tbuckley/cabot-search huggingface dataset:
CO diffusion: A graph tells more than a single point
Authors: Claire Cox, Wendy van Beurden, Frans de Jongh
Journal: European Respiratory Journal (2014)

Introduction   A pulmonary diffusion test is used to determine the lung9s gas exchange ability. In single breath diffusion a patient inhales a small amount of carbon monoxide (CO), holds his breath for 10 seconds and exhales again. The difference in the amount of CO between in- and exhaled gas is a measure for the diffusion coefficient (TL CO ) which divided by the alveolar volume yields the transfer coefficient for CO (K CO ).   Aims and objectives   Current pulmonary function devices give only 1 value for the K CO , but CO concentration constantly changes during expiration. In this study we investigate the usability of plotting the K CO  against the expired volume (V Exp ) to interpret CO diffusion.   Methods   21 subjects--8 healthy (age 52±3.6), 8 with emphysema (age 64±10.5) and 5 with fibrosis (age 66±5.8)--performed a CO diffusion test (MasterScreen™ PFT-Pro, CareFusion). CO concentration was recorded, and processed with Matlab®.   Results   The standard technique selects the K CO  via a strict algorithm, yielding different points in the expiration cycle which might not always be the best representation of the K CO  (see graph). Although the number of patients is small, results seem to cluster and the 3 groups can clearly be distinguished.   Conclusions   The diffusion transfer coefficient as function of the expired lung volume gives more detailed information about the position and severity of the diffusion defect and might, after further research, help to distinguish between disease groups.
A phase II study of gemcitabine-based chemoradiotherapy (CCRT) after triplet induction chemotherapy (ICT) for locally advanced pancreatic cancer (LAPC): A Taiwan Cooperative Oncology Group (TCOG) study
Authors: H. Ch’ang, T. Hwang, H. Wang, M. Chang, Y. Tien, J. Chen, R. Hsieh, P. Lin, Y. Shan, A. Cheng, L. Chen
Journal: Journal of Clinical Oncology (2009)

e15562 The optimal management of LAPC remains controversial. The efficacy of CCRT is hampered by early systemic dissemination. To treat undetectable metastases and to select patients who are likely to benefit from CCRT, ICT followed by CCRT has recently been extensively evaluated in LAPC. Recently, we showed that triplet chemotherapy consisting of gemcitabine 800 mg/m 2 (10 mg/m 2 /min) followed by oxaliplatin 85 mg/m 2 and 48-hour infusion of 5-FU/LV 3,000 and 150 mg/m 2 Q 2 weeks, the GOFL regimen, is feasible and active for pts with APC. Chemo-naïve pts with histo- /cytologically proven unresectable LAPC, and bi-dimensionally measurable diseases were eligible. Patients who did not experience disease progression (PD) after 6 cycles of GOFL would had CCRT consisting of weekly gemcitabine 400mg/m 2 plus 50.4Gy/28 fractions of radiation 4–6 weeks later. After CCRT, pts were re-evaluated for surgical intervention and those with unresectable disease would continue GOFL until PD, unacceptable toxicity, patient's refusal or death. Among the 50 enrolled pts (24F/26M, median age 58.5 years), 48 had definitively unresectable diseases. After induction GOFL, 16 (32%) pts were off-studied because of PD in 12 (24%) and ICT-related toxicity in 4 (8%, PD/UE group). Among the 34 (68%) with objective response or stable disease after 6 cycles of ICT, 27 (54%) who completed the assigned multimodality treatment are categorized as CCRT group; whiles 7 (14%) who either declined CCRT (in 5) or still on ICT (in 2) are categorized as non-CCRT group. The median PFS and OS for the ITT population were 9.1 and 14.5 months, respectively. The median PFS for PD/UE, non-CCRT and CCRT groups were 2.1, 8.2 and 12.8 months, respectively; whiles the OS were 8.5, 15.0 and 18.3 months, respectively. The most common grade 3–4 toxicities were neutropenia (40%), anemia (14%), infection (16%), nausea (26%), vomiting (20%). Grade 2–3 peripheral neuropathy was observed in 7 of 29 who received post-CCRT GOFL. Conclusion: Three months of triplet ICT followed by gemcitabine-based CCRT is feasible and likely to prolong the survival of selected LAPC pts. Prospective, randomization study is warranted to validate the findings. No significant financial relationships to disclose.
Phase I clinical trial of intravenous L-buthionine sulfoximine and melphalan: an attempt at modulation of glutathione.
Authors: H H Bailey, R T Mulcahy, K D Tutsch, R Z Arzoomanian, D Alberti, M B Tombes, G Wilding, M Pomplun, D R Spriggs
Journal: Journal of Clinical Oncology (1994)

