tbuckley/cabot-search huggingface dataset:
Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy
Authors: David Preiss
Journal: JAMA (2011)

A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus.To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy.We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators.We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year.Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I(2) statistic.In 5 statin trials with 32,752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I(2) = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I(2) = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events.In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.
Impaired function of regulatory T-cells in hypersensitivity pneumonitis
Authors: M. Girard, E. Israël-Assayag, Y. Cormier
Journal: European Respiratory Journal (2010)

Hypersensitivity pneumonitis (HP) is characterised by lung lymphocytosis. Most individuals exposed to HP antigens remain asymptomatic. The mechanisms involved in the impaired immune tolerance leading to HP are unclear. Normally, T-regulatory (Treg)-cells control the immune response. The aim of the present study was to determine whether Treg-cell suppressive function deficiency can explain the uncontrolled inflammation in HP. Bronchoalveolar lavage (BAL) and blood samples were obtained from normal subjects, asymptomatic individuals and HP patients. BAL and blood Treg-cells were isolated. The ability of Treg-cells to suppress T-cell proliferation and the role of interleukin (IL)-17 was verified. BAL and blood Treg-cells from normal subjects suppressed the proliferative response of activated T-cells by 47.1 and 42%, respectively. BAL and blood Treg-cells from asymptomatic subjects had a slightly decreased activity and suppressed proliferation by 29.4 and 31.8%, respectively. BAL and blood Treg-cells from HP patients were totally nonfunctional and unable to suppress proliferation. Low levels of IL-17 were detected in sera and BAL from both normal and asymptomatic individuals, whereas measurable levels were found in patients. Treg-cells may be involved in antigen tolerance in asymptomatic subjects. Defective Treg-cell function, potentially caused by increased IL-17 production, could account for the exacerbated immune response characteristic of HP.
Assessing response to treatment of exacerbations of bronchiectasis in adults
Authors: M. P. Murray, K. Turnbull, S. MacQuarrie, A. T. Hill
Journal: European Respiratory Journal (2008)

The present study aimed to assess the effect of intravenous antibiotic therapy on clinical and laboratory end-points in exacerbations of noncystic fibrosis bronchiectasis and to determine whether the outcomes were influenced by the pathogenic organism isolated. A prospective cohort study was conducted from November 2006 to March 2008 of exacerbations requiring intravenous antibiotics. End-points included 24-h sputum volume, forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), incremental shuttle walk test, qualitative sputum microbiology, white cell count, erythrocyte sedimentation rate, C-reactive protein (CRP) and St George's Respiratory Questionnaire (SGRQ). Exacerbations due to Pseudomonas aeruginosa were compared with exacerbations due to other potential pathogenic organisms. In total, 32 exacerbations were studied. Following 14 days of intravenous antibiotics, all outcomes significantly improved independent of a pathogenic organism, except FEV 1 and FVC. The most responsive markers were: 24-h sputum volume (reduced in all patients and 80% had ≥50% reduction); sputum bacterial clearance (78.1%); CRP (≥75% reduction in 62.5%) and SGRQ (≥4 unit improvement in 89.7%). CRP, 24-h sputum volume and SGRQ improved independent of microbial clearance. In the current study, 24-h sputum volume, microbial clearance, C-reactive protein and St George’s Respiratory Questionnaire were the most useful parameters to assess response to treatment of exacerbations of bronchiectasis. Outcomes were similar independent of the pathogenic organism with the exception of forced expiratory volume in one second and forced vital capacity.
Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity.
Authors: X Wei, H L McLeod, J McMurrough, F J Gonzalez, P Fernandez-Salguero
Journal: Journal of Clinical Investigation (1996)

Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria in pediatric patients and an increased risk of toxicity in cancer patients receiving 5-fluorouracil (5-FU) treatment. The molecular basis for DPD deficiency in a British family having a cancer patient that exhibited grade IV toxicity 10 d after 5-FU treatment was analyzed. A 165-bp deletion spanning a complete exon of the DPYD gene was found in some members of the pedigree having low DPD catalytic activity. Direct sequencing of lymphocyte DNA from these subjects revealed the presence of a G to A point mutation at the 5'-splicing site consensus sequence (GT to AT) that leads to skipping of the entire exon preceding the mutation during pre-RNA transcription and processing. A PCR-based diagnostic method was developed to determine that the mutation is found in Caucasian and Asian populations. This mutation was also detected in a Dutch patient with thymine-uraciluria and completely lacking DPD activity. A genotyping test for the G to A splicing point mutation could be useful in predicting cancer patients prone to toxicity upon administration of potentially toxic 5-FU and for genetic screening of heterozygous carriers and homozygous deficient subjects.
Skin capillary blood flow in scleroderma
Authors: E. Carwile LeRoy, John A. Downey, Paul J. Cannon
Journal: Journal of Clinical Investigation (1971)

