tbuckley/cabot-search huggingface dataset:
Pulmonary hypertension in childhood
Authors: S G Haworth
Journal: European Respiratory Journal (1993)

In the presence of pulmonary hypertension, the pulmonary vasculature fails to remodel after birth. Secondary changes then develop, and do so more rapidly than in the adult lung because the cells are exposed to the insult whilst still relatively undifferentiated. The commonest causes of pulmonary hypertension in newborn and young infants are alveolar hypoxia, and congenital heart disease causing a left-to-right shunt and increased pulmonary blood flow. The initial response of an increase in pulmonary arterial muscularity is common to both, but intimal proliferation can develop rapidly in those with complex congenital heart disease. The structural abnormalities are accompanied by abnormalities in the control of pulmonary vascular reactivity, a problem which is the focus of much current research activity.
<i>In vivo</i> assessment of the therapeutic effects of lyophilized leech saliva extract from (Huridinaria manillensis) on LNCaP tumor xenograft model in nude mice.
Authors: Amr Ammar, Mohamed Hessein, Emma Guns, Mei Chin, Abul Bashar Helaluddin, Abdulrahman Abdualkader, Mohamed Alaama, Ahmed Merzouk, Abbas Ghawi, Omer Kucuk
Journal: Journal of Clinical Oncology (2015)

271 Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. A large number of peptides and proteins have been identified and characterized in leech saliva extract (LSE), including anti-thrombotic agents, cancer metastasis inhibitors and anti-microbials Currently, leech therapy is established as an important tool in microsurgery and reconstructive operations having demonstrated superior clinical outcomes for the optimal salvage of grafted tissues. Methods: In the current study, we have determined the in vivo efficacy of LSE from (Huridinaria manillensis) on castration resistant LNCaP xenograft mouse model. Mice were divided into three groups of six, mice were subcutaneously injected with either LSE (5 mg/kg), docetaxel (10 mg/kg), or vehicle once a week. PSA and tumor volume were measured weekly. After four weeks of treatment, mice were euthanized, tumors and organs were collected for transcriptome and immunohistochemical (IHC) analysis. Results: There was a significant decrease in the tumor volume and PSA with either docetaxel (10mg/kg) or LSE (5 mg/kg) treated groups compared to the control. While there was no significant difference between the anti-tumor activity of docetaxel (10mg/kg) and LSE (5 mg/kg). IHC showed significant increase in caspase-3 and significant decrease in Ki-67 and PCNA expression in the LSE treated mice compared to the control group. Interestingly, transcriptome analysis of tumor samples showed that LSE modulated cytokine production, monocyte adhesion, steroidogenesis, and P38 MAPK signaling pathways. Conclusions: LSE has significant anti-tumor activity in LNCaP tumor xenograft models with no apparent side effects. This can be attributed, at least partly, to its inhibition of cellular proliferation, induction of apoptosis, modulation of immunity and steroidogenesis.
Stereotactic Radiosurgery and Bevacizumab for Recurrent Glioblastoma Multiforme
Authors: Alvin R. Cabrera, Kyle C. Cuneo, James J. Vredenburgh, John H. Sampson, John P. Kirkpatrick
Journal: Journal of the National Comprehensive Cancer Network (2012)

Despite contemporary surgery, image-guided radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) persists or relapses in nearly all patients, and tumors almost always recur locally. Management of recurrent GBM is variable, but approaches include best supportive care, reoperation, reirradiation, and/or systemic therapy. Promising novel therapies include antiangiogenic agents and stereotactic radiosurgery, which have cytotoxic effects on tumor microvasculature. Emerging data suggest the safety and efficacy of bevacizumab and radiosurgery either alone or in combination. This report presents the case of a man with locally recurrent GBM treated with stereotactic radiosurgery and concurrent bevacizumab, and reviews the preclinical and clinical data supporting this approach.
Biomechanical Dynamics of the Heart with MRI
Authors: Leon Axel
Journal: Annual Review of Biomedical Engineering (2002)