A phase I dose-escalation trial of intravenous (IV) L-buthionine-SR-sulfoximine (BSO) with melphalan (L-PAM) was performed to determine the toxicity and biologic activity of BSO, administered as a short infusion every 12 hours, and the combination of BSO plus L-PAM.Twenty-eight patients with refractory malignancies received 30-minute infusions of BSO every 12 hours for 6 to 10 doses in week 1 followed in week 2 by either IV L-PAM (15 mg/m2) alone or BSO as in week 1 with L-PAM. Patients received the combination in week 5 (course no. 2) if they received L-PAM alone during week 2 and vice versa. BSO doses ranged from 1.5 g/m2 to 13.104 g/m2.The only toxicity observed with BSO infusions was occasional nausea/vomiting. Evaluation of 23 paired courses (L-PAM plus BSO v L-PAM) showed significantly (P < .001) greater leukopenia and thrombocytopenia with L-PAM plus BSO. No other significant toxicity was noted. Measurement of intracellular glutathione (GSH) levels in peripheral mononuclear cells (PBLs) of all patients receiving BSO showed a consistent, non-dose-dependent, linear decrease in GSH with repeated BSO doses. Maximal GSH depletion (40% of baseline values, absolute values 200 to 250 ng/10(6) PBLs) was noted after the sixth BSO dose; extended BSO dosing schedules beyond six total BSO doses did not further deplete GSH. Evaluation of gamma-glutamylcysteine synthetase (GCS) activity showed marked inhibition near the end of each infusion with near complete recovery of GCS activity before the next BSO dose. The pattern of GCS inhibition mirrored the plasma BSO concentrations with peak values (level 6, 4 to 8 mmol/L L,R+L,S BSO) observed at the end of the infusion with a rapid decrease in plasma concentrations with an estimated half-life (t1/2) of less than 2 hours. Differential elimination of the R+S stereoisomers was observed. Analysis of L-PAM pharmacokinetics showed marked interpatient variability and a significant decrease in total-body clearance (P = .01) and volume of distribution (P = .03) in courses with L-PAM plus BSO as compared with L-PAM alone.This study shows that BSO alone and in combination with L-PAM can be safely given to patients, but that a schedule of short infusions every 12 hours does not result in GSH depletion less than 30% of baseline values.
Comparison of costs of community-acquired pneumonia (CAP) treatment at patients with and without bronchial obstruction
Authors: Yuriy Mostovoy, Hanna Demchuk
Journal: European Respiratory Journal (2011)

With purpose to estimate economical costs of treatment of CAP at the patients with COPD and without it the comparison of therapeutic expenses of CAP at 33 inpatients against a background COPD (basic group – BG) and 33 patients without COPD (control group - CG) was performed by case-control method. Patients were represented by age and gender (main age- 63,5±14,3 years, 54,4% male). Average duration of hospitalization was similar: BG - 11,55±2,39 days, CG - 10,91±2,65 days (p>0,1). Pneumonia severity index (PSI) was higher in BG (81,53±3,8 score) than in CG (64,27±26,9 score). Half of patients of both groups had concomitant cardiovascular diseases (51,5% Ta 45,5%, p>0,1). Average costs of treatment for patient in BG was 1229,54±46,77 UAN, but for patient of CG – 789,25±32,43 UAN (p 0,1) from total sum. More severe CAP at patients with COPD requires more intensive treatment with involving bigger therapeutic and diagnostic resources. It considerably increases costs of medical care for this group of patients.
Regulation of Long Bone Growth in Vertebrates; It Is Time to Catch Up
Authors: Alberto Roselló-Díez, Alexandra L. Joyner
Journal: Endocrine Reviews (2015)

