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  • Toward Becoming an Accomplished Physician: Maimonides versus Galen

    Although Maimonides stated that perfection in the medical art, both in theoretical and in practical expertise, is very difficult to achieve, he did not accept Galen's opinion, i.e. that perfection is beyond human capability. Any person seeking intellectual perfection should, according to Maimonides' view, be fully trained in logic, in the natural sciences, and in theology. A physician is moreover requested to study and memorize basic medical literature; he must consider each patient as a sick individual, without neglecting the patient's psychological disposition; and he should aim at inspiring confidence and trust, not only to his patient, but also to the latter's environment. Even when feeling competent and trustworthy, the physician should not be conceited; here Maimonides insists on offering his personal experience, in a quite impressive way. This approach of Maimonides to the practice of medicine should be considered, even today, as a valuable incentive for patient-oriented medical education, as already expressed in the late eleventh century.
  • Patient-Centered Bedside Education and Traditional Jewish Law and Ethics

    Background—Bedside rounds have long been a time-honored component of medical education. Recently, there have been various recommendations that residency training programs further incorporate bedside teaching into clinical curricula. Objectives—To compare these current attitudes regarding bedside education with the position of traditional Jewish law and ethics. Methods—Relevant medical journal articles and traditional Jewish sources were reviewed. Results—Halakha (the corpus of traditional Jewish law and ethics) gives greater focus to a patient-centered rather than student-centered bedside education experience. Conclusion—Residency training programs should give greater consideration to the importance of a patient-centered bedside education experience.
  • The Future in Craniofacial Surgery: Computer-Assisted Planning

    Advancements in computers, prototyping, and imaging, especially over the last 10 years, have permitted the adoption of three-dimensional imaging protocols in the health care field. In this article, the authors present an integrated simulation system for craniofacial surgical planning and treatment. Image fusion technology, which involves combining different imaging modalities, was utilized to create a realistic prototype and virtual image that can be manipulated in real time. The resultant data can then be shared over the Internet with distantly located practitioners.
  • First-in-Human Phase 1 Studies in Oncology: The New Challenge for Investigative Sites

    Phase 1 first-in-human studies with anti-cancer products differ from other phase 1 studies in that they are evaluated in patients rather than healthy volunteers. The rationale design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients. Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies. Consequently, the conduct of phase 1 clinical trials in oncology requires changes. Corresponding education with particular focus on phase 1 trials and on the complex drug development process needs to be an integrated part of the medical oncology curriculum for physicians and nursing staff. This is a crucial element for institutions to remain or become clinical research sites for phase 1 studies, and to participate in the drug development process of novel anti-cancer compounds in the future.
  • The Great Obstetrical Syndromes and the Human Microbiome - A New Frontier

    Over the last two decades, advanced molecular genetics technology has enabled analysis of complex microbial communities and the study of microbial genomics. Interest has grown in characterizing the microbiome, defined as a collective microbial community and its extensive genome, as a clue to disease mechanisms. “The Human Microbiome Project,” sponsored by the NIH Common Fund, was established to characterize the pathology-associated human microbiome in nasal passages, oral cavities, skin, the gastrointestinal tract, and the urogenital compartment. In particular, characterization of urogenital microbiota may elucidate etiologies of complex obstetrical syndromes and factors in fetal development that define risk for pathology in adulthood. This article summarizes recent findings defining the microbiome associated with the female urogenital compartment in child-bearing age women. We also describe our analysis of microbiome samples from the oral, vaginal, and rectal compartments in a cohort of pregnant women. Findings present technical considerations in the characterization of microbial diversity and composition associated with gestational diabetes as a model pregnancy-associated pathology.
  • Tell Me What You Eat and I Will Tell You Your Sociotype: Coping with Diabesity

