tbuckley/cabot-search huggingface dataset:
Dietary exposure to polychlorinated biphenyls and dioxins from infancy until adulthood: A comparison between breast-feeding, toddler, and long-term exposure.
Authors: S Patandin, P C Dagnelie, P G Mulder, E Op de Coul, J E van der Veen, N Weisglas-Kuperus, P J Sauer
Journal: Environmental Health Perspectives (1999)

Food is the major source for polychlorinated biphenyl (PCB) and dioxin accumulation in the human body. Therefore, investigating food habits from early ages until reproductive age (25 years) is important in order to assess exposure risk for the next generation. The objective of this study was to assess the PCB/dioxin exposure and the relative contribution of different foods to total exposure during preschool age. Particularly, the importance of lactational PCB/dioxin exposure vs. dietary exposure until adulthood was investigated. A cohort of 207 children was studied from birth until preschool age. Based on 3 planar PCBs and 17 2,3,7,8-substituted dibenzo-para-dioxins (PCDDs) and dibenzofurans (PCDFs) measured in breast milk, a model was developed to calculate the cumulative toxic equivalent (TEQ) intake during breast-feeding (0-1 year). In 3. 5-year-old children, daily dietary intake of planar PCB-TEQ and dioxin-TEQ was measured with a validated food questionnaire. Cumulative TEQ intake from 1 to 5 years was estimated using the PCB- and dioxin-TEQ intake measured with the food questionnaire. Cumulative TEQ intake from 6 to 25 years was estimated using national food consumption and contamination data of PCB- and dioxin-TEQ intake. In toddlers, dairy products contributed 43% to PCB-TEQ and 50% to dioxin-TEQ intake. Meat and meat products contributed 14% and 19%, respectively, and processed foods 23% and 15%, respectively. Breast-feeding for 6 months contributed to the cumulative PCB/dioxin TEQ intake until 25 years of age, 12% in boys and 14% in girls. The daily TEQ intake per kilogram body weight is 50 times higher in breast-fed infants and three times higher in toddlers than in adults. Long-term dietary exposure to PCBs and dioxins in men and women is partly due to breast-feeding (12 and 14%, respectively). After weaning, dairy products, processed foods, and meat are major contributors of PCB and dioxin accumulation until reproductive age. Instead of discouraging breast-feeding, maternal transfer of PCBs and dioxins to the next generation must be avoided by enforcement of strict regulations for PCB and dioxin discharge and by reducing consumption of animal products and processed foods in all ages.
Decision Analysis for Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer
Authors: J. Jack Lee, B. Nebiyou Bekele, Xian Zhou, Scott B. Cantor, Ritsuko Komaki, Jin Soo Lee
Journal: Journal of Clinical Oncology (2006)

Purpose Prophylactic cranial irradiation (PCI) has been shown to provide survival benefit in patients with limited disease small-cell lung cancer (LD-SCLC) who have achieved complete response. However, PCI may also produce long-term neurotoxicity (NT). The benefits and risks of PCI in LD-SCLC are evaluated. Methods We developed a decision-analytic model to compare quality-adjusted life expectancy (QALE) in a cohort of SCLC patients who do or do not receive PCI by varying survival rates and the frequency and severity of PCI-related NT. Sensitivity analyses were applied to examine the robustness of the optimal decision. Results At current published survival rates (26% 5-year survival rate with PCI and 22% without PCI) and a low NT rate, PCI offered a benefit over no PCI (QALE = 4.31 and 3.70 for mild NT severity; QALE = 4.09 and 3.70 for substantial NT severity, respectively). With a moderate NT rate, PCI was still preferred. If the PCI survival rate increased to 40%, PCI outperformed no PCI with a mild NT severity. However, no PCI was preferred over PCI (QALE = 5.72 v 5.47) with substantial NT severity. Two-way sensitivity analyses showed that PCI was preferred for low NT rates, mild NT severity, and low long-term survival rates. Otherwise, no PCI was preferred. Conclusion The current data suggest PCI offers better QALE than no PCI in LD-SCLC patients who have achieved complete response. As the survival rate for SCLC patients continues to improve, NT rate and NT severity must be controlled to maintain a favorable benefit-risk ratio for recommending PCI.
Body measures in relation to gastro-oesophageal reflux
Authors: J. Lagergren
Journal: Gut (2007)

Association between overweight and gastro-oesophageal reflux disease (GORD) has become established in large-scale analytical epidemiological research. There is a dose-dependent association between increasing body mass index and GORD