The regulation of organ size is essential to human health and has fascinated biologists for centuries. Key to the growth process is the ability of most organs to integrate organ-extrinsic cues (eg, nutritional status, inflammatory processes) with organ-intrinsic information (eg, genetic programs, local signals) into a growth response that adapts to changing environmental conditions and ensures that the size of an organ is coordinated with the rest of the body. Paired organs such as the vertebrate limbs and the long bones within them are excellent models for studying this type of regulation because it is possible to manipulate one member of the pair and leave the other as an internal control. During development, growth plates at the end of each long bone produce a transient cartilage model that is progressively replaced by bone. Here, we review how proliferation and differentiation of cells within each growth plate are tightly controlled mainly by growth plate-intrinsic mechanisms that are additionally modulated by extrinsic signals. We also discuss the involvement of several signaling hubs in the integration and modulation of growth-related signals and how they could confer remarkable plasticity to the growth plate. Indeed, long bones have a significant ability for "catch-up growth" to attain normal size after a transient growth delay. We propose that the characterization of catch-up growth, in light of recent advances in physiology and cell biology, will provide long sought clues into the molecular mechanisms that underlie organ growth regulation. Importantly, catch-up growth early in life is commonly associated with metabolic disorders in adulthood, and this association is not completely understood. Further elucidation of the molecules and cellular interactions that influence organ size coordination should allow development of novel therapies for human growth disorders that are noninvasive and have minimal side effects.
Lymphopoenia and pneumocystis jiroveci (PCP) prophylaxis experience in non-specific interstitial pneumonitis (NSIP)
Authors: Sharada Gudur, Pippa Newton, Colm Leonard, Nazia Chaudhuri
Journal: European Respiratory Journal (2014)

Introduction   Risk for Pneumocystis jiroveci (formerly P carinii) pneumonia (PCP) in non-HIV infected patients has been attributed to several causes including prolonged or intensive corticosteroid therapy.  [1]  Corticosteroids, lymphopenia and low CD4 count are risk factors for PCP in adults with autoimmune diseases. Chemoprophylaxis with co-trimoxazole is generally well tolerated with minimal adverse events. The mortality in this group without treatment is significantly high   [2]  . A patient with NSIP presenting with pneumothorax as a fatal complication of PCP, following 4 weeks of immunosuppression triggered this study. There are limited recommendations regarding PCP prophylaxis in non-HIV immunosuppressed patients with Interstitial lung disease (ILD).   Method   A retrospective review was performed of electronic letters and results of patients with MDT diagnoses of NSIP, in a tertiary hospital in North West England between Feb 05 and Jan 14.   Results   71 patients had NSIP (males 35), with median age 68.3 years (range 46 – 90). 50/71 (70%) were on immunosuppression, 21 (42%) Prednisolone alone; 29 (58%) on second line agent. Blood results were available in 56/71 patients. 11/56 (20%) had normal total lymphocyte count. Of those with low lymphocyte counts, 6 (10%) l 0.5, 18 (32%) 0.5 – 1 x 10  9  .No patients were on PCP prophylaxis.   Conclusions   We identify a significant proportion of patients treated with immunosuppression who are lymphopenic and may be at risk of PCP infection. Further randomised studies are required to evaluate the benefits of chemoprophylaxis in this patient group.   Ref  [1] Maini, cdc.gov, March 2013  [2] Green, Cochrane review of PCP prophylaxis in non-HIV, 2011.
Mesenchymal stem cells from adipose tissue reduce bleomycin-induced lung remodeling in late stage
Authors: Renato Gonçalves Felix, Alexandre Todorovic Fabro, Josy Campanhã Vicentini Oliveira, Michele Janegitz Acorci Valerio, Ondina Silvia Cotrim, Cassio Cunha, Carlos Roberto Gonçalves Lima, Ednelson Henrique Bianchi, Maria Aparecida Custódio Domingues, João Tadeu Ribeiro Paes, Elenice Deffune
Journal: European Respiratory Journal (2013)

