Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model.
Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 ml of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 ml of ozone/oxygen mixture by gavage and 2 ml of water IP for 5 days; 3) O3-IP rats were treated with 2 ml of water by gavage and 2 ml of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice.
Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover.
Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration.
The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB1 receptors) and in the periphery (primarily but not exclusively CB2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.
This paper is provided for the convenience of our readers and represents a full edited transcription of the Rambam Grand Rounds Lecture by Dr. Richard Horton, Editor-in-Chief of The Lancet. The lecture was given on October 2, 2014. The Editorial Board wishes to express its gratitude to Dr. Horton for giving permission to present his Rambam Grand Rounds lecture in Rambam Maimonides Medical Journal, in both the original video format and in this printed form.
In rare cases, the monoclonal immunoglobulin that characterizes essential monoclonal gammopathy interacts with a self-antigen with functional consequences and a resulting clinical syndrome. This event is presumably random and results from the clone of B lymphocytes making a monoclonal immunoglobulin that simulates an autoimmune antibody. Thus, by chance, the monoclonal immunoglobulin has sufficient affinity for an epitope on a normal protein that functional consequences ensue. One such rare event is the synthesis and secretion of a monoclonal immunoglobulin that binds to human insulin. Inactivation of insulin by antibody results in (1) an early postprandial hyperglycemia, (2) followed by either or both (i) a reactive overshot in insulin secretion, as a result of hypertrophied or hyperplastic islet beta cells, later falling glucose levels, and (ii) an unpredictable dissociation of insulin from the complex, and, several hours later, (3) a resultant increase in free insulin levels and severe hypoglycemia with clinical consequences, ranging from sweating, dizziness, headache, and tremors to confusion, seizures, and unconsciousness. These attacks are invariably responsive to glucose administration. This very uncommon manifestation of a monoclonal gammopathy can occur in patients with essential monoclonal gammopathy or myeloma. The monoclonal anti-insulin immunoglobulin in monoclonal gammopathy has a low affinity for insulin, but has a high capacity for insulin-binding, resulting in the syndrome of episodic hypoglycemic attacks. This phenomenon of an insulin-binding monoclonal immunoglobulin simulates the acquired insulin autoimmune syndrome, although the latter is mediated by a polyclonal antibody response in the majority of cases studied, and has linkage to HLA class II alleles.
Feelings of guilt have tormented Holocaust survivors, ranging from immediately after the liberation to later in life, for shorter or longer periods, and persisting for some throughout their entire post-war lives. Descriptions of the guilt experienced by survivors of the Nazi camps occupy an impressive amount of literature: “Why me?” was the question, when a younger and more able family member perished; “Why me?” when more productive members of the community perished; “Why me?” when a million and a half children were deprived of their lives. Many found the answer by retelling their stories, witnesses of what happened. This type of guilt is much different from the recently described phenomenon of survivor syndrome, namely the secondary guilt felt by Nazi-persecuted Jewish writers. Despite successes in all aspects of their life, these writers developed a self-incriminating guilt due to their perceived inadequacy of communicating, particularly in light of the resurging anti-Semitism worldwide. This paper deals with the survival and suicides of Nazi-persecuted Jewish writers and offers a possible explanation for their late self-destructive acts.
Introduction. The current study evaluated the rate of ependymal enhancement and whether its presence influences survival of patients with malignant glioma (GBM).
Methods. A retrospective review of all patients who were treated in our institution from 2005 to 2011 was conducted. Data extracted from the medical records included age, date of diagnosis, co-morbidities, treatment regimen, and time of death. Magnetic resonance images (MRI) were evaluated for the presence of ependymal enhancement and its extent, and the correlation to survival was investigated.