An association between overweight and gastro-oesophageal reflux disease (GORD) has long been suspected and observed in case series. Recently, this association has become established in large-scale analytical epidemiological research.1,2 In a recent meta-analysis based on the available literature, it was concluded that there is a dose-dependent association between increasing body mass index (BMI) and GORD, usually assessed as typical reflux symptoms—that is, heartburn or regurgitation.3 The precise strength of this association is difficult to assess, but it seems that persons with a BMI >30 kg/m2 are at an about twofold increased risk of GORD than persons of normal weight. Interestingly, it seems that any increase in BMI, even within the range of what is considered normal BMI, is associated with a gradually increased risk of reflux symptoms.2 A similar finding has been observed with regard to the relation between increased BMI and adenocarcinoma of the oesophagus,4 a cancer closely linked with GORD.5

In the present issue of Gut , Corley et al 6 ( see page 756 ) present a large cohort study that not only evaluates BMI in relation to GORD, but also evaluates the role of objectively measured …
EVI1 expression in childhood acute lymphoblastic leukaemia is not restricted to MLL and BCR/ABL rearrangements and is influenced by age
Authors: A Stevens, D Hanson, C de Leonibus, A Whatmore, R Donn, D J White, J Liu, M M van den Heuvel-Eibrink, V Saha, P E Clayton, S Meyer
Journal: Blood Cancer Journal (2014)

EVI1 expression in childhood acute lymphoblastic leukaemia is not restricted to MLL and BCR/ABL rearrangements and is influenced by age
Relevance of the expression “obs stable” in nursing observations: retrospective study
Authors: Gregory Scott, Roshan Vijayan, Pandora Male
Journal: BMJ (2011)

To ascertain whether use of the term "obs stable" with respect to the nursing observations is so liberal as to render it meaningless.Retrospective study.Three teaching hospitals in London, United Kingdom.We searched progress notes for the current admission of 46 inpatients for entries containing the phrases "obs stable" and "observations stable," and reviewed the nursing observations recorded during the 24 hour period preceding each entry containing at least one phrase. We calculated the frequency of abnormalities and of persistent abnormalities (defined as occurring in every observation) observed during these 24 hour periods, and the range of observation values over a 24 hour period if at least two observations had been recorded.We found at least one entry in 36 (78%) progress notes (95% confidence interval 66% to 90%). Observations in the 24 hours preceding an entry included at least one abnormality for 113 (71%) of 159 cases and at least one persistent abnormality for 31 (19%). The most frequently occurring abnormalities were tachypnoea (respiratory rate ≥20 breaths/min) and hypotension (systolic blood pressure <100 mm Hg). An abnormality occurred in the observations immediately preceding an entry in 42% of cases. Mean ranges of observations over 24 hours were within the limits of normal diurnal variation, although we found that some instances of greater than normal variability were described as "stable."The expression "obs stable" does not reliably indicate normal observations or variations in observations within physiological limits. Doctors should avoid using the expression altogether or clarify it with further information.
Imbalanced secretion of IL-1 and IL-1RA in Chlamydia pneumoniae-infected mononuclear cells from COPD patients
Authors: J. Rupp, H. Kothe, A. Mueller, M. Maass, K. Dalhoff
Journal: European Respiratory Journal (2003)

Balanced secretion of pro- and anti-inflammatory cytokines is essential in limiting pulmonary inflammation in respiratory infections. It was hypothesised that, in acute infection with Chlamydia pneumoniae , mononuclear cells from chronic obstructive pulmonary disease (COPD) patients lack the opportunity to compensate for the inflammatory immune response by secreting adequate amounts of anti-inflammatory cytokines. Alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs) from eight COPD patients and eight healthy controls were infected with C. pneumoniae in order to determine interleukin (IL)‐1β, IL‐1 receptor antagonist (IL‐1RA) and IL‐8 expression and messenger ribonucleic acid levels. Secretion of IL‐1β was significantly enhanced in AMs (six-fold) and PBMCs (four-fold) from COPD patients after infection with C. pneumoniae . Compared to the control group, release of its anti-inflammatory counterpart IL‐1RA was diminished inCOPD patients, resulting in a significantly higher IL‐1β/IL‐1RA ratio in C.pneumoniae -infected AMs and PBMCs from COPD patients. Mononuclear cells from chronic obstructive pulmonary disease patients have less capacity for balancing the pro-inflammatory immune response caused by Chlamydia pneumoniae infection than those from healthy controls. These findings suggest that, during acute exacerbation with intracellular pathogens, chronic obstructive pulmonary disease patients are predisposed to inflammatory changes in the lungs.
Does Black Ethnicity Influence the Development of Stent Thrombosis in the Drug-Eluting Stent Era?
Authors: Sara D. Collins, Rebecca Torguson, Michael A. Gaglia, Gilles Lemesle, Asmir I. Syed, Itsik Ben-Dor, Yanlin Li, Gabriel Maluenda, Kimberly Kaneshige, Zhenyi Xue, Kenneth M. Kent, Augusto D. Pichard, William O. Suddath, Lowell F. Satler, Ron Waksman
Journal: Circulation (2010)

