Replication-Defective Adenovirus Infection Reduces Helicobacter felis Colonization in the Mouse in a Gamma Interferon- and Interleukin-12-Dependent Manner

Helicobacter infection leads to chronic inflammation of the stomach. Although the infection persists in spite of an immune response, animal studies have shown that adjuvant-based oral vaccines can protect against infection and even eliminate established infection. These vaccines are thought to induce a Th2 immune response, counterbalancing the Th1 response seen with natural infections. As a prelude to using adenovirus vectors carrying cytokine genes to modulate the immune response to established Helicobacter felis infection, we first examined the effect of the replication-defective adenovirus (RDA) vector itself. C57BL/6 mice chronically infected with H. felis (8 to 10 weeks) received intramuscular injections of RDA. The effect of RDA on the severity of H. felis colonization and the degree of gastric inflammation was assessed 2 weeks later. RDA caused a significant decrease in H. felis colonization without significantly altering the associated inflammation. RDA did not alter the H. felis-specific immunoglobulin G1 (IgG1), IgG2a, and IgA responses in the serum but was associated with an increase in gamma interferon (IFN-gamma)-producing CD8(+) spleen cells. To determine if IFN-gamma or Th1 cytokines were involved in the response to RDA, we examined RDA treatment of H. felis infection in mice lacking either IFN-gamma or interleukin-12 (IL-12). RDA failed to alter H. felis colonization in either of these two mouse strains. Thus, viral infection of mice chronically infected with H. felis led to a significant decrease in H. felis colonization in an IFN-gamma- and IL-12-dependent manner. These results demonstrate that Th1 responses associated with systemic viral infection can influence an established H. felis infection.     

A randomized controlled trial on the effect of inhaled corticosteroids on airways inflammation in adult cigarette smokers.

STUDY OBJECTIVE: To determine whether inhaled corticosteroid treatment can reduce airways inflammation in adult cigarette smokers. DESIGN: This was a randomized, placebo-controlled, double-blinded clinical trial. SETTING: The subjects were recruited from the community by advertising. PARTICIPANTS: Seventy-one adults with a > or = 5 pack-year history who were current smokers, had a normal FEV1, and produced sputum daily. INTERVENTION: Sixty subjects were randomized to receive four puffs of placebo or beclomethasone dipropionate ([BDP]; total dosage, 1,000 microg/d) using a metered-dose aerosol inhaler with a valved holding chamber (AeroChamber; Trudell Medical; London, Ontario, Canada) for 28 days. MEASUREMENTS AND RESULTS: Eleven subjects were not randomized because of poor compliance. The primary outcome was fractional airway neutrophilia, as assessed by a differential cell count of sputum. Additional outcome measures were spirometry, measurement of airway responsiveness by methacholine challenge, and lung epithelial permeability measured by the clearance of radiolabeled diethylenetriamine pentaacetic acid. There were no significant differences between the two groups in any outcome measurement after 4 weeks of treatment. CONCLUSIONS: With normal spirometry, we found no benefit of treatment with inhaled BDP, 1,000 microg/d, on noninvasive measures of airways inflammation in adult smokers. This indicates that cigarette smoke-induced inflammation in its early stages (before a demonstrable airflow obstruction) is not steroid sensitive. This may occur because the site of involvement is not accessible to inhaled medications or because the inflammatory process is resistant to moderate doses of inhaled corticosteroids.     

Integrating Out-of-Office Blood Pressure in the Diagnosis and Management of Hypertension

Guidelines for the diagnosis and monitoring of hypertension were historically based on in-office blood pressure measurements. However, the US Preventive Services Task Force recently expanded their recommendations on screening for hypertension to include out-of-office blood pressure measurements to confirm the diagnosis of hypertension. Out-of-office blood pressure monitoring modalities, including ambulatory blood pressure monitoring and home blood pressure monitoring, are important tools in distinguishing between normotension, masked hypertension, white-coat hypertension, and sustained (including uncontrolled or drug-resistant) hypertension. Compared to in-office readings, out-of-office blood pressures are a greater predictor of renal and cardiac morbidity and mortality. There are multiple barriers to the implementation of out-of-office blood pressure monitoring which need to be overcome in order to promote more widespread use of these modalities.     

GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice.

The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.     

Coronary Flow Velocity Reserve during Dobutamine Stress Echocardiography

Background

A coronary flow velocity reserve (CFVR) ≥ 2 is adequate to infer a favorable prognosis or the absence of significant coronary artery disease.

Objective

To identify parameters which are relevant to obtain CFVR (adequate or inadequate) in the left anterior descending coronary artery (LAD) during dobutamine stress echocardiography (DSE).

