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  • Vulvar Cancer in the North of Israel

    Purpose. This is a population study of patients who were treated for vulvar cancer in a tertiary center in northern Israel, aimed to report clinical findings, treatment, and outcome. Methods. A retrospective chart review of all medical records of consecutive patients who were treated for vulvar cancer in the years 1993–2012 was conducted. Data extracted from the medical records included demographics, histology, size of lesion, stage of disease at diagnosis, type of treatment, radiation dose, follow-up, recurrence, and survival. Results. The study included 44 patients with a median age of 69.8 years (range, 42–93 years). Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and four were of other descent. The most common histology type was squamous cell carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II–III at time of diagnosis. Surgery was the most common primary treatment modality (54.2%). Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced stage at diagnosis were associated with increased mortality. Conclusion. Vulvar cancer is common among elderly women with co-morbidities who present in advanced disease stage; all these factors are significant for survival.
  • Rituals in Death and Dying: Modern Medical Technologies Enter the Fray

    In the absence of immortality, the human species has over the millennia developed rites and rituals to help in the passing of life to honor the person who is dying or has died or in some way demonstrate their “courage” and perseverance as well as duty even in the face of almost certain death. The centuries-old traditions of the gathering of loved ones, the chanting of prayers, the ritual religious blessings are in the process of being replaced by the “miracles” of modern medical technology.
  • Coagulation and Placenta-Mediated Complications

    Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women’s health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.
  • Pharmacology of Rasagiline, a New MAO-B Inhibitor Drug for the Treatment of Parkinson’s Disease with Neuroprotective Potential

    Rasagiline (Azilect) is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO) type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitro-gen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine. Metabolic conversion of the com-pound in vivo is by hepatic cytochrome P450-1A2, with generation of 1-aminoindan as the major me-tabolite. Rasagiline possesses no amphetamine-like properties, by contrast with the related compound selegiline (Deprenyl, Jumex, Eldepryl). Although the exact distribution of MAO isoforms in different neurons and tissues is not known, dopamine behaves largely as a MAO-A substrate in vivo, but follow-ing loss of dopaminergic axonal varicosities from the striatum, metabolism by glial MAO-B becomes increasingly important. Following subchronic administration to normal rats, rasagiline increases levels of dopamine in striatal microdialysate, possibly by the build-up of β-phenylethylamine, which is an ex-cellent substrate for MAO-B, and is an effective inhibitor of the plasma membrane dopamine trans-porter (DAT). Both of these mechanisms may participate in the anti-Parkinsonian effect of rasagiline in humans. Rasagiline possesses neuroprotective properties in a variety of primary neuronal preparations and neuron-like cell lines, which is not due to MAO inhibition. Recent clinical studies have also demon-strated possible neuroprotective properties of the drug in human Parkinsonian patients, as shown by a reduced rate of decline of symptoms over time.
  • Evolving Pandemic Diabetic Nephropathy

    The expanding impact of chronic kidney disease (CKD) due to pandemic diabetes mellitus is recounted emphasizing its epidemiology that has induced global socioeconomic stress on health care systems in industrialized nations now attempting to proffer optimal therapy for end stage renal disease (ESRD). Strategies to delay and perhaps prevent progression of diabetic nephropathy from minimal proteinuria through nephrotic range proteinuria and azotemia to ESRD appear to have decreased the rate of persons with diabetes who develop ESRD. For those with ESRD attributed to diabetes, kidney transplantation affords better survival and rehabilitation than either hemodialysis or peritoneal dialysis. It is likely that advances in genetics and molecular biology will suggest early interventions that will preempt diabetic complications including renal failure.
  • Why Do We Need Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson’s and Alzheimer’s Disorders?

