tbuckley/cabot-search huggingface dataset:
The correlation of echocardiographic findings with BNP, blood uric acid and CPR in OSAS patients with manifest right cardiac pathologies
Authors: Omer Araz, Elif Yilmazel Ucar, Hüsnü Degirmenci, Didem Pulur, Metin Gorguner, Metin Akgun
Journal: European Respiratory Journal (2012)

Purpose:  BNP can increase in various disease states including left cardiac disorders and many others out of the former. We aimed in the present study to evaluate, possible relationship between B-type Brain Natriuretic Peptide (BNP) and some other non-invasive indicators of hypoxia, such as blood uric acid and C-reactive protein CRP, and the right cardiac pathologies.   Method:  A total of 98 subjects, 31 (31.6%) normal, 33 mild-moderate OSAS (33.7%) and 34 (34.7%) severe OSAS, with mean age 48.5±12.3 were included in the study. All the cases underwent the PSG and TDE examinations. BNP, CRP and blood uric acid levels were measured in all the cases.   Results:  Upon evaluating the relationship between BNP and TDE-related parameters, BNP level is found to be positively correlated with such TDE-related parameters as pulmonary artery pressure (PAP) and left atrium dimension. Moreover, uric acid was found to be statistically correlated positively with the left ventricle end diastole volume, right atrium dimension (RA), interventricular septum (IVS) thickness, but a negative correlation with mitral deceleration time (DT) and ratio of early and lately mitral flow velocity (E/A). Upon adjustment of all the findings for age and body mass index (BMI), three parameters were detected to have statistically significant relationship with PAP, RV, RA and IVS thickness.   Conclusion:  In conclusion BNP, CRP and blood uric acid levels can be used as adjunctive parameters in the diagnosis and follow-up of right heart pathologies in patients with severe OSAS.
Sleep Pharmacogenetics: Personalized Sleep-Wake Therapy
Authors: Sebastian C. Holst, Amandine Valomon, Hans-Peter Landolt
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players in the regulation and maintenance of sleep-wake-dependent changes in neuronal activity and the sleep-wake continuum. Dysregulation of these neurochemical systems leads to sleep-wake disorders. Most currently available pharmacological treatments are symptomatic rather than causal, and their beneficial and adverse effects are often variable and in part genetically determined. To evaluate opportunities for evidence-based personalized medicine with present and future sleep-wake therapeutics, we review here the impact of known genetic variants affecting exposure of and sensitivity to drugs targeting the neurochemistry of sleep-wake regulation and the pathophysiology of sleep-wake disturbances. Many functional polymorphisms modify drug response phenotypes relevant for sleep. To corroborate the importance of these and newly identified variants for personalized sleep-wake therapy, human sleep pharmacogenetics should be complemented with pharmacogenomic investigations, research about sleep-wake-dependent pharmacological actions, and studies in mice lacking specific genes. These strategies, together with future knowledge about epigenetic mechanisms affecting sleep-wake physiology and treatment outcomes, may lead to potent and safe novel therapies for the increasing number of sleep-disordered patients (e.g., in aged populations).
Comparison of outcomes of the Actigraph and the Dynaport activity monitor in patients with COPD; results from PROactive
Authors: Juliana Maria Sousa Pinto, Thierry Troosters, Laurence Vranken, Miek Hornikx, Heleen Demeyer, Wim Janssens, Marc Decramer, Judith Garcia-Aymerich
Journal: European Respiratory Journal (2012)

Activity monitors are increasingly used to assess physical activity. We aimed to compare wearing time and walking between two activity monitors in COPD. Fifty four patients (FEV1 62±22%pred, 6MWD 495±138m) wore the Actigraph (AG) and Dynaport (DP) twice for 14 days with 14 days in between, in the frame of the PROactive project. Wearing time (h/d); walking time(min/d) of DP (DPWT) and steps/day of AG (AGsteps) were retrieved. Calculations were done on the mean wearing and walking variables obtained over 28 days (Inter-patient correlations). Intra-patient correlations were calculated over the 28 days obtained in each patient, as well as between mean weekly values of the 4 weeks (6 contrasts). Results: wearing time of the AG and DP were strongly related (R=0.80 p  These data show that both monitors provide comparable outcomes and are capable of measuring differences between separate weeks of assessment. The difference in wearing time needs clarification.
Neovascularization Induced by Intraocular Xenografts of Normal, Preneoplastic, and Neoplastic Mouse Mammary Tissues
Authors: Michael A. Gimbrone, Pietro M. Gullino
Journal: JNCI Journal of the National Cancer Institute (1976)