Skin blood flow was measured by the clearance of radioactive xenon ((133)Xe) injected intracutaneously in eight patients with scleroderma and nine control subjects under conditions of controlled temperature and humidity. Scleroderma patients, on being cooled 1 hr at 18 degrees C, had a rate constant of (133)Xe clearance from the dorsal finger skin which was 0.04 +/-0.07 min(-1) (mean +/-SD), compared with 0.23 +/-0.15 min(-1) in normal subjects (P < 0.005). The corresponding mean cutaneous blood flows were 2.9 ml/100 g per min in the scleroderma patients and 16.4 ml/100 g per min in normal subjects. After reflex warming by waterbath, clearance was similar in the two groups (0.33 +/-0.1 vs. 0.40 +/-0.09); these data suggest that diminished clearance in scleroderma patients on cooling resulted, at least in part, from functional or reversible interruption of the circulation. The skin temperatures of scleroderma patients after reflex warming remained lower than those of normal subjects, despite similar increases in sublingual temperatures. The dissociation of (133)Xe clearance and skin temperature in scleroderma patients (i.e. subnormal skin temperatures with normal (133)Xe clearance after reflex warming) suggests either abnormal thermal properties of scleroderma skin or selective vasoconstriction of the vessels which regulate heat exchange. The demonstrated interruption of the capillary circulation on cooling of the skin in patients with scleroderma may be important in the pathogenesis of this disorder. After oral pretreatment with guanethidine, five patients with scleroderma had increased (133)Xe clearance and calculated blood flow on cooling, rising to normal in three of these patients. The potential of this technique for the quantitative sequential evaluation of skin blood flow in subjects with scleroderma and for the evaluation of empirical therapy is suggested.
Epidemiological insights into the public health burden of sleep disordered breathing: sex differences in survival among sleep clinic patients
Authors: T. Young, L. Finn
Journal: Thorax (1998)

<h3>Purpose</h3> To investigate the characteristics of human orbital fibroblasts (OFs) cultivated from intraconal, nasal and central adipose tissues. <h3>Methods</h3> Intraconal adipose tissues were obtained during orbital decompression surgery for severe proptosis in nine patients with Graves’ orbitopathy (GO). Nasal and central adipose tissues were obtained during upper eyelid blepharoplasty in nine patients with no history of GO. Human OFs were separately cultured from GO intraconal, non-GO nasal, non-GO central orbital adipose deposits. Human dermal fibroblasts were also cultured from redundant resected skin tissue obtained during upper eyelid blepharoplasty in normal controls. Expression of insulin-like growth factor 1 (IGF-1) and thyroid-stimulating hormone (TSH) receptors were investigated using real-time quantitative reverse transcription PCR. Protein levels of interleukin-1β (IL-1β)-induced inflammatory cytokines and generated intracellular reactive oxygen species (ROS) were determined. <h3>Results</h3> IGF-1 and TSH receptor RNA expressions of GO intraconal OFs and non-GO nasal OFs were higher than non-GO central OFs and dermal fibroblasts. The expression of IL-1β induced the IL-6, IL-8, intercellular adhesion molecule-1 and cyclooxygenase-2 of GO intraconal OFs, and non-GO nasal OFs were higher than non-GO central OFs and dermal fibroblasts. Intracellular ROS generation in GO intraconal OFs and non-GO nasal OFs were higher than in non-GO central OFs and dermal fibroblasts, although the differences were not statistically significant. <h3>Conclusions</h3> Non-GO nasal OFs had similar characteristics to GO intraconal OFs. We recommend the use of nasal adipose tissue in order to culture OFs as a normal control involving in vitro experiments.
Relationship between bronchial and arterial diameters in normal human lungs.
Authors: N Berend, A J Woolcock, G E Marlin
Journal: Thorax (1979)

In order to find an objective method for measuring narrowing of small airways, eight lungs from four people without lung disease were inflated and fixed at 25 cm of water pressure. Eight to nine blocks were taken at random from each of six parasaggital slices from each lung, sectioned, and stained. The size of the bronchioles (airways without cartilage) in relation to their accompanying arteries was determined. The internal bronchiolar diameter was compared with three different arterial diameters (the internal, external medial, and external adventitial). The ratio of the internal bronchiolar diameter to the external adventitial arterial diameter was constant between lungs (0.62 +/- 0.02) and independent of the method of inflation or the position within the lungs. This ratio may provide a useful index of bronchiolar narrowing in disease.
Cerebral edema after rapid dialysis is not caused by an increase in brain organic osmolytes.
Authors: S M Silver
Journal: Journal of the American Society of Nephrology (1995)