    The term sociotype has been introduced to describe the dynamic relationship of an individual with his/her social environment throughout life. The sociotype is a conceptual framework to highlight, in addition to bio-medical pathways, the psycho-social and environmental factors necessary to understand responses to life stresses and patient self-management for chronic illness. The sociotype interacts with genotype expression through mate selection and metabolic programming, and with the phenotype to determine adaptation throughout life from birth to old age. Following on the work of Antonovsky, Engel, and McEwen, and others in the life and social sciences, the sociotype details and expands the many factors generally included in the environmental influences on a person’s life identified here as the domains of health, relationships, and environment. Physiological mediators for sociotypic influences include: adrenal steroids and the sympathetic nervous system (allostatic load), and oxytocin (social neuroscience). The biological pathways are multiple through nutrition (essential dietary-derived amino- and fatty acids for neurotransmitter synthesis, caloric restriction, and diet–gene interactions), epigenesis, and metabolic programming. Nutrition influences growth and development, fertility and longevity, and also determines susceptibility to non-communicable diseases such as cardiovascular disease and cancer, and particularly diabetes and obesity, through in-utero effects, the development of intestinal flora (microbiome), and chronic stress. Thus the sociotype and nutrition are reciprocally related in both health and disease.
  • Novel Strategies for the Treatment of Heart Failure

    Heart failure is a leading cause of morbidity and mortality with a prevalence that is rising throughout the world. Currently the pharmaceutical therapy of heart failure is mainly based on inhibition of the neurohumoral pathways that are activated secondary to the deterioration of cardiac function, and diuretics to alleviate the salt and water overload. With our increasing understanding of the pathophysiology of heart failure, it is now clear that the macroscopic and functional changes in the failing heart result from remodeling at the cellular, interstitial, and molecular levels. Therefore, emerging therapies propose to intervene directly in the remodeling process at the cellular and the molecular levels. Here, several experimental strategies that aim to correct the abnormalities in receptor and post-receptor-function, calcium handling, excitation and contraction coupling, signaling, and changes in the extra-cellular matrix in the failing heart will be discussed. These novel approaches, aiming to reverse the remodeling process at multiple levels, may appear on the clinical arena in the coming years.
  • Randomized Trials Built on Sand: Examples from COPD, Hormone Therapy, and Cancer

    The randomized controlled trial is the fundamental study design to evaluate the effectiveness of medications and receive regulatory approval. Observational studies, on the other hand, are essential to address post-marketing drug safety issues but have also been used to uncover new indications or new benefits for already marketed drugs. For example, hormone replacement therapy (HRT), effective for menopausal symptoms, was reported in several observational studies during the 1980s and 1990s to also significantly reduce the incidence of coronary heart disease. This hypothesis was disproved in 2002 by the large-scale Women’s Health Initiative randomized trial. An example of a new indication for an old drug is that of metformin, an anti-diabetic medication, which is being hailed as a potential anti-cancer agent, primarily on the basis of several recent observational studies that reported impressive reductions in cancer incidence and mortality. These observational studies have also sparked the conduct of large-scale randomized controlled trials in cancer. We show in this paper that the spectacular effects on new indications or new outcomes reported in many observational studies in chronic obstructive pulmonary disease (COPD), HRT, and cancer are the result of time-related biases, such as immortal time bias, that tend to seriously exaggerate the benefits of a drug and that eventually disappear with the proper statistical analysis. In all, while observational studies are central to assess the effects of drugs, their proper design and analysis are essential to avoid bias. The scientific evidence on the potential beneficial effects in new indications of existing drugs will need to be more carefully assessed before embarking on long and expensive unsubstantiated trials.
  • Multidetector Computed Tomographic Angiography (MDCTA) for Penetrating Neck Injuries

    Evaluation of patients after penetrating neck injury has evolved over time. Previously, location of injury and symptoms were used to determine management. The contemporary management of penetrating neck injuries relies on physical examination. Patients with hard signs of vascular or aerodigestive tract injury require immediate operation, regardless of location of injury. Those with no signs can be observed. For the remainder with soft signs multidetector, computed tomographic angiography (MDCTA) is a highly sensitive and specific screening modality for evaluating the vasculature and aerodigestive structures in the neck. Utilizing MDCTA, the patient can be safely directed towards operative intervention, observation, or further investigation.
  • Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes. Both proteins are key contributors to the intracellular Ca2+ handling process, and play a pivotal role in Ca2+ release from the SR to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive SR Ca2+ leak, which initiates delayed afterdepolarizations (DADs) and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC) generated from somatic cells (e.g., fibroblasts, keratinocytes), now enables researches to investigate mutated cardiomyocytes generated from the patient's iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.