Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Effects of magnetic resonance imaging diffusion gradient recalled echo on a patient with an intracranial hemorrhage presenting to the emergency department.

Generally, a computed tomography scan is conducted for the diagnosis of stroke in the emergency department, because these scans are easier and faster in the detection of stroke. If there are no signs of hemorrhage on computed tomography scan, an ischemic stroke is diagnosed and treated accordingly. A magnetic resonance imaging scan may be taken in order to verify ischemic stroke. This process may lead to improper treatment and is time consuming. To address this situation, case studies are presented in which magnetic resonance imaging diffusion-weighted imaging and gradient recalled echo were performed to detect hemorrhagic and ischemic stroke and particularly, subarachnoid hemorrhage, which is undetectable with a computed tomography scan.     

Posttraumatic stress disorder and associated risk factors in Canadian peacekeeping veterans with health-related disabilities.

OBJECTIVES: This study investigates posttraumatic stress disorder (PTSD) and its associated risk factors in a random, national, Canadian sample of United Nations peacekeeping veterans with service-related disabilities. METHODS: Participants included 1016 male veterans (age < 65 years) who served in the Canadian Forces from 1990 to 1999 and were selected from a larger random sample of 1968 veterans who voluntarily and anonymously completed a general health survey conducted by Veterans Affairs Canada in 1999. Survey instruments included the PTSD Checklist-Military Version (PCL-M), Center for Epidemiological Studies-Depression Scale (CES-D), and questionnaires regarding life events during the past year, current stressors, sociodemographic characteristics, and military history. RESULTS: We found that rates of probable PTSD (PCL-M score > 50) among veterans were 10.92% for veterans deployed once and 14.84% for those deployed more than once. The rates of probable clinical depression (CES-D score > 16) were 30.35% for veterans deployed once and 32.62% for those deployed more than once. We found that, in multivariate analyses, probable PTSD rates and PTSD severity were associated with younger age, single marital status, and deployment frequency. CONCLUSIONS: PTSD is an important health concern in the veteran population. Understanding such risk factors as younger age and unmarried status can help predict morbidity among trauma-exposed veterans.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Critical size defect in the canine mandible.

OBJECTIVE: The purpose of this study was to determine the minimum size defect in a canine mandible that would not spontaneously heal during the dog's natural life (the critical size defect). STUDY DESIGN: Sixteen adult female mongrel dogs underwent continuity resection on both sides of the mandible to create bilateral defects. In 8 dogs, mandibular defects ranging from 5 to 20 mm were created with periosteal resection. In the other 8 dogs, mandibular defects ranging from 30 to 60 mm were created preserving the periosteum. The dogs were then killed at 6 months and the defects examined using radiographs and histologic analysis. RESULTS: When the periosteum was removed, mandibular defects greater than 15 mm failed to heal across the entire defect. However, when the periosteum was preserved, mandibular defects needed to be greater than 50 mm in order to fail to heal. CONCLUSION: The critical size defect in a canine mandible model is 15 mm when the periosteum is removed and 50 mm when the periosteum is preserved.