tbuckley/cabot-search huggingface dataset:
Aortic Pulse Wave Velocity and Albuminuria in Patients with Type 2 Diabetes
Authors: Andrew Smith, Janaka Karalliedde, Lorenita De Angelis, David Goldsmith, Giancarlo Viberti
Journal: Journal of the American Society of Nephrology (2005)

Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.
Stress fractures of the femoral shaft in athletes: a new treatment algorithm
Authors: A Ivkovic, I Bojanic, M Pecina
Journal: British Journal of Sports Medicine (2006)

Background: Femoral shaft stress fractures in athletes are not common but pose a great diagnostic challenge to clinicians. Because of few clinical signs, diagnosis and treatment are often delayed. Furthermore, if not treated correctly, these fractures are well known for complications and difficulties. Objective: To develop a well structured and reproducible treatment algorithm for athletes with femoral shaft stress fractures. Methods: The proposed algorithm is carried out in four phases, each lasting three weeks, and the move to the next phase is based on the result of the tests carried out at the end of the previous phase. Over nine years, we treated seven top level athletes, aged 17–21. In all athletes, diagnosis was based on physical examination, plain radiographs, and bone scan. Results: As a result of the treatment method, all the athletes were fully engaged in athletic activity 12–18 weeks after the beginning of treatment. After completion of the treatment, the athletes were followed up for 48–96 months. During the follow up, there was no recurrence of discomfort or pain, and all the athletes eventually returned to competition level. Conclusion: These results and data available from the literature suggest that the algorithm is the optimal treatment protocol for femoral shaft stress fractures in athletes, avoiding the common complications and difficulties.
Proteinase-Activated Receptor-1–Triggered Activation of Tumor Progression Locus-2 Promotes Actin Cytoskeleton Reorganization and Cell Migration
Authors: Maria Hatziapostolou, Christos Polytarchou, Dimitrios Panutsopulos, Lidija Covic, Philip N. Tsichlis
Journal: Cancer Research (2008)

Abstract Tumor progression locus 2 (Tpl2), a mitogen-activated protein kinase kinase kinase (MAP3K) that is activated by provirus insertion in retrovirus-induced rodent lymphomas and mammary adenocarcinomas, is known to transduce Toll-like receptor, interleukin 1, tumor necrosis factor α, and CD40 signals and to play an important role in inflammation. Here we show that Tpl2 is also required for the transduction of cell migration and gene expression signals originating in the G-protein–coupled receptor proteinase-activated receptor 1 (PAR1). PAR1 signals transduced by Tpl2 activate Rac1 and focal adhesion kinase, and they are required for reorganization of the actin cytoskeleton and cell migration. PAR1 expressed in fibroblasts can be triggered by proteinases produced by tumor cells, and PAR1 expressed in tumor cells can be triggered by proteinases produced by fibroblasts. These data suggest that signals that regulate cell migration and gene expression flow between stromal and tumor cells in both directions and that Tpl2 plays a pivotal role in this process. [Cancer Res 2008;68(6):1851–61]
Platelet Immunoreceptor Tyrosine-Based Activation Motif (ITAM) Signaling and Vascular Integrity
Authors: Yacine Boulaftali, Paul R. Hess, Mark L. Kahn, Wolfgang Bergmeier
Journal: Circulation Research (2014)

