tbuckley/cabot-search huggingface dataset:
How long should outpatient pulmonary rehabilitation be? A randomised controlled trial of 4 weeks versus 7 weeks
Authors: L Sewell, S J Singh, J E A Williams, R Collier, M D L Morgan
Journal: Thorax (2006)

<b>Background:</b> The evidence of benefit for pulmonary rehabilitation (PR) programmes is established. However, the optimal duration of a PR programme is not known. A randomised controlled trial was undertaken in patients with chronic obstructive pulmonary disease (COPD) to assess whether a 4 week PR programme was equivalent to our conventional 7 week PR programme at equivalent time points of 7 weeks and 6 months. <b>Methods:</b> One hundred patients (56 men) with stable COPD of mean (SD) age 70 (8) years and forced expiratory volume in 1 second (FEV<sub>1</sub>) 1.13 (0.50) litres were randomised to either a 7 week (n = 50) or 4 week (n = 50) supervised PR programme. Patients were assessed at baseline, at completion of the supervised PR programme, and 6 months later. Patients randomised to the 4 week group were also assessed at the 7 week time point. Outcome measures were the Incremental Shuttle Walk Test, Endurance Shuttle Walk Test (ESWT), Chronic Respiratory Questionnaire-Self Reported, and the Breathing Problems Questionnaire. <b>Results:</b> Forty one patients in each group completed the PR programme. Patients made significant within group improvements after supervised rehabilitation. There were no statistically significant differences between the groups for any other measure at the 7 week or 6 month time points, except that patients in the 4 week group attained higher ESWT times (mean difference 124 seconds (95% CI 17.00 to 232.16), p = 0.024) at the 7 week time point. <b>Conclusions:</b> A shortened 4 week supervised PR programme is equivalent to a 7 week supervised PR programme at the comparable time points of 7 weeks and 6 months.
A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC
Authors: N.G. Chau, S.J. Hotte, E.X. Chen, S.F. Chin, S. Turner, L. Wang, L.L. Siu
Journal: Annals of Oncology (2011)
Superficial venous thrombosis associated with congenital absence of the inferior vena cava and previous episode of deep venous thrombosis
Authors: Darren M. Evanchuk, Ann Von Gehr, James L. Zehnder
Journal: American Journal of Hematology (2007)

Abstract Congenital malformations of the inferior vena cava (IVC) are uncommon and may be associated with an increased risk of venous thrombosis. We report the case of a man with congenital absence of the IVC and remote history of deep venous thrombosis who now presents with severe abdominal wall superficial thrombophlebitis. To our knowledge, this is the first report of a patient with IVC absence who has developed both deep and superficial venous thromboses. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Effects of p38 mitogen-activated protein kinase inhibition on anti-neutrophil cytoplasmic autoantibody pathogenicity in vitro and in vivo
Authors: B. S. van der Veen, M. Chen, R. Muller, M. M. van Timmeren, A. H. Petersen, P. A. Lee, S. C. Satchell, P. W. Mathieson, M. A. Saleem, C. A. Stegeman, J. Zwerina, G. Molema, P. Heeringa
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To determine whether inhibition of p38 mitogen-activated protein kinase (p38MAPK) reduces the pathogenicity of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in vitro and in vivo. <h3>Methods</h3> The effects of the p38MAPK-specific inhibitor AR-447 were studied in vitro using neutrophil respiratory burst and degranulation assays, and in lipopolysaccharide (LPS)-stimulated human glomerular endothelial cells. In vivo, p38MAPK inhibition was investigated in a mouse anti-myeloperoxidase (MPO) IgG/LPS glomerulonephritis model. Mice were treated orally with AR-447 daily, starting before (pretreatment group) or 24 h after disease onset (treatment group), and killed after 1 or 7 day(s). <h3>Results</h3> In vitro, AR-447 diminished neutrophil respiratory burst and degranulation induced by patient-derived MPO-ANCA and proteinase 3 (Pr3)-ANCA. In glomerular endothelial cells, AR-447 reduced LPS-induced secretion of IL-6 and IL-8, but not of MCP-1. In mice, pretreatment with AR-447 reduced albuminuria 1 day after induction of glomerulonephritis. After 7 days, no effects on urinary abnormalities were observed upon AR-447 pretreatment or treatment. Also, glomerular neutrophil accumulation was not diminished. In contrast, glomerular macrophage accumulation and the formation of glomerular crescents was significantly reduced by AR-447 pretreatment (vehicle: 12.5 ± 5.6% crescentic glomeruli; AR-447: 7.7 ± 2.7%) and treatment (vehicle 14.6 ± 1.8%; AR-447 6.0 ± 3.4%) at 7 days. <h3>Conclusion</h3> This study shows that p38MAPK inhibition markedly reduces ANCA-induced neutrophil activation in vitro. In vivo, p38MAPK inhibition partly reduced crescent formation when the drug was administered prior to disease induction and after disease onset, suggesting that besides p38MAPK activity other signalling pathways contribute to the disease activity.
Optimal Management of Esophageal Adenocarcinoma: Should We Be CROSS?
Authors: Elizabeth C. Smyth, Tom S. Waddell, David Cunningham
Journal: Journal of Clinical Oncology (2014)

