tbuckley/cabot-search huggingface dataset:
KCa3.1 mediates αSMA expression in human lung myofibroblast via the Smad2/3 and TGFβ1 signalling pathway
Authors: K.M. Roach, C. Feghali-Bostwick, H. Wulff, P. Bradding
Journal: European Respiratory Journal (2014)

Introduction 

Idiopathic pulmonary fibrosis (IPF) is a common and invariably lethal interstitial lung disease with no effective therapy. KCa3.1 ion channel blockade inhibits several TGFβ1-dependent cell processes in human lung myofibroblasts (HLMFs), including contraction and collagen secretion. We hypothesised that KCa3.1 channel-dependent cell processes regulate HLMF αSMA expression via TGFβ1 signalling pathways.

Methods 

HLMFs grown in vitro were examined for αSMA expression by immunofluorescence (IF), RT-PCR and flow cytommetry. Two specific and distinct KCa3.1 blockers (TRAM-34 200 nM and ICA-17043 [Senicapoc] 100nM) were used to determine their effects on TGFβ1-dependent processes. Expression of phosphorylated and total Smad 2/3 following TGFβ1 stimulation were examined by western blot and Smad 2/3 nuclear translocation examined by immunofluorescence.

Results 

Constitutive αSMA expression in HLMFs was inhibited by the TRAM-34 and ICA-17043 (P<0.0001). TGFβ1-dependent increases in αSMA protein and mRNA expression in HLMFs were also inhibited by KCa3.1 channel blockers . TGFβ1- stimulated cells also showed increased mRNA expression of collagen type I (P=0.0378), and KCa3.1 (P=0.0313), which were inhibited by TRAM-34 and ICA-17043. After 1 hour of TGFβ1 stimulation, both phosphorylation of Smad 2/3 and Smad 2/3 nuclear translocation were inhibited by KCa3.1 channel block.

Conclusions 

KCa3.1 activity promotes αSMA expression and myofibroblast differentiation through the TGFβ1/Smad signaling pathway. KCa3.1 blockers may offer a novel approach to treating IPF with the potential for rapid translation to the clinic.

This work was funded by the The Dunhill Medical Trust.
Different patterns of exhaled NO response to acute bronchodilation in asthma
Authors: Isabelle Etienne, Andrei Malinovschi, Alain Van Muylem, Alain Michils
Journal: European Respiratory Journal (2013)

Background : It is known that exhaled nitric oxide (FENO) decrease after bronchial provocation. Divergent results on the bronchodilators effect on FENO have been reported in asthma patients.

Aim: To investigate the acute effects of bronchodilation on FENO and peripheral lung function in patients with stable asthma.

Methods : FENO, FEV1, and the slope of phase III of He (SHe), and SF6 (SSF6) from a FRC+1L single-breath test (lower slope indicating less peripheral obstruction) were measured in 46 asthma patients before and 15 minutes after inhaled salbutamol (400µg via pMDI).

Results : As a whole group, no significant effect of acute bronchodilation was observed on FENO. (D=6.0±24.6%, p=0.26). FENO increased in 22 patients (Δ=15.6±11.4%; p<0.001) (NO+ group) and decreased in 24 patients (Δ=-25.8±14.5%; p<0.001) (NO- group). Baseline values were similar in the NO+ and NO- groups for FENO (p=0.94), FEV1 (p=0.91), SHe (p=0.26) and SSF6 (p=0.25).

Similar FEV1 improvements were found in both groups (15% vs 14.6%, p=0.93) In the NO+ group, neither SHe nor SSF6 decreased significantly (-18.4±34.8% p=0.146; -6.9±42.2% p=0.52), whereas in the NO-, both SHe and SSF6 decreased significantly (-20.8±40.2% p=0.007; -21.0±28.4% p=0.004).

Discussion : A large proportion of asthma patients decreased FENO. This paradoxical behaviour may be due to a more pronounced peripheral bronchodilator effect, which would amplify back-diffusion of NO and, hence, reduce FENO. Subjects increasing FENO after bronchodilation may have a predominant dilation of more central airways.

