tbuckley/cabot-search huggingface dataset:
Loading Sequence Plays an Important Role in Enhanced Load Sensitivity of Left Ventricular Relaxation in Conscious Dogs With Tachycardia-Induced Cardiomyopathy
Authors: Shinji Ishizaka, Hidetsugu Asanoi, Osamu Wada, Tomoki Kameyama, Hiroshi Inoue
Journal: Circulation (1995)

Background Left ventricular relaxation rate in the failing heart depends more on the systolic load than in the normal heart. To elucidate the mechanisms for the enhanced load sensitivity of left ventricular relaxation in heart failure, we examined the relative contributions of changes in end-systolic volume and loading sequence to the left ventricular relaxation rate. Methods and Results In seven conscious dogs, the time constant (T d ) of left ventricular pressure decay, end-systolic volume, systolic circumferential force, and time to peak force during caval occlusion were compared before and after development of tachycardia-induced heart failure. Rapid ventricular pacing decreased the slope of the end-systolic pressure-volume relation from 4.5 to 2.8 mm Hg/mL ( P &lt;.01) and prolonged T d from 33 to 49 ms ( P &lt;.01). In normal conditions, caval occlusion reduced end-systolic force (−580 g, P &lt;.01) and end-systolic volume (−7 mL, P &lt;.01) but did not change T d or time to peak force. In heart failure, however, caval occlusion shortened T d (−11 ms, P &lt;.01), with a concomitant decrease in the time to peak force (−30 ms, P &lt;.01), while end-systolic volume and force declined slightly. Consequently, for a comparable reduction in end-systolic force, T d decreased more in heart failure than in normal hearts, suggesting enhanced load sensitivity. Moreover, changes in T d correlated well with those in the time to peak force ( r =.79, P &lt;.01) but not with those in end-systolic volume. Conclusions Loading sequence rather than elastic recoil seems to play the predominant role in the enhanced load sensitivity of left ventricular relaxation in heart failure.
Expression of X-Linked Inhibitor of Apoptosis Protein Is a Strong Predictor of Human Prostate Cancer Recurrence
Authors: David B. Seligson, Fumiya Hongo, Sara Huerta-Yepez, Yoichi Mizutani, Tsuneharu Miki, Hong Yu, Steve Horvath, David Chia, Lee Goodglick, Benjamin Bonavida
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The X-linked inhibitor of apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. We examined the expression patterns of XIAP with regard to human prostate cancer, predicting that XIAP status may predict cancer recurrence and/or clinical outcome. Experimental Design: Immunohistochemistry was done on tissue microarrays constructed from 226 primary prostate cancer specimen. The protein expression distribution was examined across the spectrum of epithelial tissues and its association with standard clinicopathologic covariates and tumor recurrence was examined in 192 outcome-informative patients. Results: The mean XIAP expression was significantly higher in prostate cancer compared with prostatic intraepithelial neoplasia (PIN), normal, and benign prostatic hyperplasia. We observed that XIAP is an independent predictor of tumor recurrence in multivariate Cox proportional hazards analysis in all patients as well as after substratifying by Gleason score. Interestingly, patients with high XIAP levels had a much lower probability of tumor recurrence than those with lower XIAP expression. Even patients with high-grade tumors who had higher XIAP levels had a lower risk of recurrence compared with any patient whose tumors express lower XIAP. Conclusions: XIAP is expressed at higher levels in prostate cancers compared with matched normal tissues. High XIAP expression is strongly associated with a reduced risk of tumor recurrence and is not directly associated with Gleason score, tumor stage, capsular involvement, or preoperative prostate-specific antigen status, suggesting that it is a novel prognosticator and a potential target for prostate cancer diagnosis and therapy. Significantly, these findings provide important and extensive validation of previous results.
Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease
Authors: N. Soler, C. Agusti, J. Angrill, J. Puig De la Bellacasa, A. Torres
Journal: Thorax (2006)

