Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.
Autoinflammatory diseases (AID) are characterized by seemingly unprovoked self-limited attacks of fever and systemic inflammation potentially leading to amyloidosis. Familial Mediterranean fever (FMF) is the most common AID and therefore the most studied. Besides FMF, the other main hereditary AID are tumor necrosis factor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic fever syndrome (CAPS). These hereditary diseases result from a mutant gene that is involved in the regulation of inflammation, resulting in a characteristic clinical phenotype. The differential diagnosis of AID can be challenging due to a wide overlap in clinical manifestations. Moreover, a considerable proportion of patients present with autoinflammatory symptoms but without a pathogenetic variant on genetic analysis. Furthermore, non-hereditary AID, such as the periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome, which is the most common AID in children worldwide, must be excluded in certain circumstances. Herein we shall review the main AID and describe a practical approach to diagnosis in a patient with a clinical suspicion of AID.
Objective: During July–August 2014,the military operation “Protective Edge” presented Israel with a threat of missile attacks. We aimed to investigate the influence of the “Protective Edge” operation on the rate of pregnancy complications among the population exposed to missile attacks, compared to the population not exposed.
Study Design: This was a retrospective study. Pregnancy outcomes were compared between women who during pregnancy were exposed to the stress of the military operation (exposed group, n=4,673) and gave birth at the Wolfson Medical Center, and women who gave birth in the previous year (unexposed group, n=4,735).
Results: Rates of pregnancy complications did not differ between the groups.
Conclusion: Exposure to environmental stress during pregnancy, for a period of almost two months, was not found to be associated with increased risk for pregnancy complications.
Medicine has evolved in two opposite directions. Evidence-based medicine focuses more on laboratory and computer data than on the patient. Yet experimental data also provide growing evidence for the importance of the patient’s social-psychological “demand” side of medicine, to complement the doctor’s bio-cognitive “supply” side. The patient’s mindset has major diagnostic and therapeutic effects. The patient’s experience is shaped by perceptions of four dimensions: meaning, agency, self-image, and temporal focus. The patient’s perceptions are linked in part to the therapeutic context, through the interaction between doctor and patient. In that proximal setting, the dimensions can be reshaped, for better and worse. These dynamics point to the inherently interactional nature of medicine and to the significant role of medical social sciences in the therapeutic context.
Alfred Nobel was one of the most successful chemists, inventors, entrepreneurs, and businessmen of the late nineteenth century. In a decision later in life, he rewrote his will to leave virtually all his fortune to establish prizes for persons of any nationality who made the most compelling achievement for the benefit of mankind in the fields of chemistry, physics, physiology or medicine, literature, and peace among nations. The prizes were first awarded in 1901, five years after his death. In considering his choice of prizes, it may be pertinent that he used the principles of chemistry and physics in his inventions and he had a lifelong devotion to science, he suffered and died from severe coronary and cerebral atherosclerosis, and he was a bibliophile, an author, and mingled with the literati of Paris. His interest in harmony among nations may have derived from the effects of the applications of his inventions in warfare (“merchant of death”) and his friendship with a leader in the movement to bring peace to nations of Europe. After some controversy, including Nobel’s citizenship, the mechanisms to choose the laureates and make four of the awards were developed by a foundation established in Stockholm; the choice of the laureate for promoting harmony among nations was assigned to the Norwegian Storting, another controversy. The Nobel Prizes after 115 years remain the most prestigious of awards. This review describes the man, his foundation, and the prizes with a special commentary on the Nobel Prize in Physiology or Medicine.
The evolution of medicine is quite remarkable and astounding. Modern medicine is successfully treating or providing long-term control of conditions which in the not-so-distant past were lethal or resulted in permanent disability. The strong emphasis on evidence-based medicine in today’s medical profession has led to a more organized approach toward evaluating the safety and efficacy of new medical treatments. Despite attempts to meet the complex needs of an ever-aging population, an almost cynical or inherent distrust of physicians in general and their medical claims is being increasingly noted. For many physicians this has led to an uncomfortable sense of professional frustration as doubt is cast on themselves or the medical profession in general when the expectations and goals of patients or their families are not achieved. The causes of this apparent malady of contemporary medicine are myriad and may be explored from various perspectives, depending on the particular issue. To understand better the issues and challenges involved, today’s medical practitioner needs to be aware of the complex mix of organizational, professional, ethical, and at times anthropological perspectives contributing to this dissonance between medical professionals and the public. Improving our insight into the forces at work in this dissonance will help medical professionals improve medical services to the public and contribute to the preservation of medicine’s admirable historical legacy.