The capacity to induce neovascularization was compared in normal, preneoplastic, and neoplastic mouse mammary tumors from strains with a high incidence of tumors (C3H, C3H-Avy, C3H-AvyfB) by implantation of small biopsy fragments on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: 1) direct, in vivo slit-lamp stereomicroscopy and fluorescein angiography; 2) filling of the microvasculature with colloidal carbon; and 3) histologic examination. Ninety percent of mammary tumor implants elicited iris neovascularization after 48-72 hours, regardless of their histologic classification or the presence or absence of mammary tumor virus. Corticosteroid treatment reduced immediate postoperative inflammation (12-36 hr) but did not abolish subsequent growth of new vessels. Necrotic tumor fragments failed to elicit any neovascular response. In contrast, only 6% of normal tissues from resting mammary glands caused any vasoproliferation. Hormone-stimulated mammary tissues from pregnant and lactating mice exhibited a transient neovascular capacity that was lost during postweaning involution. Of the implants from premalignant hyperplastic alveolar nodules (HAN's), 30% produced a pattern of vessel growth similar to that of tumor implants. D-1 line (HAN outgrowth) tissues, which have a predicted low incidence of tumors, induced significantly fewer neovascular responses (P less than 0.002) than morphologically and biochemically similar D-2 line tissues, which have a predicted high incidence of tumors. These data suggest that the capacity to induce neovascularization is acquired during malignant progression of mouse mammary tissues; therefore, demonstration of this property may be useful in the identification of those intermediate populations most at risk for neoplastic transformation.
Baseline characteristics of an Italian cohort of pulmonary alveolar proteinosis (PAP) patients
Authors: Ilaria Campo, Zamir Kadija, Francesca Mariani, Giuseppe Rodi, Elena Paracchini, Claudia Chalk, Bruce C. Trapnell, Maurizio Luisetti
Journal: European Respiratory Journal (2011)

PAP is a rare disorder, characterized by accumulation of lipoproteinaceous material within alveolar spaces.The clinical course of PAP ranges from spontaneous remission to respiratory failure and whole lung lavage (WLL) currently remains the therapeutic standard.

Methods: Clinical assessment was performed by HRCT scan, BAL, lung biopsy, pulmonary function tests, serum markers (LDH,CYFRA,CEA,NSE) and GM-CSF autoantibodies.

Results: We enrolled 76 PAP patients from 1989 to 2011, divided as follows: Idiopathic PAP (n=70) of which the autoimmune nature was confirmed in 76%, Secondary PAP (n=3, 4%), Congenital PAP (n=1, 1.3%) and PAP-like disorders (n=2, 2.7%). The idiopathic PAP patients showed a prevalence of males (72.8%) over females, with a mean age at diagnosis of 40.7±13. A smoking history (current or former smokers) occurred in 68.5%, with a mean of 27pack/years. The most common presenting symptom was dyspnea, alone (27 patients) or in combination with cough (16 patients). 4 patients were completely asymptomatic. Intercurrent infections were present in 14 cases. Mean GMAbs level was 261±240 μg/mL (n.v. <3 μg/mL). From our whole series, 43 patients were submitted to WLL: 30 (43%) received 1 WLL, whereas 13 (30%) received 2 or more WLLs. Comparison of pulmonary function testing data between not lavaged and lavaged PAP patients showed a significant difference for the TLCO% pred (mean value 60.3±18.4 vs 46±13.7, p=0.011) and for the A-aO2 gradient (35±17vs 45±15.8 mmHg, p=0.043).

Conclusion: The establishment of a reference center for PAP in Italy has allowed to gather and well characterize one of the largest series of PAP patients worldwide.