Conclusion : Specific NO behaviour after acute bronchodilation may help to identify different asthma phenotypes based on the bronchoconstriction location.
First long-term experience with intravenous treprostinil administered by the implantable infusion pump LenusPro. A single-center pilot study
Authors: Regina Steringer-Mascherbauer, Veronika Eder, Charlotte Huber, Susanne Wittrich, Reinhold Fuegger, Uwe Fröschl, Hans Joachim Nesser
Journal: European Respiratory Journal (2012)

Introduction  Parenteral prostanoids are considered to be the most potent agents in the treatment of pulmonary arterial hypertension (PAH). However, administration of prostanoids with external pump systems is technically challenging and associated with side effects such as infusion site pain with subcutaneous (s.c.) and possibly life-threatening catheter-related infections with intravenous (i.v.) administration. The Lenus Pro implantable infusion pump was specifically developed to overcome the drawbacks of s.c. administration. In 2010, we reported the first implantation of a Lenus Pro pump with a filling interval of 28 days.  Results  Between September 2010 and October 2011, 14 patients underwent implantation at our center. All patients had previously shown significant clinical response to s.c. Treprostinil but suffered from site pain. Implantations were performed under general anesthesia. After preparation of the pump pocket in the abdominal wall the pump was connected to the central venous access. No intraoperative complications occurred. Postoperatively two patients developed a mild seroma. No other complications especially no infections were observed. Up to now more than 100 refill procedures were performed.  Conclusions  This first pilot study demonstrates that i.v. Treprostinil, delivered by the implantable pump Lenus Pro® is safe, effective and feasible in PAH patients transitioned from s.c. Treprostinil. Filling intervals of 28 days ensure optimal compliance and long-term patient management. The absence of side effects such as infusion site pain is associated with a dramatic increase in quality of life.
Comorbidity, hospitalization and mortality in COPD: Results from a longitudinal study
Authors: Fabio Di Stefamo, Vittoria Conti, Angelo Petroianni, Claudio Terzano
Journal: European Respiratory Journal (2012)

Objective   To evaluate comorbidity, hospitalization and mortality in COPD patients.   Design   Prospective longitudinal study.   Participants    95 COPD patients admitted consecutively to a Respiratory Medicine ward from 1999 to 2000 for an acute exacerbation of the disease and followed up from the date of discharge to september 2007.   Results   Mean follow up period of 6 +/- 1.4 yrs. Hypertension the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), cardiac diseases (22.1%) and peripheral arterial vascular diseases (17.9%). 359 hospitalizations with the leading cause being exacerbation of COPD (41.2%); cardiovascular disease (34.4%); COPD exacerbation concomitant with an other acute disease (8.4 %). 19 deaths (20%) by the end of follow up with causes being mostly cardiovascular (13 patients, 13.7%). Survival analysis through Cox regression showing mortality risk depending on age, current smoking, pO2, Charlson index, presence of ischemic heart disease and lung cancer as comorbidity. Multivariate logistic regression analyses showing number and length of hospital admissions depending on Charlson index and degree of dyspnoea. Presence of diabetes as comorbidity independent predictor of longer hospital admission.   Conclusions High prevalence of comorbidity, particularly cardiovascular disease being the main cause of death. Level of frailty depending on comorbidities of COPD geriatric hospitalized patients related to their prognosis. Implementation of aggressive strategies to prevent or treat comorbidities necessary for a better care of patients, together with the correct management of the respiratory disease.
Breast Cancer and Artificial Menopause: A Cohort Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Manning Feinleib
Journal: JNCI Journal of the National Cancer Institute (1968)

