over the past decade. Initial reports from these groups are consistent in suggesting that immersive virtual reality is logistically feasible, safe and effective in ameliorating the pain and anxiety experienced in various settings of post-burn pain. Furthermore, the technique appears applicable to a wide age range of patients and may be particularly well-adapted for use in children, one of the most challenging populations of burn victims to treat. However, confirmation and extension of these results in larger numbers of patients in various types of burn-related pain is necessary to more clearly define the specific benefits and limitations of virtual reality analgesia in the burn care setting.     

Prospects of embryonic stem cells in treatment of hematopoietic disorders

Cellular therapies derived from embryonic stem (ES) cells have gained a renewed interest with the experimental demonstration that an embryonic stem cell lines can be established from human blastocyst-stage embryos and prompted to differentiate into almost all types of cells present in the body including hematopoietic cells. Hematopoiesis is a series of cellular processes whereby short-lived mature blood cells are continuously replenished from a pool of rare pluripotential hematopoietic stem cells, in a highly orchestrated process. Aberrances in this intricate process may lead to a malignancy of essential blood-forming organs, causing diseases such as leukemia, aplastic anemia, lymphoma, myelodysplasia and myeloproliferative disorders. Embryonic stem cells show great potential and it may be technologically feasible to transplant differentiated ES cells and to cure various kinds of blood disorders. Understanding the biology of ES cell derived hematopoiesis may lead to the development of co-transplantation protocols that will result in a decreased morbidity and mortality by providing safer and simpler transplantation procedures for patients with malignant and non-malignant conditions. The potential utility of ES cells for gene therapy, tissue engineering and the treatment of a wide variety of currently untreatable diseases is simply too essential to ignore, however, our knowledge and ability to deliver these forms of therapy in a safe and efficient manner requires additional advances in the understanding of the basic biology of ES cells. In this article, we will discuss the factors and methodologies responsible for the differentiation of ES cells into hematopoietic progenitors and their potential to treat different blood related diseases.     

Abdominal aorta screening during transthoracic echocardiography

OBJECTIVE: The purpose of this study was to investigate the use of a modified abdominal ultrasound examination, performed as an extension of a routine diagnostic transthoracic echocardiography. This modified examination is arguably a simple, safe, quick, and accurate way to identify patients with abdominal aortic aneurysm (AAA). METHODS: This prospective study, conducted over a 6-month period, sought to obtain the maximum diameter of the abdominal aorta through a routine transthoracic echocardiography. RESULTS: In 1285 patients, 1175 abdominal aortas were visualized (91.4%). The prevalence of AAA was 3.8% (45/1175), which increased with age. Six patients, who had diameters more than 5 cm, were referred to a surgeon. In the patients with AAA, left ventricular hypertrophy and left ventricular dilatation were more frequent. CONCLUSION: Routine screening of the abdominal aorta during transthoracic echocardiography is recommended on account of the prevalence of AAA in unselected and, in particular, older patients.     

Canine visceral leishmaniasis: relationships between oxidative stress, liver and kidney variables, trace elements, and clinical status

The aim of this study was to investigate the role of oxidative stress in the pathology of canine visceral leishmaniasis (CVL). We therefore studied the relationships between oxidative stress markers, liver and kidney variables, trace elements, and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [asymptomatic (AD, n?=?14) and symptomatic (SD, n?=?16)] were assessed and compared with a group of non-infected control dogs (CD, n?=?30). A significant decrease (p?相似文献   

Mechanisms underlying cortical activity during value-guided choice

When choosing between two options, correlates of their value are represented in neural activity throughout the brain. Whether these representations reflect activity that is fundamental to the computational process of value comparison, as opposed to other computations covarying with value, is unknown. We investigated activity in a biophysically plausible network model that transforms inputs relating to value into categorical choices. A set of characteristic time-varying signals emerged that reflect value comparison. We tested these model predictions using magnetoencephalography data recorded from human subjects performing value-guided decisions. Parietal and prefrontal signals matched closely with model predictions. These results provide a mechanistic explanation of neural signals recorded during value-guided choice and a means of distinguishing computational roles of different cortical regions whose activity covaries with value.     

Quantitative proteomic profiling identifies protein correlates to EGFR kinase inhibition

Clinical oncology is hampered by lack of tools to accurately assess a patient's response to pathway-targeted therapies. Serum and tumor cell surface proteins whose abundance, or change in abundance in response to therapy, differentiates patients responding to a therapy from patients not responding to a therapy could be usefully incorporated into tools for monitoring response. Here, we posit and then verify that proteomic discovery in in vitro tissue culture models can identify proteins with concordant in vivo behavior and further, can be a valuable approach for identifying tumor-derived serum proteins. In this study, we use stable isotope labeling of amino acids in culture (SILAC) with proteomic technologies to quantitatively analyze the gefitinib-related protein changes in a model system for sensitivity to EGF receptor (EGFR)-targeted tyrosine kinase inhibitors. We identified 3,707 intracellular proteins, 1,276 cell surface proteins, and 879 shed proteins. More than 75% of the proteins identified had quantitative information, and a subset consisting of 400 proteins showed a statistically significant change in abundance following gefitinib treatment. We validated the change in expression profile in vitro and screened our panel of response markers in an in vivo isogenic resistant model and showed that these were markers of gefitinib response and not simply markers of phospho-EGFR downregulation. In doing so, we also were able to identify which proteins might be useful as markers for monitoring response and which proteins might be useful as markers for a priori prediction of response.