tbuckley/cabot-search huggingface dataset:
Etiology pathogens structure in community-acquired pneumonias and COPD exacerbations
Authors: Alina Martynova, Ekaterina Nosuch, Alexander Sheparyov
Journal: European Respiratory Journal (2011)

Significance of the microbiology lab diagnostics results in community-acquired pneumoniae (CAP) and exacerbations of COPD still requires evaluation. As the most of them are ubiquitous, the microbiology peculiarities between them remains the keen medical and biological problem. Aim of our research was to define etiology structure of the main microbiology pathogens in CAP patients (1st group) and in COPD exacerbations (2nd group), and to estimate the microbiology differences in isolated strains of S. pneumoniae and H. influenzae.

Materials and methods: We examined 200 adults with CAP and 200 adults with COPD exacerbations of the same age (20-45 years), isolated strains of S.pneumoniae and H.influenzae were checked for antimicrobial agents resistance according to NCCLS standards, typed and studied by MLST.

Results: In the 1st group S. pneumoniae was isolated in 42%, H. influenzae in 26%. In the 2nd group pneumococci were isolated in 36%. Antimicrobial resistance (1st group vs 2nd group) of S. pneumoniae were characterized with resistance to erythromycine (14%/18%), levofloxacine (9%/7%).H. influenzae strains were resistant to co-trimoxazole (20%/27%) and ampicillin (24%/28%). Serotyping of S. pneumoniae revealed that the most of the 2nd group strains were of the serotypes including to the 23-polysaccharide vaccine. H. influenzae strains of the I, II, and III were the prevalent biotypes. MLST of S. pneumoniae showed the prevalence of several lineage clones in CAP strains (1st group).

Conclusion: The microbiological monitoring of the main respiratory pathogens could be significant instrument both in clinical diagnostics and in epidemiology surveillance of the lower respiratory tract infections.
Phase I/II lapatinib plus carboplatin and paclitaxel in stage III or IV relapsed ovarian cancer patients
Authors: S. E. Rivkin, C. Muller, D. Iriarte, J. Arthur, A. Canoy, H. Reid
Journal: Journal of Clinical Oncology (2008)

5556 Background: To establish the maximum-tolerated dose (MTD) and evaluate dose-limiting toxicities (DLTs) and response to therapy of combination therapy with carboplatin/paclitaxel and lapatinib, an oral dual tyrosine kinase inhibitor of both ErbB1 and ErbB2, in Stage III /IV relapsed ovarian cancer. Methods: This was an open-label, multicenter, phase I/II study of carboplatin/paclitaxel in combination with single agent lapatinib in Stage III/IV relapsed ovarian cancer patients. Measurable disease, adequate organ function and ECOG performance status of 0–2 were required. Patients received the metronomic maximum tolerated dose therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4 with lapatinib 1,000 mg po qd. Patients received combination therapy until disease progression. Patients were assessed for toxicity weekly and response to therapy every 8 weeks. The primary endpoints were toxicity and response to therapy. Results: 25 ovarian cancer patients are enrolled and four are too early to be evaluable. The median age is 57 (range 39–81). The median number of prior therapeutic regimens is 4 (range 1–10). GI toxicities were primarily ≤ grade 2 and were successfully treated with aggressive bowel management. 10 patients experienced grade 3 toxicities. 4- leukopenia, 2-neutropenia, 2-hyperglycemia, 2-allergic reactions to carboplatin, 1-thrombocytopenia, 1-lymphopenia, 1-hypokalemia, 1-nausea, 1-diarrhea, 1-bowel obstruction. Response to therapy to date is: CR=21%, PR=29%, SD=29%, PD=21%. Two patients who were in complete remission both stopped IV chemotherapy and were maintained only with lapatinib. One is still in remission after six months and one relapsed. Conclusions: Lapatinib, an oral targeted molecular therapy which inhibits both EGFR 1 and 2 tyrosine kinase activity, can be safely administered with a weekly regimen of carboplatin and paclitaxel in heavily pretreated, ovarian cancer patients. The high response rates seen warrant further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline
Origins of the new influenza A(H1N1) virus: time to take action
Authors: G M Nava, M S Attene-Ramos, J K Ang, M Escorcia
Journal: Eurosurveillance (2009)