Platelets are well-known for their critical role in hemostasis, that is, the prevention of blood loss at sites of mechanical vessel injury. Inappropriate platelet activation and adhesion, however, can lead to thrombotic complications, such as myocardial infarction and stroke. To fulfill its role in hemostasis, the platelet is equipped with various G protein-coupled receptors that mediate the response to soluble agonists such as thrombin, ADP, and thromboxane A2. In addition to G protein-coupled receptors, platelets express 3 glycoproteins that belong to the family of immunoreceptor tyrosine-based activation motif receptors: Fc receptor γ chain, which is noncovalently associated with the glycoprotein VI collagen receptor, C-type lectin 2, the receptor for podoplanin, and Fc receptor γII A, a low-affinity receptor for immune complexes. Although both genetic and chemical approaches have documented a critical role for platelet G protein-coupled receptors in hemostasis, the contribution of immunoreceptor tyrosine-based activation motif receptors to this process is less defined. Studies performed during the past decade, however, have identified new roles for platelet immunoreceptor tyrosine-based activation motif signaling in vascular integrity in utero and at sites of inflammation. The purpose of this review is to summarize recent findings on how platelet immunoreceptor tyrosine-based activation motif signaling controls vascular integrity, both in the presence and absence of mechanical injury.
Kidney Function Alters the Relationship between Postoperative Troponin T Level and Death
Authors: Michael Walsh, Chew-Yin Wang, Gracie S.Y. Ong, Alvin S.B. Tan, Marzida Mansor, Ina I. Shariffuddin, Noorjahan H.M. Hashim, Hou Yee Lai, A. Wahab Undok, Ushananthini N. Kolandaivel, Vasanthan Vajiravelu, Amit X. Garg, Meaghan Cuerden, Gordon Guyatt, Lehana Thabane, John Mooney, Vincent Lee, Clara Chow, Phillip J. Devereaux
Journal: Journal of the American Society of Nephrology (2015)

Cardiac troponin T (cTnT), even at low concentrations, is a risk factor for 30-day mortality in patients undergoing noncardiac surgery, but it is uncertain whether that risk is generalizable to patients with poor kidney function. We, therefore, evaluated the relationship between cTnT concentration and kidney function on the outcome of 30-day mortality in a post hoc analysis of a prospective cohort study of patients undergoing noncardiac surgery. cTnT was measured for 3 days after surgery and considered abnormal if the peak was ≥0.02 ng/ml. Of the included 14,037 patients, 267 (1.9%) patients died within 30 days of surgery. The adjusted hazard ratios for death with an abnormal cTnT concentration were 4.37 (95% confidence intervals [95% CI], 3.21 to 6.22), 6.15 (95% CI, 2.95 to 140.9), 6.30 (95% CI, 3.12 to 21.23), 1.33 (95% CI, 0.56 to 4.85), and 1.46 (95% CI, 0.46 to 9.21) for eGFR≥60, 45 to <60, 30 to <45, 15 to <30, and <15 ml/min per 1.73 m(2) or on dialysis, respectively. Compared with patients with eGFR≥60 ml/min per 1.73 m(2), the adjusted hazard ratio was significantly lower for patients with eGFR=15 to <30 ml/min per 1.73 m(2) (interaction P value=0.02). Redefining abnormal cTnT concentration as ≥0.03 ng/ml or a change of ≥0.02 ng/ml did not alter results. Because the risk associated with postoperative cTnT levels may be different for patients with eGFR<30 ml/min per 1.73 m(2), additional research is required to determine how to interpret perioperative cTnT values for patients with low kidney function.
Long-term Exposure to PM <sub>10</sub> and NO <sub>2</sub> in Association with Lung Volume and Airway Resistance in the MAAS Birth Cohort
Authors: Anna Mölter, Raymond M. Agius, Frank de Vocht, Sarah Lindley, William Gerrard, Lesley Lowe, Danielle Belgrave, Adnan Custovic, Angela Simpson
Journal: Environmental Health Perspectives (2013)