    Parkinson’s disease (PD) and Alzheimer’s disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of pa-tients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources. KEY WORDS: Rasagiline multimodal drugs, antiapoptotic, neuroprotection, neurorestoration, Parkinson’s disease, Alzheimer’s disease
  • MRI-Guided Electrophysiology Intervention

    Catheter ablation is a first-line treatment for many cardiac arrhythmias and is generally performed under X-ray fluoroscopy guidance. However, current techniques for ablating complex arrhythmias such as atrial fibrillation and ventricular tachycardia are associated with sub-optimal success rates and prolonged radiation exposure. Pre-procedure 3-D magnetic resonance imaging (MRI) has improved understanding of the anatomic basis of complex arrhythmias and is being used for planning and guidance of ablation procedures. A particular strength of MRI compared to other imaging modalities is the ability to visualize ablation lesions. Post-procedure MRI is now being applied to assess ablation lesion location and permanence with the goal of identifying factors leading to procedure success and failure. In the future, intra-procedure real-time MRI, together with the ability to image complex 3-D arrhythmogenic anatomy and target additional ablation to regions of incomplete lesion formation, may allow for more successful treatment of even complex arrhythmias without exposure to ionizing radiation. Development of clinical grade MRI-compatible electrophysiology devices is required to transition intra-procedure MRI from preclinical studies to more routine use in patients.
  • The Next Revolution: Percutaneous Aortic Valve Replacement

    Aortic valve replacement (AVR) is a treatment of choice for patients with symptomatic severe aortic stenosis (AS). However, a significant proportion of these patients do not undergo surgical AVR due to high-risk features. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative for patients with severe AS who are not candidates for open-heart surgery. Since the introduction of TAVI to the medical community in 2002, there has been an explosive growth in procedures. The balloon-expandable Edwards SAPIEN valve and the self-expanding CoreValve ReValvingTM system contribute the largest patient experience with more than 10,000 patients treated with TAVI to date. Clinical out-comes have stabilized in experienced hands, with 30-day mortality less than 10%. Careful patient selection, growing operator experience, and an integrated multidisciplinary team approach contribute to notable improvement in outcomes. In the first randomized pivotal PARTNER trial, in patients with severe AS not suitable candidates for surgical AVR, TAVI compared with standard therapy, significantly improved survival and cardiac symptoms, but was associated with higher incidence of major strokes and major vascular events. The results of randomized comparison of TAVI with AVR among high-risk patients with AS for whom surgery is a viable option are eagerly awaited to provide further evidence on the applicability of TAVI in these patients.
  • Maimonides' Appreciation for Medicine

    Moses Maimonides, the illustrious medieval rabbi and philosopher, dedicated the last decade of his life primarily to medicine. His strong interest in medicine was an integral component of his religious-philosophical teachings and world view. In this paper various sources from his rabbinic writings are presented that explain Maimonides’ motivation regarding and deep appreciation for medicine: (A) The physician fulfills the basic biblical obligation to return lost objects to their owner, for with his knowledge and experience the physician can restore good health to his sick fellow human being; (B) medicine provides a unique opportunity to practice imitatio dei, as it reflects the religious duty to maintain a healthy life-style; (C) as an important natural science, medicine offers tools to recognize, love and fear God. These three aspects address man’s relationship and obligation towards his fellow man, himself and God. Biographical insights supported by additional sources from Maimonides’ writings are discussed.
  • Progress in Teaching Physician–Patient Communication in Medical School; Personal Observations and Experience of a Medical Educator

    In spite of the enormous progress of Western medicine during the past century there has not be a concomitant rise in the public’s satisfaction with the medical profession. Much of the discontent relates to problems in physician–patient communication. The multiple advantages of good communication have been clearly demonstrated by numerous careful studies. While the past few decades have witnessed much more attention given to teaching communication skills in medical schools, there are a number of factors that create new problems in physician–patient communication and counteract the positive teaching efforts. The “hidden curriculum”, the increased emphasis on technology, the greater time pressures, and the introduction of the computer in the interface between physician and patient present new challenges for the teaching of physician–patient communication.