A cohort study of the occurrence of breast cancer among 6,908 women undergoing artificial menopause from 1920 through 1940 and among 1,479 women having natural menopause is presented. The nature of the artificial menopause was determined from surgical and pathologic records in each case, and follow-up information through 1961 was obtained from hospital records, death certificates, and Tumor Registry data. The expected mortality from, and incidence of, breast cancer among the study cohorts were calculated from published rates and adjusted for estimated migration and incompleteness of follow-up. Among 1,278 women with artificial menopause induced by hysterectomy with bilateral oophorectomy before age 40, six had breast cancer, 3 of whom died, as compared to an expected incidence of 24.0 patients with 11.3 deaths. The differences in both the incidence and mortality rates were highly significant. Incidence of, and mortality from, breast cancer in the cohorts of women undergoing noncastrating gynecologic surgery or receiving pelvic irradiation before age 40 did not differ significantly from expected values or from the rates among a control group of women undergoing cholecystectomy. Breast cancer rates among women undergoing gynecologic surgery after age 40, with or without castration, also did not differ significantly from expected values or from the rates among appropriate controls, but the incidence of breast cancer among women age 40–44, receiving pelvic irradiation, was significantly lower than expected. The protective effect of early surgical castration was observed in both parous and nulliparous women. It is concluded that, by curtailing cyclic ovarian function, surgical castration before age 40 reduces the risk of developing breast cancer by approximately 75%, but that other forms of artificial menopause or castration after age 40 does not afford such protection. Pelvic irradiation may also have a protective effect, but the relationship to age is not entirely clear.
Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial.
Authors: D W Northfelt, B J Dezube, J A Thommes, B J Miller, M A Fischl, A Friedman-Kien, L D Kaplan, C Du Mond, R D Mamelok, D H Henry
Journal: Journal of Clinical Oncology (1998)

PURPOSE Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS). PATIENTS AND METHODS Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes. RESULTS Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P &lt; .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin. CONCLUSION Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.
Clinical use of a standard kit-preparation of radiolabeled monoclonal antibody 96.5 in the diagnostic imaging of metastatic melanoma.
Authors: M N Saleh, D M Miller, L Peterson, C D Russell, M W Unger, M M Urist, R H Wheeler, A F LoBuglio
Journal: Journal of Clinical Oncology (1988)

We studied the efficiency of a standard-kit preparation using 1 mg 111In-labeled 96.5 monoclonal antibody in combination with 19 mg of unlabeled antibody in the diagnostic imaging of 27 patients with documented metastatic melanoma. Twenty-three of 26 patients (88%) demonstrated immunoscintigraphic localization of tumor. Of 104 metastatic sites previously documented by conventional studies, 62 (60%) were identified by immunoscintigraphy. A total of 77 sites demonstrated localization of radiolabeled antibody. Fifty-four (70%) corresponded to known sites of disease; eight sites (10%) were "discovered" by immunoscintigraphy and subsequently confirmed by conventional studies; 15 imaged sites (20%) could not be confirmed by conventional studies. Size and location of metastasis appear to be important features that influence imaging efficiency. Tumor size (greater than or equal to 2 cm v less than 2 cm) appears to be the statistical dominant determinant. The feasibility and potential clinical use of radioimmune imaging of tumors is discussed.
Conventional TBNA - A underutilized but valuable technique during bronchoscopy in comparsion with other conventional diagnostic techniques (CDTs) in diagnosing lung malignancies
Authors: Patil Shital, Agarwal Kailash, Gopal Purohit, Sharvan Rao, C.C. Deepu, J. Mohan
Journal: European Respiratory Journal (2013)