Findings from previous studies on the effects of air pollution exposure on lung function during childhood have been inconsistent. A common limitation has been the quality of exposure data used, and few studies have modeled exposure longitudinally throughout early life.We sought to study the long-term effects of exposure to particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) and to nitrogen dioxide (NO2) on specific airway resistance (sR(aw)) and forced expiratory volume in 1 sec (FEV1) before and after bronchodilator treatment. Subjects were from the Manchester Asthma and Allergy Study (MAAS) birth cohort (n = 1,185).Spirometry was performed during clinic visits at ages 3, 5, 8, and 11 years. Individual-level PM10 and NO2 exposures were estimated from birth to 11 years of age through a microenvironmental exposure model. Longitudinal and cross-sectional associations were estimated using generalized estimating equations and multivariable linear regression models.Lifetime exposure to PM10 and NO2 was associated with significantly less growth in FEV1 (percent predicted) over time, both before (-1.37%; 95% CI: -2.52, -0.23 for a 1-unit increase in PM10 and -0.83%; 95% CI: -1.39, -0.28 for a 1-unit increase in NO2) and after bronchodilator treatment (-3.59%; 95% CI: -5.36, -1.83 and -1.20%; 95% CI: -1.97, -0.43, respectively). We found no association between lifetime exposure and sR(aw) over time. Cross-sectional analyses of detailed exposure estimates for the summer and winter before 11 years of age and lung function at 11 years indicated no significant associations.Long-term PM10 and NO2 exposures were associated with small but statistically significant reductions in lung volume growth in children of elementary-school age.
Cost Effectiveness in Context
Authors: Clyde B. Schechter
Journal: Journal of Clinical Oncology (2007)

Leung 1 present an extensive and detailed analysis of the cost effectiveness of various approaches to cancer screening for women in Hong Kong. This article includes much more information than is typically reported in cost-effectiveness analyses in the medical literature, and the difference is worthy of both commendation and comment. A typical medical cost-effectiveness article considers only a single intervention in comparison to no intervention or to some representation of usual practice. Such an article typically presents a cost-effectiveness ratio and explicitly or implicitly concludes that the intervention is (or, less commonly, is not) sufficiently cost effective to warrant adoption. Another segment of the cost-effectiveness literature will examine a single intervention in varyingdegreesofintensity(typicallyfrequency),andcalculatethe incremental cost-effectiveness ratio for each step-up in intensity. In either situation, the criterion of cost-effectiveness is either an arbitraryfigure(often$100,000or$50,000perqualityadjustedlife year[QALY])orisbasedoncomparabilitytothecost-effectiveness ratios of practices believed to be widely in use. The problem with those approaches is that they ignore the context within which cost-effectiveness analysis is applied. Cost effectiveness analysis was developed to guide decision makers in the optimal allocation of a fixed budget of resources. 2 The greatest healthbenefitcanbeextractedfromagivenbudgetbystartingwith the activity that has the lowest cost per QALY, and working one’s wayuptheleaguetable,addingtheactivitywiththelowestremaining cost per QALY as far as one can go until the budget is consumed. The remaining activities cannot be undertaken without exceeding the budget or displacing other, more productive, activities.ThisistheapproachtakenbyWooetal. 1 Byperformingthese analyses using common assumptions and approaches, the rank ordering of the programs they suggest is more reliable than one deriving from a league table filled in from numerous, separate single-intervention analyses. 3
Aerosol bolus dispersion in healthy subjects
Authors: P Brand, C Rieger, H Schulz, T Beinert, J Heyder
Journal: European Respiratory Journal (1997)

Aerosol bolus dispersion is a physiological test of lungs, which uses monodisperse submicron particles to measure intrapulmonary convective gas mixing. In this study, aerosol bolus dispersion was measured in healthy subjects in order to assess reference values for possible clinical applications, to assess the reproducibility of these values, and to identify physical and physiological factors influencing aerosol bolus dispersion. Aerosol bolus dispersion was measured in 79 healthy subjects using 20 cm3 aerosol boluses consisting of monodisperse di-2-ethylhexyl sebacate (DEHS) particles. The reproducibility of parameters characterizing the width of the exhaled bolus was of the same order as that of parameters of the flow-volume curve (10%). Aerosol bolus dispersion was independent of the level of lung inflation, and the slope of the relationship between flow rate and dispersion was on average not significantly different from zero (range 100-700 cm3.s-1). Multiple linear regression showed that aerosol bolus dispersion increased with increasing total lung capacity of the subject. We conclude that differences in total lung capacity between individuals should be taken into account when using measures of aerosol bolus dispersion for possible clinical applications.
The 3rd International Patellofemoral Research Retreat: An international expert consensus meeting to improve the scientific understanding and clinical management of patellofemoral pain
Authors: Erik Witvrouw, Kay Crossley, Irene Davis, Jenny McConnell, Christopher M Powers
Journal: British Journal of Sports Medicine (2014)