<b>Background:</b> Antibiotics are commonly prescribed in exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of bacteria in these exacerbations is controversial. <b>Objective:</b> To identify clinical predictors of bacterial infection as a cause of exacerbation, considering the protected specimen brush (PSB) as the gold standard. <b>Methods:</b> Clinical data, sputum and PSB samples were collected from 40 patients with COPD requiring hospitalisation due to severe exacerbations who had not received previous antibiotic treatment. <b>Results:</b> Quantitative cultures of PSB samples (n = 40) yielded 23 potential pathogenic microorganisms (PPMs) at concentrations of ⩾10<sup>2</sup> colony-forming units/ml in 18 (45%) patients. Sputum samples were obtained from all 40 patients. Culture of good-quality sputum samples (n = 18) yielded 16 PPMs corresponding to 14 (35%) patients. The concordance between the PSB and sputum rate was high (κ = 0.85, p&lt;0.002). The self-reporting patient observation of sputum purulence (odds ratio (OR) 27.20 (95% confidence interval (CI) 4.60 to 60.69), p = 0.001), the percentage predicted forced expiratory volume in 1 s (FEV<sub>1</sub>%) &lt;50 (OR 2.27 (95% CI 1.55 to 3.21), p = 0.014), &gt;4 exacerbations in the past year (OR 6.9 (95% CI 0.08 to 1.08), p = 0.028) and previous hospitalisations due to COPD (OR 4.13 (95% CI 1.02 to 16.07), p = 0.041) were associated with the presence of PPMs in the distal airways. The operative characteristics for predicting distal airway infection when patients presented with purulent exacerbation were as follows: sensitivity 89.5%, specificity 76.2%, positive predicted value 77.3% and negative predicted value 88.9%. <b>Conclusions:</b> The self-reporting presence of purulence in the sputum, as well as common previous exacerbations and hospitalisations due to COPD in patients with severe airflow obstruction (FEV<sub>1</sub>% &lt;50) predict the presence of bacterial infection in the distal airways. The use of these clinical variables may help in selecting candidates to receive antibiotic treatment.
ON TWO CASES OF REMOVAL OF PART OF THE PERICARDIUM, AND ITS REPAIR BY MEANS OF THE PECTORAL MUSCLE
Authors: A. W. M. Robson
Journal: BMJ (1911)

thc ,duodenunm, as advocated by Zeller.1This gives a better view' into the bowel; its 'wall can' be mh'ore securely 'closed, and as an additional protection the 'peritoneum passing between the walls of the duodenum and the transverse colon, which is often loose and redundant, can be drawn up over the wound;-'REFERENCE.
Inherited Thyroxine-Binding Globulin Abnormalities in Man*
Authors: SAMUEL REFETOFF
Journal: Endocrine Reviews (1989)

IN 1959, Beierwaltes and Robbins (1) reported a family with T4-binding globulin (TBG) excess thus recognizing for the first time the existence of inherited TBG abnormalities in man. Subsequently, the occurrence of inherited complete (2–4) and partial (5–7) TBG deficiencies were described. These three forms of TBG abnormalities (complete deficiency, partial deficiency, and excess) followed, in general, an X-chromosome-linked inheritance pattern (7–9). Because earlier studies of these subjects failed to show physical or chemical changes of their TBG (7, 10), nor circulating substances interfering with hormone binding to the molecule (4, 11), and because labeled normal TBG tracer had normal survival time when given to the affected subjects (12), it was postulated that inherited TBG defects represent either mutations of a gene controlling TBG synthesis (12) or mutations at the promoter site of the TBG gene proper (13). In the 1980s, two new inherited TBG types were described, both involving distinct ethnic groups. In 1980/1981, Dick and Watson (14, 15) reported that the low serum total T4 (TT4) concentration found in approximately 40% of Australian Aborigines was due to a TBG variant with low affinity for T4. In 1981, Daiger et al. (16, 17) reported a TBG with slow electrophoretic mobility and with isoelectric focusing (IEF) pattern exhibiting a cathodal shift in 5–16% of subjects from African and Oceanian origin. Inheritance of these two variant TBGs was shown also to be X-chromosome-linked (16, 18), suggesting that the structural gene of the molecule is located on the X-chromosome. Over the past 3 yr, five additional TBG variants were detected (19–22). Four were associated with partial TBG deficiency (19–21), and three of these were found to have high serum levels of denatured TBG (19, 20), which was measured using an antibody directed against the primary structure of the molecule. Another TBG variant had, as a sole abnormality, resistance to denaturation at high temperatures and in acid conditions (22).
Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis
Authors: Jason R. Lees, Paul T. Golumbek, Julia Sim, Denise Dorsey, John H. Russell
Journal: The Journal of Experimental Medicine (2008)

