We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.
Platinum-based drugs that induce DNA damage are commonly used first-line chemotherapy agents for testicular, bladder, head and neck, lung, esophageal, stomach, and ovarian cancers. The inherent resistance of tumors to DNA damage often limits the therapeutic efficacy of these agents, such as cisplatin. An enhanced DNA repair and telomere maintenance response by the Mre11/Rad50/Nbs1 (MRN) complex is critical in driving this chemoresistance. We hypothesized therefore that the targeted impairment of native cellular MRN function could sensitize tumor cells to cisplatin. To test this, we designed what we believe to be a novel dominantnegative adenoviral vector containing a mutant RAD50 gene that significantly downregulated MRN expression and markedly disrupted MRN function in human squamous cell carcinoma cells. A combination of cisplatin and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage and telomere shortening. In cisplatin-resistant human squamous cell cancer xenografts in nude mice, this combination therapy caused dramatic tumor regression with increased apoptosis. Our findings suggest the use of targeted RAD50 disruption as what we believe to be a novel chemosensitizing approach for cancer therapy in the context of chemoresistance. This strategy is potentially applicable to several types of malignant tumors that demonstrate chemoresistance and may positively impact the treatment of these patients.
Failure to localize an unknown primary tumor often results in widespread irradiation of the upper aerodigestive tract, inducing significant morbidity. Robot-assisted biopsies of the tongue base may identify unknown primaries that would otherwise have been missed through standard directed biopsy techniques.
BackgroundThere is increasing evidence that biofilms are critical to the pathophysiology of chronic infections including chronic rhinosinusitis (CRS). Until relatively recently, our understanding of biofilms was limited. Recent advances in methods for biofilm identification and molecular biology have offered new insights into the role of biofilms in CRS. With these insights, investigators have begun to investigate novel therapeutic strategies that may disrupt or eradicate biofilms in CRS.ObjectiveThis review seeks to explore the evidence implicating biofilms in CRS, discuss potential anti-biofilm therapeutic strategies, and suggest future directions for research.ResultsThe existing evidence strongly supports the role of biofilms in the pathogenesis of CRS. Several anti-biofilm therapies have been investigated for use in CRS and these are at variable stages of development. Generally, these strategies: 1) neutralize biofilm microbes; 2) disperse existing biofilms; or 3) disrupt quorum sensing. Several of the most promising anti-biofilm therapeutic strategies are reviewed.ConclusionsA better understanding of biofilm function and their contribution to the CRS disease process will be pivotal to the development of novel treatments that may augment and, potentially, redefine the CRS treatment paradigm. There is tremendous potential for future research.
Background-Nasal polyps influence the burden of aspirin exacerbated respiratory disease (AERD) by contributing to eicosanoid production. AERD is diagnosed through graded aspirin challenges. It is not known how sinus surgery affects aspirin challenge outcomes.Objective-To investigate the effects of endoscopic sinus surgery (ESS) on aspirin-induced reaction severity and on the levels of eicosanoids associated with these reactions.Methods-Twenty-eight AERD patients were challenged with aspirin before and 3-4 weeks after ESS. Respiratory parameters and plasma and urine levels of eicosanoids were compared before and after challenges.Results-Before ESS, AERD diagnosis was confirmed in all study patients by aspirin challenges that resulted in hypersensitivity reactions. After ESS, reactions to aspirin were less severe in all patients and twelve out of twenty-eight patients (43%, p<0.001) had no detectable reaction. A lack of clinical reaction to aspirin was associated with lower peripheral blood eosinophilia [0.1 K/μL
When the perioperative management of antithrombotic therapy is being decided, 3 critical factors must be considered systematically: the patient's inherent thromboembolic risk, the risk and potential consequences of bleeding related to the procedure, and the timing of interruption of thromboembolic therapy.
The correlation between aspirin sensitivity, asthma, and nasal polyposis was recognized in the early 20th century. Today, this classic triad of symptoms, eponymously named Samter’s Triad, is known as aspirin exacerbated respiratory disease (AERD). Aspirin exacerbated respiratory disease affects approximately 0.3–0.9% of the general population in the USA and approximately 7% of asthmatic patients. The management of AERD is challenging as no single modality has proven to have high rates of symptom control. Consequently, disease management typically involves a multimodality approach across both medical and surgical disciplines. This review describes the epidemiology of AERD and the current state-of-the-art as it relates to the underlying pathophysiologic mechanisms of this disease process. A significant proportion of the review is focused on the appropriate diagnostic workup for AERD patients including the utility of aspirin provocation testing. The spectrum of medical treatments, including aspirin desensitization and recently introduced immunotherapies, are discussed in detail. Furthermore, surgical approaches to disease control, including advanced endoscopic techniques, are reviewed and treatment outcomes presented.
RATIONALE: Dengue is a self-limited, viral infection transmitted by mosquitoes with clinical presentations, from undifferentiated fever to severe dengue that may cause death. Epidemiologic studies had associated asthma with severe dengue, our study aims to describe demographic characteristics and clinical manifestations of laboratory confirmed dengue cases with past medical history of asthma. METHODS: Data was collected from patients enrolled in the Sentinel Enhanced Dengue Surveillance System (SEDSS) established in St. Luke's Episcopal Hospitals in Ponce and Guayama, Puerto Rico from May 7, 2012 to May 6, 2015. We compared asthmatic cases with intermittent and persistent disease to determine their risk for severe dengue. SEDSS collects clinical and demographic data and specimens for testing with RT-PCR appropriate for dengue virus. RESULTS: Of 1,691 enrolled patients with history of asthma, 169 had confirmed dengue. 50.9% were male; median age 14.0 years (range: 1-73). 77.5% were under 19 years. 46.7% were admitted to the hospital, 55.7% were between 10-19 years. One case was transferred to another institution (0.6%) no deaths were reported. Common symptoms upon presentation were headache (148, 88.1%), fever (126, 76.4%), muscle pain (114, 68.7%), facial flush (100, 59%) and rash (81, 50.3%). CONCLUSIONS: Patients with a history of asthma and laboratory confirmed dengue had similar symptoms as dengue cases described in the medical literature. Admission rates were high for this group, further analysis is being conducted to characterize and compare asthma severity among patients enrolled in SEDSS who developed severe dengue during their clinical course.
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