Bleomycin (BLM) model is usefull to identify new therapeutic targets. Mesenchymal stem cells (MSC) can modulate inflammatory and immune reponse. However, the long-term effect of MSCs could increase fibroblast and collagen. To determine the therapeutic effects of MSC from adipocyte on lung remodeling in late stage, wistar mice were treated with (BLM-W,n=14) intratracheal BLM (1,5U/kg) or (CTR-W,n=15) saline. At 14d 1x106 MSCs were infused into half of placebo (CTR-MSC,n=14) and BLM-treated mice (BLM-MSC,n=15). MSCs were selected by adhesion, CD90 expression and differentiation into 3 lineages. At 28d all mice were sacrificed and body weight, saturation index (SI), macroscopic aspect (MA) were measured. HE and Picro-sirius Red were stained. Quantification and image analysis was performed by two double-blind pathologists following a stereological method. BLM-MSC mice showed a reduction in lung fibrosis compared with BLM-W mice (fig1). Damaged lung structure with contiguous fibrotic masses in BLM-W were replaced after MSC therapy by focal fibrotic walls. Weight gain, SI and MA were improved BLM-MSC (p=0,05). Collagen fibers were decreased in BLM-MSC in compared to BLM-W (1.5+/-0.1X5.9+/-0.4;p=0.0005). Surprisingly, collagen fibers in CTR-MSC were slightly reduced compared to CTR-W (1.2+/-0.1X1.6+/-0.1;p=0.04). MSC is a effective therapy to decrease collagen expression and may contribute to a new therapeutic targets.

![Figure][1]  [1]: pending:yes
Resistance to Imatinib: Mechanisms and Management
Authors: Michael Deininger
Journal: Journal of the National Comprehensive Cancer Network (2005)

Imatinib, a specific small molecule inhibitor of the Abl kinase, has become the standard drug therapy for chronic myelogenous leukemia in all phases. More than 80% of newly diagnosed patients with chronic phase attain a complete cytogenetic response (CCR). Although remissions in patients with early disease are generally durable, acquired resistance after an initial response is common in advanced disease. Reactivation of Bcr-Abl signaling is almost invariably present at the time of relapse, consistent with re-establishment of the initial pathogenetic mechanism. Mutations in the kinase domain (KD) of Bcr-Abl that impair drug binding and increased expression of Bcr-Abl have been identified as major mechanism of acquired drug resistance. The fact that Bcr-Abl remains central to disease pathogenesis at the time of relapse implies that it also remains the optimal drug target. Alternative Abl kinase inhibitors with increased potency and activity against most Bcr-Abl KD mutants are currently undergoing phase I/II clinical testing, with encouraging early results. Despite the high rates of CCR, persistence of residual leukemia as assessed by reverse transcription polymerase chain reaction is the rule even in patients with chronic phase, suggesting that even these patients may remain at risk of relapse. Understanding the mechanisms underlying disease persistence will be crucial for developing strategies to eradicate residual leukemia.
P12 A pragmatic traffic light system for triage of liver disease: results in a cohort of 710 subjects
Authors: Nick Sheron, Stacy Harris, Mike Moore, Emily Williams, Michelle Ledbury, Will Mackintosh, Lisa Kramer, Nina Kapoor, Nur Johari, Alicia Watts, Adrian Bateman
Journal: Gut (2010)

