tbuckley/cabot-search huggingface dataset:
The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers
Authors: L A Houghton
Journal: Gut (2002)

Background: We have previously shown that the menstrual cycle has no effect on rectal sensitivity of normal healthy women, despite them having looser stools at the time of menses. Patients with irritable bowel syndrome (IBS) often report significant exacerbation of their IBS symptoms with menses, raising the possibility that IBS patients may respond differently to the menstrual cycle. Aim and methods: Rectal responses to balloon distension during days 1–4 (menses), 8–10 (follicular phase), 18–20 (luteal phase), and 24–28 (premenstrual phase) of the menstrual cycle were assessed in 29 female IBS patients (aged 21–44 years), diagnosed by the Rome I criteria. During the course of the study patients completed symptom diaries to assess abdominal pain and bloating (visual analogue scale), and frequency and consistency of bowel habits. In addition, levels of anxiety and depression were assessed using the hospital anxiety and depression questionnaire. Results: Menses was associated with a worsening of abdominal pain and bloating compared with most other phases of the menstrual cycle (p&lt;0.05). Bowel habits also became more frequent (p&lt;0.05) and patients tended to have a lower general well being. Rectal sensitivity increased at menses compared with all other phases of the cycle (p&lt;0.05). There was no associated change in rectal compliance, wall tension, or motility index. Neither was there any difference in resting anal pressure or the distension volumes required to relax the internal anal sphincter during the menstrual cycle. Conclusion: These data (1) confirm that IBS symptomatology is exacerbated at menses and (2) show for the first time that in contrast with healthy women, rectal sensitivity changes with the menstrual cycle. These cyclical changes in sensitivity suggest that women with IBS respond differently to fluctuations in their sex hormonal environment or its consequences compared with healthy females.
Interleukin (IL)-15 and IL-7 Jointly Regulate Homeostatic Proliferation of Memory Phenotype CD8+ Cells but Are Not Required for Memory Phenotype CD4+ Cells
Authors: Joyce T. Tan, Bettina Ernst, William C. Kieper, Eric LeRoy, Jonathan Sprent, Charles D. Surh
Journal: The Journal of Experimental Medicine (2002)

The overall size and composition of the pool of naive and memory T cells are tightly regulated by homeostatic mechanisms. Recent work has shown that homeostasis of naive T cells is controlled by two factors, self-major histocompatibility complex (MHC)/peptide ligands and a cytokine, interleukin (IL)-7. In particular, contact with these two factors is required for naive CD4+ and CD8+ cells to undergo “homeostatic” proliferation, i.e., proliferation induced as a consequence of severe T cell depletion. In contrast to naive T cells, the factors that drive memory T cells to undergo homeostatic proliferation are poorly understood. To address this issue, purified memory phenotype CD4+ and CD8+ cells from normal mice were adoptively transferred into various gene-knockout mice rendered T cell–deficient by sublethal irradiation. Three findings are reported. First, unlike naive T cells, homeostatic proliferation of memory T cells is largely MHC independent. Second, memory CD8+ cells can utilize either IL-7 or IL-15 to undergo homeostatic proliferation; however, in the absence of both IL-7 and IL-15, homeostatic proliferation fails to occur. Third, unlike memory CD8+ cells, homeostatic proliferation of memory CD4+ cells is independent of IL-7 and IL-15 (also IL-4). Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct.
Carrier detection in xeroderma pigmentosum.
Authors: R Parshad, K K Sanford, K H Kraemer, G M Jones, R E Tarone
Journal: Journal of Clinical Investigation (1990)