The localization of inflammatory foci within the cerebellum is correlated to severe clinical outcomes in multiple sclerosis (MS). Previous studies of experimental autoimmune encephalomyelitis (EAE), a model of MS, revealed distinct clinical outcomes correlated with the capacity of the animal to produce IFN-γ. Outcomes were linked to localization of inflammatory cells in either the spinal cord (wild type [WT]) or the cerebellum and brain stem (IFN-γ deficient). We demonstrate, using an adoptive transfer system, that the ability of the central nervous system (CNS) to sense pathogenic T cell–produced IFN-γ during EAE initiation determines the sites of CNS pathogenesis. Transfer of WT Th1 cells into IFN-γ receptor–deficient mice results in pathogenic invasion of the brain stem and cerebellum with attendant clinical symptoms, which are identical to the disease observed after transfer of IFN-γ–deficient T cells to WT hosts. Inflammation of the spinal cord associated with classical EAE is abrogated in both IFN-γ–deficient systems. Cotransfer of CNS antigen-specific WT Th1 cells with IFN-γ–deficient T cells is sufficient to restore spinal cord invasion and block cerebellar and brain stem invasion. These data demonstrate that interaction between IFN-γ and host CNS cells during the initiation of EAE can selectively promote or suppress neuroinflammation and pathogenesis.
Trends in Prescription Drug Use Among Adults in the United States From 1999-2012
Authors: Elizabeth D. Kantor, Colin D. Rehm, Jennifer S. Haas, Andrew T. Chan, Edward L. Giovannucci
Journal: JAMA (2015)

It is important to document patterns of prescription drug use to inform both clinical practice and research.To evaluate trends in prescription drug use among adults living in the United States.Temporal trends in prescription drug use were evaluated using nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Participants included 37,959 noninstitutionalized US adults, aged 20 years and older. Seven NHANES cycles were included (1999-2000 to 2011-2012), and the sample size per cycle ranged from 4861 to 6212.Calendar year, as represented by continuous NHANES cycle.Within each NHANES cycle, use of prescription drugs in the prior 30 days was assessed overall and by drug class. Temporal trends across cycles were evaluated. Analyses were weighted to represent the US adult population.Results indicate an increase in overall use of prescription drugs among US adults between 1999-2000 and 2011-2012 with an estimated 51% of US adults reporting use of any prescription drugs in 1999-2000 and an estimated 59% reporting use of any prescription drugs in 2011-2012 (difference, 8% [95% CI, 3.8%-12%]; P for trend <.001). The prevalence of polypharmacy (use of ≥5 prescription drugs) increased from an estimated 8.2% in 1999-2000 to 15% in 2011-2012 (difference, 6.6% [95% CI, 4.4%-8.2%]; P for trend <.001). These trends remained statistically significant with age adjustment. Among the 18 drug classes used by more than 2.5% of the population at any point over the study period, the prevalence of use increased in 11 drug classes including antihyperlipidemic agents, antidepressants, prescription proton-pump inhibitors, and muscle relaxants.In this nationally representative survey, significant increases in overall prescription drug use and polypharmacy were observed. These increases persisted after accounting for changes in the age distribution of the population. The prevalence of prescription drug use increased in the majority of, but not all, drug classes.
Impaired STAT Phosphorylation in T Cells from Melanoma Patients in Response to IL-2: Association with Clinical Stage
Authors: Roberta Mortarini, Claudia Vegetti, Alessandra Molla, Flavio Arienti, Fernando Ravagnani, Andrea Maurichi, Roberto Patuzzo, Mario Santinami, Andrea Anichini
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To assess the extent of signal transducer and activator of transcription (STAT) activation in response to interleukin 2 (IL-2) in melanoma patients' T cells, along with clinical stage of tumor progression. Experimental Design: T lymphocytes from peripheral blood of healthy donors and of American Joint Committee on Cancer stage I to IV melanoma patients, as well as from metastatic lymph nodes of patients, were evaluated for responsiveness to IL-2. CFSE assays and single-cell phospho-STAT–specific flow cytometry screening were used. Results. T cells from advanced melanoma patients, in comparison with healthy donors, showed reduced proliferation to IL-2 and IL-15, but not to anti-CD3 monoclonal antibody. Impaired response occurred in CCR7+ and CCR7− T-cell subsets, but not in CD3− CD8+ natural killer (NK) cells, and was not explained by induction of apoptosis, increased cytokine consumption, or altered IL-2R subunit expression in patients' T lymphocytes. By phospho-specific flow cytometry, defective STAT1 and STAT5 activation in response to IL-2 was found mainly in T lymphocytes from peripheral blood and/or tumor site of American Joint Committee on Cancer stage III and IV patients, compared with stage I and II patients and to donors, and in melanoma antigen-specific T cells isolated from metastatic lymph nodes. At tumor site, impaired STAT activation in T cells did not correlate with frequency of CD4+ CD25+ Foxp3+ T cells. Serum from advanced melanoma patients inhibited IL-2–dependent STAT activation in donors' T cells and a neutralizing monoclonal antibody to transforming growth factor β1 counteracted such inhibition. Conclusions: These results provide evidence for development of impaired STAT signaling in response to IL-2, along with clinical evolution of the disease, in melanoma patients' T cells.
A Future for Epidemiology?
Authors: S. Schwartz, E. Susser, M. Susser
Journal: Annual Review of Public Health (1999)