Introduction  At a time when mortality for many diseases is falling, deaths from liver disease have increased fivefold over the last 30 years and have almost doubled over the last 10 years. In order to reduce liver deaths we need to pick up liver disease at a much earlier stage in the community so we need easier more accurate diagnostic methodologies. We used two serum markers and standard tests to develop a simple traffic light diagnostic modality.  Aim  To develop a simple one-step traffic light diagnostic modality that could be used to triage liver disease of all aetiologies in the community.  Method  Subjects were out-patients or in-patients at Southampton University Hospitals Trust between 2003 and 2009. Serum fibrosis markers hyaluronic acid and collagen P3NP were combined with FBC, INR and LFTs in a test cohort (n=119) with a firm diagnosis of the stage of fibrosis. On the basis of the test data, a simple clinical traffic light algorithm was created using HA, P3NP, INR, Albumin, and platelets. An evaluation cohort of 591 subjects, of whom 278 had independent staging of fibrosis, was used to AUROC validate the model and compare a modified binary logistic model—in the abstract data sets are combined.  Results  Conclusion  The traffic light system detected 98% of subjects with cirrhosis and 88% of subjects with progressive fibrosis, in the latter mortality over 5 years was not increased. We envisage this system being used to inform subjects about the need to moderate high risk behaviour, and triage subjects with severe disease to secondary care. Repeat testing at 5-year intervals in increased risk groups should have the potential to pick up most cases of significant liver disease before a fatal presentation to hospital. The traffic light system has been applied to the detection of liver disease in a community sample of 10 000 in the ALDES study funded by NIHR.
Abstract 18945: Baseline Myocardium At-Risk Predicts Subsequent Myocardial Injury in Non ST-Segment Elevation Acute Coronary Syndrome
Authors: Henry Chang, Jennifer A Dickerson, David Verhaert, Orlando P Simonetti, Giuseppe Ambrosio, Elliott D Crouser, Subha V Raman
Journal: Circulation (2014)

BACKGROUND: Increased myocardial injury visualized by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) portends worse outcomes in patients with acute coronary syndromes (ACS). Although non ST-segment acute coronary syndromes (NSTE-ACS) comprise 70% of all ACS and 1-year mortality rates are similar to the more readily-diagnosed and uniformly-treated ST-elevation myocardial infarction, ischemic changes and treatment strategies in NSTE-ACS are not well-defined, Studies have shown that T2-weighted (T2W) cardiac magnetic resonance (CMR) may be a marker of acute myocardial injury in ACS. We hypothesized that the presence of at-risk myocardium, identified by T2W CMR at presentation, predicts increased subsequent myocardial injury by LGE beyond traditional risk predictors in NSTE-ACS. METHODS &amp; RESULTS: 48 patients enrolled in a prospective study of NSTE-ACS underwent CMR with short tau inversion recovery (T2W STIR) imaging and LGE prior to intervention and repeat CMR 61 ± 27 days later. Baseline presence/absence of increased myocardial signal intensity by T2W STIR was determined by consensus of two expert reviewers blinded to other data. In 13 patients (27%), follow-up LGE images showed more extensive injury compared to baseline. Peak troponin at time of event, baseline TIMI risk score and baseline LGE score did not predict subsequent LGE score increase (p=0.13, p=0.48, p=0.55, respectively). Conversely, a much higher proportion of patients with vs. without increased T2W STIR SI at baseline demonstrated increased myocardial injury by LGE at follow-up (12/31 vs. 1/17, p&lt;0.01; Figure). CONCLUSION: Myocardium at-risk by T2-weighted STIR CMR in patients with NSTE-ACS predicts subsequent myocardial injury, more so than clinical predictors or extent of baseline myocardial damage. Prospective studies that intensify care for patients with at-risk myocardium may help identify strategies to improve myocardial salvage and reduce mortality in NSTE-ACS.
Predictors of improvement in peak exercise capacity with helium-hyperoxia in severely-impaired COPD patients under long-term oxygen therapy
Authors: Marcos Nunes, Fernando Queiroga-Jr., Ethiane Meda, Gaspar Chiappa, Maria-Christina Machado, Luiz Eduardo Nery, J. Alberto Neder
Journal: European Respiratory Journal (2011)