by Surgery Study (CROSS), and Mamon and Tepper 2 provided an accompanying editorial. CROSS provided definitive evidence of the benefit of preoperative CRT compared with surgery alone for patients with operable esophageal cancer and led to a paradigm shift in practice for many oncologists. 3 However, we question the wisdom of applying these results to all patients with esophageal and junctional cancers, given that the stratified analysis demonstrates a significantly reduced survival advantage for patients with adenocarcinoma compared with squamous cell carcinoma (HR, 0.74 v 0.42). In fact, the benefits of CRT were not statistically significant in either the adenocarcinoma or node-positive subgroups, despite the fact that the vast majority of recruited patients were in these groups. These data suggest that the overall findings of CROSS were strongly driven by the undisputable benefits of CRT in node-negative squamous cell tumors. This argumentisfurtherstrengthenedbythecurrentupdateregardingpatterns of recurrence. ThemultivariableanalysisconfirmsthatthebenefitsofCRTwith respect to local recurrence are markedly greater for patients with squamous cell carcinoma than adenocarcinoma (HR, 0.49; 95% CI, 0.29to0.82).Furthermore,CRTdidnotsignificantlyaffecttheoccurrenceofisolateddistantmetastasesand,incontrasttolocalrecurrence, no breakdown by histologic subtype was provided for distant metastatic disease. We suspect that these distant recurrences may be dominatedbypatientswithadenocarcinoma,inwhichsystemicmetastatic
New Targetable Oncogenes in Non–Small-Cell Lung Cancer
Authors: Geoffrey R. Oxnard, Adam Binder, Pasi A. Jänne
Journal: Journal of Clinical Oncology (2013)

The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non-small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development.
cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia.
Authors: J J Smith, M J Welsh
Journal: Journal of Clinical Investigation (1992)