▪ Abstract This paper considers ways of thinking about causes and prevention that could guide epidemiology beyond the present era. Discontent with modern epidemiology, in the face of its substantial achievements, is taken as a sign that the guiding principles of the discipline warrant reconsideration. To begin this task, current practices are placed within an historical perspective, in a review of the dominant ideas of successive eras in epidemiology. Then the premises and constraints of the present era of chronic disease epidemiology, with its risk factor paradigm, are specified. Finally, elements of a causal paradigm for an emerging era are proposed. This paradigm encourages thinking about causes at multiple levels of organization and within the historical context of both societies and individuals. The proposed approach aims to preserve and build on the contributions of past eras, as well as the present one.
Arrhythmogenesis after cell transplantation post-myocardial infarction. Four burning questions—And some answers
Authors: T KOLETTIS
Journal: Cardiovascular Research (2006)

See article by Fernandes et al.  [5]  (pages 348–358) in this issue. 

Post-myocardial infarction heart failure remains a major public health problem [1]. Cell transplantation therapy is a promising new therapy, and several studies have shown that transplanted cells can form viable grafts within the host myocardium [2]. Similarly, in small-scale clinical trials, cultured autologous skeletal myoblasts were transplanted into the heart, with significant improvement in contractile indices [3,4]. However, enthusiasm was hampered by possible proarrhythmic effects; within weeks following cell transplantation, ventricular tachycardia or sudden cardiac death occurred in over 40% of patients [3,4].

The first ‘burning’ question arises: Does the increased incidence of ventricular arrhythmias reported in clinical studies [3,4] represent a true proarrhythmic effect of myoblast transplantation therapy, or do these arrhythmias reflect the natural history of ischaemic cardiomyopathy? In this issue of Cardiovascular Research , Fernandes et al. [5] provide important answers to this question. Seven days after coronary ligation in rats, myoblasts were injected in the infarcted area. In fact, Fernandes et al. [5] break down the first question into two secondary questions: Do myoblast injections constitute a substrate for ventricular arrhythmias? They answered this question by performing programmed electrical stimulation, using standard protocols including up to three extrastimuli (although no … 

*Tel.: +30 265 1097227; fax: +30 265 1097053. Email address: thkolet{at}cc.uoi.gr
Chromium and disease: review of epidemiologic studies with particular reference to etiologic information provided by measures of exposure.
Authors: P S Lees
Journal: Environmental Health Perspectives (1991)

