tbuckley/cabot-search huggingface dataset:
Relationship Between Markers of Insulin Resistance, Markers of Adiposity, HbA1c, and Cognitive Functions in a Middle-Aged Population–Based Sample: the MONA LISA Study
Authors: Caroline M. Sanz, Jean-Bernard Ruidavets, Vanina Bongard, Jean-Claude Marquié, Hélène Hanaire, Jean Ferrières, Sandrine Andrieu
Journal: Diabetes Care (2012)

OBJECTIVE To determine the relationship between markers of insulin resistance (fasting insulin and homeostasis model assessment of insulin resistance), markers of adiposity (BMI, waist circumference, and body fat), HbA1c, and cognitive performances in a middle-aged population–based sample free of diabetes. RESEARCH DESIGN AND METHODS Our study sample consisted of 1,172 people aged 35–64 years (49% women), free of diabetes, and recruited between 2005 and 2007 in the MONA LISA survey. Cognitive functions (memory, attention, and processing speed) were evaluated by neuropsychological tests: word-list learning test, digit symbol substitution test (DSST), word fluency test, and Stroop Test. Multiple logistic regressions were used to estimate the relationship between cognitive performance and metabolic markers. We serially adjusted for age, sex, education, and occupational status (model A), additionally for income, smoking, alcohol consumption, sedentarity, and psychotropic substance use (model B), and finally, included variables linked to the metabolic syndrome (hypertension, dyslipidemia, vascular disease, and C-reactive protein) and depression (model C). RESULTS Elevated markers of adiposity were associated with poor cognitive performance in tests evaluating processing speed. The probability of being in the lowest quartile of each test was nearly doubled for participants in the upper quartile of BMI, compared with those in the lowest one [BMI, adjusted odds ratio (OR) 2.18, P = 0.003 (DSST), and OR 2.09, P = 0.005 (Stroop Test)]. High HbA1c was associated with poor cognitive performance in DSST (adjusted OR 1.75, P = 0.037). Waist circumference was linked to poor cognitive performance in men but not in women. CONCLUSIONS Poor cognitive performance is associated with adiposity and hyperglycemia in healthy middle-aged people.
Predicting Risk of Breast Cancer in Postmenopausal Women by Hormone Receptor Status
Authors: Rowan T. Chlebowski, Garnet L. Anderson, Dorothy S. Lane, Aaron K. Aragaki, Thomas Rohan, Shagufta Yasmeen, Gloria Sarto, Carol A. Rosenberg, F. Allan Hubbell
Journal: JNCI Journal of the National Cancer Institute (2007)

Strategies for estrogen receptor (ER)-positive breast cancer risk reduction in postmenopausal women require screening of large populations to identify those with potential benefit. We evaluated and attempted to improve the performance of the Breast Cancer Risk Assessment Tool (i.e., the Gail model) for estimating invasive breast cancer risk by receptor status in postmenopausal women.In The Women's Health Initiative cohort, breast cancer risk estimates from the Gail model and models incorporating additional or fewer risk factors and 5-year incidence of ER-positive and ER-negative invasive breast cancers were determined and compared by use of receiver operating characteristics and area under the curve (AUC) statistics. All statistical tests were two-sided.Among 147,916 eligible women, 3236 were diagnosed with invasive breast cancer. The overall AUC for the Gail model was 0.58 (95% confidence interval [CI]=0.56 to 0.60). The Gail model underestimated 5-year invasive breast cancer incidence by approximately 20% (P<.001), mostly among those with a low estimated risk. Discriminatory performance was better for the risk of ER-positive cancer (AUC = 0.60, 95% CI = 0.58 to 0.62) than for the risk of ER-negative cancer (AUC = 0.50, 95% CI = 0.45 to 0.54). Age and age at menopause were statistically significantly associated with ER-positive but not ER-negative cancers (P=.05 and P=.04 for heterogeneity, respectively). For ER-positive cancers, no additional risk factors substantially improved the Gail model prediction. However, a simpler model that included only age, breast cancer in first-degree relatives, and previous breast biopsy examination performed similarly for ER-positive breast cancer prediction (AUC=0.58, 95% CI= 0.56 to 0.60); postmenopausal women who were 55 years or older with either a previous breast biopsy examination or a family history of breast cancer had a 5-year breast cancer risk of 1.8% or higher.In postmenopausal women, the Gail model identified populations at increased risk for ER-positive but not ER-negative breast cancers. A model with fewer variables appears to provide a simpler approach for screening for breast cancer risk.
Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study
Authors: Hans J Schlitt, Annette Barkmann, Klaus HW Böker, Nikos Emmanouilidis, Jens Rosenau, Matthias J Bahr, Günter Tusch, Michael P Manns, Björn Nashan, Jürgen Klempnauer
Journal: The Lancet (2001)
Crime and LSD: The Insanity Plea
Authors: JAMES T. BARTER, MARTIN REITE
Journal: American Journal of Psychiatry (1969)