Adenosine 3',5'-cyclic monophosphate stimulates chloride (Cl-) secretion across airway epithelia. To determine whether cAMP also stimulates HCO3- secretion, we studied cultured canine and human airway epithelial cells bathed in a HCO3-/CO2-buffered, Cl(-)-free solution. Addition of forskolin stimulated an increase in short-circuit current that was likely a result of bicarbonate secretion because it was inhibited by a HCO3(-)-free solution, by addition of the carbonic anhydrase inhibitor, acetazolamide, or by mucosal addition of the anion channel blocker, diphenylamine 2-carboxylate. The current was dependent on Na+ because it was inhibited by removal of Na+ from the submucosal bathing solution, by addition of the Na+ pump inhibitor, ouabain, or by addition of amiloride (1 mM) to the submucosal solution. An increase in cytosolic Ca2+ produced by addition of a Ca2+ ionophore also stimulated short-circuit current. These data suggest that cAMP and Ca2+ stimulate HCO3- secretion across airway epithelium, and suggest that HCO3- leaves the cell across the apical membrane via conductive pathways. These results may explain previous observations that the short-circuit current across airway epithelia was not entirely accounted for by the sum of Na+ absorption and Cl- secretion. The cAMP-induced secretory response was absent in cystic fibrosis (CF) airway epithelial cells, although Ca(2+)-stimulated secretion was intact. This result suggests that HCO3- exist at the apical membrane is through the Cl- channel that is defectively regulated in CF epithelia. These results suggest the possibility that a defect in HCO3- secretion may contribute to the pathophysiology of CF pulmonary disease.
N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial Tumors
Authors: Isabelle Lascombe, Anne Clairotte, Sylvie Fauconnet, Stéphane Bernardini, Hervé Wallerand, Bernadette Kantelip, Hugues Bittard
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion and spreading. In bladder cancer, loss or reduced E-cadherin expression has been associated with poor survival, and aberrant expression of N-cadherin has been associated with the invasive phenotype of bladder carcinoma cells. The purpose of this study was to investigate whether N-cadherin expression was associated with the bladder tumor progression. Experimental Design: E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101 tumors (pT1 and pT2-T3) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pTa, pT1, and pT2-T3). Results: N-cadherin expression was absent in normal urothelium, appeared in stage pT1, and increased in pT2-pT3 tumors. In most cases, increased N-cadherin expression in invasive tumors was associated with loss of E-cadherin expression. Progression-free survival and multivariate analyses revealed that N-cadherin expression is an independent prognostic marker for pT1 tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT1 and pT2-T3 tumors. Interestingly, in pTa tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases. Conclusion: Regulatory defects in the N-cadherin promoter, abnormalities at the translational, or protein processing levels could explain the discrepancies between protein and mRNA expression. Most importantly, this study identified N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clearly, N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated.
An open, prospective comparison of beta 2 agonists given via nebuliser, Nebuhaler, or pressurised inhaler by ambulance crew as emergency treatment.
Authors: I A Campbell, S B Colman, J H Mao, R J Prescott, C F Weston
Journal: Thorax (1995)

BACKGROUND--The merits of the use of beta 2 agonists by ambulance crew and best methods of delivery have not been fully explored. METHODS--A prospective comparison has been made of treatments applied in three districts in South Wales (200 micrograms salbutamol by pressurised inhaler, 5 mg salbutamol via nebuliser, and 5 mg terbutaline via Nebuhaler) by emergency ambulance personnel to acutely wheezy patients en route to hospital. Pulse rate, respiratory rate, peak expiratory flow rate (PEFR), and breathlessness scored on a visual analogue scale were compared before and after treatment. Data were collected on diagnosis, artificial ventilation, cardiorespiratory arrest, and death. RESULTS--Thirty eight patients received salbutamol inhaler, 51 salbutamol via nebuliser, and 41 terbutaline via Nebuhaler. There were greater reductions in respiratory rate and breathlessness score and more improvement in PEFR in the group receiving nebulised salbutamol than in the other two groups. No patient was ventilated and of the five deaths none was caused by asthma. CONCLUSIONS--For wheezy, breathless patients treated en route to hospital by emergency ambulance personnel, 5 mg salbutamol given by an oxygen-driven nebuliser was more effective than either 5 mg terbutaline via a Nebuhaler or 200 micrograms salbutamol via a pressurised inhaler.
Prevalence of residual sleep apnea in patients treated with APAP and its predictive factors
Authors: Filipa Soares Pires, Marta Drummond, Inês Neves, Cláudia Pinto, Anabela Marinho, Maria Sucena, João Almeida, João Winck
Journal: European Respiratory Journal (2012)

INTRODUCTION: Auto-adjusting continuous positive airway pressure (APAP) is a safe and proven effective treatment for obstructive sleep apnea (OSA). There are limited data on prevalence of persistent OSA in patients under APAP therapy.

AIM: To determine the prevalence of residual sleep apnea (RSA) in patients under APAP and its predictive factors.

