High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler.
Research over the past 10 years in our laboratory has led to two major findings. The first is that haptoglobin (Hp) genotype can predict the risk of developing vascular complications in individuals with diabetes mellitus (DM), and the second, more far-reaching discovery, is that vitamin E treatment can significantly reduce vascular complications in individuals with DM and the Hp 2-2 genotype. The former finding has been well documented in numerous studies which included over 50,000 patients of diverse geographical and ethnic backgrounds. The latter discovery is more recent and less well accepted by the medical community due to confounding reports over the past 30 years regarding the efficacy of vitamin E treatment for vascular disease. We propose that the benefit of vitamin E treatment was not obvious in earlier studies due to the absence of any genetic basis for patient selection. Our studies dividing DM individuals into vitamin E treatment subgroups based on Hp genotype show a clear benefit for individuals of the Hp 2-2 genotype, while patients carrying the other two Hp genotypes are not affected or may be adversely affected by receiving vitamin E. These findings may explain the overall lack of benefit seen in previous vitamin E studies and emphasize the importance of carefully selecting which patients should receive vitamin E therapy. The pharmacogenomic paradigm discussed in this review potentially could result in a dramatic improvement in the health of millions of individuals worldwide using a treatment that is both accessible and affordable to all.
In this brief review, written from the perspective of a physician-leader who has fostered the development of comprehensive quality improvement efforts at two academic medical centers, I review the need for improvement, some conceptual barriers that must be overcome, the goals of a comprehensive quality improvement (QI) effort, some of the results we have obtained, and some observations on how to develop a culture of continuous improvement in an academic medical center. The mandate for quality improvement is clear; current healthcare is wasteful and error-prone, leading to excessive morbidity and mortality and unsustainably high costs. Successful quality improvement requires the abandonment of two paradigms: the craft model of medical practice and the notion that many forms of harm to patients are not preventable. I will describe how dramatic improvement has been achieved in reducing, by up to 10-fold, rates of central line infections, ventilator-associated pneumonias, peritonitis in peritoneal dialysis patients, and mortality due to cardiac arrest in hospital. I will describe as well how these methods can improve access to out-patient clinics dramatically and enhance the reliability and safety of hand-offs between covering physicians. To develop and maintain systematic quality improvement in all phases of medical care we must articulate a culture in which: everyone working at the medical center makes improvements every day; front-line staff, who know best how the work is done, are empowered to improve the processes of care; and multidisciplinary teams create the protocols that reduce variation that is due to physician preference, leaving only the variation required by the individual needs of patients. I will review as well the crucial elements of education of trainees and faculty members needed to guide and sustain a culture of quality. Finally, I will add some observations on how oversight boards and medical center leaders can help create systematic quality improvement in their medical centers.
Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.
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.
Celiac disease (CD) is an autoimmune disorder occurring in genetically susceptible subjects. The incidence of CD is around 1%, and it is much more common in first-degree relatives of CD patients, 10%–18%. However, the pattern of the genetic inheritance is still obscure. Environmental factors are undoubtedly affecting the disease’s clinical presentation, time at presentation, and maybe effect on the characteristics of the disease. The clinical presentation of CD has shifted during the previous decades from the classical presentation in which the toddler suffers from diarrhea, constipation, vomiting, failure to thrive, abdominal distension, etc., to the child with a monosymptomatic presentation, such as anemia, as well as an enlarged list of extra-intestinal disorders. The diagnosis of CD is being established by symptoms consistent with CD and positive serology. The ultimate diagnosis should be made upon histological evaluation of the small bowel mucosa. The treatment of CD is a lifelong, strict gluten-free diet (GFD). Compliance with a GFD is quite difficult. Therefore, new strategies for prevention and treatment modalities other than GFD are greatly needed. Recently several promising therapeutic modalities have been developed; these include resuming traditional baking techniques. Another methodology is using probiotic-driven prolylendopeptidase. Another pathway to tackle the therapeutic option in CD is by down-regulation of the activity of zonulin—the active pump enabling gluten to enter the enterocytes. We are facing an era where other modalities beyond a GFD might allow CD patients to be able to tolerate occasionally a small amount of gluten in their diet.
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.
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.
Lipman Halpern was born in 1902 into a family of Grand Rabbis who lived in Bialystok from the mid-nineteenth century. Inspired by his son’s decision to study medicine, Halpern’s father authored a comprehensive and innovative book on medicine according to Rabbinic Law. After completing his initial medical studies in Königsberg, Halpern went on to specialize in neuropsychiatry in Berlin and then in Zurich.
In 1934, Halpern immigrated to Eretz-Israel (then Palestine), where he founded and expanded the Department of Neurology at the Hadassah University Hospital in Jerusalem. Under his guidance, the department became a leader in clinical neurology, clinical and basic neurological research, and teaching. For the graduation of the first class of the Faculty of Medicine of the Hebrew University of Jerusalem in 1952, he authored the “Oath of the Hebrew Physician,”which went on to become the official oath for all new physicians graduating from Israeli faculties of medicine.
Halpern authored many clinical and research articles in English, German, French, and Hebrew. His studies on the relationship between the vestibular, cerebellar, and visual systems resulted in the description of the phenomenon of “monocular disequilibrium”and the “sensory motor induction syndrome,”also known as “Halpern’s syndrome.”In 1953 he became the first Israel Prize laureate in Medicine. Halpern died in 1968 while serving his second term as Dean of the Faculty of Medicine at Hebrew University.
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.