We were able to detect clinically normal carriers of xeroderma pigmentosum (XP) genes with coded samples of either peripheral blood lymphocytes or skin fibroblasts, using a cytogenetic assay shown previously to detect individuals with cancer-prone genetic disorders. Metaphase cells of phytohemagglutinin-stimulated T-lymphocytes from eight individuals who are obligate heterozygotes for XP were compared with those from nine normal controls at 1.3, 2.3, and 3.3 h after x-irradiation (58 R) during the G2 phase of the cell cycle. Lymphocytes from the XP heterozygotes had twofold higher frequencies of chromatid breaks or chromatid gaps than normal (P less than 10(-5)) when fixed at 2.3 or 3.3 h after irradiation. Lymphocytes from six XP homozygotes had frequencies of breaks and gaps threefold higher than normal. Skin fibroblasts from an additional obligate XP heterozygote, when fixed approximately 2 h after x-irradiation (68 R), had a twofold higher frequency of chromatid breaks and a fourfold higher frequency of gaps than fibroblasts from a normal control. This frequency of aberrations in cells from the XP heterozygote was approximately half that observed in the XP homozygote. The elevated frequencies of chromatid breaks and gaps after G2 phase x-irradiation may provide the basis of a test for identifying carriers of the XP gene(s) within known XP families.
Influence of the volume of osteonecrosis on the outcome of core decompression of the femoral head
Authors: B. Mazieres, F. Marin, P. Chiron, L. Moulinier, J.-M. Amigues, M. Laroche, A. Cantagrel
Journal: Annals of the Rheumatic Diseases (1997)

To assess the outcome of core decompression in the treatment of osteonecrosis of the femoral head related to the volume of necrotic bone measured according to a previously reported method.Twenty hips corresponding to strictly Ficat stage II underwent magnetic resonance imaging and the volume of necrotic bone was expressed as a percentage of the volume of the entire head measured on each slice. All hips underwent core decompression and the outcome was evaluated at 24 months. The primary evaluation criterion was radiological appearance: the outcome was considered as good if the hip remained stage II and poor if the disease progressed.Twenty four months after core decompression, half the cases remained stable and in half the disease had progressed. Outcome seemed to be related to the volume of necrotic bone (average 22% in the good outcome group versus 45% in the poor outcome group (p = 0.0051)) and was independent of risk factors, age, and histological type.The volume of necrotic bone should be taken into account in the evaluation of any treatment, bearing in mind that in more than one third of cases this volume will probably decrease, especially at the beginning of the disease process.
Reduced Mortality with Hospital Pay for Performance in England
Authors: Matt Sutton, Silviya Nikolova, Ruth Boaden, Helen Lester, Ruth McDonald, Martin Roland
Journal: New England Journal of Medicine (2012)

Pay-for-performance programs are being adopted internationally despite little evidence that they improve patient outcomes. In 2008, a program called Advancing Quality, based on the Hospital Quality Incentive Demonstration in the United States, was introduced in all National Health Service (NHS) hospitals in the northwest region of England (population, 6.8 million).We analyzed 30-day in-hospital mortality among 134,435 patients admitted for pneumonia, heart failure, or acute myocardial infarction to 24 hospitals covered by the pay-for-performance program. We used difference-in-differences regression analysis to compare mortality 18 months before and 18 months after the introduction of the program with mortality in two comparators: 722,139 patients admitted for the same three conditions to the 132 other hospitals in England and 241,009 patients admitted for six other conditions to both groups of hospitals.Risk-adjusted, absolute mortality for the conditions included in the pay-for-performance program decreased significantly, with an absolute reduction of 1.3 percentage points (95% confidence interval [CI], 0.4 to 2.1; P=0.006) and a relative reduction of 6%, equivalent to 890 fewer deaths (95% CI, 260 to 1500) during the 18-month period. The largest reduction, for pneumonia, was significant (1.9 percentage points; 95% CI, 0.9 to 3.0; P<0.001), with nonsignificant reductions for acute myocardial infarction (0.6 percentage points; 95% CI, -0.4 to 1.7; P=0.23) and heart failure (0.6 percentage points; 95% CI, -0.6 to 1.8; P=0.30).The introduction of pay for performance in all NHS hospitals in one region of England was associated with a clinically significant reduction in mortality. As compared with a similar U.S. program, the U.K. program had larger bonuses and a greater investment by hospitals in quality-improvement activities. Further research is needed on how implementation of pay-for-performance programs influences their effects. (Funded by the NHS National Institute for Health Research.).
Epidermal 'turnover time'—a new examination
Authors: PAUL R. BERGSTRESSER, J. RICHARD TAYLOR
Journal: British Journal of Dermatology (1977)