The authors outline some of the problems involved in making a determination of legal insanity when a crime is committed following the use of LSD. Three cases of murder known to be associated with the use of LSD are described, one of them involving an individual examined personally by the authors. Five specific criteria that the authors have found to be useful aids in forensic examinations of such cases are offered. Finally, the differences between alcoholic intoxication and LSD-induced psychosis are discussed to help clarify the issue of voluntary intoxication in regard to criminal responsibility.
STUDY OF THE AUDITORY APPARATUS IN PATIENTS EXPERIENCING AUDITORY HALLUCINATIONS
Authors: Elvin V. Semrad
Journal: American Journal of Psychiatry (1938)

1. The experiences termed auditory hallucinations are individual experiences, which require to be resolved into many factors. 2. To investigate auditory hallucinations more precisely audiometer examinations of 100 cases with auditory hallucinations were made. 3. Of these 100 cases there were 31 cases of deafness, 19 toxic deafness, 10 catarrhal deafness, and 2 nerve deafness. 4. Of the 19 cases of toxic deafness, 18 patients gave a history of a definite toxic factor, 16 alcoholism, 1 drug addiction, 1 toxemia with a septic infection of the throat. 5. No evidence of auditory hyperæsthesia was noted. 6. It was noted that the occurrence of an auditory hallucination during the audiometer examination interfered with the response of the patient. The author wishes to express his appreciation to Dr. C. MacFie Campbell for his assistance in preparation of the paper, and to Dr. Leon E. White for his cooperation in interpretation of the otologic and audiometer findings.
<i>VDR</i> and <i>SRD5A2</i> Polymorphisms Combine to Increase Risk for Prostate Cancer in Both Non–Hispanic White and Hispanic White Men
Authors: Kathleen C. Torkko, Adrie van Bokhoven, Phoung Mai, Joke Beuten, Ivana Balic, Tim E. Byers, John E. Hokanson, Jill M. Norris, Anna E. Barón, M. Scott Lucia, Ian M. Thompson, Robin J. Leach
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Vitamin D and dihydrotestosterone pathways interact to promote the growth of prostatic tissue. The nuclear vitamin D receptor (VDR) moderates the actions of vitamin D. 5α-Reductase type II (SRD5A2) codes for the enzyme that converts testosterone to dihydrotestosterone in the prostate. This study tested the interactions of VDR (CDX2, FokI) and SRD5A2 (V89L, A49T) polymorphisms, and their associations with prostate cancer. Experimental Design: This genetic association study included 932 non–Hispanic White (NHW) men and 414 Hispanic White (HW) men from South Texas. Cases had biopsy-confirmed cancer; controls had normal digital rectal exams and serum prostate-specific antigen levels of &amp;lt;2.5 ng/mL. Results: Using logistic regression analyses to test associations with prostate cancer, only the V89L polymorphism (VV genotype compared with LL/LV) in HW men was statistically significant [odds ratios (OR), 0.64; 95% confidence intervals (95% CI), 0.41-0.99]. The interaction terms for FokI and V89L in NHW men and CDX2 and V89L in HW men in the logistic model were significant (P = 0.02 and 0.03, respectively). When stratified by V89L genotype, the FokI polymorphism (TT/TC versus CC) was significantly associated with prostate cancer in NHW men with the V89L VV genotype (FokI OR, 1.53; 95% CI, 1.06-2.23). The CDX2 polymorphism (GG versus AG/AA) was significantly associated with prostate cancer only in HW men with the V89L VV genotype (CDX2 OR, 3.16; 95% CI, 1.39-7.19; interaction term P = 0.02). Conclusion: Our results indicate that the SRD5A2 V89L VV genotype interacts with VDR FokI TT/CT genotypes in NHW men and VDR CDX2 GG genotypes in HW men to increase the risk for prostate cancer.
Effect of Behavioral Training With or Without Pelvic Floor Electrical Stimulation on Stress Incontinence in Women
Authors: Patricia S. Goode, Kathryn L. Burgio, Julie L. Locher, David L. Roth, Mary G. Umlauf, Holly E. Richter, R. Edward Varner, L. Keith Lloyd
Journal: JAMA (2003)