Patellofemoral pain (PFP) is a common and often chronic musculoskeletal condition, affecting young and physically active adults. It is a particularly common diagnosis of patients seen at sports medicine practices, with the incidence rates varying from 2% to 30%.

Despite its high prevalence, the exact aetiology of PFP remains unclear, although evidence suggests a multifactorial origin. It is likely that the underlying cause of PFP is not the same for all patients. Because of the diverse origin of PFP, many rehabilitation programmes with various approaches have been proposed to treat this disorder. Several studies have demonstrated that physical therapy is effective in treating PFP; however, a high variation in …
Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area
Authors: Sheng-Yuan Ruan, Yu-Chung Chuang, Jann-Yuan Wang, Jou-Wei Lin, Jung-Yien Chien, Chun-Ta Huang, Yao-Wen Kuo, Li-Na Lee, Chong-Jen J Yu
Journal: Thorax (2012)

<h3>Background</h3> Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. <h3>Methods</h3> From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. <h3>Results</h3> A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64–95%) and 17% of cases had a lymphocyte percentage of &lt;50%. The lymphocyte percentage was negatively associated with the probability of a positive effusion culture (OR 0.97; 95% CI 0.96 to 0.99). The diagnostic yields were 63% for effusion culture, 48% for sputum culture, 79% for the combination of effusion and sputum cultures, and 74% for histological examination of pleural biopsy specimens. <h3>Conclusion</h3> The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield.
Kinase Inhibitors and Cytotoxic Drug Resistance
Authors: Steven Grant, Paul Dent
Journal: Clinical Cancer Research (2004)

The Src family consists of a group of nonreceptor tyrosine kinases and includes Src, Lyn, Hck, Yes, and Fyn [(1)][1] . These kinases are critically involved in diverse cellular processes, including cell survival, proliferation, motililty, adhesion, and transformation, among others. Elevated or
Toward an Effective Targeted Chemotherapy for Multiple Myeloma
Authors: Andrew G. Polson, Mark X. Sliwkowski
Journal: Clinical Cancer Research (2009)

Abstract Antibody-drug conjugates (ADCs), cytotoxic drugs chemically linked to antibodies, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells. Anti-CD138 ADCs show promising preclinical efficacy for the treatment of multiple myeloma; however, the safety aspects of targeting CD138 have yet to be explored.
Is There a Role for Routine <i>p53</i> Testing in Colorectal Cancer?
Authors: Paulo M. Hoff
Journal: Journal of Clinical Oncology (2005)