Dozens of epidemiologic studies have been conducted since the late 1940s in an attempt to elucidate the relationship between exposure to chromium compounds and increased rates of certain cancers observed in several industries. The relationship between employment in industries producing chromium compounds from chromite ore and lung cancer has been well established in numerous studies. The relationship between exposure to certain chromium-based pigments and chromic acid and lung cancer, although not as strong, is fairly well accepted. The data concerning emissions from stainless-steel manufacturing and disease are contradictory. Although individual studies have indicated excesses of gastrointestinal and occasionally other cancers in these industries, results are not consistent and not universally accepted. There is general agreement that chromite ore does not have an associated risk of cancer. Although the chromium compound (or compounds) responsible for disease have yet to be identified, there is general agreement that hexavalent species are responsible for these diseases and that the trivalent species are not. Hypotheses about the carcinogenicity of specific chromium compounds generally relate to their solubility in body fluids. These hypotheses, however, have generally been produced as a result of toxicologic, not epidemiologic, investigation. Well-designed epidemiologic studies incorporating detailed assessments of worker exposures have the potential to help elucidate causality, identify specific carcinogenic compounds, and quantify risk in humans, eliminating the need to extrapolate from animal data. Although the need for exposure data crucial to this effort was identified in the earliest epidemiologic studies of chromium, such studies have not been conducted. As a result, little more is known today about the relationship between this chemical and disease in humans than was known 40 years ago.
Light chain deposition disease involving the airways: diagnosis by fibreoptic bronchoscopy
Authors: M. Colombat, V. Gounant, H. Mal, P. Callard, B. Milleron
Journal: European Respiratory Journal (2007)

Light chain deposition disease (LCDD) infrequently affects the lungs and usually causes damage to the parenchyma, while bronchial involvement appears to be very rare. The present authors report the case of a 64-yr-old female with LCDD characterised by asymptomatic airway involvement. Ten months after excision of a poorly differentiated vaginal carcinoma, a routine chest computed tomography (CT) scan revealed two lung cysts, several bilateral nodules and diffuse bronchial thickening. Pulmonary function tests were normal. Fibreoptic bronchoscopy showed marked diffuse mucosal thickening with highly conspicuous vascular plexuses. Nonamyloidal deposits were found in the bronchial wall, but no definite diagnosis could be proposed. On follow-up, the patient was still asymptomatic and the CT scan and endoscopic appearance remained unchanged. The final diagnosis of κ LCDD was established 18 months later by another series of bronchial biopsies with frozen samples. Interestingly, electron microscopy showed dense granular deposits associated with nonamyloidal fibrils. An increased number of lung cysts were observed 32 months after identification of bronchial abnormalities, confirming the progressive nature of the disease. No extrapulmonary deposits or immunoproliferative disorder were found. In conclusion, light chain deposition disease, which may remain latent for several years, can entirely involve large airways and may be diagnosed by bronchial biopsy.
DNA Integrity Assay: A Plasma-Based Screening Tool for the Detection of Prostate Cancer
Authors: Robert Hanley, Kimberly M. Rieger-Christ, David Canes, Norah R. Emara, Anthony P. Shuber, Kevin A. Boynton, John A. Libertino, Ian C. Summerhayes
Journal: Clinical Cancer Research (2006)

The aim of this study was to evaluate the utility of the DNA integrity assay (DIA) as a plasma-based screening tool for the detection of prostate cancer.Blood samples were collected from patients with biopsy-proven prostate cancer prior to prostatectomy (n = 123) and processed as two-spin plasma preparations. The three control groups included: males <40 years old with no history of cancer (group 1, n = 20); cancer-free postprostatectomy patients (group 2, n = 25), and patients with a negative prostate biopsy (group 3, n = 22). DNA in plasma preparations were isolated, hybrid-captured, and DNA fragments (200 bp, 1.3, 1.8, and 2.4 kb) were multiplexed in real-time PCR. A baseline cutoff was determined for individual fragment lengths to establish a DIA score for each patient sample.Patients with prostate cancer (86 of 123; 69.9%) were determined to have a positive DIA score of >or=7. The DIA results from control groups 1, 2, and 3 showed specificities of 90%, 92%, and 68.2%, respectively. Of the patients with negative age-adjusted prostate-specific antigen (PSA) and prostate cancer, 19 of 30 (63%) had a positive DIA score. The area under the receiver operating characteristic curve for DIA was 0.788.While detecting 69.9% of those with prostate cancer, DIA maintained an overall specificity of 68.2% to 92%, a range favorably comparable to that currently accepted for PSA (60-70%). The variability in specificity between control groups is likely explained by the established 19% to 30% detection of prostate cancer on subsequent biopsies associated with control group 3. DIA detected 63% of the prostate cancers undetected by currently accepted PSA ranges.