To gain insight into the possible origins of the 2009 outbreak of new influenza A(H1N1), we performed two independent analyses of genetic evolution of the new influenza A(H1N1) virus. Firstly, protein homology analyses of more than 400 sequences revealed that this virus most likely evolved from recent swine viruses. Secondly, phylogenetic analyses of 5,214 protein sequences of influenza A(H1N1) viruses (avian, swine and human) circulating in North America for the last two decades (from 1989 to 2009) indicated that the new influenza A(H1N1) virus possesses a distinctive evolutionary trait (genetic distinctness). This appears to be a particular characteristic in pig-human interspecies transmission of influenza A. Thus these analyses contribute to the evidence of the role of pig populations as “mixing vessels” for influenza A(H1N1) viruses.
LSC 2013 abstract - Peripheral blood neutrophil chemotaxis and apoptosis in patients with allergic asthma challenged with dermatophagoides pteronyssinus
Authors: Simona Lavinskiene, Ieva Bajoriuniene, Jolanta Jeroch, Kestutis Malakauskas, Raimundas Sakalauskas
Journal: European Respiratory Journal (2013)

Background: Recent investigations suggest that neutrophils may play an important role in the allergen-induced inflammation in asthma [Monteseirin J., 2009; Kampe M. et al . 2011].

Aim: To analyze the changes of peripheral blood neutrophil chemotaxis and apoptosis in patients with allergic asthma after bronchial allergen challenge with Dermatophagoides pteronyssinus .

Methods: Thirty patients with allergic asthma (AA) and sensitized to D.pteronyssinus were enrolled into the study. They were compared with 30 patients with allergic rhinitis (AR), sensitized to D.pteronyssinus and 20 healthy individuals (HI). All subjects underwent bronchial challenge with D.pteronyssinus . Peripheral blood collection and neutrophil isolation were performed 24 h before as well as 7 h and 24 h after bronchial challenge. Neutrophil chemotaxis was evaluated after stimulation with IL-8. Annexin-V FITC was used to detect apoptotic neutrophils. Neutrophil chemotaxis and apoptosis were analyzed by flow cytometer.

Results: Before, 7 h and 24 h after the bronchial allergen challenge, neutrophil chemotaxis was greater in patients with AA compared with those with AR and HI as well. The apoptotic activity of neutrophils was lower before, 7 h as well as 24 h after the challenge in patients with AA than in HI. Meanwhile, differences on neutrophil apoptosis between AA and AR patients was found only 7 h and 24 h after the challenge.

Conclusions: Inhaled D.pteronyssinus activates peripheral blood neutrophil chemotaxis and reduces apoptosis in sensitized patients, that demonstrates enhancement of systemic inflammation.

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Usefulness of pulse transit time in diagnostics of paediatric sleep disorders
Authors: Marcin Kawalski, Grzegorz Namyslowski, Maciej Misiolek, Maciej Tazbirek
Journal: European Respiratory Journal (2013)

Sleep disordered breathing is common yet relatively rarely diagnosed. If left untreated, it leads to a number of consequences, ranging from primary snoring to complete sleep apnea syndrome with impaired intellectual and physical development.  Polysomnography is considered the diagnostic gold standard, however it has limitations, which prevent the widespread use such as limited number of properly staffed and equipped sleep laboratories and financial constraints. A sensitive, specific and economically viable method, which could be used for rapid identification of patients with sleep-disordered breathing is necessary.  The aim of the study was to evaluate the usefulness of pulse transit time in the screening diagnostics of sleep-disordered breathing in children. This method was compared with nocturnal oximetry, heart rate variability and evaluation of the cortical arousals.  The study included a group of 153 children aged 3-14 years, treated at the I.Moscicki Hospital because of suspected sleep-disordered breathing. All children underwent full polysomnography. Screening methods were assessed in regards of their ability to predict the outcome of the complete polysomnography examination. Pulse transit time (PTT) proved to be significantly correlated with the apnea-hypopnea index in all age groups.  Assessment of PTT has proved to be a more effective diagnostic tool than the other analyzed methods Pulse transit time is a sensitive indicator of the presence of sleep-disordered breathing in children and can distinguish among its various types. As a simple and inexpensive method it can be used in screening studies of respiratory sleep disorders in children.
Pituitary Gland
Authors: Nilsa Patritti-Laborde, Ada R. Wolfsen, David Heber, William D. Odell
Journal: Journal of Clinical Investigation (1979)

