Case Western Reserve University School of Medicine researchers have identified a major indicator of two deadly diseases of the heart and blood vessels: heart failure and aortic aneurysm.
The absence of the Kruppel-like Factor 15 (KLF15), when combined with stress, leads to both heart failure and aortic aneurysms. The genetic factor, KLF15, protects the heart and aorta’s ability to maintain structural and functional integrity. Patients with these diseases were found to have reduced levels of the protective gene, and in an animal study, the researchers proved that deficiency of this single gene predisposes one to these cardiovascular diseases. Furthermore, they show that KLF15 exerts its protective effects in the heart and aorta through a common molecular mechanism. Lastly, the researchers show that drugs targeting this molecular pathway can be used to treat heart failure and aortic aneurysms. The unprecedented findings are published in the April 7th online edition of Science Translational Medicine, an American Association for the Advancement of Science publication.
All the blood circulating through the human body must be pumped out by the heart and flow though the aorta. These two vital organs must maintain structural integrity in the face of mechanical and biochemical stress, otherwise lethal consequences such as heart failure, aortic aneurysms, and aortic dissection can develop. While it has been known that diseases of the heart and aorta can co-exist, for example in Marfan’s syndrome, pregnancy, aging, and growth hormone excess, the cardiovascular diseases are typically treated independently. The identification of shared molecular mechanism offers new promise for current and future treatment options.
“This is very rare to find a singular genetic factor that governs the response of the entire cardiovascular system. Our research proves KLF15 governs the shared diseases of the heart and blood vessels,” says Mukesh K. Jain, M.D., F.A.H.A., senior author of the study and Director of the Case Cardiovascular Research Institute at Case Western Reserve University and the Chief Research Officer for the Harrington Heart & Vascular Institute at University Hospitals Case Medical Center. In 2002, while at Brigham and Women’s Hospital/Harvard Medical School, Dr. Jain and his team of researchers discovered KLF15.
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Case Western Reserve University and University Hospitals are pleased to announce the awarding of a $4.7 million contract from the Defense Advanced Research Projects Agency (DARPA) to Dr. Jonathan Stamler, Director of the Institute for Transformative Molecular Medicine (ITMM).
The grant will fund development of a new class of drugs that selectively vasodilate under hypoxia and thereby enhance performance at high altitude (e.g. soldiers on mountains in Afganistan).
It is also anticipated that the grant will generate new physiologic information on high-altitude adaptation and new therapeutic interventions to treat patients suffering from conditions where oxygen delivery is impaired, including heart failure, ischemic heart disease, stroke, sickle cell disease and diabetes.
Studies will involve a transdisciplinary approach, including the Department of Anesthesia (James Reynolds) the division of Pulmonary Medicine (Kingman Stroh), and the Harrington Heart & Vascular Institute (Sahil Parikh).
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We explored the association of antibiotic-resistant phenotypes and genotypes in Acinetobacter spp with clinical outcomes and characteristics in 75 patients from a major military treatment facility. Amikacin resistance was associated with nosocomial acquisition of A baumannii, and carbapenem resistance and bla(OXA-23) were associated with the need for mechanical ventilation. The presence of bla(OXA-23) also correlated with longer hospital and ICU stay. Associations between bla(OXA-23) and complexity, duration, and changes made to antibiotic regimens also existed. Copyright 2010.
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Practicing and perfecting the art of medicine demands recognition that uncertainty permeates all clinical decisions. When delivering clinical care, clinicians face a multiplicity of potential diagnoses, limitations in diagnostic capacity, and “sub-clinical” disease identified by tests rather than by clinical manifestations. In addition, clinicians must recognize the rapid changes in scientific knowledge needed to guide decisions. Cushing’s syndrome is one of several disorders in which there may be considerable difficulty and delay in diagnosis. This article describes a current model of clinical reasoning, some of its challenges, and the application of the principles of clinical epidemiology to meet some of those challenges.
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The expansion of older population segments and the continuous increase in the incidence of non-Hodgkin’s lymphoma (NHL) makes this group of neoplasms an important and growing problem. Older NHL patients have increased risk of therapy-related toxicity as a result of age-related physiological changes and frequent co-morbidities. A functional assessment of the elderly patient is necessary to determine the likelihood of tolerating and responding to therapy. The comprehensive geriatric assessment (CGA) is one multidisciplinary tool that has been applied successfully to older cancer patients and aids in identification of subjects who will or will not benefit from anti-neoplastic treatment. Although indolent lymphomas present more frequently at advanced stage, randomized trials do not show better outcomes with early therapy, supporting close observation until specific therapeutic indications arise. Use of the monoclonal antibody rituximab as a single agent or in combination with chemotherapy improves survival and has become the standard of care in first-line treatment. Radioimmunoconjugates, bendamustine, and other monoclonal antibodies as well as novel targeted agents also are active against indolent lymphomas. Diffuse large B-cell lymphoma is an aggressive but potentially curable disease. Several trials performed exclusively in elderly patients have demonstrated improved response rates and survival with the addition of rituximab to CHOP (cyclophosphamide, doxorubicin [adriamycin], vincristine, prednisone) chemotherapy in the front-line setting. Salvage chemotherapy followed by autologous haematopoietic cell transplant (autoHCT) has been shown to have better failure-free and overall survival in randomized trials involving younger patients. Highly selected individuals up to age 70 years may attain long-term survival benefit from autoHCT, although transplant-related mortality is higher than in younger patients.
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