Funding: AIFA (FARM7MCPK4), eRARE (EuPAPNet).
Peripheral blood B cell labeling indices are a measure of disease activity in patients with monoclonal gammopathies.
Authors: T E Witzig, N J Gonchoroff, J A Katzmann, T M Therneau, R A Kyle, P R Greipp
Journal: Journal of Clinical Oncology (1988)

Labeling indices (LI) provide a rapid measure of the bone marrow (BM) plasma cell proliferation rate and are useful in the diagnosis and prognosis of monoclonal gammopathies. Because circulating B cells may be a part of the neoplastic clone, we examined peripheral blood B cells that were producing the same cytoplasmic light chain isotype as the patient's monoclonal; protein (M-protein) and determined the peripheral blood LI (PBLI) by a two-color immunofluorescence bromodeoxyuridine method. The 105 patients studied were divided into three disease activity groups by standard clinical criteria. Median PBLI was 0.2% for the 29 patients with inactive monoclonal gammopathies (monoclonal gammopathy of undetermined significance [MGUS] and smoldering multiple myeloma [SMM]), 0.8% for the 35 patients with new, untreated multiple myeloma (MM), and 1.7% for the 41 patients with relapsed MM. These differences between groups were statistically significant (P less than .001, Wilcoxon). Four patients had high PBLI but clinically inactive gammopathy at the time of study, and all developed active MM within 6 months that required treatment. In 92 patients a BMLI was performed simultaneously with the PBLI (rank correlation coefficient, 0.69). In patients with new, untreated MM, use of both tests identified 72% of patients (23 of 32) with high LI, rather than 56% (18 of 32) by BMLI alone or 63% (20 of 32) by PBLI alone. These results suggest that PB B cells bearing the same cytoplasmic light chain isotype as the monoclonal protein are part of the malignant clone and can be kinetically active. The LI of these cells can provide a measure of disease activity and may help to differentiate active from inactive disease.
Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage
Authors: Nicole A. Zelenski, Holly A. Leddy, Johannah Sanchez‐Adams, Jinzi Zhang, Paolo Bonaldo, Wolfgang Liedtke, Farshid Guilak
Journal: Arthritis & Rheumatology (2015)

Mechanical factors play a critical role in the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. We undertook this study to test the hypothesis that type VI collagen is necessary for mechanotransduction in articular cartilage by determining the effects of type VI collagen knockout on the activation of the mechano-osmosensitive, calcium-permeable channel TRPV4 (transient receptor potential vanilloid channel 4) as well as on osmotically induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties.Confocal laser scanning microscopy was used to image TRPV4-mediated calcium signaling and osmotically induced cell swelling in intact femora from 2- and 9-month-old wild-type (WT) and type VI collagen-deficient (Col6a1(-/-)) mice. Immunofluorescence-guided atomic force microscopy was used to map PCM mechanical properties based on the presence of perlecan.Hypo-osmotic stress-induced TRPV4-mediated calcium signaling was increased in Col6a1(-/-) mice relative to WT controls at 2 months. Col6a1(-/-) mice exhibited significantly increased osmotically induced cell swelling and decreased PCM moduli relative to WT controls at both ages.In contrast to our original hypothesis, type VI collagen was not required for TRPV4-mediated Ca(2+) signaling; however, knockout of type VI collagen altered the mechanical properties of the PCM, which in turn increased the extent of cell swelling and osmotically induced TRPV4 signaling in an age-dependent manner. These findings emphasize the role of the PCM as a transducer of mechanical and physicochemical signals, and they suggest that alterations in PCM properties, as may occur with aging or osteoarthritis, can influence mechanotransduction via TRPV4 or other ion channels.
Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response.
Authors: K Winkler, G Beron, G Delling, U Heise, H Kabisch, C Purfürst, J Berger, J Ritter, H Jürgens, V Gerein
Journal: Journal of Clinical Oncology (1988)