Methods-Prospective study during 2011-12 at K N Chest Hospital Jodhpur,India to find the role of TBNA technique during FOB in comparision to other CDTs in Diagnosing Lung malignancies,having 210 patients on the basis of clinical and radiological features of malignancy.FOB abnormalities were categorized as Exophytic Endobronchial Lesions (EEL), Submucosal Lesions(SML), Peribronchial Lesions(PBL) and No abnormality.TBNA and other CDTs like FB,BB and BWwere performed.Chi Square test was used.Results-In EEL yield of TBNA, CDTs and TBNA plus CDTs were 62.60%, 79.67% and 84.55% respectively.Yield difference of all these techniques is highly significant (p 0.8). In PBL TBNA has significant yield i.e. 63.41% individually as compared to Forcep biopsy 26.82% and CDT 39.02% (p
Clinical Implications of Circulating Angiogenic Factors in Cancer Patients
Authors: Ronnie Tung-Ping Poon, Sheung-Tat Fan, John Wong
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Angiogenesis, a process fundamental to tumor growth, is regulated by angiogenic factors. This article reviews prognostic and other clinical implications of circulating angiogenic factors in cancer patients. METHODS: A MEDLINE search of literature was performed using the names of various angiogenic factors as the key words. Studies pertaining to circulating angiogenic factors in cancer patients were reviewed. Pertinent literature regarding tumor expression of common angiogenic factors and their prognostic relevance in human cancers were also examined. RESULTS: A substantial number of studies have demonstrated a strong association between elevated tumor expression of vascular endothelial growth factor (VEGF) and advanced disease or poor prognosis in various cancers. This supports the pivotal role of VEGF in regulating tumor angiogenesis. More recently, there is mounting evidence that the level of circulating VEGF in patients with different types of cancer may be predictive of tumor status and prognosis. Preliminary data also suggest that circulating VEGF may be useful in predicting and monitoring tumor response to anticancer therapies and in follow-up surveillance for tumor relapse. There are reports supporting the prognostic value of other circulating angiogenic factors such as basic fibroblast growth factor, platelet-derived endothelial cell growth factor, transforming growth factor-beta, and angiogenin, but their clinical significance is less conclusive because of limited data. CONCLUSION: Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.
Immunological Determinants of Avian Sarcoma Viruses: Presence of Group-Specific Antibodies in Fowl Sera Demonstrated by Complement-Fixation Inhibition Test
Authors: G. F. Rabotti, E. Blackham
Journal: JNCI Journal of the National Cancer Institute (1970)

A complement-fixation inhibition test revealed antibodies in the sera of fowls immunized with Rous sarcoma virus (RSV). These antibodies were specific for antigen preparations of representative members of the avian leukosis complex and cross reacted with all antigens tested with the characteristics of group-specific antibodies. The antigens studied included: 1) chick-embryo tissue-cultured cells infected with the following strains of RSV—Bryan high-titer (BH-RSV), Schmidt-Ruppin (SR-RSV), Harris (H-RSV), and a strain of avian lymphomatosis RPL12; 2) tumors induced in chickens, turkeys, and Japanese quail with BH-RSV and SR-RSV; and 3) hamster tumors induced by SR-RSV. The RSV group-specific antibodies in fowl sera had no neutralizing activity.
Prevention and reversal of endotoxin-induced pulmonary hypertension by a leukotriene antagonist
Authors: T Ahmed, B Weichman, M A Wasserman, R Muccitelli, S Tucker, B Marchette
Journal: European Respiratory Journal (1988)

We investigated the role of leukotrienes in endotoxin-induced changes in pulmonary circulation. In six conscious sheep, haemodynamic measurements were obtained for the calculation of pulmonary vascular resistance (PVR), along with measurements of arterial oxygen tension (PaO2), leucocyte count (WBC), thromboxane B2 (TxB2), 6-Keto-PgF1 alpha and PgF2 alpha, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 microgram/kg), with and without treatment with the leukotriene receptor antagonist, FPL-57231. Endotoxin caused a biphasic response (i.e., phase I = 0-1 h, phase II = 1.5-4 h), with a mean +/- SE increase in PVR to 415 +/- 112% of baseline during phase I and a lesser increase of 175% (range = 153-199%) of baseline during phase II. Mean +/- SE PaO2 decreased from 86 +/- 4 to 67 +/- 6 mmHg and WBC count decreased from 8.6 +/- 0.6 to 2.8 +/- 0.7 thousand/mm3 during phase I, whereas TxB2 increased from 145 +/- 28 to 3164 +/- 1082 pg/ml, 6-Keto-PgF1 alpha from 129 +/- 14 to 438 +/- 114 pg/ml and PgF2 alpha from 122 +/- 7 to 242 +/- 43 pg/ml. One hour infusion of FPL-57231 (1 mg/kg/min) administered prior to and throughout phase I attenuated the phase I increases in PVR without preventing the increases in TxB2; however, it partly attenuated 6-Keto-PgF1 alpha and enhanced generation of PgF2 alpha during phase I. Discontinuation of FPL-57231 was followed by an exaggerated response of PVR during phase II to an average of 209% of baseline (range = 186-235%).(ABSTRACT TRUNCATED AT 250 WORDS)
Patients' experiences immediately prior to admission for an acute exacerbation of chronic obstructive pulmonary Disease (AECOPD)
Authors: Charlotte Spencer, Doytchin Dimov
Journal: European Respiratory Journal (2014)

Introduction

There are ever increasing pressures for hospital beds with COPD being one of the top three leading causes of medical admission. The aim of this observational study was to analyse the events immediately prior to hospital admission for AECOPD and identify targets for interventions to reduce burden on the emergency departments.