Background: While medical cannabis has been used for thousands of years in the treatment of pain and other symptoms, evidence-based use is limited and practitioners face multiple areas of uncertainty regarding the rational use of these compounds. Nonetheless, an increasing public interest and advocacy in favor of medical cannabis is causing the issue to be encountered ever more frequently by physicians in different fields of medicine and particularly in rheumatology. In view of this situation, we have surveyed the attitudes of Israeli rheumatologists to the use of medical cannabis.
Objectives: As rheumatologists are specialized in caring for patients presenting with musculoskeletal complaints, the confidence of rheumatologists’ knowledge of cannabinoids was surveyed.
Methods: All members of the Israeli Society of Rheumatology were surveyed by e-mail for their confidence and knowledge of cannabinoids and their perceived competence to prescribe herbal cannabis.
Results: A total of 23 out of 119 (19.3%) Israeli rheumatologists approached returned the questionnaire. Three-quarters of responders were not confident about their knowledge of cannabinoid molecules or ability to write a prescription for herbal cannabis, and 78% were not confident to write a prescription for herbal cannabis; 74% of responders held the opinion that there was some role for cannabinoids in the management of rheumatic disease.
Conclusion: Israeli rheumatologists lack confidence in their knowledge of cannabinoids in general, yet are open to the possibility of introducing this treatment. Additional data and guidance are necessary in order to allow rational utilization of cannabinoids for management of rheumatic pain.
Jewish medical ethics is arguably the oldest recorded system of bioethics still in use. It should be of interest to practicing nephrologists because of its influence on the ethical systems of Christianity, Islam, and Western secular society; because of the extensive written documentation of rabbinical response in addressing a broad range of bioethical dilemmas; and in understanding the values of patients who choose to adhere to religious Jewish law. The goal of this review is to provide a brief overview of the basic principles underlying mainstream traditional Jewish medical ethics, apply them to common clinical scenarios experienced in nephrology practice, and contrast them with that of secular medical ethics.
The use of medical cannabis in children is rapidly growing. While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD). Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity. As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during childhood and adolescence should be made with caution and based on evidence. This review summarizes the current evidence for safety, tolerability, and efficacy of medical cannabis in children with epilepsy and in children with ASD. The main risks associated with use of Δ9-tetrahydrocannabinol (THC) and CBD in the pediatric population are described, as well as the debate regarding the use of whole-plant extract to retain a possible “entourage effect” as opposed to pure cannabinoids that are more standardized and reproducible.
Cannabis is the most widely used recreational drug worldwide and is used by some patients with inflam-matory bowel disease (IBD) to ameliorate their disease. Whereas epidemiological studies indicate that as many as 15% of IBD patients use cannabis, studies inspecting cannabis use in IBD are few and small. We have conducted several studies looking at the use of cannabis in IBD. In Crohn’s disease, we demonstrated that cannabis reduces the Crohn’s disease activity index (CDAI) by >100 points (on a scale from 0-450).Two small studies in ulcerative colitis showed a marginal benefit. However, no improvement was observed in inflammatory markers or in endoscopic score in either disease. Many questions regarding cannabis use in IBD remain unanswered. For example, cannabis is a complex plant containing many ingredients, and the synergism or antagonism between them likely plays a role in the relative efficacy of various cannabis strains. The optimal doses and mode of consumption are not determined, and the most common form of consump¬tion, i.e. smoking, is unacceptable for delivering medical treatment. Cannabis is a psychotropic drug, and the consequences of long-term use are unknown. Despite all these limitations, public opinion regards cannabis as a harmless drug with substantial medical efficacy. In Israel, the number of licenses issued for the medical use of cannabis is rising rapidly, as are the acknowledged indications for such use, but good-quality evidence for the effectiveness of cannabis is still lacking. Further studies investigating the medical use of cannabis are urgently needed.
