Low expression of the putative tumour suppressor gene gravin in chronic myeloid leukaemia, myelodysplastic syndromes and acute myeloid leukaemia

The putative tumour suppressor gene gravin is down-regulated in several solid tumours and is implicated in tumorigenesis. We have evaluated the expression levels of the gravin gene in the CD34(+)/blast cells of a range of myeloid malignancies as compared with controls using real-time quantitative polymerase chain reaction (PCR). Gravin was markedly down-regulated in 41 of 41 patients with acute myeloid leukaemia (AML), nine of 10 patients with myelodysplastic syndromes (MDS) and 33 of 33 patients with chronic myeloid leukaemia (CML), of whom 24 were in blast crisis (BC). We have shown that gravin is consistently down-regulated in the CD34(+)/blast cells of myeloid malignancies and may play a role in the molecular pathogenesis of these disorders.     

Syringe Administration of Epinephrine by Emergency Medical Technicians for Anaphylaxis

Objective: In recent years, the costs of epinephrine autoinjectors (EAIs) in the United States have risen substantially. King County Emergency Medical Services implemented the “Check and Inject” program to replace EAIs by teaching emergency medical technicians (EMTs) to manually aspirate epinephrine from a single-use 1 mg/mL epinephrine vial using a needle and syringe followed by prehospital intramuscular administration of the correct adult or pediatric dose of epinephrine for anaphylaxis or serious allergic reaction. Treatment was guided by an EMT protocol that required a trigger and symptoms. We sought to determine if the “Check and Inject” program was safely implemented by EMTs treating presumed prehospital anaphylaxis or serious allergic reaction. Methods: We conducted a prospective investigation of all cases treated as part of the “Check and Inject” program from July 2014 through December 2016 in suburban King County, Washington, and January 2016 through December 2016 within the city of Seattle. All cases were prospectively collected using a custom quality improvement data form completed by the first responding EMTs. Two physicians completed a structured review of each EMS medical record to determine if the EMTs followed the Check and Inject protocol and determine if epinephrine was clinically-indicated based on physician review. Results: Of the 411 cases eligible for analysis, EMTs followed the protocol appropriately in 367 (89.3%) cases. In the remaining 44 (10.7%) cases, the EMS incident report form failed to document either a clear inciting allergic trigger or an appropriate symptom from the protocol list. Physician review determined that epinephrine was clinically indicated in 36 of the 44 cases. Among the remaining 8 cases (1.9%) that did not meet protocol criteria and were not clinically-indicated based on physician review, none had a documented adverse reaction to the epinephrine. Conclusion: We observed that EMTs successfully implemented the manual “Check and Inject” program for severe allergic reactions and anaphylaxis in a manner that typically agreed with physician review and without any overt identified safety issues.     

Recognition and management of idiopathic systemic capillary leak syndrome: an evidence-based review

Introduction: Idiopathic systemic capillary leak syndrome (SCLS) is a unique disorder characterized by episodes of massive systemic leak of intravascular fluid leading to volume depletion and shock. A typical attack of SCLS consists of prodromal, leak and post-leak phases. Complications, such as compartment syndrome and pulmonary edema, usually develop during the leak and post-leak phases respectively. Judicious intravenous hydration and early use of vasopressors is the cornerstone of management in such cases.

Areas covered: The purpose of the present review is to provide an up-to-date, evidence-based review of our understanding of SCLS and its management in the light of currently available evidence.

Commentary: Idiopathic SCLS was first described in 1960 and, since then, more than 250 cases have been reported. A large number of cases have been reported over the past one decade, most likely due to improved recognition. In the acute care setting, most patients with SCLS are managed as per the Surviving Sepsis guidelines and receive aggressive volume resuscitation – which is not the optimal management strategy for such patients. There is a need to raise awareness amongst physicians and clinicians in order to improve recognition of this disorder and ensure its appropriate management.     