Results. Between 2005 and 2011, 230 patients were treated for GBM. Eighty-nine patients were excluded from the study due to insufficient data, leaving 141 patients for analysis. Median age at diagnosis was 60 years. Sixty-seven (40.6%) patients had evidence of ependymal enhancement on MRI (group A), and 70 (42.4%) patients did not have evidence of enhancement. The assessment of ependymal enhancement was inconclusive due to mass effect and ventricular compression that precluded accurate assessment for 28 (17%) patients (group C). Median survival was 14 months for group A (range, 12–16 months), 15.9 months for group B (range, 14.28–17.65 months), and 11.7 months for group C (range, 6.47–16.92 months) (P>0.05). A multivariate analysis to predict survival indicated that male gender (P=0.039), hypertension (P=0.012), and biopsy only compared to complete gross tumor resection (P=0.001) were significant for poor survival.
Conclusions. Pretreatment ependymal enhancement on MRI was not found to be associated with poorer survival. These results might be due to better treatments options compared to prior reports.
Medicine is developing through biomedical technology and innovations. The goal of any innovation in medicine is to improve patient care. Exponential growth in technology has led to the unprecedented growth of medical technology over the last 50 years. Clinician-scientists need to understand the complexity of the innovation process, from concept to product release, when working to bring new clinical solutions to the bedside. Hence, an overview of the innovation process is provided herein. The process involves an invention designed to solve an unmet need, followed by prototype design and optimization, animal studies, pilot and pivotal studies, and regulatory approval. The post-marketing strategy relative to funding, along with analysis of cost benefit, is a critical component for the adoption of new technologies. Examples of the road to innovation are provided, based on the experience with development of the transcatheter aortic valve. Finally, ideas are presented to contribute to the further development of this worldwide trend in innovation.
An anniversary is not only a point of memory—it provides the opportunity for self-examination and paves the way to the future. Every anniversary marks a starting-point that was preceded by a vision. The beginning of any vision is a personal dream—someone wants to improve or repair the world as far as he is able. The vision motivates action; in its aftermath comes the reality. This is the 21st issue of Rambam Maimonides Medical Journal. This issue is particularly important as it marks the completion of five years of creative work pursuing our vision for a high-caliber scientific medical journal. Our vision has become reality.
Background: Following the announcement of actress Angelina Jolie’s prophylactic bilateral mastectomies and subsequent prophylactic oophorectomy, there has been a dramatic increase in interest in BRCA testing and prophylactic surgery.
Objective: To review current medical literature on the benefits of prophylactic mastectomy and oophorectomy among BRCA-positive women and its permissibility under Jewish law.
Results: Recent literature suggests that in BRCA-positive women who undergo prophylactic oophorectomy the risk of dying of breast cancer is reduced by 90%, the risk of dying of ovarian cancer is reduced by 95%, and the risk of dying of any cause is reduced by 77%. The risk of breast cancer is further reduced by prophylactic mastectomy. Prophylactic oophorectomy and prophylactic mastectomy pose several challenges within Jewish law that call into question the permissibility of surgery, including mutilation of a healthy organ, termination of fertility, self-wounding, and castration. A growing number of Jewish legal scholars have found grounds to permit prophylactic surgery among BRCA carriers, with some even obligating prophylactic mastectomy and oophorectomy.
Conclusion: Current data suggest a significant reduction in mortality from prophylactic mastectomy and oophorectomy in BRCA carriers. While mutilation of healthy organs is intrinsically forbidden in Jewish law, the ability to preserve human life may contravene and even mandate prophylactic surgery.
Whilst painting the vault of the Sistine Chapel, Michelangelo Buonarroti left an autographical sketch that revealed a prominence at the front of his hyper-extended neck. This image was recently diagnosed as goiter. The poet Michelangelo in a sonnet dated 1509 described himself as being afflicted by goiter similarly to the cats in the northern Italian Lombardy, a region with endemic goiter. Several narratives extended this sonnet into a pathological theory. The analyses of Michelangelo’s works, however, his portraits and self-portraits, of poems and major biographies, have not indicated the likelihood of goiter. This investigation makes an attempt to assess the diagnosis on clinical as well as iconographical grounds.