Following observation of the predictive value of the histologic extent of tumor cell destruction after preoperative chemotherapy for metastasis-free survival (MFS) in osteosarcoma, a randomized study was undertaken with the aim of (1) sparing some patients the unpleasant side effects of highly toxic drugs like doxorubicin (DOX) and cisplatin (CPDD) by administering these drugs postoperatively only after poor response with a milder preoperative regimen, and (2) improving the prognosis of patients responding poorly to the initial treatment by use of a salvage chemotherapy postoperatively. The available patients were divided into two groups. Those in the study arm received a preoperative chemotherapy consisting of high-dose methotrexate (HDMTX) and the triple drug combination of bleomycin, cyclophosphamide, and dactinomycin (BCD) and were switched to DOX/CPDD postoperatively in case of poor response. DOX/CPDD was used besides HDMTX for initial treatment in the control arm, and BCD alternatively with CPDD/ifosfamide (IFO) for postoperative salvage treatment. The response rate of the study arm was significantly inferior to the control arm (26% v 60%; P less than .001). The actuarial 4-year MFS rate of poor responders after salvage chemotherapy also was poorest in the study arm (41%); it was unchanged in the control arm (53%) as compared with that of poor responders from the COSS-80 study without salvage chemotherapy (52%). The actuarial 4-year MFS rate of good responders was 73% in the study arm, 79% in the control arm, and not significantly different from that of the COSS-80 study (84%), although postoperative chemotherapy of good responders had been markedly shortened as compared with the COSS-80 study. The actuarial 4-year MFS rate of the study arm as a whole was inferior to that of the control arm (49% v 68%; P less than .1) and also inferior to the COSS-80 study (68%; P less than .01), indicating a failure of the employed salvage strategy in general and especially of the effort to restrict the use of the very effective but highly toxic drugs DOX and CPDD to patients resistant to a less toxic initial treatment.
Is ventilatory efficiency impaired during progressive exercise in mild COPD
Authors: Amany Elbehairy, Azmy Faisal, Casey Ciavaglia, Daniel Langer, Megan Preston, Katherine Webb, J. Alberto Neder, Denis O'Donnell
Journal: European Respiratory Journal (2014)

Abnormalities in ventilation-perfusion matching may start early in the natural history of COPD. These disturbances are likely to worsen under increased ventilatory demands – as those elicited by exercise. Therefore, measurements of exercise ventilatory efficiency (ventilation (V'E) to carbon dioxide output (V'CO2)) could be valuable to uncover those abnormalities in mild COPD. Forty GOLD grade I patients and 20 controls underwent an incremental cardiopulmonary exercise test. The V'E-to-V'CO2 relationship was expressed as slope and intercept or as a ratio (V'E/V'CO2) at its lowest point (nadir). Peak exercise capacity and sub-maximal O2 saturation were lower in patients (p  median) had lower lung diffusing capacity (p= 0.05) and peak oxygen uptake (p<0.05).

![Figure][1] 



Excessive ventilatory responses to metabolic demand and impaired oxygenation in GOLD grade I patients indicates that the efficiency of the lung as gas exchanger is compromised despite a preserved FEV1. The impact of treatment strategies on these outcomes deserves further consideration in this patient sub-population.

 [1]: pending:yes
Cytokine and chemokine release in response to Pseudomonas aeruginosa (PA), by bronchial epithelium of the native airway and transplanted lung of paediatric cystic fibrosis (CF) lung transplant recipients
Authors: Biju Thomas, P.P.E. Freestone, Paul Aurora, Helen Spencer, Rob A. Hirst, G. Williams, Chris O'Callaghan
Journal: European Respiratory Journal (2012)

Introduction 

Infection and inflammation are implicated in the pathophysiology of Bronchiolitis Obliterans Syndrome (BOS), the major cause of mortality following lung transplantation. It is unclear if the cytokine and chemokine release by Cystic Fibrosis (CF) airway epithelium in response to pathogens differs from that of the transplanted lung.

Aims 

We hypothesised that there is no difference in the cytokine and chemokine release in response to Pseudomonas aeruginosa (PA), by the epithelium of the native CF airway and the transplanted lung.

Methods 

5 children who had lung transplantations for CF (Great Ormond Street Hospital for Children, London, UK), were studied. Bronchoscopic brushings from above and below the airway anastomosis were cultured to differentiated ciliated epithelium in an air-liquid interface (ALI). The epithelium was exposed to late exponential cultures of PA (106 CFU per ml). The culture supernatants were harvested at baseline and 5 hours post PA exposure. The cytokines and chemokines in the culture supernatants were measured using a multiplex ELISA based protein array (SECTOR Imager 6000, MSD).

Results 

There were no differences in baseline levels of cytokines and chemokines. 5 hours after exposure to PA, the release of chemokines - CCL2, CCL5, CCL13, CXCL8 and the cytokines - IL1β, IL13 and TNFα, by the native CF epithelium was significantly higher (p<0.01) compared to that from the transplanted lung.