The availability of new and more effective chemotherapeutic and molecular targeted agents has resulted in improved treatment of regional and advanced colorectal cancer. However, thefinancial cost and the morbidity associated with the new treatments have increased as well, and to date no reliable marker capable of selecting patients who will benefit from a specific treatment has been identified. Individualizingtreatmentbasedonthemolecularprofileof the patient and the tumor could lead to considerable improvement in treatment cost and outcomes. Although all patients with colorectal cancer would benefit from better prognostic and predictive markers, risk-benefit is particularly important for candidates for adjuvant therapy, which may expose patients already cured by surgery to unnecessary risk or to a treatment that fails to maximize their chances of cure from micrometastasis. The use of adjuvant oxaliplatin regimens after resection of stage II or III colon cancer is a good example of this clinicalconundrum.Theadditionofoxaliplatintofluorouracil and leucovorin improves the 3-year disease-free survival rate, and has been approved for high-risk resected coloncancerbytheUSFoodandDrugAdministration,but it is clear that not all patients benefit equally from oxaliplatin. In fact, when patients already cured by surgery alone and patients who experience disease recurrence despite treatment are excluded, fewer than 30% of stage II and III patients actually benefit from the use of any adjuvant chemotherapy.Unfortunately,wecurrentlyhavenopracticalwayofidentifyingthosewhowillandthosewhowillnot benefit from the treatment. We still identify which patients should receive adjuvant chemotherapy by their pathologic staging, a tool that has changed little since originally proposed by Dukes more than 70 years ago. 1 The choice of the chemotherapy regimen to be used also lacks sophistication and the currently accepted regimens are applied to the entire patient population without consideration for individual tumor sensitivity or for the patient’s tolerance for
HSV-sr39TK Positron Emission Tomography and Suicide Gene Elimination of Human Hematopoietic Stem Cells and Their Progeny in Humanized Mice
Authors: Eric H. Gschweng, Melissa N. McCracken, Michael L. Kaufman, Michelle Ho, Roger P. Hollis, Xiaoyan Wang, Navdeep Saini, Richard C. Koya, Thinle Chodon, Antoni Ribas, Owen N. Witte, Donald B. Kohn
Journal: Cancer Research (2014)

Abstract Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen receptors generates a continual supply of effector T cells, potentially providing superior anticancer efficacy compared with the infusion of terminally differentiated T cells. Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK. Ex vivo analysis of T cells showed antigen- and HLA-restricted effector function against melanoma. Robust engraftment of gene-modified human cells was demonstrated with PET reporter imaging in hematopoietic niches such as femurs, humeri, vertebrae, and the thymus. Safety was demonstrated by the in vivo ablation of PET signal, NY-ESO-1-TCR–bearing cells, and integrated lentiviral vector genomes upon treatment with ganciclovir, but not with vehicle control. Our study provides support for the efficacy and safety of gene-modified HSCs as a therapeutic modality for engineered cancer immunotherapy. Cancer Res; 74(18); 5173–83. ©2014 AACR.
Recovery From Major Depression in Older Adults Receiving Augmentation of Antidepressant Pharmacotherapy
Authors: Mary Amanda Dew, Ellen M Whyte, Eric J Lenze, Patricia R Houck, Benoit H Mulsant, Bruce G Pollock, Jacqueline A Stack, Salem Bensasi, Charles F Reynolds
Journal: American Journal of Psychiatry (2007)

Objective: Few data are available concerning the utility of augmentation in late-life depression treatment. The authors examined likelihood, speed, and predictors of recovery in older adults receiving augmentation pharmacotherapy after inadequate response to standardized treatment with paroxetine plus interpersonal psychotherapy. Method: Depression levels were monitored during open treatment in 195 adults age 70 or older. Patients were grouped by whether they required augmentation (bupropion, nortriptyline, or lithium) and compared on likelihood, time, and predictors of recovery. Results: Augmentation was required for 105 patients (53.8%) because of inadequate treatment response (N=77) or response followed by relapse (N=28). Of these patients, 69 received augmentation and 36 did not (primarily because of consent withdrawal or comorbid medical conditions). Patients receiving augmentation showed lower recovery rates than patients never requiring augmentation: recovery occurred in 50.0% of patients receiving it because of inadequate response, 66.7% of those receiving it after early relapse, and 86.7% of patients never requiring augmentation. Patients receiving augmentation because of inadequate response recovered more slowly, with modestly more side effects than other patients. Greater medical burden and anxiety predicted slower recovery. Conclusions: Despite a lower likelihood of recovery in elderly people receiving augmentation, the recovery by over one-half of such patients suggests the value of augmentation for those able to tolerate it. Need for augmentation presages slower recovery in patients showing initial inadequate response; those requiring it after early relapse recovered more quickly. Strategies to further improve the likelihood and speed of recovery after initial treatment failure are needed.