Magnetic resonance imaging (MRI) provides a noninvasive way to evaluate the biomechanical dynamics of the heart. MRI can provide spatially registered tomographic images of the heart in different phases of the cardiac cycle, which can be used to assess global cardiac function and regional endocardial surface motion. In addition, MRI can provide detailed information on the patterns of motion within the heart wall, permitting calculation of the evolution of regional strain and related motion variables within the wall. These show consistent patterns of spatial and temporal variation in normal subjects, which are affected by alterations of function due to disease. Although still an evolving technique, MRI shows promise as a new method for research and clinical evaluation of cardiac dynamics.
Positherapy: Targeted Nuclear Therapy of Breast Cancer with 18F-2-Deoxy-2-Fluoro-<scp>d</scp>-Glucose
Authors: Renee M. Moadel, Richard H. Weldon, Ellen B. Katz, Ping Lu, Joseph Mani, Mark Stahl, M. Donald Blaufox, Richard G. Pestell, Maureen J. Charron, Ekaterina Dadachova
Journal: Cancer Research (2005)

Breast cancer remains a major cause of cancer death in women in the United States. Novel therapies are needed for patients when standard treatments are ineffective. We have recently shown on a cellular level the therapeutic potential of positrons in malignancy. Here, we report for the first time positron therapy with (18)F-2-deoxy-2-fluoro-D-glucose ((18)F-FDG) in a breast cancer animal model to affect tumor growth rate and survival (positherapy). We used xenografted mammary tumors in nude mice using Notch mammary cancer cells which also express ras oncogene. Notch xenografted tumors actively took up (18)F-FDG with a tumor to normal tissue ratio of 3.24. Tumor-bearing mice were treated with 2.5 mCi (18)F-FDG, which is equivalent to the physiological human maximum tolerated dose. Positherapy resulted in both significant prolongation of survival and decrease in tumor growth rate in comparison with nontreated controls. Immunoblot of Notch tumors showed the presence of glucose transporters (GLUT) 1, 4, and 8. Substantial differences between GLUT1, GLUT4, and GLUT8 were observed in their distribution within the tumor mass. Whereas GLUT4 and GLUT8 were distributed relatively homogeneously throughout the tumor, GLUT1 was confined to necrotic areas. Immunofluorescence double labeling was used to determine cellular localization of GLUTs. GLUT1 was expressed mostly at the cell membrane. GLUT4 and GLUT8 were mostly localized to cytoplasmic compartments with some GLUT4 expressed at or near the cell membrane in close proximity to GLUT1. Thus, GLUT1 was likely responsible for the (18)F-FDG uptake by tumor cells with some possible contribution from GLUT4. These results are important for the development of positherapy with (18)F-FDG for refractory metastatic breast and other cancers.
UK government criticised over “confusing” fitness to work mortality figures
Authors: Matthew Limb
Journal: BMJ (2015)

The UK Department for Work and Pensions (DWP) has been accused by a leading academic of creating “confusion” with their response to freedom of information requests for data on deaths among people declared fit for work.

The data released show that 2380 people claiming sickness benefits died within weeks of being judged “fit for work” by work capability assessments in a period of a little over two years.

Ben Goldacre, senior clinical research fellow at Oxford University’s Centre for Evidence Based Medicine, said that the people requesting information had wanted the department to shed light on whether sickness benefit claimants died after being found fit for work. But the department had issued raw numbers without denominators or age standardised mortality rates, …
Effect of imatinib and nilotinib on lipopolysaccharide-induced acute lung injury during neutropenia recovery in a mouse model
Authors: Sook Young Lee, Chin Kook Rhee
Journal: European Respiratory Journal (2012)

Objective: Neutropenia recovery is associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. We aimed to evaluate effect of imatinib and nilotinib on lipopolysaccharide (LPS) - induced acute lung injury (ALI) during neutropenia recovery in a mouse model.  Method: We developed a mouse model of ALI during neutropenia recovery. Cyclophosphamide was administrated to induce neutropenia. During neutropenia recovery, ALI was induced by intratracheal instillation of LPS. Imatinib or nilotinib was administrated during neutropenia recovery.  Result: The numbers of inflammatory cells and neutrophil in bronchoalveolar lavage fluid in imatinib or nilotinib group were significatly lower than LPS group. Imatinib or nilotinib administration significantly reduced wet/dry ratio and ALI score. The level of myeloperoxidase and tumor necrosis factor-α in imatinib or nilotinib group were significantly lower than LPS group. Attenuation of ALI by imatinib or nilotinib was associated with PDGFRβ and C-kit pathway.  Consult: Imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery.
A phase I study of capecitabine, oxaliplatin (CapOx), and lapatinib (L) in metastatic or advanced solid tumors
Authors: T. Dennie, D. Alberti, K. Oliver, N. LoConte, D. Mulkerin, G. Wilding, K. Holen, R. Fleming, C. Bowen, V. O'Neill
Journal: Journal of Clinical Oncology (2009)