Pelvic floor electrical stimulation (PFES) has been shown to be effective for stress incontinence. However, its role in a multicomponent behavioral training program has not been defined.To determine if PFES increases efficacy of behavioral training for community-dwelling women with stress incontinence.Prospective randomized controlled trial conducted from October 1, 1995, through May 1, 2001, at a university-based outpatient continence clinic in the United States.Volunteer sample of 200 ambulatory, nondemented, community-dwelling women aged 40 to 78 years with stress or mixed incontinence with stress as the predominant pattern; stratified by race, type of incontinence (stress only vs mixed), and severity (frequency of episodes).Patients were randomly assigned to 8 weeks (4 visits) of behavioral training, 8 weeks (4 visits) of the behavioral training plus home PFES, or 8 weeks of self-administered behavioral treatment using a self-help booklet (control condition).Primary outcome was percentage reduction in the number of incontinent episodes as documented in bladder diaries. Secondary outcomes were patient satisfaction and changes in quality of life.Intention-to-treat analysis showed that incontinence was reduced a mean of 68.6% with behavioral training, 71.9% with behavioral training plus PFES, and 52.5% with the self-help booklet (P =.005). In comparison with the self-help booklet, behavioral training (P =.02) and behavioral training plus PFES (P =.002) were significantly more effective, but they were not significantly different from each other (P =.60). The PFES group had significantly better patient self-perception of outcome (P<.001) and satisfaction with progress (P =.02). Significant improvements were seen across all 3 groups on the Incontinence Impact Questionnaire but with no between-group differences.Treatment with PFES did not increase effectiveness of a comprehensive behavioral program for women with stress incontinence. A self-help booklet reduced incontinence and improved quality of life but not as much as the clinic-based programs.
Validity of physical activity monitors during daily life in patients with COPD
Authors: Roberto A. Rabinovich, Zafeiris Louvaris, Yogini Raste, Daniel Langer, Hans Van Remoortel, Santiago Giavedoni, Chris Burtin, Eloisa M.G. Regueiro, Ioannis Vogiatzis, Nicholas S. Hopkinson, Michael I. Polkey, Frederick J. Wilson, William MacNee, Klaas R. Westerterp, Thierry Troosters
Journal: European Respiratory Journal (2013)

Symptoms during physical activity and physical inactivity are hallmarks of chronic obstructive pulmonary disease (COPD). Our aim was to evaluate the validity and usability of six activity monitors in patients with COPD against the doubly labelled water (DLW) indirect calorimetry method. 80 COPD patients (mean±sd age 68±6 years and forced expiratory volume in 1 s 57±19% predicted) recruited in four centres each wore simultaneously three or four out of six commercially available monitors validated in chronic conditions for 14 consecutive days. <i>A priori</i> validity criteria were defined. These included the ability to explain total energy expenditure (TEE) variance through multiple regression analysis, using TEE as the dependent variable with total body water (TBW) plus several physical activity monitor outputs as independent variables; and correlation with activity energy expenditure (AEE) measured by DLW. The Actigraph GT3X (Actigraph LLC, Pensacola, FL, USA), and DynaPort MoveMonitor (McRoberts BV, The Hague, the Netherlands) best explained the majority of the TEE variance not explained by TBW (53% and 70%, respectively) and showed the most significant correlations with AEE (r=0.71, p&lt;0.001 and r=0.70, p&lt;0.0001, respectively). The results of this study should guide users in choosing valid activity monitors for research or for clinical use in patients with chronic diseases such as COPD.
Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke
Authors: T.E. Wessendorf, Y-;M. Wang, A.F. Thilmann, U. Sorgenfrei, N. Konietzko, H. Teschler
Journal: European Respiratory Journal (2001)

The prevalence of obstructive sleep apnoea (OSA) following stroke is high and OSA is associated with increased morbidity, mortality and poor functional outcome. Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA, but its effects in stroke patients are unknown. The effectiveness and acceptance of treatment with nCPAP in 105 stroke patients with OSA, admitted to rehabilitation was prospectively investigated. Subjective wellbeing was measured with a visual analogue scale in 41 patients and 24-;h blood pressure was determined in 16 patients before and after 10 days of treatment. Differences were compared between patients who did and did not accept treatment. There was an 80% reduction of respiratory events with concomitant increase in oxygen saturation and improvement in sleep architecture. No serious side-effects were noticed. Seventy-four patients (70.5%) continued treatment at home. Nonacceptance was associated with a lower functional status, as measured by the Barthel Index, and the presence of aphasia. Ten days after initiation of nCPAP, compliant users showed a clear improvement in wellbeing (differences in visual analogue scale (ΔVAS) mean±sd 26±26 mm) versus noncompliant patients (ΔVAS 2±25 mm, p=0.021). Only the compliant group had a reduction in mean nocturnal blood pressure (ΔBP; −8±7.3 mmHg versus 0.8±8.4 mmHg, p=0.037). Stroke patients with obstructive sleep apnoea can be treated effectively with nasal continuous positive airway pressure and show a similar improvement and primary acceptance to obstructive sleep apnoea patients without stroke. Continuous positive airway pressure acceptance is associated with improved wellbeing and decreased nocturnal blood pressure.
Pathomechanisms of cyst formation in pulmonary light chain deposition disease
Authors: M. Colombat, S. Caudroy, E. Lagonotte, H. Mal, C. Danel, M. Stern, M. Fournier, P. Birembaut
Journal: European Respiratory Journal (2008)

