Systemic interleukin 1 administration suppresses arachidonic acid-induced ear oedema in the mouse

Recombinant human interleukin 1 beta (IL-1 beta), given intraperitoneally to mice as a single injection, significantly suppressed the development of arachidonic acid (AA)-induced ear oedema. This effect was noted 2 h after administration and for at least 5 days afterwards. IL-1 beta was effective in the dose range of 250 ng-20 micrograms/mouse. Injection of IL-1 beta per se resulted in erythema of the ears, and thus, IL-1 beta has the capacity not only to induce and augment but also to suppress inflammatory responses. Indomethacin administered as subcutaneously-implanted pellets did not influence the IL-1 beta induced-ear erythema, but suppressed to some extent the effect of IL-1 beta on the AA-induced ear oedema.     

Spindle cell variant of epithelioid sarcoma: an easily misdiagnosed tumour

Epithelioid sarcoma is a histologically distinct soft tissue sarcoma of high grade malignancy. We report a case of epithelioid sarcoma in a young man who presented with multiple nodules over the left forearm, with bony invasion and pulmonary metastases. The histological features of the dermal tumour were those of a malignant spindle cell tumour with positive cytokeratin and vimentin staining and differed from the classical epithelioid sarcoma in its absence of typical necrobiotic nodular epithelioid pattern. It was the clinical presentation and the histology of the subcutaneous nodules that led to the final diagnosis of epithelioid sarcoma. This case illustrates a predominance of spindle cell pattern in the dermal tumour of epithelioid sarcoma, which has previously been reported as fibroma-like variant of epithelioid sarcoma.     

Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry

OBJECTIVES: This study was designed to evaluate whether rapid endothelialization of stainless steel stents with a functional endothelium prevents stent thrombosis and reduces the restenotic process. BACKGROUND: A "pro-healing" approach for prevention of post-stenting restenosis is theoretically favored over the use of cytotoxic or cytostatic local pharmacologic therapies. It is believed that the central role of the vascular endothelium is to maintain quiescence of the underlying media and adventitia. METHODS: Sixteen patients with de novo coronary artery disease were successfully treated with implantation of endothelial progenitor cell (EPC) capture stents. RESULTS: Complete procedural and angiographic success was achieved in all 16 patients. The nine-month composite major adverse cardiac and cerebrovascular events (MACCE) rate was 6.3% as a result of a symptom-driven target vessel revascularization in a single patient. There were no other MACCE despite only one month of clopidogrel treatment. At six-month follow-up, mean angiographic late luminal loss was 0.63 +/- 0.52 mm, and percent stent volume obstruction by intravascular ultrasound analysis was 27.2 +/- 20.9%. CONCLUSIONS: This first human clinical investigation of this technology demonstrates that the EPC capture coronary stent is safe and feasible for the treatment of de novo coronary artery disease. Further developments in this technology are warranted to evaluate the efficacy of this device for the treatment of coronary artery disease.     

Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination,accessory, and epigenetic profiles