The development of a species specific radioimmunoassay for rabbit luteinizing hormone (LH) has permitted the direct demonstration of LH feedback control of LH secretion (short-loop feedback control). In previous studies we showed that small bolus injections of human LH (hLH) intravenously administered to castrate female rabbits suppressed rabbit LH for 20-30 min. Human LH had no effect on rabbit follicle-stimulating hormone secretion. This control system was responsive to amounts of hLH estimated to be present in blood of eugonadal men and women. These studies were designed to determine whether this feedback control was exerted at a pituitary or hypothalamic level. Two groups of studies were carried out: (a) in vivo studies: Rabbit LH was quantified in the blood of castrated female New Zealand White rabbits receiving either constant hLH perfusion (2.75 IU/min) or saline perfusion, plus a bolus injection of 0.5, 6, or 20 mug of gonadotropin-releasing hormone (GnRH). Human LH decreased the response to 6 and 20 mug of GnRH by 31 and 36%, respectively, and abolished the response to 0.5 mug, GnRH. (b) in vitro studies: Rabbit pituitary slices were incubated in the presence of medium alone, medium plus hLH (25 mIU/ml), medium plus GnRH (20 mug/ml), and medium plus both GnRH and hLH. hLH decreased basal rabbit LH release into the medium and abolished GnRH-stimulated rabbit LH release. hLH had no effect on rabbit follicle-stimulating hormone release. From these results we conclude that a direct and specific feedback control of LH on LH exists at a pituitary level.
Pulmonary infections as a result of stroke induced immunodepression
Authors: Claudia Dames, Levent Akyüz, Odilo Engel, Katarzyna Winek, Hans-Dieter Volk, Andreas Meisel, Christian Meisel
Journal: European Respiratory Journal (2013)

Pulmonary infection is a highly relevant complication and leading cause of death in patients with acute CNS injury. The high incidence of pneumonia in these patients is likely to be the result of temporary stroke induced immunodepression. We here analysed changes in cellularity and function of lung immune and epithelial cells by FACS and  ex vivo  stimulation at different time points after experimental stroke in mice. In addition, we monitored pulmonary host responses  in vivo  during the course of pneumococcal pneumonia by analyzing cellular changes, cytokine/ chemokine levels and barrier function in lungs of stroke mice and sham controls.  Analysis of cellularity at different time points after stroke showed a loss of interstitial macrophages within the first day after stroke as well as decreased numbers of dendritic cells and lymphocytes in lung. Functional analysis of immune cells indicates an impaired cytokine production in lung cells after  ex vivo  TLR stimulation. In a model of induced pneumonia we analysed the  in vivo  host response to  Streptococcus pneumonia  after stroke. Our data suggest that pulmonary phagocytes in stroke mice are not able to clear the bacteria. It seems that this results in a prolonged hyper-inflammatory response with increased cytokine levels in lungs followed by a disruption of the epithelial cell barrier function.  The correlation between impaired activation of pulmonary antimicrobial immune responses and development of infectious complications is still incompletely understood. A detailed knowledge of leukocyte recruitment and defects in anti-bacterial defences may lead to new therapeutic strategies such as local immunostimulatory treatment to prevent infections and improve outcome.
Lung ultrasonography as “porometry” of a frothy substrate
Authors: Andrea Smargiassi, Riccardo Inchingolo, Gino Soldati, Sara Sher, Roberta Marra, Rosanna Nenna, Cosimo Damiano Inchingolo, Salvatore Valente, Giuseppe Maria Corbo
Journal: European Respiratory Journal (2014)

Background:  Interaction of ultrasounds with aerated peripheral lung parenchyma can determine echographic artifactual vertical phenomena, often associated to pathological patterns. A fine scientific explanation of these artefacts hasn9t been yet proposed. The “spongy” nature of the lung in its liquid and dry components might be the key point to understand these phenomena in case of changing of superficial density and porosity.   Methods:  Six excised right lungs were obtained from 6 white rabbits. Each lung underwent directly ultrasound (US) evaluation in two different condition: at complete tissue elastic recoil and at pulmonary expansion achieved by applying a constant positive pressure(12 cmH2O) through the bronchial lumen. Lung volumes and densities were reported in both conditions. Histological examination was performed after fixing in formalin solution 3 lungs while applying positive pressure and 3 lungs naturally collapsed.   Results:  Mean volumes of collapsed and expanded lungs were 10.6±0.4 and 47±5mL respectively (p   Conclusions: Airspace geometry, frothy nature and porosity are determinants of the different behaviour of US interacting with the peripheral lung parenchyma. Lung US may be interpreted as indirect “estimator” of lung porosity.
Changing demographics of locally advanced breast cancer: Data from a regional cancer centre
Authors: R. Segal, S. F. Dent, S. Verma, C. M. Canil, J. Azzi, L. Vandermeer, J. Spaans
Journal: Journal of Clinical Oncology (2006)