Cystic lung light chain deposition disease (CL-LCDD) is a recently described rare disorder characterised by numerous cysts and diffuse monoclonal nonamyloid light chain deposits surrounded by macrophagic giant cells. The mechanisms responsible for cyst development remain unknown. The objectives of the present study were to analyse the major components of the pulmonary extracellular matrix in CL-LCDD and to determine the influence of metalloproteinases (MMPs) by comparison with other cystic lung disorders. A virtually complete degradation of the elastic network was found in CL-LCDD. To a lesser degree, loss of fibrillar and basement membrane collagens was also observed. Macrophagic giant cells expressed MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14 and in situ zymography highlighted a strong gelatinolytic activity. As in CL-LCDD, cystic lesions in Langerhans' cell histiocytosis (LCH) and lymphangioleiomyomatosis (LAM) were characterised by the lack of elastic fibres. Similarly, MMP were expressed in CL-LCDD and LCH but the labelled cells were different. In contrast, few MMPs were detected in LAM. In conclusion, elastolysis is common to cystic lung light chain deposition disease and other cystic lung disorders, suggesting its implication in cyst formation. Moreover, in cystic lung light chain deposition disease, a role of metalloproteinases in elastolysis is strongly indicated by the metalloproteinase expression and activity pattern.
Abstract 4687: The PI3K inhibitor GDC-0941 is synergistic with lapatinib, and mediates endocrine sensitivity in uterine papillary serous carcinoma
Authors: Kelly S. Levano, Alicia Rodriguez-Gabin, Gary L. Goldberg, Susan B. Horwitz, June Y. Hou
Journal: Cancer Research (2014)

