Enhanced external counter pulsation in treatment of refractory angina pectoris: two year outcome and baseline factors associated with treatment failure

<p>Abstract</p> <p>Background</p> <p>Enhanced external counter pulsation (EECP) is a non-invasive treatment option for patients with refractory angina pectoris ineligible to further traditional treatment. The aim of this study was to evaluate the effect of EECP on patients at a Scandinavian medical centre and to investigate if outcome can be predicted by analysing baseline factors.</p> <p>Methods</p> <p>86 consecutive patients (70 male, 16 female) were treated with EECP and followed for two years post treatment. Canadian cardiovascular society (CCS) class was analysed, and medication and adverse clinical events were researched prior to EECP, at the end of the treatment, and at six, 12 and 24 months thereafter. Patients responding to therapy by improving at least one CCS class were compared with those who failed to respond. Any differences in background factors were recorded and analysed.</p> <p>Results</p> <p>79% of the patients responded to therapy by improving at least one CCS class. In general, the CCS class improved by one class after EECP treatment (3.05 before versus 2.14 after treatment). A total of 61.5% of the initial responders showed sustained improvement at the 12 month follow-up while 29% presented sustained improvement after 24 months. Treatment was most effective among patients suffering from CCS class III-IV angina pectoris, while patients suffering from CCS class II angina pectoris improved transiently but failed to show sustained improvement after the 12 month follow-up. Diabetes mellitus and calcium channel antagonists were more common among the non-responders (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This study confirms the safety and efficiency of EECP as a treatment option for patients suffering from refractory angina pectoris. The therapy is most beneficial in patients suffering from severe angina (CCS III-IV) while sustained response to therapy could not be verified among patients suffering from CCS class II angina pectoris.</p

Effects of Hypericum Perforatum, in a rodent model of periodontitis

<p>Abstract</p> <p>Background</p> <p><it>Hypericum perforatum </it>is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. In this study we evaluate the effect of <it>Hypericum perforatum </it>in animal model of periodontitis.</p> <p>Methods</p> <p>Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Hypericum perforatum was administered at the dose of 2 mg/kg os, daily for eight days. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed.</p> <p>Results</p> <p>Periodontitis in rats resulted in an inflammatory process characterized by edema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators such as NF-κB and iNOS expression, the nitration of tyrosine residues and activation of the nuclear enzyme poly (ADP-ribose) polymerase; apoptosis and the degree of gingivomucosal tissues injury. We report here that Hypericum perforatum exerts potent anti-inflammatory effects significantly reducing all of the parameters of inflammation as described above.</p> <p>Conclusions</p> <p>Taken together, our results clearly demonstrate that treatment with Hypericum reduces the development of inflammation and tissue injury, events associated with periodontitis.</p

One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation

BACKGROUND: Enhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to be effective in reducing both angina and myocardial ischemia in patients not responding to medical therapy and without revascularization alternatives. The aim of the present study was to assess the long-term outcome of EECP treatment at a Scandinavian centre, in relieving angina in patients with chronic refractory angina pectoris. METHODS: 55 patients were treated with EECP. Canadian cardiovascular society (CCS) class, antianginal medication and adverse clinical events were collected prior to EECP, at the end of the treatment, and at six and 12 months after EECP treatment. Clinical signs and symptoms were recorded. RESULTS: EECP treatment significantly improved the CCS class in 79 ± 6% of the patients with chronic angina pectoris (p < 0.001). The reduction in CCS angina class was seen in patients with CCS class III and IV and persisted 12 months after EECP treatment. There was no significant relief in angina in patients with CCS class II prior to EECP treatment. 73 ± 7% of the patients with a reduction in CCS class after EECP treatment improved one CCS class, and 22 ± 7% of the patients improved two CCS classes. The improvement of two CCS classes could progress over a six months period and tended to be more prominent in patients with CCS class IV. In accordance with the reduction in CCS classes there was a significant decrease in the weekly nitroglycerin usage (p < 0.05). CONCLUSION: The results from the present study show that EECP is a safe treatment for highly symptomatic patients with refractory angina. The beneficial effects were sustained during a 12-months follow-up period

Development and evaluation of a cultural competency training curriculum

BACKGROUND: Increasing the cultural competence of physicians and other health care providers has been suggested as one mechanism for reducing health disparities by improving the quality of care across racial/ethnic groups. While cultural competency training for physicians is increasingly promoted, relatively few studies evaluating the impact of training have been published. METHODS: We recruited 53 primary care physicians at 4 diverse practice sites and enrolled 429 of their patients with diabetes and/or hypertension. Patients completed a baseline survey which included a measure of physician culturally competent behaviors. Cultural competency training was then provided to physicians at 2 of the sites. At all 4 sites, physicians received feedback in the form of their aggregated cultural competency scores compared to the aggregated scores from other physicians in the practice. The primary outcome at 6 months was change in the Patient-Reported Physician Cultural Competence (PRPCC) score; secondary outcomes were changes in patient trust, satisfaction, weight, systolic blood pressure, and glycosylated hemoglobin. Multiple analysis of variance was used to control for differences patient characteristics and baseline levels of the outcome measure between groups. RESULTS: Patients had a mean of 2.8 + 2.2 visits to the study physician during the study period. Changes in all outcomes were similar in the "Training + Feedback" group compared to the "Feedback Only" group (PRPCC: 3.7 vs.1.8; trust: -0.7 vs. -0.2 ; satisfaction: 1.9 vs. 2.5; weight: -2.5 lbs vs. -0.7 lbs; systolic blood pressure: 1.7 mm Hg vs. 0.1 mm Hg; glycosylated hemoglobin 0.02% vs. 0.07%; p = NS for all). CONCLUSION: The lack of measurable impact of physician training on patient-reported and disease-specific outcomes in the current has several possible explanations, including the relatively limited nature of the intervention. We hope that the current study will help provide a basis for future studies, using more intensive interventions with different provider groups