10780 Background: Locally advanced breast cancer (LABC) (including inflammatory breast cancer (IBC)) accounts for less than 5% of women diagnosed with breast cancer in North America each year. This population of women continues to represent a challenge in terms of timely diagnosis and treatment. Methods: A retrospective database was developed using the American Joint Committee on Cancer (AJCC)2002 staging classification for all women who presented to TOHRCC with LABC between Jan 1/02 - April 1/05. Information was abstracted from clinic charts and the patient self-reported health questionnaires. Results: These results reflect the demographics of the first 50 women entered into our database. Median age at presentation was 57 years (range 28–88); 62% were post-menopausal and 28% had a 1 st /2 nd degree relative with breast cancer. Clinical diagnosis was made by: self-detection (79%); mammography (5%), routine physical exam (9%) and CT scan (2%). Clinical tumour stage at presentation was: IIIA (25.6%); IIIB (53.5%) and IIIC (9.3%). The majority of women were diagnosed with infiltrating ductal carcinoma (72%). Women with T4d tumours (IBC) (38%) tended to be younger (54.5 vs 59.2 years); presented earlier (2.7 vs. 6.3 months); had larger tumours at the time of diagnosis (9.7 vs 5.5 cm); were more likely grade III (30 vs 20%) and were more often ER negative (42.1% vs 33.3%) and PR negative (63.2% vs. 50%). Only 13% of women in this database were tested for HER-2 of whom 70% were positive. Conclusions: This data utilizing the new AJCC (2002) staging system reflects important shifts in LABC that will influence clinical care in the future. Compared to historical databases, patients tended to be younger and have more aggressive disease including ER negative and HER-2 positive disease. Supplemental microarray studies to further explore this entity are planned. We will present clinical management outcomes in an additional submission. No significant financial relationships to disclose.
Combination chemotherapy (5-fluorouracil, methyl-CCNU, mitomycin C) versus 5-fluorouracil alone for advanced previously untreated colorectal carcinoma. A phase III study of the Piedmont Oncology Association.
Authors: F Richards, L D Case, D R White, H B Muss, C L Spurr, D V Jackson, M R Cooper, P Zekan, J Cruz, J J Stuart
Journal: Journal of Clinical Oncology (1986)

One-hundred thirty eligible patients with advanced colorectal carcinoma who had received no prior chemotherapy were randomized to either methyl-CCNU, 70 mg/m2 orally every 6 weeks on day 1, mitomycin C, 10 mg/m2 intravenously every 6 weeks on day 1, and 5-fluorouracil (5-FU), 400 mg/m2 intravenously weekly--(MMF)--or 5-FU, 600 mg/m2 intravenously weekly (5-FU). One hundred twenty-six patients are evaluable for response. Of 62 patients treated with MMF, one (2%) achieved complete remission, and three (5%) attained partial remission. Of 64 patients treated with 5-FU, two (3%) achieved complete remission, and eight (13%) attained partial remission. The median survival for patients receiving MMF was 9.5 months compared with 10.3 months for patients receiving 5-FU. The survival distributions for the two regimens were not significantly different, either unadjusted or adjusted for pretreatment characteristics. Performance status and lactic dehydrogenase (LDH) were both significantly associated with survival. Patients with liver metastases only and normal liver function tests had a median survival of 19.8 months and a 40% response rate. This randomized phase III trial did not show any therapeutic advantage for MMF compared to 5-FU therapy alone in advanced colorectal cancer. In addition, hematologic toxicity was significantly greater with the combination (MMF) regimen.
Salicylate-induced increases in free triiodothyronine in human serum
Authors: P. R. Larsen
Journal: Journal of Clinical Investigation (1972)