A new model for assaying epidermal cell turnover times is presented. It is based on desquamation rates of the stratum corneum and the consequent obligatory turnover time of the keratinocyte layer. A total epidermal turnover time of 45 days is derived from the model for the human volar forearms.
Screening for HIV: A Review of the Evidence for the U.S. Preventive Services Task Force
Authors: Roger Chou, Laurie Hoyt Huffman, Rongwei Fu, Ariel K. Smits, P. Todd Korthuis
Journal: Annals of Internal Medicine (2005)

Background: HIV infection affects 850 000 to 950 000 persons in the United States. The management and outcomes of HIV infection have changed substantially since the U.S. Preventive Services Task Force issued recommendations in 1996. Purpose: To synthesize the evidence on risks and benefits of screening for HIV infection. Data Sources: MEDLINE, the Cochrane Library, reference lists, and experts. Study Selection: Studies of screening, risk factor assessment, accuracy of testing, follow-up testing, and efficacy of interventions. Data Extraction: Data on settings, patients, interventions, and outcomes were abstracted for included studies; quality was graded according to criteria developed by the Task Force. Data Synthesis: No trials directly link screening for HIV with clinical outcomes. Many HIV-infected persons in the United States currently receive diagnosis at advanced stages of disease, and almost all will progress to AIDS if untreated. Screening based on risk factors could identify persons at substantially higher risk but would miss a substantial proportion of those infected. Screening tests for HIV are extremely (>99%) accurate. Acceptance rates for screening and use of recommended interventions vary widely. Highly active antiretroviral therapy (HAART) substantially reduces the risk for clinical progression or death in patients with immunologically advanced disease. Along with other adverse events, HAART is associated with an increased risk for cardiovascular complications, although absolute rates are low after 3 to 4 years. Limitations: Data are insufficient to estimate the effects of screening and interventions on transmission rates or in patients with less immunologically advanced disease. Long-term data on adverse events associated with HAART are not yet available. Conclusions: Benefits of HIV screening appear to outweigh harms. The yield from screening higher-prevalence populations would be substantially higher than that from screening the general population.
Differential Expression of Adenosine Receptors in Human Endothelial Cells
Authors: Igor Feoktistov, Anna E. Goldstein, Sergey Ryzhov, Dewan Zeng, Luiz Belardinelli, Tatyana Voyno-Yasenetskaya, Italo Biaggioni
Journal: Circulation Research (2002)

Adenosine has been reported to stimulate or inhibit the release of angiogenic factors depending on the cell type examined. To test the hypothesis that differential expression of adenosine receptor subtypes contributes to endothelial cell heterogeneity, we studied microvascular (HMEC-1) and umbilical vein (HUVEC) human endothelial cells. Based on mRNA level and stimulation of adenylate cyclase, we found that HUVECs preferentially express A 2A adenosine receptors and HMEC-1 preferentially express A 2B receptors. Neither cells expressed A 1 or A 3 receptors. The nonselective adenosine agonist 5′- N -ethylcarboxamidoadenosine (NECA) increased expression of interleukin-8 (IL-8), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in HMEC-1, but had no effect in HUVECs. In contrast, the selective A 2A agonist 2- p -(2-carboxyethyl)phenylethylamino-NECA (CGS 21680) had no effect on expression of these angiogenic factors. Cotransfection of each type of adenosine receptors with a luciferase reporter in HMEC-1 showed that A 2B receptors, but not A 1 , A 2A , or A 3 , activated IL-8 and VEGF promoters. These effects were mimicked by constitutively active αG q , αG 12 , and αG 13 , but not αG s or αG i1-3 . Furthermore, stimulation of phospholipase C indicated coupling of A 2B receptors to G q proteins in HMEC-1. Thus, differential expression of adenosine receptor subtypes contributes to functional heterogeneity of human endothelial cells. A 2B receptors, predominantly expressed in human microvascular cells, modulate expression of angiogenic factors via coupling to G q , and possibly via G 12/13 .
Sources of variation in forced expiratory volume in one second and forced vital capacity
Authors: S. Chinn, D. Jarvis, C. Svanes, P. Burney
Journal: European Respiratory Journal (2006)