2579 Background: CapOx is a standard treatment for patients (pts) with metastatic colorectal cancer (mCRC) and has been shown to be equivalent to FOLFOX in a phase III study. L is a tyrosine kinase inhibitor with targeting of the EGF and Her-2 receptors. Preclinical data suggest there may be synergy between L and Cap as well as L and Ox. This phase I study was designed to determine the maximum tolerated dose (MTD) of CapOx and L. Methods: Pts eligible for treatment included those with advanced or metastatic cancers, ECOG PS 2 or less, adequate renal and liver function, and ≤ 3 prior chemotherapy regimens. Treatment over a 21-day cycle was as follows: Ox, single IV infusion on Day 1; Cap, twice-daily oral administration on Days 1 through 14; L, continuous once-daily oral administration. Pts were treated with escalating doses of L (starting at 1000 mg daily) and Cap (starting at 1500 mg/m 2 /day), while Ox was kept at 130 mg/m 2 . The primary endpoint was determination of MTD. Results: Ten pts (9/10 female, median age 62 yrs.) were enrolled. One pt had breast cancer and the remainder had non- colorectal GI malignancies (esophagus, hepatobiliary, and pancreas). One pt at dose level 0 experienced dose-limiting toxicity (DLT) (dehydration, elevated bilirubin, hypokalemia). Two pts at dose level 1 (L 1000, Ox 130, Cap 2000) had DLTs of hypokalemia and diarrhea. At an intermediate dose level of L 1000, Cap 1700, Ox 130, two pts experienced DLTs (grade 2 fatigue/anorexia, grade 3 fatigue and dizziness). The MTD was determined to be L 1000 mg daily, Cap 1500 mg/m 2 /day, Ox 130 mg/m 2 . There were no treatment-related grade 4 toxicities. The most common grade 3 toxicity was diarrhea (4 pts). There were no grade 3 neuropathies, hematologic toxicities, or rash, and only one case of grade 3 fatigue. One pt with pancreatic cancer had a confirmed partial response (PR) to treatment, and 3 others had stable disease for &gt; 90 days. Conclusions: The regimen of CapOx and L has efficacy in the treatment of solid tumors with established responsiveness to fluoropyrimidines or Ox. The MTD was L 1000 mg daily, Ox 130 mg/m 2 , and Cap 1500 mg/m 2 /day. This regimen will be investigated further in a Phase II study involving pts with mCRC. [Table: see text]
Abstract 2: Orexin-A Improves Arousal from Post--Cardiac Arrest Coma in a Rodent Model
Authors: Yama Akbari, Anil Maybhate, Cheng Chen, Elliot Greenwald, Lydia Liang, Manuel Buitrago-Blanco, Xiaofeng Jia, Nitish Thakor, Romergryko Geocadin
Journal: Circulation (2012)

Introduction: Coma after cardiac arrest (CA) is common and leads to suffering for patients while being an emotional and financial burden to families and society. Other than hypothermia, there is currently no therapy to improve neurological outcome after CA. The hypothalamic Orexin pathway provides a potential pharmacologic target towards improving arousal after coma. Hypothesis: Post-resuscitaion, Orexin-A intracerebroventricular (icv) infusion after bolus injection will provide immediate and long term term arousal after CA which can be assessed by quantitative EEG (qEEG) and behavioral testing (neurologic deficit scale; NDS). Methods: Rats (N=17; Adult Male Wistar; 300-350gms) were implanted with icv cannula attached to an osmotic pump. One week later, rats underwent baseline EEG followed by intubation, mechanical ventilation, cannulation of the femoral vessels, followed by 7 minutes of asphyxial cardiac arrest. Forty-five minutes after the resuscitation, rats were randomized to either Orexin-A (n=8) or saline (n=9) icv bolus and infusion. EEG was monitored continuously for 4 hours after CA, and for 30 minutes at 24hrs, 48hrs, 72hrs, and 12 days post-CA. NDS was also conducted at these times. EEG was analyzed using a custom algorithm to analyze the information quantity (IQ), an entropy based nonlinear measure for the entire frequency domain and clinical sub-bands. Results: Orexin-A treated rats demonstrated higher normalized IQ immediately after receiving the Orexin-A in comparison to saline (0.731±0.028[AM1] vs. 0.613±0.021; p&lt;0.01). This acute improvement in IQ sustained for 4hrs Post-CA. Moreover, the band-specific analysis [RG2] showed that Orexin-A improved the IQ in β-band at 72hrs (1.160±0.039 vs. 1.052±0.029; p&lt;0.05). Behaviorally, Orexin-A allows rats to perform significantly better on the NDS at 4hrs (38.3±3.2 vs. 30.1±1.9; p&lt;0.05); 24hrs (67.1±4.1 vs. 49.8±3.8; p&lt;0.01); 48hrs (73.4±4.3 vs. 61.0±3.6; p&lt;0.05), and 72hrs (75.0±3.3 vs. 65.2±2.9; p&lt;0.05). Conclusions: Rats receiving icv Orexin-A post-CA showed better arousal on both qEEG and behavioral (NDS) testing. Orexin-A may have therapeutic potential in disorders of arousal and coma after CA.
Keratin 17: A Critical Player in the Pathogenesis of Psoriasis
Authors: Liang Jin, Gang Wang
Journal: Medicinal Research Reviews (2013)