Abstract Objectives: Our objective is to determine the effect of PI3K activity in mediating ligand-independent estrogen signaling and endocrine sensitivity in Uterine Papillary Serous Carcinoma (UPSC). Methods: Drug effect on cell proliferation was calculated via Calcusyn in patient-derived UPSC cell lines ARK 1 and 2. PI3K mutation was analyzed after laser capture microdissection of tumor DNA in 7 consecutive patients with UPSC. Protein expression, via Western Blot, was correlated prospectively with clinical parameters. Results: Table 1 shows cells line baseline characteristics and IC50 to drugs. Fulvestrant, an ER antagonist, rendered the cells significantly more resistant to taxol in ARK1 and 2(p=0.035, 0.021 respectively). The concomitant decrease in pERS167 and pAKTS473 with Fulvestrant treatment is independent of baseline ER expression and PI3K mutation. In ARK2, a cell line that is ER-, disrupting AKT signaling via the PI3K inhibitor GDC-0941, or with the lapatinib is synergistic with Fulvestrant with Combination Index (CI)50 of 0.441 and 0.229, respectively. Independent of HER2 amplification or PI3K mutation, lapatinib and GDC-0941 exhibited synergistic cytotoxicity in both UPSC cell lines (CI50 of 0.577, ARK 1 and 0.233, ARK2). Finally, PI3K mutation and pAKTS473 expression was analyzed in 7 tumor samples. While none harbored PI3K mutation, patients who are chemotherapy resistant had significantly lower expression of baseline pAKTS473 in their tumor samples than those who are chemosensitive, similar to our cell line data. Conclusions: PI3K pathway dysregulation, either via upstream erbB amplification, or downstream constitutive activation of AKT, may be important in mediating endocrine and taxol sensitivity in UPSC. pAKTS473 may be an important biomarker of drug sensitivity. The combination of PI3K inhibitor and lapatinib is synergistic and warrant further therapeutic investigation. Baseline characteristics and drug sensitivities in UPSC cell linesARK1ARK2PI3KCA mutationfExon 9NoERα (WB)YesNopERα167 (WB)YesNopHER (WB)NoYesIC50 nM (mean ± STD)GDC-094193.1±5.9271±116.5LapatinibNo effect135.6±29.2FulvestrantNo effectNo effectTaxol4.6±1.97.8±5.6Cisplatin1103±65.72632.6±1797.9 Citation Format: Kelly S. Levano, Alicia Rodriguez-Gabin, Gary L. Goldberg, Susan B. Horwitz, June Y. Hou. The PI3K inhibitor GDC-0941 is synergistic with lapatinib, and mediates endocrine sensitivity in uterine papillary serous carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4687. doi:10.1158/1538-7445.AM2014-4687
Pathological and Molecular Advances in Pediatric Low-Grade Astrocytoma
Authors: Fausto J. Rodriguez, Kah Suan Lim, Daniel Bowers, Charles G. Eberhart
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Pediatric low-grade astrocytomas are the most common brain tumors in children. They can have similar microscopic and clinical features, making accurate diagnosis difficult. For patients whose tumors are in locations that do not permit full resection, or those with an intrinsically aggressive biology, more effective therapies are required. Until recently, little was known about the molecular changes that drive the initiation and growth of pilocytic and other low-grade astrocytomas beyond the association of a minority of cases, primarily in the optic nerve, with neurofibromatosis type 1. Over the past several years, a wide range of studies have implicated the BRAF oncogene and other members of this signaling cascade in the pathobiology of pediatric low-grade astrocytoma. In this review, we attempt to summarize this rapidly developing field and discuss the potential for translating our growing molecular knowledge into improved diagnostic and prognostic biomarkers and new targeted therapies.
THE STUDY OF SERUM PROTEINS AND LIPIDS WITH THE AID OF THE QUANTITY ULTRACENTRIFUGE. I. PROCEDURE AND PRINCIPAL FEATURES OF THE CENTRIFUGATE OF UNTREATED NORMAL SERUM AS DETERMINED BY QUANTITATIVE ANALYSIS OF SAMPLES FROM TEN LEVELS 12
Authors: Roy H. Turner, John Robert Snavely, William H. Goldwater, Malcolm L. Randolph, Charles C. Sprague, Walter G. Unglaub
Journal: Journal of Clinical Investigation (1951)
Differential expression of interleukin-32 in chronic rhinosinusitis with and without nasal polyps
Authors: A. Keswani, R. T. Chustz, L. Suh, R. Carter, A. T. Peters, B. K. Tan, R. Chandra, S.‐H. Kim, T. Azam, C. A. Dinarello, R. C. Kern, R. P. Schleimer, A. Kato
Journal: Allergy (2011)

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses and is frequently divided into polypoid CRS (CRSwNP) and nonpolypoid CRS (CRSsNP). However, the mechanism of inflammation in CRS has still not been fully elucidated. The aim of the study was to investigate the role of interleukin-32 (IL-32), a recently discovered proinflammatory cytokine, in CRS. We collected nasal epithelial cells and nasal tissue from patients with CRS and control subjects. We assayed mRNA for IL-32 by real-time PCR and measured IL-32 protein using ELISA, Western blot, and immunohistochemistry. The expression of mRNA for IL-32 was elevated in epithelial cells from uncinate tissue from patients with CRSsNP compared with patients with CRSwNP (P < 0.05), control subjects (P=0.06), and epithelial cells from nasal polyp (NP) tissue (P < 0.05). Production of IL-32 was induced by IFN-γ, TNF, and dsRNA in primary airway epithelial cells. In whole-tissue extracts, the expression of IL-32 protein was significantly elevated in patients with CRSwNP compared with patients with CRSsNP and control subjects. Immunohistochemistry data showed that IL-32 was detected in mucosal epithelial cells and inflammatory cells in the lamina propria. Levels of IL-32 were correlated with the levels of CD3 and macrophage mannose receptor in NP tissue. Immunofluorescence data showed IL-32 co-localization with CD3-positive T cells and CD68-positive macrophages in NPs. Overproduction of IL-32 may be involved in the pathogenesis of CRS, although the role of IL-32 in the inflammation in CRSsNP and CRSwNP may be different.
Relation between pressure difference across the aortic valve and left ventricular outflow
Authors: C. CLARK
Journal: Cardiovascular Research (1978)

Equations are presented to relate left ventricular-aortic pressure difference and flow. The relative importance of fluid inertia and friction are evaluated and the errors introduced by the neglect of compliance are estimated. The equations are used to calculate pressure differences for both normal conditions and simulated aortic stenosis and to explain the timing of the reversal of the pressure difference.