METHODS: A transversal study was performed, including patients newly diagnosed with OSA, that initiated APAP 6 months before (51.9% under iSleep; 46.8% under AutoSet Spirit II or S9). Exclusion criteria: Obesity-Hypoventilation Syndrome and Central Sleep Apnea. Data were downloaded from devices and residual apnea-hypopnea index (AHI) was registered. Patients were considered to have RSA if AHI≥5. Only patients with acceptable leak were considered. Baseline demographic, clinical and sleep study were evaluated.

RESULTS: 107 patients were included; 77 (72%) had acceptable leak, being considered for statistical analysis. Prevalence of RSA was 22.1%. Factors at baseline associated with RSA were: lower BMI (30.4±5.1 vs. 33.3±4.6) – p=0.028; severe OSA (31.2% RSA in severe OSA vs. 7.4% in moderate OSA) – p=0.018; higher central apnea index (3.11±4.24 vs. 0.98±2.25) – p=0.016; and higher apnea/hypopnea duration (24.0±7.3 sec vs. 20.8±4.1 sec) – p=0.045. Higher APAP pressures (95th percentile) were related to the occurrence of RSA (12.5±2.4 vs. 10.0±2.7) – p=0.001. APAP device was not related to RSA.

CONCLUSION: Residual OSA is common in patients treated with APAP. Lower BMI, severe OSA, higher central apnea index and longer duration of apnea/hypopnea are baseline predictors of RSA. These patients should be followed more closely to avoid suboptimal treatment.
Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease
Authors: Bilge Aktas, Yusuf Yilmaz, Fatih Eren, Oya Yonal, Ramazan Kurt, Yesim Ozen Alahdab, Cigdem Ataizi Celikel, Osman Ozdogan, Nese Imeryuz, Cem Kalayci, Erol Avsar
Journal: Metabolism (2010)
The effects of antigen on the migration of recirculating lymphocytes through single lymph nodes.
Authors: R N Cahill, H Frost, Z Trnka
Journal: The Journal of Experimental Medicine (1976)

The increased input of RL into LN starts within 3 h after antigenic stimulation and is due to an increase in the number of RL passing through a LN. It is not associated with an altered transit time through a LN of the majority of RL and it cannot occur in the absence of high endothelial PCV. The immediate decrease in the output of RL from an antigen-stimulated LN is due to a delay in the exit from that LN of RL which had entered the LN before antigen was given. The decrease in cell output from a LN after antigen administration affects blast cells produced within the LN as well as small lymphocytes and is not specific for RL. There are at least two distinct mechanisms controlling the migration of RL through an antigen-stimulated LN. The first controls the increased input of RL which occurs only through high endothelial PCV. The second controls the immediate decrease in cell output, which although it does not occur at the level of the high endothelial PCV, can only occur in organized lymphoid tissue. The increased input of RL into an antigen-stimulated LN and the decreased cell output from the LN can occur independently and are possibly controlled by different mechanisms.
The antiangiogenic agents TNP-470 and 2-methoxyestradiol inhibit the growth of angiosarcoma in mice
Authors: Jack L. Arbiser, Dipak Panigrathy, Nancy Klauber, Maria Rupnick, Evelyn Flynnb, Taturo Udagawa, Robert J. D'Amato
Journal: Journal of the American Academy of Dermatology (1999)
Gastrointestinal Absorption of Intact Proteins
Authors: M L G Gardner
Journal: Annual Review of Nutrition (1988)