Keratin 17 (K17) is an intermediate filament protein present in the basal cells of complex epithelia, such as nails, hair follicles, sebaceous glands, and eccrine sweat glands. Studies have shown that it is expressed aberrantly in the suprabasal keratinocytes of psoriatic lesions, compared to in normal epidermis. K17 is also closely associated with the immune system and plays an important role in the pathogenesis of psoriasis. In this review, we present our experimental findings concerning the role of K17 in psoriasis, and compare them to results published in the literature. Our results show that cytokines related to Th17 and IL-22-producing (where Th17 is T helper cells, type 17 and IL is interleukin) CD4+ T cells, including IL-17A and IL-22, upregulate the expression of K17 in keratinocytes. In addition, K17 stimulates autoreactive T cells and promotes the production of psoriasis-associated cytokines. Our findings lend support to the hypothesis that a K17/T-cell/cytokine autoimmune loop is involved in the pathogenesis of psoriasis. We therefore review the current understanding of the K17 immunoregulation, including its expression and direct/indirect effects on immune responses. Pertinent strategies for the treatment of psoriasis are also discussed.
The diagnostic puzzle of ALK rearrangement in lung cancer. A novel intron related abnormality
Authors: Nir Peled, Gary Palmer, Fred R. Hirsch, Murry W. Wynes, Maya Ilouze, Marileila Varella-Garcia, Lior Soussan-Gutman, Geoff A. Otto, Philip J. Stephens, Jeffrey S. Ross, Maureen T. Cronin, Doron Lipson, Vincent A. Miller
Journal: European Respiratory Journal (2013)

Introduction:  The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase ( EML4 - ALK ) gene fusion occurs in 2%-7% of non–small-cell lung cancer (NSCLC) and is typically identified by fluorescent in situ hybridization (FISH).   Patient/Methods  :  We present two patients with NSCLC who carried unique, previously unpublished ALK rearrangement. Both were presented as advanced adenocarcinomas of the lung, who were wild type for EGFR and  ALK  rearrangement. Thanks to a high clinical suspicious for gene abnormality, further study was performed including comprehen-sive genomic profiling using a next-generation sequenc-ing (NGS) assay and ALK protein expression through IHC.   Results:  In both cases, we noticed high expression of the ALK protein. NGS analysis of genomic DNA revealed a complex rear-rangement of ALK, involving breakpoints in at least five dif-ferent genomic loci without a clear fusion product. The cDNA sequence showed that the expressed product of the complex rearrange-ment was the canonical  EML4 - ALK  fusion gene. We hypothesized that at the genomic level the fused  EML4  and  ALK  genes were sepa-rated by other small genomic shards. Based on these results, crizotinib was begun. The first patient showed an immediate benefit and is still a complete responder for 16 months. The other patient died before he was treated.   Conclusions:  This is the first report associated intron abnormality with ALK rearrangement abnormality. Further, we provide a tremendous clinical benefit from ALK related therapy that turned a metastatic patient to a complete responder. We recommend performing advanced molecular analysis through crossing technologies in any all patients.
Pathogen profile of lung infections in systemic autoimmune diseases
Authors: Balázs Odler, Nóra Perlényi, Krisztina Vincze, Noémi Eszes, Zsuzsanna Kováts, Aniko Bohács, Veronika Müller
Journal: European Respiratory Journal (2014)