Methods: We surveyed 40 consecutive patients admitted to the respiratory wards with AECOPD with a questionnaire covering areas such as home support, self management resources, usual treatment, recent contact with health care professionals, acute treatments and management on arrival to hospital.

Results: 40% of the patients admitted to hospital lived in their own home alone, 52% own home with somebody while 3% were admitted from care homes. 71% of the patients reported that the first point to call prior to the admission was a family member. This suggests that the availability of a suitably trained carer may be a factor influencing the decision to present to the hospital versus treatment at home. 37% of the patients were referred to the hospital by a clinician while 41% made the decision themselves or were advised by a family member raising the possibility that access to reliable out of hospital point of contact in case of crisis may be important factor in avoiding admissions.

Conclusion: Our results suggest that education of carers and family members as part of a COPD action plan and providing reliable access to out of hospital clinical assessment and advice have the potential to help reducing the burden on emergency departments.
Outcome of patients discharged from rapid access lung clinic (RALC) with non cancer diagnosis: Five year follow up
Authors: Andrew Wight, R. Sarkar, Lorraine Creech, Robert Stead, Marta Babores
Journal: European Respiratory Journal (2011)

Introduction:  Since publication of NICE guidelines in 2000 RALC has become standard practice. These clinics target service towards diagnosis of lung cancer, with streamlined investigation and MDT discussion. We set up our RALC in 2003.   Aim:  To assess if patients discharged from RALC without a diagnosis of cancer had received adequate care and were not re-presenting with malignancy.   Methods:  We analysed a random selection of patients discharged from RALC without diagnosis of cancer from 2003-5.  Data collected: investigations, duration of follow-up, diagnosis on discharge and 5 year outcome   Results:  A total of 220 patients were discharged during the study period from or RALC without a diagnosis of lung cancer and 55 were analysed. Male: 28. Average (SD) age 63 (14). CT scan was done in 43 patients (78%) and bronchoscopy in 20 (36%). All the cases were discussed at MDT. 30% of patients were discharged from RALC with 70% discharged to respiratory out patient follow-up. Main diagnoses on discharge were: infection (38%), COPD (15%), benign nodules/plaques (10%), interstitial lung disease (7%), bronchiectasis (7%), vascular (7%), others (15%). Median (range) follow-up in RALC was 24 (0-700) days. 14 (25%) patients died over the 5 years, with average age when first seen of 76 (range 61-86). Cause of death was: non respiratory malignancy (5), cardiac disease (3) and infective causes (6). None of these deaths was related to initial presentation to RALC. No patients developed lung cancer over the duration of study.   Conclusion:  Our five year follow up study shows that streamlined investigations and MDT input in RALC is effective in ruling out lung cancer.
Dendritic Cells in Chronic Obstructive Pulmonary Disease
Authors: Maria Tsoumakidou, Ingel K. Demedts, Guy G. Brusselle, Peter K. Jeffery
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Section:ChooseTop of pageAbstract <<CURRENT VIEWS ON DENDRITI...DC ALTERATIONS INDUCED BY...HYPOTHESIS LINKING DCS TO...CONCLUSIONSReferencesCITING ARTICLES
Compassion can be learnt and must be integrated into practice
Authors: Susan Maciver, Chris McGregor, Jenny Robertson, Tom C Russ, Christine Wilson
Journal: BMJ (2015)

The word compassion is often heard in connection with care provided by health and social care professionals but often without the thoughtful attitude seen in Chadwick’s article.1 We have previously suggested that compassion is in danger of becoming a jargon term and, as a result, losing some of its …