Addition of sodium salicylate to human serum at concentrations often obtained during aspirin therapy causes 100-200% increases in free triiodothyronine (T(3)) and free thyroxine (T(4)) as estimated by ultrafiltration. The increase in free T(3) was unexpected since previous data had suggested that salicylate inhibits binding of T(4) only to thyroxine-binding prealbumin (TBPA) and that T(3) is not bound to this protein. Using ultrafiltration techniques, we demonstrated binding of T(3) to TBPA. The affinity constant for T(3)-TBPA binding appears to be slightly greater than that for albumin-T(3) binding. While salicylate inhibits the binding of T(3) (and T(4)) to TBPA, it can be predicted that little change will be observed in the free T(3) (or free T(4)) without inhibition of thyroid hormone binding to thyroxine-binding globulin (TBG). Using a competitive-binding protein displacement technique, it has been shown that sodium salicylate, like diphenylhydantoin (DPH), inhibits the binding of T(3) and T(4) to TBG. The magnitude of the increase in free T(3) and free T(4) induced by salicylates suggests that interference with TBG binding is its major effect. Aspirin was administered orally to two normal subjects in quantities sufficient to obtain serum salicylate levels of 20-25 mg/100 ml. This resulted in a decrease of 20-30% in total serum T(3) and T(4) levels. This decrease in T(4) levels is similar in magnitude to that previously observed in subjects receiving DPH. Unlike what has been observed with DPH treatment, therapeutic salicylate levels are associated with increases of 50-75% in the unbound fraction of both T(3) and T(4) which persist throughout an 8-10 day treatment period.
Serial interferon-gamma release assays for screening and monitoring of tuberculosis infection during treatment with biologic agents
Authors: Adriana Socaci, Gheorghe Nini, Constantin Marica, Erdin Borgazi
Journal: European Respiratory Journal (2013)

Introduction. Screening for latent tuberculosis infection (LTBI) prior to the prescribing of anti-TNF agents and monitoring for infection during treatment are recommended. Aims. We assessed the efficacy of serial interferon-gamma release assays (IGRAs) for the diagnosis and monitoring of latent tuberculosis infection (LTBI) in patients receiving immunosuppressive agents for treatment of rheumatic diseases, in an endemic area. Methods. We conducted a prospective study on patient candidates to biologic agents. QuantiFERON-TB Gold In-Tube (QFT-GIT) was performed at baseline and after 3 and 6 months since biologic onset. A further follow-up period of 6 months was observed. Results. Among patients enrolled (n = 66, F = 57.6%), 13 (19.7%) had at least 1 risk factor for LTBI. Fifty-three were taking immunosuppressants at the time of TB testing. At baseline, 16 (24.2%) patients displayed positive, 43 (65.2%) negative, and 7 (10.6%) indeterminate QFT-GIT results.69.7% (n=46) pacients showed consistent IGRA results during follow-up, and, 19.7% (n=13) had consistently positive results. QFT-GIT conversion rate was 12.1% (8/66) and reversion rate was 4.5% (3/66). QFT-GIT results changed of 28 % at month 3 and of 21 % at month 6; the greatest change was observed in patients with indeterminate results that became negative (15 %; p
Asthma registry, a path to uncover pitfalls in asthma
Authors: Syed Alireza Mahdaviani, Seyed Amir Mohajerani, Majid Malekmohammad, Soheila Khalilzadeh, Atefeh Fakharian, Alireza Eslaminejad, Maryam Hasanzad, Mohammad Reza Masjedi, Ali Akbar Velayati, Mazaher Ebrahimian
Journal: European Respiratory Journal (2012)

Background: Demographic aspects of different variants of asthma are not well known. It seems necessary to register and follow all age patients with asthma in a tertiary respiratory referral center to uncover many pitfalls in diagnosis and treatment.  Aim: We have developed Asthma Registry System which includes pediatrics and adolescents9 patients in NRITLD, the largest respiratory referral center in Iran, in order to register and report asthma prevalence, demographic characteristics and follow-ups.  Methods: Asthma Registry software was developed and launched in September 2011, and thereafter all patients referred to our clinics were visited, diagnosed and followed up by Allergist. All demographic and follow data were recorded in the system.  Results: 163 patients with proved asthma based on clinical and labs were recorded in the Registry System. Among this, 79 males and 84 females were recorded. 26.6% of patients had less than 6 years age, 27.2% between 6-18 years old and 34.8 % had more than 18 years old. 71.2% of patients symptoms aggravated with upper respiratory tract infections, 45% had exercise induced asthma, and 21% aggravated with aeroallergens, and more interestingly 88% aggravated with air pollution. 2.2% had mild intermittent asthma, 31% had mild persistent, 60% had moderate persistent, and 6.5% had severe persistent asthma. Accompanying disease were allergic rhinitis in 39.7%, dermatitis atopic in 15%, drug allergies in 4.9%, and urticaria in 7.6%. Chief complaints were cough in73%, wheeze in 46%, and dyspnea in 88%.  Conclusion: Our study indicates the need for a thorough analysis of demographic data, labs, and follow ups in asthma patients by a Registry System in a respiratory referral center.