Immune Modulation by Vitamin D and Its Relevance to Food Allergy

Apart from its classical function in bone and calcium metabolism, vitamin D is also involved in immune regulation and has been linked to various cancers, immune disorders and allergic diseases. Within the innate and adaptive immune systems, the vitamin D receptor and enzymes in monocytes, dendritic cells, epithelial cells, T lymphocytes and B lymphocytes mediate the immune modulatory actions of vitamin D. Vitamin D insufficiency/deficiency early in life has been identified as one of the risk factors for food allergy. Several studies have observed an association between increasing latitude and food allergy prevalence, plausibly linked to lower ultraviolet radiation (UVR) exposure and vitamin D synthesis in the skin. Along with mounting epidemiological evidence of a link between vitamin D status and food allergy, mice and human studies have shed light on the modulatory properties of vitamin D on the innate and adaptive immune systems. This review will summarize the literature on the metabolism and immune modulatory properties of vitamin D, with particular reference to food allergy.     

Analysis of misoprostol and chlorhexidine policy gains in Pakistan: the advocacy experience of Mercy Corps Pakistan

While Pakistan has made progress toward achieving Millennium Development Goal 5 for maternal health, it is unlikely to achieve the target; further, it is also not on track for Millennium Development Goal 4 regarding child health. Two low-cost, temperature stable and life-saving drugs, misoprostol and chlorhexidine, can respectively avert maternal and newborn deaths, and are particularly pertinent for poor and marginalized areas which bear the brunt of maternal and newborn deaths in Pakistan. In response, Mercy Corps led focused advocacy efforts to promote changes in policies, protocols, and regulatory environments for misoprostol (2012–2014) and for chlorhexidine (2014). These short-duration advocacy projects facilitated significant policy gains, such as inclusion of misoprostol and chlorhexidine into province-specific essential drug lists, development and endorsement of clinical protocols for the two drugs by provincial health departments, inclusion of misoprostol into pre-service training curriculum for several health cadres, and application for registration of chlorhexidine (at the concentration required for newborn care) by two pharmaceutical companies. These results were achieved by a consultative and evidence-based process which generated feedback from community members, program implementers, and policymakers, and ultimately put the government in the driver’s seat to facilitate change. Community Action Dialogue forums were linked with provincial-level Technical Working Groups and Provincial Steering Committees, who passed on endorsed recommendations to the Health Secretary. The key factors which facilitated change were the identification of champions within the provincial health departments, prioritization of relationship building and follow-up, focus on concrete advocacy aims rather than broad objectives, and the use of multi-stakeholder forums to secure an enabling environment for the policy changes to take root. While these advocacy initiatives resulted in significant policy changes in Pakistan’s devolved health system, to ensure these policy changes have an impact on health outcomes, Pakistan should focus on the scale-up of appropriate use of chlorhexidine and misoprostol. Further, future policy initiatives in Pakistan should make use of similar multi-stakeholder policy forums, while ensuring a third party to facilitate the process so that civil society and community voices are not lost in the policy development discussion.     

Characteristics,evolution, and outcome of patients with non-infectious uveitis referred for rheumatologic assessment and management: an Egyptian multicenter retrospective study

Clinical Rheumatology - To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84...     

Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait

Clinical Rheumatology - Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or...     

Changes in beta 2-adrenoceptor and other signaling proteins produced by chronic administration of 'beta-blockers' in a murine asthma model

BACKGROUND: We have previously reported that chronic treatment with certain 'beta-blockers' reduces airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma. METHODS: Airway resistance was measured using the forced oscillation technique in ovalbulmin-sensitized and ovalbulmin-challenged mice treated with several beta-adrenoceptor (beta-AR) ligands. We used the selective beta 2-AR ligand ICI 118,551 and the preferential beta 1-AR ligand metoprolol to investigate the receptor subtype mediating the beneficial effect. Expression of beta-ARs was evaluated using immunofluorescence. We evaluated several signaling proteins by western blot using lung homogenates, and measured the relaxation of the isolated trachea produced by EP2 and IP receptor agonists. RESULTS: Four findings were associated with the decreased AHR after chronic beta-blocker treatment: (1) the highly selective beta 2-AR antagonist/inverse agonist, ICI 118,551 produced the bronchoprotective effect; (2) beta 2-AR up-regulation resulted from chronic 'beta-blocker' treatment; (3) reduced expression of certain proteins involved in regulating bronchial tone, namely, Gi, phosphodiesterase 4D and phospholipase C-beta 1; and (4) an enhanced bronchodilatory response to prostanoid agonists for the IP and EP2 receptors. CONCLUSIONS: These data suggest that in the murine model of asthma, several compensatory changes associated with either increased bronchodilator signaling or decreased bronchoconstrictive signaling, result from the chronic administration of certain 'beta-blockers'.