Burkholderia pseudomallei (Bp) is the causative agent of the infectious disease melioidosis. To investigate population diversity, recombination, and horizontal gene transfer in closely related Bp isolates, we performed whole-genome sequencing (WGS) on 106 clinical, animal, and environmental strains from a restricted Asian locale. Whole-genome phylogenies resolved multiple genomic clades of Bp, largely congruent with multilocus sequence typing (MLST). We discovered widespread recombination in the Bp core genome, involving hundreds of regions associated with multiple haplotypes. Highly recombinant regions exhibited functional enrichments that may contribute to virulence. We observed clade-specific patterns of recombination and accessory gene exchange, and provide evidence that this is likely due to ongoing recombination between clade members. Reciprocally, interclade exchanges were rarely observed, suggesting mechanisms restricting gene flow between clades. Interrogation of accessory elements revealed that each clade harbored a distinct complement of restriction-modification (RM) systems, predicted to cause clade-specific patterns of DNA methylation. Using methylome sequencing, we confirmed that representative strains from separate clades indeed exhibit distinct methylation profiles. Finally, using an E. coli system, we demonstrate that Bp RM systems can inhibit uptake of non-self DNA. Our data suggest that RM systems borne on mobile elements, besides preventing foreign DNA invasion, may also contribute to limiting exchanges of genetic material between individuals of the same species. Genomic clades may thus represent functional units of genetic isolation in Bp, modulating intraspecies genetic diversity.Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a serious infectious disease of humans and animals and a leading cause of community-acquired sepsis and pneumonia in endemic regions (Currie et al. 2010). Initially thought to be confined to Southeast Asia and Northern Australia, the prevalence of Bp appears to be spreading (Wiersinga et al. 2012), and Bp has been designated a biothreat select agent in the United States. Bp can persist in extreme environmental conditions and can infect several plant and animal hosts, including birds, dolphins, and humans (Wuthiekanun et al. 1995; Howard and Inglis 2003; Sprague and Neubauer 2004; Larsen et al. 2013). Treatment of clinical melioidosis is challenging because the bacterium is inherently resistant to many antibiotics, and Bp infections can persist in humans for more than a decade (Hayden et al. 2012; Wiersinga et al. 2012).The Bp genome comprises one of the largest and most complex bacterial genomes sequenced to date. Consisting of two large circular replicons (chromosomes) with a combined 7.2-Mb genome size (Holden et al. 2004), it contains a rich arsenal of genes related to virulence (e.g., Type III and Type VI secretion systems, polysaccharide biosynthesis clusters), metabolic pathways, and environmental adaptation (Wiersinga et al. 2012). Besides conserved regions, accessory genes on mobile elements and genomic islands may also contribute to phenotypic and clinical differences in microbial behavior (Currie et al. 2000; Sim et al. 2008). Analysis of the Bp genome has revealed previously unknown toxins and mechanisms of antibiotic resistance (Chantratita et al. 2011; Cruz-Migoni et al. 2011).Most large-scale studies of Bp genetic diversity to date have analyzed strains using multilocus sequence typing (MLST). These studies have suggested a high degree of genetic variability between Bp strains and related Burkholderia species (Cheng et al. 2008), and have shown that Bp strains belonging to different sequence types (STs) can often coexist in the same locale and sometimes even within the same sample (Pitt et al. 2007; Wuthiekanun et al. 2009). However, due to the limited number of genes analyzed by MLST, these studies cannot comment on the global proportion of genetic material shared between strains of different STs nor on the relative contribution of recombination, mutation, and horizontal gene transfer on intraspecies genetic diversity. Moreover, although previous studies have applied whole-genome sequencing (WGS) to study global patterns of Bp genetic heterogeneity and evolution, earlier Bp WGS reports have been confined to a limited number of isolates (10–12) derived from diverse geographical regions (Nandi et al. 2010), where geophysical barriers likely limit the propensity of the analyzed strains to exchange genetic material. To achieve a comprehensive understanding of genetic variation among closely related Bp strains, WGS analysis of much larger strain panels, ideally performed on strains isolated from a common region and belonging to the same (or closely related) ST groups, is required.In this study, we attempted to fill this important knowledge gap by performing WGS on 106 Bp strains drawn from a restricted Asian locale (Singapore and Malaysia). The WGS data, exceeding previous Bp WGS studies by 10-fold, enabled us to identify specific genomic clades of Bp, molecular features of Bp recombination at the whole-genome level, and accessory genome features contributing to recombination and horizontal gene transfer. We found a consistent pattern of genetic separation correlating with MLST, recombination haplotypes, shared accessory genes, and restriction modification (RM) systems. We provide evidence that restriction modification, beyond its role as defense against foreign DNA invasion, may have also partitioned the Bp species by restricting gene flow, resulting in the other observed correlations. Because RM systems are widely dispersed through the bacterial kingdom, it is possible that similar principles may apply to other bacterial species, implicating a potential role for epigenetic barriers as a driver of early incipient speciation.     