Conclusion 

The differential cytokine and chemokine release in response to pathogens may be contributory to the exaggerated inflammatory response of the CF epithelium.
Adjuvant-free mouse model of allergic asthma
Authors: Igor Shilovskiy, Mariya Prozorova, Alina Gaisina, Alexander Babakhin, Musa Khaitov
Journal: European Respiratory Journal (2014)

Background : Aluminum hydroxide (alum) is widely used for sensitization in mouse models of allergic asthma (MMA). The purpose of this study was to develop a phenotype of allergic airway inflammation in adjuvant-free MMA.   Methods:  BALB/c mice were sensitized according to two protocols. Adjuvant protocol (AP) consisted of three i.p. injections of 20 μg ovalbumin (OVA) with 2 mg of alum/mouse on days 0, 14 and 28 followed by five intranasal applications (INA) with 50 μl OVA (10 mg/ml) on days 41-45. Adjuvant-free protocol (AFP) included by three s.c. injections of the same OVA dose followed by INA with OVA at the same manner. 24 hours after the last INA airway hyperresponsiveness (AHR) to methacholine was measured by plethysmography. 48 hours after the last INA bronchoalveolar lavage (BAL) was performed for differential cell counts and lungs were removed for histological examination. OVA-specific serum IgE-, IgG1- and IgG2a- antibodies were detected by ELISA.   Results:  OVA-specific IgE production in AFP group was 1.6 fold higher than that of AP group. OVA-specific IgG2a level in AFP group was 3 times lower than that of AP group while levels of anti-OVA IgG1 were similar in both groups. AHR in AP and AFP groups was higher than that of normal mice but did not differ from each other. Both AP and AFP groups have an equal amount of inflammatory cells in BAL while lung histology picture (perivascular and peribronchial inflammation) was more expressive in AFP group.   Conclusion:  Adjuvant-free protocol generates an experimental asthma phenotype similar to that of adjuvant protocol which is widely used in the literature. The adjuvant-free MMA can be a relevant model for testing of new approaches in treatment or prevention of bronchial asthma.
Peculiarities of an ARDS and respiratory support in patients with severe viral (H1N1) pneumonia
Authors: Tatiana Martynenko, Maxim Bukchtoyarov, Vladimir Martynenko, Irina Balatskaya, Anastasiya Grebenyuk
Journal: European Respiratory Journal (2012)

Background: We aimed to evaluate clinical features of an ARDS and effectiveness of sequential differentiated respiratory support (SDRS) in patients with viral H1N1 pneumonia.

Methods: Retrospective analysis of 39 patients witth severe H1N1 viral pneumonia treated at Respiratory Intensive Care Unit (RICU).

Results: Age of patients ranged from 17 to 52 years old. There were 12 (30.8%) men and 27 (69.2%) women, 13 (33.3%) of whom were pregnant. In all patients a leading resuscitation syndrome was an acute respiratory failure (ARF). ARDS was diagnosed in 26 (66.6%) patients. The phenomena of sepsis, multiple organ failure, septic shock were not detected in any patient in the first 7 days of hospitalization. SDRS consisted of two phases: Controlled oxygen therapy (COT) with an oxygen flow 6-8 l/min was effective in 11 (28.2%) patients. Intubation of trachea was undertaken in cases of refractory hypoxemia that lasted for 30-45 min. Mechanical ventilation was carried out in 28 (71.8%) patients in the regime of PCV with «aggressive» parameters: FiO2 - 0.8-1.0, PEEP - 15-20 cm H2O, PIP - 30-40 cm H2O, I: E - 1:1. Vt - 500-600 ml was achieved easily, indicating about preserved lung compliance. All patients required sedation at the beginning of mechanical ventilation in order to synchronize with the respirator. Muscle neuromuscular relaxants was not used. Duration of mechanical ventilation ranged from 7 to 83 days. NIV was excluded from the scheme of SDRS due to inefficiency.

Conclusion : A peculiar form of ARDS, without reducing elasticity of lung tissue, without sepsis, developed in patients with severe viral pneumonia. SDRS consisted of two phases: controlled oxygen therapy → invasive ventilation.