Published prediction equations for lung function differ considerably, but the components of population variation responsible for the differences are unknown. Data were analysed for 6,323 never-smoking adults who did not report wheeze or asthma, from 42 centres participating in the European Community Respiratory Health Survey. Means and components of variance were estimated for males and females aged 20–24 yrs, and the relationships with age and height were examined in those aged 25–44 yrs. Mean lung function for those aged 20–24 yrs differed between centres, but variation could not be wholly attributed to differences in population or equipment. The maximum difference in means by equipment type was 101 mL for FVC in males. Equipment differences were not statistically significant adjusted for country, but differences in mean forced expiratory volume in one second and forced vital capacity by country, adjusted for instrument, were statistically significant in males. Differences between centres in relation to age and height had less influence on predicted values. In conclusion, there are unexplained differences in lung function between ethnically similar nonsmoking symptom-free populations. Neither national reference curves nor those based on the same ethnic group can be guaranteed to give accurate norms of lung health.
Genetic Basis for In Vivo Daptomycin Resistance in Enterococci
Authors: Cesar A. Arias, Diana Panesso, Danielle M. McGrath, Xiang Qin, Maria F. Mojica, Corwin Miller, Lorena Diaz, Truc T. Tran, Sandra Rincon, E. Magda Barbu, Jinnethe Reyes, Jung H. Roh, Elizabeth Lobos, Erica Sodergren, Renata Pasqualini, Wadih Arap, John P. Quinn, Yousif Shamoo, Barbara E. Murray, George M. Weinstock
Journal: New England Journal of Medicine (2011)

Daptomycin is a lipopeptide with bactericidal activity that acts on the cell membrane of enterococci and is often used off-label to treat patients infected with vancomycin-resistant enterococci. However, the emergence of resistance to daptomycin during therapy threatens its usefulness.We performed whole-genome sequencing and characterization of the cell envelope of a clinical pair of vancomycin-resistant Enterococcus faecalis isolates from the blood of a patient with fatal bacteremia; one isolate (S613) was from blood drawn before treatment and the other isolate (R712) was from blood drawn after treatment with daptomycin. The minimal inhibitory concentrations (MICs) of these two isolates were 1 and 12 μg per milliliter, respectively. Gene replacements were made to exchange the alleles found in isolate S613 with those in isolate R712.Isolate R712 had in-frame deletions in three genes. Two genes encoded putative enzymes involved in phospholipid metabolism, GdpD (which denotes glycerophosphoryl diester phosphodiesterase) and Cls (which denotes cardiolipin synthetase), and one gene encoded a putative membrane protein, LiaF (which denotes lipid II cycle-interfering antibiotics protein but whose exact function is not known). LiaF is predicted to be a member of a three-component regulatory system (LiaFSR) involved in the stress-sensing response of the cell envelope to antibiotics. Replacement of the liaF allele of isolate S613 with the liaF allele from isolate R712 quadrupled the MIC of daptomycin, whereas replacement of the gdpD allele had no effect on MIC. Replacement of both the liaF and gdpD alleles of isolate S613 with the liaF and gdpD alleles of isolate R712 raised the daptomycin MIC for isolate S613 to 12 μg per milliliter. As compared with isolate S613, isolate R712--the daptomycin-resistant isolate--had changes in the structure of the cell envelope and alterations in membrane permeability and membrane potential.Mutations in genes encoding LiaF and a GdpD-family protein were necessary and sufficient for the development of resistance to daptomycin during the treatment of vancomycin-resistant enterococci. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health.).
CD4+8- thymocytes bearing major histocompatibility complex class I-restricted T cell receptors: evidence for homeostatic control of early stages of CD4/CD8 lineage development.
Authors: T Crompton, H Pircher, H R MacDonald
Journal: The Journal of Experimental Medicine (1992)

