776 research outputs found

    Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae

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    Intranasal infection of mice with certain strains of capsular group 19 Streptococcus pneumoniae can result in focal pneumonia in the absence of bacteremia. Using this model of murine pneumonia, we demonstrated that immunization with recombinant forms of either pneumococcal surface protein A (PspA) or PdB (a genetically detoxified derivative of pneumolysin) elicited significant protection against focal pulmonary infection. This may be the first demonstration that a proposed vaccine antigen can protect against pneumococcal pneumonia. The best protection was obtained by immunizing mice with a mixture of PspA and PdB, indicating that the protection elicited by these antigens can complement each other. This result is in agreement with previous studies that used pneumococcal sepsis and nasal colonization models and demonstrate that the best protein vaccines for prevention of infection may be those that include more than one protection-eliciting pneumococcal protein.David E. Briles, Susan K. Hollingshead, James C. Paton, Edwin W. Ades, Lea Novak, Frederik W. van Ginkel, and William H. Benjamin, Jr

    Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae

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    Intranasal infection of mice with certain strains of capsular group 19 Streptococcus pneumoniae can result in focal pneumonia in the absence of bacteremia. Using this model of murine pneumonia, we demonstrated that immunization with recombinant forms of either pneumococcal surface protein A (PspA) or PdB (a genetically detoxified derivative of pneumolysin) elicited significant protection against focal pulmonary infection. This may be the first demonstration that a proposed vaccine antigen can protect against pneumococcal pneumonia. The best protection was obtained by immunizing mice with a mixture of PspA and PdB, indicating that the protection elicited by these antigens can complement each other. This result is in agreement with previous studies that used pneumococcal sepsis and nasal colonization models and demonstrate that the best protein vaccines for prevention of infection may be those that include more than one protection-eliciting pneumococcal protein.David E. Briles, Susan K. Hollingshead, James C. Paton, Edwin W. Ades, Lea Novak, Frederik W. van Ginkel, and William H. Benjamin, Jr

    Hyperthermic Isolated Limb Perfusion with TNF α and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs

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    Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNFα ) and cisplatin for the management of osteosarcoma was studied in the canine model

    Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

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    Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires life-long dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life

    Morbidity After Inguinal Lymph Node Dissections:It Is Time for a Change

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    Inguinal lymph node dissection (ILND) for stage 3 melanoma is accompanied by high wound complication rates. During the past decades, several changes in perioperative care have been instituted to decrease the incidence of these complications. This study aimed to evaluate the effect of these different care protocols on wound complications after ILND. A retrospective analysis of prospectively collected data was performed with 240 patients who underwent an ILND in the University Medical Center Groningen between 1989 and 2014. Four groups with different treatment protocols were analyzed: A (>= 10 days of bed rest with a Bohler Braun splint), B (10 days of bed rest without a splint), C (5 days of bed rest), and D (1 day of bed rest). The effect of early mobilization, abolishment of the Bohler Braun splint and postural restrictions, and the introduction of prophylactic antibiotics were analyzed. One or more wound complications occurred in 51.2 % of the patients including wound infection (29.8 %), seroma (21.5 %), wound necrosis (13.6 %), and hematoma (5 %). In consecutive periods, respectively 44.4, 60.3, 44.9 and 55.2 % of the patients experienced wound complications. None of the instituted changes in protocols led to a decrease in wound complications. Changes in perioperative care protocols did not affect the rate of wound complications. Perhaps a change in the surgical procedure itself can lead to the necessary reduction of wound complications after ILND

    Nodular Histologic Subtype and Ulceration are Tumor Factors Associated with High Risk of Recurrence in Sentinel Node-Negative Melanoma Patients

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    Since its introduction, the sentinel lymph node biopsy (SLNB) has become the standard staging procedure in clinical node-negative melanoma patients. A negative SLNB, however, does not guarantee a recurrence-free survival. Insight into metastatic patterns and risk factors for recurrence in SLNB negative melanoma patients can provide patient tailored guidelines. Data concerning melanoma patients who underwent SLNB between 1996 and 2015 in a single center were prospectively collected. Cox regression analyses were used to determine variables associated with overall recurrence and distant first site of recurrence in SLNB-negative patients. In 668 patients, SLNBs were performed between 1996 and 2015. Of these patients, 50.4 % were male and 49.6 % female with a median age of 55.2 (range 5.7-88.8) years. Median Breslow thickness was 2.2 (range 0.3-20) mm. The SLNB was positive in 27.8 % of patients. Recurrence rates were 53.2 % in SLNB-positive and 17.9 % in SLNB-negative patients (p <0.001). For SLNB-negative patients, the site of first recurrence was distant in 58.5 %. Melanoma located in the head and neck region (hazard ratio 4.88, p = 0.003) and increasing Breslow thickness (hazard ratio 1.15, p = 0.013) were predictive for distant first site of recurrence in SLNB-negative patients. SLNB-negative patients with a nodular melanoma and ulceration had a recurrence rate of 43.1 %; the site of recurrence was distant in 64 % of these patients. The recurrence rates of SLNB-negative nodular ulcerative melanoma patients approach those of SLNB-positive patients. Stringent follow-up is recommended in this subset of patients

    Parotid salivary sodium levels of Sjögren's syndrome patients suggest B-cell mediated epithelial sodium channel disruption

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    Patients with primary Sjögren's syndrome (SS) suffer widely from lack of saliva production. Here we investigate potential mechanisms underpinning changes in SS patient saliva composition. Sodium concentration was significantly higher in all saliva samples collected: unstimulated submandibular/sublingual (SmSl) saliva (p<0.0001), stimulated SmSl saliva (p=0.002) and stimulated parotid (PG) (p<0.0001) saliva, compared to non-SS sicca controls. Chloride, phosphate and potassium ion concentrations, α-amylase activity and total protein content correlations were less consistently changed between SS and non-SS saliva types. Stimulated PG salivary sodium levels correlated with the degree of CD45+ lymphocytic cell infiltrate in the parotid glands (r=0.69, p<0.001), and even more strongly so with infiltrating CD20+ B cells (r=0.73, p<0.0001). CD3+ T cells were only moderately correlated with salivary sodium (r=0.23, p=0.015). In non-SS control or focus score (FS) negative SS PG tissue, the epithelial sodium channel (ENaC), responsible for sodium transport out of saliva, was localised to the apical membrane of luminal striated duct cells. In PG tissue from FS+ SS patients, apical ENaC expression appeared absent. We hypothesise that B cell-related proinflammatory cytokines in SS salivary glands may dysregulate sodium transport channels in SS
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