Dialysis disequilibrium syndrome (DDS) is characterized by the neurologic deterioration and cerebral edema that occurs after hemodialysis. To investigate the pathogenesis of DDS, the effects of rapid hemodialysis on brain electrolytes, urea, and several organic osmolytes were studied in the rat. Forty-two h after bilateral ureteral ligation, 11 uremic rats were hemodialyzed for 90 min, yielding a decrease in plasma urea from 96 +/- 4 to 44 +/- 5 mM (p < 0.01). This group was compared with 10 uremic and 11 nonuremic animals that were not dialyzed. In dialyzed animals, compared with nondialyzed uremic controls, there was an increase in brain water (3.98 +/- 0.02 versus 3.77 +/- 0.02 L/kg dry wt; P < 0.01) and the brain to plasma (urea) ratio (1.32 versus 0.65). There was no significant difference in the brain content of sodium and potassium between groups. The retention of brain urea, despite the large decrease in plasma urea concentration, was able to account for the increase in brain water observed in rapidly dialyzed animals. Major organic osmolytes in the brain, including glutamine, glutamate, taurine and myoinositol, did not increase significantly after rapid dialysis. Cerebral edema in this model of DDS was primarily due to a large brain-to-plasma urea gradient, not to the formation of organic osmolytes.
Inotropic effects of different calcium ion concentration on the embryonic chick ventricle. Comparison of single cultured cells and intact muscle strips.
Authors: W H Barry, R Pitzen, K Protas, D C Harrison
Journal: Circulation Research (1975)

The effects of changes in the calcium ion concentration in the medium bathin single beating cultured chick embryo ventricular cells were determined using an electro-optical monitoring technique for measuring the amplitude and velocity of cell wall motion. Although single cells showed significant decreases in the amplitude and velocity of cell wall motion during contraction when the calcium ion concentration was lowered from 1.8 mM to 0.9 mM, there were no significant changes in these parameters when the concentration was increased from 1.8 mM to 3.6 mM, and the magnitude of this response increased with increasing embryonic age. These results suggest that there is a reduced positive inotropic responsiveness in young chick embryo ventricular cells, which is particularly marked in the single cultured cell preparation because of the tendency of culturing techniques to select out immature cell populations.
Reduction of Cancer-Specific Thought Intrusions and Anxiety Symptoms With a Stress Management Intervention Among Women Undergoing Treatment for Breast Cancer
Authors: Michael H. Antoni, Sarah R. Wimberly, Suzanne C. Lechner, Aisha Kazi, Tammy Sifre, Kenya R. Urcuyo, Kristin Phillips, Roselyn G. Smith, Vida M. Petronis, Sophie Guellati, Kurrie A. Wells, Bonnie Blomberg, Charles S. Carver
Journal: American Journal of Psychiatry (2006)

After surgery for breast cancer, many women experience anxiety relating to the cancer that can adversely affect quality of life and emotional functioning during the year postsurgery. Symptoms such as intrusive thoughts may be ameliorated during this period with a structured, group-based cognitive behavior intervention.
Marijuana and Other Drug Use by Graduate and Professional Students
Authors: BEATRICE A. ROUSE, JOHN A. EWING
Journal: American Journal of Psychiatry (1972)

A random sample of 169 graduate students revealed that 95 percent used alcohol, 31 percent used marijuana, 17 percent used amphetamines, and four percent used LSD. Details of marijuana use are presented. Marijuana users and nonusers differed significantly in background, attitudes, and risk taking; nonusers were less willing to achieve certain preferred mental states with a drug, even one perceived to be risk-free. This study supports the authors' previous findings regarding drug use among undergraduates.
Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies
Authors: P Sullivan, D Stephens, T Ansari, J Costello, P Jeffery
Journal: European Respiratory Journal (1998)