Visualization of Allostery in P-Selectin Lectin Domain Using MD Simulations

Allostery of P-selectin lectin (Lec) domain followed by an epithelial growth factor (EGF)-like domain is essential for its biological functionality, but the underlying pathways have not been well understood. Here the molecular dynamics simulations were performed on the crystallized structures to visualize the dynamic conformational change for state 1 (S1) or state 2 (S2) Lec domain with respective bent (B) or extended (E) EGF orientation. Simulations illustrated that both S1 and S2 conformations were unable to switch from one to another directly. Instead, a novel S1' conformation was observed from S1 when crystallized B-S1 or reconstructed “E-S1” structure was employed, which was superposed well with that of equilibrated S1 Lec domain alone. It was also indicated that the corresponding allosteric pathway from S1 to S1' conformation started with the separation between residues Q30 and K67 and terminated with the release of residue N87 from residue C109. These results provided an insight into understanding the structural transition and the structure-function relationship of P-selectin allostery

Methacholine bronchial provocation measured by spirometry versus wheeze detection in preschool children

BACKGROUND: Determination of PC(20)-FEV(1) during Methacholine bronchial provocation test (MCT) is considered to be impossible in preschool children, as it requires repetitive spirometry sets. The aim of this study was to assess the feasibility of determining PC(20)-FEV(1) in preschool age children and compares the results to the wheeze detection (PCW) method. METHODS: 55 preschool children (ages 2.8–6.4 years) with recurrent respiratory symptoms were recruited. Baseline spirometry and MCT were performed according to ATS/ERS guidelines and the following parameters were determined at baseline and after each inhalation: spirometry-indices, lung auscultation at tidal breathing, oxygen saturation, respiratory and heart rate. Comparison between PCW and PC(20)-FEV(1) and clinical parameters at these end-points was done by paired Student's t-tests. RESULTS AND DISCUSSION: Thirty-six of 55 children (65.4%) successfully performed spirometry-sets up to the point of PCW. PC(20)-FEV(1) occurred at a mean concentration of 1.70+/-2.01 while PCW occurred at a mean concentration of 4.37+/-3.40 mg/ml (p < 0.05). At PCW, all spirometry-parameters were markedly reduced: FVC by 41.3+/-16.4% (mean +/-SD); FEV(1) by 44.7+/-14.5%; PEFR by 40.5+/-14.5 and FEF(25–75) by 54.7+/-14.4% (P < 0.01 for all parameters). This reduction was accompanied by de-saturation, hyperpnoea, tachycardia and a response to bronchodilators. CONCLUSION: Determination of PC(20)-FEV(1) by spirometry is feasible in many preschool children. PC(20)-FEV(1) often appears at lower provocation dose than PCW. The lower dose may shorten the test and encourage participation. Significant decrease in spirometry indices at PCW suggests that PC(20)-FEV(1) determination may be safer

Caloric Restriction Suppresses Microglial Activation and Prevents Neuroapoptosis Following Cortical Injury in Rats

Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI

Designing a HER2/neu promoter to drive α1,3galactosyltransferase expression for targeted anti-αGal antibody-mediated tumor cell killing

INTRODUCTION: Our goal was to specifically render tumor cells susceptible to natural cytolytic anti-αGal antibodies by using a murine α1,3galactosyltransferase (mαGalT) transgene driven by a designed form of HER2/neu promoter (pNeu), the transcription of which is frequently observed to be above basal in breast tumors. Indeed, the αGalT activity that promotes Galα1,3Galβ1,4GlcNAc-R (αGal) epitope expression has been mutationally disrupted during the course of evolution, starting from Old World primates, and this has led to the counter-production of large amounts of cytotoxic anti-αGal antibodies in recent primates, including man. METHOD: Expression of the endogenous c-erbB-2 gene was investigated in various cell lines by northern blotting. A mαGalT cDNA was constructed into pcDNA3 vector downstream of the original CMV promoter (pCMV/mαGalT) and various forms of pNeu were prepared by PCR amplification and inserted in the pCMV/mαGalT construct upstream of the mαGalT cDNA, in the place of the CMV promoter. These constructs were transferred into HEK-293 control and breast tumor cell lines. Stably transfected cells were analyzed by northern blotting for their expression of αGalT and c-erbB-2, and by flow cytometry for their binding with fluorescein isothiocyanate-conjugated Griffonia simplicifolia/isolectin B4. RESULTS: We show that expression of the mαGalT was up- or down-modulated according to the level of endogenous pNeu activity and the particular form of constructed pNeu. Among several constructs, two particular forms of the promoter, pNeu250 containing the CCAAT box and the PEA3 motif adjacent to the TATAA box, and pNeu664, which has three additional PEA3 motifs upstream of the CCAAT box, were found to promote differential αGalT expression. CONCLUSION: Our results strengthen current concepts about the crucial role played by the proximal PEA3 motif of pNeu, and may represent a novel therapeutic approach for the development of targeted transgene expression