During thymus development CD4+ CD8+ precursor cells differentiate into mature CD4+ and CD8+ T cells expressing T cell receptors (TCR) that recognize foreign antigens in association with major histocompatibility complex (MHC) class II or I molecules, respectively. Studies with TCR transgenic mice have shown that the accumulation of mature CD4+ and CD8+ thymocytes is strongly skewed by the MHC restriction specificity of the TCR, thus suggesting that commitment of CD4+ CD8+ precursors to the CD4 or CD8 lineage is a direct consequence of TCR/MHC interactions. However, we show here that CD4+ cells expressing an inappropriate (MHC class I-specific) TCR appear transiently in the neonatal thymus of TCR transgenic mice and can also be found in the periphery of adult TCR transgenic recombination-deficient SCID mice. These data argue that the early stages of CD4 and CD8 lineage development in the thymus are (at least in part) controlled by homeostatic mechanisms independent of appropriate TCR/MHC interactions.
Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity.
Authors: M Bonneville, S Itohara, E G Krecko, P Mombaerts, I Ishida, M Katsuki, A Berns, A G Farr, C A Janeway, S Tonegawa
Journal: The Journal of Experimental Medicine (1990)

gamma/delta T cells with different TCR repertoires are compartmentalized in different epithelia. This raises the possibility that the TCR-gamma/delta directs homing of T cells to these epithelia. Alternatively, the signals that induce TCR-gamma/delta expression in developing T cells may also induce homing properties in such cells, presumably in the form of cell surface receptors. We have examined this issue by studying the homing of gamma/delta T cells in transgenic mice constructed with specific pairs of rearranged gamma and delta genes. In such mice, most gamma/delta T cells express the transgene-encoded TCR. We find that homing to both skin and gut epithelia is a property of T cells and is not determined by the type of gamma and delta genes used to encode their TCR. We also studied the effect of TCR replacement on the expression of Thy-1 and CD8 proteins on the gamma/delta T cells associated with gut epithelia. Our results show that the expression of the appropriate type of TCR-gamma/delta is not required for the Thy-1 expression by these T cells, suggesting that Thy-1 is not an activation marker. In contrast, CD8 expression by gut gamma/delta T cells seems to depend on the expression of the appropriate type of TCR.
Effect of Bilateral Internal Mammary Artery Grafts on Long-Term Survival
Authors: Gijong Yi, Brian Shine, Syed M. Rehman, Douglas G. Altman, David P. Taggart
Journal: Circulation (2014)

Background— Although the potential survival benefit of bilateral internal mammary artery (BIMA) grafting in comparison with single internal mammary artery (SIMA) grafting has been emphasized by many investigators, the use of BIMA is still low in clinical practice in the absence of randomized trials and long-term results. In the current study, we aimed to assess if there is a long-term survival benefit of BIMA up to 10 years after coronary bypass surgery. Methods and Results— We selected published articles comparing survival between SIMA and BIMA patients with follow-up duration of more than a mean of 9 years. We evaluated the log hazard ratio with 95% confidence interval for included studies by using a random-effects meta-analysis. Nine eligible observational studies provided 15 583 patients (8270 SIMA and 7313 BIMA) for meta-analysis. Five studies used propensity score methods for statistical adjustment, 2 with a propensity score–based patient-matching method and 3 with quintile-based stratification. A significant reduction in mortality by using BIMA was observed (hazard ratio, 0.79; 95% confidence interval, 0.75–0.84); no study showed any significantly harmful effect of BIMA on survival. Subgroups of studies using different statistical approaches—unmatched, quintile-based propensity score analysis, and propensity score–based exact patient matching—all showed the survival benefit of BIMA grafting. Conclusions— BIMA grafting appears to have better survival with up to 10 years follow-up in comparison with SIMA grafting. Long-term survival benefit of BIMA seems to continue in the second decade after surgery. An ongoing randomized trial comparing SIMA and BIMA groups will add evidence on this issue.