We do not have an estimate of how much tissue is needed for a reliable measure of bronchial epithelial reticular basement membrane (RBM) thickness or for counts of inflammatory cells. An assessment of the frequency distribution and variance of data from repeat measurements of RBM thickness and biopsy section inflammatory cell counts in cases with asthma (n=6), chronic obstructive pulmonary disease (COPD; n=5), and normal healthy subjects (n=7) was made. Tissue sections were stained with haematoxylin and eosin or by immunohistochemistry for EG2, mast cell tryptase and CD3-positive cells. Measurements of RBM thickness in individuals followed a log-normal distribution. For a precision of approximately +/-15%, 31-45 measurements were required. In contrast, inflammatory cell counts for each individual did not follow a normal distribution. There was high variance such that the cumulative weighted mean did not become stable until at least 5-10 mm of tissue underlying the RBM had been included. In conclusion multiple measurements of reticular basement membrane thickness or tissue section cell counts should be made for each individual in studies of bronchial biopsies. It is recommended that reticular basement membrane thickness should be measured at 20 mm intervals over a 1 mm reticular basement membrane length and that a zone beneath it of at least 5-10 mm of reticular basement membrane should be included for counts of inflammatory cells.
PTEN Loss Is Associated with Worse Outcome in <i>HER2</i>-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance
Authors: Howard M. Stern, Humphrey Gardner, Tomasz Burzykowski, Wafaa Elatre, Carol O'Brien, Mark R. Lackner, Gary A. Pestano, Angela Santiago, Ivonne Villalobos, Wolfgang Eiermann, Tadeusz Pienkowski, Miguel Martin, Nicholas Robert, John Crown, Paolo Nuciforo, Valerie Bee, John Mackey, Dennis J. Slamon, Michael F. Press
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To investigate the clinical relevance of PTEN in HER2-amplified and HER2-nonamplified disease. Experimental Design: We assessed PTEN status in two large adjuvant breast cancer trials (BCIRG-006 and BCIRG-005) using a PTEN immunohistochemical (IHC) assay that was previously validated in a panel of 33 breast cancer cell lines and prostate cancer tissues with known PTEN gene deletion. Results: In the HER2-positive patient population, absence of tumor cell PTEN staining occurred at a rate of 5.4% and was independent of ER/PR status. In contrast, 15.9% of HER2-negative patients exhibited absence of PTEN staining with the highest frequency seen in triple-negative breast cancer (TNBC) subgroup versus ER/PR-positive patients (35.1% vs. 10.9%). Complete absence of PTEN staining in tumor cells was associated with poor clinical outcome in HER2-positive disease. Those patients whose cancers demonstrated absent PTEN staining had a significant decrease in disease-free survival (DFS) and overall survival (OS) compared with patients with tumors exhibiting any PTEN staining patterns (low, moderate, or high). Trastuzumab appeared to provide clinical benefit even for patients lacking PTEN staining. In the HER2-negative population, there were no statistically significant differences in clinical outcome based on PTEN status. Conclusions: This study is the largest to date examining PTEN status in breast cancer and the data suggest that the rate and significance of PTEN status differ between HER2-positive and HER2-negative disease. Furthermore, the data clearly suggest that HER2-positive patients with PTEN loss still benefit from trastuzumab. Clin Cancer Res; 21(9); 2065–74. ©2015 AACR.
Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells
Authors: Fenghuang Zhan, Johanna Hardin, Bob Kordsmeier, Klaus Bumm, Mingzhong Zheng, Erming Tian, Ralph Sanderson, Yang Yang, Carla Wilson, Maurizio Zangari, Elias Anaissie, Christopher Morris, Firas Muwalla, Frits van Rhee, Athanasios Fassas, John Crowley, Guido Tricot, Bart Barlogie, John Shaughnessy
Journal: Blood (2002)
Radical Psychiatry: An Examination of the Issues
Authors: JOHN A. TALBOTT
Journal: American Journal of Psychiatry (1974)

Articles that appeared in the Radical Therapist, an "alternate journal" in the mental health field that published 12 issues between 1970 and 1972, voiced pointed criticisms of psychiatrists during this period: little interest was paid to these issues in "establishment" publications. The author seeks to remedy this inattention by discussing power politics in the mental health field, the coopting of the community psychiatry movement, the psychiatric oppression of minority groups, and the rights of patients. The discussion points out the naïveté of the radicals' position, as well as noting the usefulness of their role, particularly in provoking closer examination of established positions.
Long Interspersed Nuclear Element 1 Hypomethylation Is a Marker of Poor Prognosis in Stage IA Non–Small Cell Lung Cancer
Authors: Kenichiro Saito, Kazuyuki Kawakami, Isao Matsumoto, Makoto Oda, Go Watanabe, Toshinari Minamoto
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non–small cell lung cancer (NSCLC). Experimental Design: Genomic DNA was obtained from the tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. Results: Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients in multivariate analysis. Conclusions: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC. Clin Cancer Res; 16(8); 2418–26. ©2010 AACR.