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: To examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth.
Methods: Pregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis.
Results: As the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count.
Conclusion: In a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.
Functional sexual pain disorders in women are a particular challenge to the gynecologist, inasmuch as phobic avoidance and guarding on the part of the patient lead to difficulties in the gynecological examination and diagnosis. In some such cases examination may even be impossible. Vaginismus is the commonly diagnosed etiology of such cases. This article offers an overview of vaginismus and approaches to its treatment but also examines a subset of penetration-avoidant patients who do not appear to have a pain component. We have reviewed this separate category conceptually and clinically, and propose that this case subset be separated from the diagnosis of vaginismus and designated as vaginal penetration phobia (VPP). We further propose that this category be diagnosed as one of several possible presentations of phobic disorder, under the rubric of mental health disorder, and thus be separated from gynecology. The nosological implications are raised.
Objective: Increased inflammatory response may be associated with adverse clinical outcomes, especially in the neonatal period. The aims of this study were to determine whether N-acetyl-cysteine (NAC), an anti-inflammatory agent, attenuates the inflammatory response in young rats and to determine the most effective route of administration.
Methods: Four groups of Sprague-Dawley rats (in each group four rats) were studied at 30 days of age. One hour following intraperitoneal (IP) injection of lipopolysaccharide 50 µg/kg, the rats were randomized to subcutaneous (SC), per os (PO), or intraperitoneal (IP) injection of NAC 300 mg/kg, or saline. The control group received saline injection (IP). Three hours following the N-acetyl-cysteine injection the rats were sacrificed, then serum tumor necrosis factor-α (TNF-α) and IL-6 levels were determined by ELISA.
Results: Lipopolysaccharide significantly increased the neonatal serum IL-6 and TNF-α (2051.0±349 and 147.0±25.8 pg/mL, respectively; P<0.01) levels compared to 10 pg/mL in the controls. N-acetyl-cysteine administered one hour following lipopolysaccharide injection significantly attenuated the inflammatory response. Intraperitoneal administration of NAC decreased IL-6 and TNF-α concentration to 294.6 and 17.1 pg/mL, respectively, and was more effective than SC or PO administration.
Conclusions: N-acetyl-cysteine attenuated the inflammatory response in the neonatal rats, and IP was the most effective administration route.
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.
Two paintings of older men by Rembrandt (1609–1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person’s response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt’s own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject’s foot and the second involving the subject’s hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age.
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.
Objective: The optimal treatment of deep vein thrombosis (DVT) is anticoagulation therapy. Inferior vena cava filter (IVC) placement is another option for the prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This is used mostly in patients with a contraindication to anticoagulant therapy. The purpose of the present study was to compare the two options.
Methods: A retrospective cohort study of two groups of patients with DVT: patients who received an IVC filter and did not receive anticoagulation due to contraindications; and patients with DVT and similar burden of comorbidity treated with anticoagulation without IVC insertion. To adjust for a potential misbalance in baseline characteristics between the two groups, we performed matching for age, gender, and Charlson’s index, which is used to compute the burden of comorbid conditions. The primary outcome was an occurrence of a PE.
Results: We studied 1,742 patients hospitalized with the diagnosis of DVT in our hospital;93 patients from this population received IVC filters. Charlson’s score index was significantly higher in the IVC filter group compared with the anticoagulation group. After matching of the groups of patients according to Charlson’s score index there were no significant differences in primary outcomes.
Conclusion: Inferior vena cava filter without anticoagulation may be an alternative option for prevention of PE in patients with contraindications to anticoagulant therapy.
Arabs are a large minority group in the Israeli society. With the increasing use of medical cannabis throughout Israel due to changing governmental policies, the interactions of the Arab society with medical cannabis becomes of scientific and medical relevance. Recreational cannabis use is considered haram (forbidden) in Islam. However, most religious scholars agree that medical cannabis usage might be justified as zarurat (emergency and life-saving, therefore allowed) use. Obstacles to medical cannabis use within the Arabic population may relate to language barrier and/or cultural barriers. There are few Arabic-speaking web-based medical-cannabis support groups, and little official information about it is available in the Arabic language. In order for the full benefits of medical cannabis to reach the entire Israeli population, a government-sponsored web-based educational program is necessary in Hebrew and Arabic, both of which are among the nation’s official languages, thereby contributing to the equalization of health resource accessibility.
Objective: The aim of this cross-sectional questionnaire-based study was to identify associations between the doses of cannabinoids and terpenes administered, and symptoms of attention deficit hyperactivity disorder (ADHD).
Methods: Participants were adult patients licensed for medical cannabis (MC) treatment who also reported a diagnosis of ADHD by a physician. Data on demographics, ADHD, sleep, and anxiety were collected using self-report questionnaires. Data collected on MC treatment included administration route, cultivator, cultivar name, and monthly dose. Comparison statistics were used to evaluate differences in reported parameters between low (20–30 g, n=18) and high (40–70 g, n=35) MC monthly dose and low adult ADHD self-report scale (ASRS, 0–5) score (i.e. ≤3.17 score, n=30) or high ASRS score (i.e. ≥3.18 score, n=29) subgroups.
Results: From the 59 patients that answered the questionnaire, MC chemovar could be calculated for 27 (45%) of them. The high MC monthly dose group consumed higher levels of most phyto-cannabinoids and terpenes, but that was not the case for all of the cannabis components. The high dose consumers and the ones with lower ASRS score reported a higher occurrence of stopping all ADHD medications. Moreover, there was an association between lower ASRS score subgroup and lower anxiety scores. In addition, we found an association between lower ASRS score and consumption of high doses of cannabinol (CBN), but not with ∆-9-tetrahydrocannabinol (THC).
Conclusion: These findings reveal that the higher-dose consumption of MC components (phyto-cannabinoids and terpenes) is associated with ADHD medication reduction. In addition, high dosage of CBN was associated with a lower ASRS score. However, more studies are needed in order to fully understand if cannabis and its constituents can be used for management of ADHD.