Introduction: Systemic autoimmune diseases are often associated with pleuropulmonary manifestations, so it is necessary to know whether underlying disease, infection or drug toxicity results in the observed changes. As confirmation of lung infection has therapeutic consequences, our aim was to determine pathogen profile of pulmonary infections in systemic autoimmune disease patients. Methods: Microbiology samples of patient with systemic autoimmune disease (N=38) referred to the Department of Pulmonology in 2012 were analyzed (age: 61,81±14,79 years; female: male= 2:1). In 42% of patients (n=16) pulmonary infection was microbiologically confirmed. Pathogen profile in rheumatoid arthritis (RA) and other connective tissue disease (CTD) subgroups were analyzed. Results: The most common bacterial infections were caused by Gram negative bacilli ( Chlamydia pneumoniae (20%), Mycoplasma pneumoniae (12%), Pseudomonas aeruginosa (20%) , Klebsiella pneumoniae (9%) and Stenotrophomas maltophilia (7%)) . Pulmonary fungal infections (30%) were mainly caused by Candida albicans (58%) and Aspergillus species (26%). Comparing RA and CTD groups, RA patients showed lower number of yearly infection rate and lower number of concomitantly detected pathogens than CTD patients resulting in significantly shorter overall hospital stay (128 vs. 217 days). Conclusion: Pulmonary infections are common in systemic autoimmune patients, especially caused by Gram negative bacilli and fungi. Thorough microbial screening for possible pathogens is mandatory in all systemic autoimmune patients presenting with pulmonary symptoms.
Cafestrol, a coffee-specific diterpene, increases expression of NQO1 in pancreatic tumor cells
Authors: Skeetora Taylor, Beverly Word, George Hammons, Beverly D. Lyn-Cook
Journal: Cancer Research (2004)

1382  Coffee components kahweol and cafestol have been reported to be protective against mutagenic damage by heterocylic amines and aflatoxin B1 in rat models. Further, human consumption of these agents has been associated with lower rates of colon tumors. Possible mechanisms proposed have involved the modulation of several enzymes responsible for carcinogen detoxification. The present study demonstrates that cafestol, a diterpene found in unfiltered coffee, increased the expression of the phase II enzyme, NQO1, in both PANC-1 and Mia PaCa pancreatic tumor cells (p
Comparison of muscle strength and functional exercise capacity between two different groups according to combined assessment COPD
Authors: Ismail Özsoy, Sema Savci, Serap Acar, Sevgi Özalevli, Atila Akkoçlu
Journal: European Respiratory Journal (2014)

PURPOSE:  The Global initiative for chronic Obstructive Lung Disease (GOLD) 2011 document proposed a new category system for Chronic Obstructive Pulmonary Disease (COPD) combine system assessed by COPD Assessment Test (CAT) or Modified Medical Research Council (MMRC) Dyspnea Scale and exacerbation risk. The aim of the study was to compare muscle strength and functional exercise capacity between Group B and C.  METHODS:  The patients were categorized into Group B (n=18) and C (n=18) according to Combined Assessment COPD in GOLD 2011; patients were categorized with MMRC and CAT score for symptom assessment respectively. Pulmonary function test was performed. Dyspnea perception was determined using MMRC Dyspnea Scale. Exacerbation events were reported. Inspiratory and expiratory muscle strength (maximal inspiratory pressure and maximal expiratory pressure) were measured. Peripheral muscle strength (knee extension, shoulder flexion, shoulder abduction, elbow flexion and hand grip strength) were measured. Functional exercise capacity was evaluated 6 Minute Walk Test and 6 Minute Pegboard and Ring Test.  RESULTS:  The results of the study showed that shoulder flexion (p=0,015), shoulder abduction (p=0,009), elbow flexion (p=0,023) strength and maximal expiratory pressure (p=0,037) were significantly higher in Group B than Group C.  CONCLUSION:  Group B showed better upper extremity and expiratory muscle strength. Therefore, comprehensive assessment for COPD is important in clinical decision making pulmonary rehabilitation. As COPD progression is heterogenic, multi-directional assessments of COPD would provide different point of view in COPD management.
Decreased Corneal Sensation and Subbasal Nerve Density, and Thinned Corneal Epithelium as a Result of 360-Degree Laser Retinopexy
Authors: Nacim Bouheraoua, Linda Hrarat, Cameron F. Parsa, Jad Akesbi, Otman Sandali, Isabelle Goemaere, Taous Hamiche, Laurent Laroche, Vincent Borderie
Journal: Ophthalmology (2015)