There is now no reasonable doubt that small quantities of intact proteins do cross the gastrointestinal tract in animals and adult humans, and that this is a physiologically normal process required for antigen sampling by subepithelial immune tissue in the gut. It is too small to be nutritionally significant in terms of gross acquisition of amino-nitrogen, but since it has important implications relating to dietary composition it must receive consideration from nutritionists. The process of intact protein absorption occurs without eliciting harmful consequences for most individuals, but it appears likely that a small number of people absorbing these "normal" amounts may react idiosyncratically; also, some individuals may absorb excessive amounts, and they may suffer clinically significant consequences. Likewise, individuals with diminished absorption of intact protein may be at risk. Normal absorption probably occurs predominantly by transcellular endocytosis with some possible contribution by a route between cells; increased net entry of protein to the circulation may reflect (a) increased paracellular (intercellular) passage, (b) increased transcellular passage, and/or (c) decreased lysosomal proteolysis. Tests to distinguish among these possibilities are strongly desirable. Intact protein absorption may be involved in the pathogenesis of inflammatory bowel disease, "food allergies," and other diseases, including even major psychiatric disorders, but the current evidence is mainly indirect and suggestive. Great caution and careful objective studies are needed to establish whether such relationships with disease do exist and to unravel the underlying basic physiological mechanisms. Now that interest has developed in the assessment of intestinal permeability to small- and medium-sized molecules, it is hoped that equally simple methods for studying macromolecular permeability will be developed and applied. Therapeutic methods for enhancing intact polypeptide absorption would be valuable for vaccine and peptide drug administration by the oral route. Therapeutic reduction of the process may be relevant in food-sensitive patients.
PTP1B inhibition suggests a therapeutic strategy for Rett syndrome
Authors: Navasona Krishnan, Keerthi Krishnan, Christopher R. Connors, Meng S. Choy, Rebecca Page, Wolfgang Peti, Linda Van Aelst, Stephen D. Shea, Nicholas K. Tonks
Journal: Journal of Clinical Investigation (2015)

The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.
Phase I and pharmacokinetic study of the new vinca alkaloid vinflunine administered as a 10-min infusion every 3 weeks in patients with advanced solid tumours
Authors: J. Bennouna, P. Fumoleau, J.-P. Armand, E. Raymond, M. Campone, F.-M. Delgado, C. Puozzo, M. Marty
Journal: Annals of Oncology (2003)
Alport's Syndrome, Goodpasture's Syndrome, and Type IV Collagen
Authors: Billy G. Hudson, Karl Tryggvason, Munirathinam Sundaramoorthy, Eric G. Neilson
Journal: New England Journal of Medicine (2003)

Defects in type IV collagen, a collagenous protein involved in the formation of basement membranes, have been implicated in hereditary Alport's syndrome and acquired Goodpasture's syndrome. Mutations in genes corresponding to the building blocks of type IV collagen cause Alport's syndrome, whereas autoantibodies against structures that are usually hidden in the recesses of collagen IV cause Goodpasture's syndrome.
Variations of Left Ventricular End-Diastolic Pressure, Volume, and Ejection Fraction with Changes in Outflow Resistance in Anesthetized Intact Dogs
Authors: ANASTASIOS G. TSAKIRIS, RUSSELL A. VANDENBERG, NATALIO BANCHERO, RALPH E. STURM, EARL H. WOOD
Journal: Circulation Research (1968)

Multiple measurements of left ventricular volumes, ejection fractions, and circulatory pressures were made under conditions of varied outflow resistance in five intact anesthetized dogs by using a biplane videoangiographic recording system which displays simultaneously two roentgen images on the same television screen, records the images on video tape, and requires low radiation levels and small amounts of contrast medium. Aortic pressure was controlled by intra-aortic infusion of angiotensin or acetylcholine. With spontaneous sinus rhythm and normal aortic pressure, end-diastolic volume averaged 35 ml (2.3 ml/kg), and ejection fraction averaged 47% of end-diastolic volume. When aortic pressure was increased, average end-diastolic volumes increased to 53 ml and ejection fractions decreased to 29%. Conversely, when aortic pressure was decreased, average ejection fraction increased to 73%, although changes in stroke volume were usually not large under these conditions. Concomitant large changes in the shape of the left ventricular cavity were also observed. Similar changes were observed when heart rate was maintained constant by electrical pacing of the atria and ventricles with a constant atrial-ventricular stimulus interval. The variability in left ventricular volume and ejection fraction observed in the same animal during different circulatory states may account in part for the differences in values for these variables reported by different investigators.