Heliox can improve exercise tolerance in ventilatory-limited patients with chronic obstructive pulmonary disease (COPD). Unfortunately, however, these benefits are quite heterogeneous in patients with similar levels of resting airflow obstruction. In order to gain further insight into the determinants of such variability in hypoxaemic patients with advanced COPD, we evaluated 24 males (GOLD stage IV) who were under long-term O 2  therapy. Patients underwent maximum incremental cardiopulmonary exercise tests while breathing hyperoxia (HiOX= 40% O 2 ) or helium-hyperoxia (He-HiOX= 60% He/40%O 2 ). Peak work rate (WR) was significantly improved with He-HiOX compared to HiOX (54±26 W vs. 48±23 W). This was associated with increased mean ins and expiratory flows and larger tidal volumes; in addition, end-expiratory lung volume was lower at peak exercise (5.57±1.12 L vs 5.65±1.13 L; p 2 = 0.66; p
Abstract 9616: Does “Men Are from Mars and Women are from Venus” hold true for Tako-Stubo Cardiomyopathy - A Nationwide Analysis?
Authors: Abhishek Deshmukh, Gagan Kumar, Sandeep Singla, Freij Gobal, Chiranjit Rihal, Mehta L Jawahar
Journal: Circulation (2011)

Background: Recent case series and smaller registries from around the world have reported higher frequency of Takotsubo Cardiomyopathy (TTC) in females.The aim of this study was to look for gender difference and age - gender interactions for TTC across the nation. Methods: This was a cross sectional study using the Nationwide Inpatient Sample (NIS) 2007 database. TTC or Broken heart syndrome or Reversible left ventricular dysfunction following sudden emotional stress or Stress induced Cardiomyopathy or Transient left ventricular apical ballooning syndrome was defined as patients discharged with any ICD code of 429.83 ( http://www.cdc.gov/nchs/data/icd9/agendasept05.pdf ). Multivariate logistic regression with interaction variable between age and sex was performed. Results: There were 6229 estimated discharges in 2007 NIS. Of these, 5558 (89.2 %) were females and 671 (10.8%) were males. 11.1 % were between 18-50 years, 32% between 50-65 years,58% were more than 65 years. Overall females had significantly higher odds of developing TTC (OR, 7.5; 95% CI, 6.31-9.13). In age group &gt; 55yrs, the odds of developing TTC was 9.5 times higher in females than in males, while in age 55yrs had 2.9 times higher odds of developing TTC while there was no such age difference in males. Conclusions: We conclude that women have 7.5 times higher odds of developing TTC than males. Females with age &gt; 55 years have 2.9 times higher odds of developing TTC than females with age &lt; 55 years. Further research needs to be done on hormonal influence and its effect on TTC.
Remission of Severe Neonatal Diabetes With Very Early Sulfonylurea Treatment
Authors: Bess A. Marshall, Rebecca P. Green, Jennifer Wambach, Neil H. White, Maria S. Remedi, Colin G. Nichols
Journal: Diabetes Care (2015)

Mutations in KCNJ11 and ABCC8 can cause neonatal diabetes mellitus (NDM) (1) that may respond to sulfonylureas (2).

We report three NDM infants treated with glyburide very early in life who were able to maintain good glycemic control with minimal dosing.

This 6-year-old male (Case-1-male) was previously reported at birth (3). Mother and sister (Case-1-female) both had NDM and were given insulin for 24 and 6 years, respectively, then treated with high-dose glyburide; mother still requires some insulin. Case-1-male had NDM at 3 days and was given glyburide 0.2 mg/kg/day, weaned to 0.05 mg/kg/day, and maintained normal hemoglobin A1c for 5 years (Fig. 1 A ) continuing glyburide 0.075 mg thrice daily (mixing a crushed 5 mg tablet with 10 cc water, giving 0.15 cc for each dose, 0.012 mg/kg/day). All had a heterozygous mutation in KCNJ11 (R201H).



Figure 1 
A : Hemoglobin A …