Psychological Comfort of Paramedics with Field Death Pronouncement: A National Asian Study to Prepare Paramedics for Field Termination of Resuscitation

Objectives: Paramedics' decision to terminate field resuscitation without a physician present may depend on personal and external factors. This study investigates factors associated with paramedic psychological comfort with termination of resuscitation (TOR) to inform future training. Methods: We administered an anonymous survey to all practicing paramedics in a large urban Asian Emergency Medical Services system where formal TOR training had not yet been conducted and field TOR was not routinely applied. The survey assessed psychological comfort using the validated Psychological Comfort Total (PCT) scale (summed score of 28 items, with higher scores representing greater comfort). We examined scores associated with four personal (prior resolution of personal loss, knowledge of survival probability, religious affiliation and experience with death pronouncements) and two external (location of patient and perceived trust of family) factors. Data were entered into Excel and analyzed by t-tests and ANOVA. Results: Response rate was 73.6% (254/345). Respondents were 30.3 years (mean, SD 7.1) with 7.2 years (mean, SD 5.54) of practice experience. Over 60% had been involved in 6 or more field death pronouncements in the prior 12 months. Higher PCT scores were associated with prior resolution of personal loss and knowledge of survival probability. Lower PCT scores were associated with patient location in a public place and perceived family lack of trust. PCT scores were not associated with paramedic religious affiliation or number of prior death pronouncements. Conclusions: Paramedic psychological comfort with field death pronouncement is associated with personal and external factors. Since paramedic comfort is important for protocol adoption, TOR education should target not only knowledge, but also public arena management, communication skills for engaging with families, and help paramedics resolve prior personal loss.     

Epicardial Coronary Spasm in Women With Angina Pectoris and Unobstructed Coronary Arteries Is Linked With a Positive Family History: An Observational Study

Purpose

Coronary spasm is frequently found in patients with angina and unobstructed coronaries. The pathophysiology is incompletely understood, although sex differences have been described. Often a positive family history (PFH) is encountered. We assessed the relationship between sex, coronary spasm, and a PFH for cardiovascular disease.

Treatment of Dural Carotid-Cavernous Fistulas via the Medial Ophthalmic Vein

Aim: To present a novel approach to treatment of dural carotid-cavernous fistulas via the medial ophthalmic vein.

Design: Retrospective case series.

Material and Methods: In this retrospective case series, we present 2 patients (3 eyes) with Type C dural CCFs, who had failed cannulation via the conventional transfemoral route and the transorbital superior ophthalmic vein approach. They subsequently underwent CCF occlusion via an anterior orbital approach through the medial ophthalmic veins, at the Department of Ophthalmology, National University Hospital Singapore. CCF occlusion was confirmed intraoperatively using angiography. Both patients were evaluated postoperatively for best-corrected visual acuity and resolution of clinical signs and symptoms.

Results: Successful occlusion of CCFs via the medial ophthalmic veins were achieved in all three orbits, with excellent visual and cosmetic outcomes postoperatively.

Conclusion: Dural CCFs may potentially lead to severe visual dysfunction and should be diagnosed and treated promptly. When all venous routes have been exhausted, the transorbital approach via the medial ophthalmic vein remains an excellent and viable alternative to access the fistula. Close cooperation between the orbital, anesthetic and radiological teams is essential in ensuring success of the operation.     

Shoulder injuries in the athlete

Shoulder injuries are common in the athletic population. Injuries can be a result of repetitive overhead use or from direct trauma. Common injury sites include the rotator cuff, glenohumeral joint, acromioclavicular joint, biceps tendon, scapulothoracic articulation, and sternoclavicular joint. The identification, physical exam, and treatment options of these conditions will be discussed.