Methods

100 patients referred for detection of myocardial ischemia by DSE were evaluated; they were instructed to discontinue the use of β-blockers 72 hours prior to the test. CFVR was calculated as a ratio of the diastolic peak velocity (cm/s) (DPV) on DSE (DPV-DSE) to baseline DPV at rest (DPV-Rest). In group I, CFVR was < 2 and, in group II, CFVR was ≥ 2. The Fisher''s exact test and Student''s t test were used for the statistical analyses. P values < 0.05 were considered statistically significant.

Results

At rest, the time (in seconds) to obtain Doppler in LAD in groups I and II was not different (53±31 vs. 45±32; p=0.23). During DSE, LAD was recorded in 92 patients. Group I patients were older (65.9±9.3 vs. 61.2±10.8 years; p=0.04), had lower ejection fraction (61±10 vs. 66±6%; p=0.005), higher DPV-Rest (36.81±08 vs. 25.63 ± 06cm/s; p<0.0001) and lower CFVR (1.67 ± 0.24 vs. 2.53 ± 0.57; p<0.0001), but no difference was observed regarding DPVDSE (61.40±16 vs. 64.23±16cm/s; p=0.42). β-blocker discontinuation was associated with a 4-fold higher chance of a CFVR < 2 (OR= 4; 95% CI [1.171-13.63], p=0.027).

Conclusion

DPV-Rest was the main parameter to determine an adequate CFVR. β-blocker discontinuation was significantly associated with inadequate CFVR. The high feasibility and the time to record the LAD corroborate the use of this methodology.     

Mortality,Cost, and Health Outcomes of Total Knee Arthroplasty in Medicare Patients

There are little data that quantify the long term costs, mortality, and downstream disease after Total Knee Arthroplasty (TKA). The purpose of this study is to compare differences in cost and health outcomes between Medicare patients with OA who undergo TKA and those who avoid the procedure. The Medicare 5% sample was used to identify patients diagnosed with OA during 1997–2009. All OA patients were separated into non-arthroplasty and arthroplasty groups. Differences in costs, mortality, and new disease diagnoses were adjusted using logistic regression for age, sex, race, buy-in status, region, and Charlson score. The 7-year cumulative average Medicare payments for all treatments were $63,940 for the non-TKA group and $83,783 for the TKA group. The risk adjusted mortality hazard ratio (HR) of the TKA group ranged from 0.48 to 0.54 through seven years (all P < 0.001). The risk of heart failure in the TKA group was 40.9% at 7 years (HR = 0.93, P < 0.001). The results demonstrate the patients in the TKA cohort as having a lower probability of heart failure and mortality, at a total incremental cost of $19,843.     

Effect of different surface treatments on the biaxial flexure strength,Weibull characteristics,roughness, and surface topography of bonded CAD/CAM silica-based ceramics

ObjectiveTo investigate the influence of different surface treatments on biaxial flexure strength, roughness, and surface topography of lithium silicate/disilicate-based ceramics.Methods225 discs (?: 12 mm; 1.2 mm – ISO 6872) were made from three ceramics: IPS e.max CAD (LD – Ivoclar Vivadent), Suprinity (LSS - Vita) and Celtra Duo (LSC - Dentsply). The samples were randomly divided into 5 groups (n = 15): no treatment (C); 10% hydrofluoric acid + silane (HF); sandblasting Al₂O₃ + silane (SB); silicatization + silane (SC); and self-etching ceramic primer (SEP). After surface treatment, a resin cement layer was applied to the disc surface (RelyX U200, 3M ESPE), mechanical cycled (1.2 × 10⁶ cycles, 50 N, 3.8 Hz) and submitted to biaxial flexural strength test (1 mm/min, 1000 Kgf). Roughness, EDS and SEM were also performed. Data were analyzed by one-way ANOVA, Tukey test (5%) and Weibull.ResultsANOVA revealed that the “surface treatment” factor was significant for all ceramics (p < 0.05). The groups LD-HF (289.30 ± 40) LD-SEP (298. 87 ± 53.29), LSC-HF (195.51 ± 42.12), LSS-HF (269.58 ± 27.07) and LSS-SEP (207.45 ± 28.63) presented significantly higher biaxial flexure strength than respective control groups, except for the LSC-SEP (165.41 ± 33.86), which was statistically similar to the control. The Weibull modulus was significantly higher for the LD-SB, LSC-SC groups. Additionally, the LD-SB, LSC-SC and LSS-HF groups showed higher roughness compared to the other treatments.SignificanceHF etching followed by silanization and self-etching ceramic primer are the most suitable surface treatments for lithium silicate/disilicate-based glass-ceramics.