The effects of neuromuscular electrical stimulation for dysphagia in opercular syndrome: a case study

A 76-year-old man with opercular syndrome characterized by complete bilateral loss of voluntary control of facial, lingual, pharyngeal and masticatory muscles is presented with focus on the severe dysphagia. Three years earlier the patient had experienced two strokes resulting in opercular syndrome with severe dysphagia. Despite initial logopedic dysphagia treatment, swallowing did not improve. A new treatment for dysphagia, consisting of neuromuscular electrical stimulation was applied on the patient. He returned to oral feeding. Clinical and treatment observations are reported

Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

<p>Abstract</p> <p>Background</p> <p>Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident.</p> <p>Methods</p> <p>To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection.</p> <p>Results</p> <p>After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1)-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS). While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only.</p> <p>Conclusions</p> <p>Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.</p

Mechanisms of toxic smoke inhalation and burn injury: Role of neutral endopeptidase and vascular leakage in mice

The effects of neutral endopeptidase (NEP) in acute inflammation in the lung were studied using a newly developed murine model of smoke and burn (SB) injury. C57BL/6 mice were pretreated with an i.v. dose of a specific NEP antagonist CGS-24592 (10 mg/Kg) 1 h prior to SB injury (n = 5–8/group). Mice were anesthetized with i.p. ketamine/xylazine, intubated, and exposed to cooled cotton smoke (2 × 30 s). After s.c. injection of 1 ml 0.9% saline, each received a 40% total body surface area (TBSA) flame burn. Buprenorphene (2 mg/kg) was given i.p. and resuscitated by saline. Evans Blue dye (EB) was injected i.v. 15 min before sacrifice. Lung wet/dry weight ratio was measured. After vascular perfusion, lungs were analyzed for their levels of EB dye and myeloperoxidase (MPO). In mice pretreated with CGS-24592 followed by SB injury the EB levels were significantly higher (61%, p = 0.043) than those with SB injury alone. There was a significant increase (144%, p = 0.035) in EB dye in animals with SB injury alone as compared to shams. In mice pretreated with CGS-24592 prior to SB injury wet/dry weight ratios were significantly (27%, p = 0.042) higher compared to animals with SB injury alone. CGS-24592 pretreatment also caused a significant increase in MPO (29%, p = 0.026) as compared to mice with SB injury alone. In conclusion the current study indicates that specific NEP inhibitor CGS 24592 exacerbates the SB-induced lung injury and inflammation in mice

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT)

© 2017 The Author(s). Background: People with psychosis have a reduced life expectancy of 10-20years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. Methods: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. Results: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p= 0.034). The 22% of patients who received > 180min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. Conclusion: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. Trial registration: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926

Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

<p>Abstract</p> <p>Background</p> <p>Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with <it>P. aeruginosa </it>by a Th17-mediated mechanism.</p> <p>Results</p> <p>Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the <it>P. aeruginosa </it>strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against <it>P. aeruginosa </it>in vitro.</p> <p>Conclusions</p> <p>Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with <it>P. aeruginosa </it>in the CF lung.</p

Surrogate markers and survival in women receiving first-line combination anthracycline chemotherapy for advanced breast cancer

Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC) . From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R2=34%), complete tumour response (P=0.02, R2=12%), progressive disease (P<0.001, R2=38%) and time to progression (P<0.0001, R2=56%); R2 is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good

Effects of Therapy in Oropharyngeal Dysphagia by Speech and Language Therapists: A Systematic Review

Medical and paramedical treatments should be evaluated according to current standards of evidence-based medicine. Evaluation of therapy in oropharyngeal dysphagia fits into this growing interest. A systematic review is given of the literature on the effects of therapy in oropharyngeal dysphagia carried out by speech therapists. Thus, the review excludes reports of surgical or pharmacological treatments. The literature search was performed using the electronic databases PubMed and Embase. All available inclusion dates up to November 2008 were used. The search was limited to English, German, French, Spanish, and Dutch publications. MESH terms were supplemented by using free-text words (for the period after January 2005). Fifty-nine studies were included. In general, statistically significant positive therapy effects were found. However, the number of papers was rather small. Moreover, diverse methodological problems were found in many of these studies. For most studies, the conclusions could not be generalized; comparison was hindered by the range of diagnoses, types of therapies, and evaluation techniques. Many questions remain about the effects of therapy in oropharyngeal dysphagia as performed by speech and language therapists. Although some positive significant outcome studies have been published, further research based on randomized controlled trials is needed

Role of the Chemokine Receptors CCR1, CCR2 and CCR4 in the Pathogenesis of Experimental Dengue Infection in Mice

Dengue virus (DENV), a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1-/- mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2-/- mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4-/- mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection

Elevated 17β-Estradiol Protects Females from Influenza A Virus Pathogenesis by Suppressing Inflammatory Responses

Studies of the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the 2009 H1N1 pandemic illustrate that sex and pregnancy contribute to severe outcome from infection, suggesting a role for sex steroids. To test the hypothesis that the sexes respond differently to influenza, the pathogenesis of influenza A virus infection was investigated in adult male and female C57BL/6 mice. Influenza infection reduced reproductive function in females and resulted in greater body mass loss, hypothermia, and mortality in females than males. Whereas lung virus titers were similar between the sexes, females had higher induction of proinflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-6, and CCL2, in their lungs than males. Removal of the gonads in both sexes eliminated the sex difference in influenza pathogenesis. Manipulation of testosterone or dihydrotestosterone concentrations in males did not significantly impact virus pathogenesis. Conversely, females administered high doses of estradiol had a ≥10-fold lower induction of TNF-α and CCL2 in the lungs and increased rates of survival as compared with females that had either low or no estradiol. The protective effects of estradiol on proinflammatory cytokines and chemokines, morbidity, and mortality were primarily mediated by signaling through estrogen receptor α (ERα). In summary, females suffer a worse outcome from influenza A virus infection than males, which can be reversed by administration of high doses of estradiol to females and reflects differences in the induction of proinflammatory responses and not in virus load