It has been suggested that black race predicts stent thrombosis (ST) after drug-eluting stent implantation. Whether socioeconomic status or comorbid conditions confound the contribution of black race to the development of ST is unclear.We compared 1594 black patients who underwent drug-eluting stent implantation with 5642 nonblack patients. Overall, 108 definite STs were reported. Multivariable Cox regression analysis was performed with adjustment for comorbidities, including median household income as a marker of socioeconomic status, to assess the impact that black race may have on the development of ST. On univariable analysis, black patients were younger (63.43±12.42 versus 65.15±12.59 years; P<0.001) and more likely to have a history of hypertension (89.8% versus 81.7%; P<0.001), diabetes mellitus (45.5% versus 30.8%; P<0.001), chronic renal insufficiency (19.2% versus 10.7%; P<0.001), and congestive heart failure (18.7% versus 13.1%; P<0.001). Clopidogrel compliance at the time of the ST event was higher in the black than in the nonblack population (87.5% versus 77.8%; P=0.068). After multivariable analysis, including adjustment for median income and clopidogrel compliance, black race emerged as a strong predictor of definite late ST.Black race is an independent predictor of definite drug-eluting stent ST. Because clopidogrel compliance was higher in black patients and socioeconomic status was not associated with ST, further investigation into the potential mechanisms of this influence of race on ST must be pursued.
Prone position in mechanically ventilated patients with severe acute respiratory failure.
Authors: G Chatte, J M Sab, J M Dubois, M Sirodot, P Gaussorgues, D Robert
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The purpose of this study was to characterize changes in oxygenation, expressed as PaO2/F(I)O2, when patients with severe acute respiratory failure (PaO2/F(I)O2 < 150), unrelated to left ventricular failure to atelectasis, were turned to and from a supine to prone position at 1- and 4-h intervals. Ventilator settings were unchanged. Thirty-two consecutive patients were studied 1 h before, 1 and 4 h during and 1 h after placing in a prone position with PaO2/F(I)O2 of 103 +/- 28, 158 +/- 62, 159 +/- 59, and 128 +/- 52, respectively (ANOVA, p < 0.001). After 1 h in a prone position, improvement of PaO2/F(I)O2 by 20 mm Hg or more was considered a positive response. Seven patients studied had no response (22%), hereafter referred to as nonresponders, and 25 had a positive response (78%), hereafter referred to as responders. Among the seven nonresponders, two did not tolerate the prone position and were returned supine before the end of the 4-h trial. With the remaining five, PaO2/F(I)O2 evolution was 83 +/- 29, 77 +/- 19, 83 +/- 33, and 81 +/- 47, respectively. For two of the 25 responders, measurements are missing after returning to the supine position. In 10 of the 23 responders (43%) who completed the 4 h prone trial, the PaO2/F(I)O2 returned to its starting value when patients were repositioned supine: 117 +/- 24, 164 +/- 44, 156 +/- 55, and 110 +/- 34, respectively (ANOVA, p < 0.01). In 13 of the 23 (57%) improvement persisted: 105 +/- 27, 187 +/- 58, 189 +/- 49, and 157 +/- 49, respectively (ANOVA, p < 0.001). Repeated improvements after turning to a prone position were frequently observed. Side effects in the 32 patients after a total of 294 periods in a prone position included minor skin injury and edema, two instances of apical atelectasis, one catheter removal, one catheter compression, one extubation, and one transient supraventricular tachycardia.
Limited Gene Misregulation Is Exacerbated by Allele-Specific Upregulation in Lethal Hybrids between Drosophila melanogaster and Drosophila simulans
Authors: Kevin H-C Wei, Andrew G Clark, Daniel A Barbash
Journal: Molecular Biology and Evolution (2014)

Misregulation of gene expression is often observed in interspecific hybrids and is generally attributed to regulatory incompatibilities caused by divergence between the two genomes. However, it has been challenging to distinguish effects of regulatory divergence from secondary effects including developmental and physiological defects common to hybrids. Here, we use RNA-Seq to profile gene expression in F1 hybrid male larvae from crosses of Drosophila melanogaster to its sibling species D. simulans. We analyze lethal and viable hybrid males, the latter produced using a mutation in the X-linked D. melanogaster Hybrid male rescue (Hmr) gene and compare them with their parental species and to public data sets of gene expression across development. We find that Hmr has drastically different effects on the parental and hybrid genomes, demonstrating that hybrid incompatibility genes can exhibit novel properties in the hybrid genetic background. Additionally, we find that D. melanogaster alleles are preferentially affected between lethal and viable hybrids. We further determine that many of the differences between the hybrids result from developmental delay in the Hmr+ hybrids. Finally, we find surprisingly modest expression differences in hybrids when compared with the parents, with only 9% and 4% of genes deviating from additivity or expressed outside of the parental range, respectively. Most of these differences can be attributed to developmental delay and differences in tissue types. Overall, our study suggests that hybrid gene misexpression is prone to overestimation and that even between species separated by approximately 2.5 Ma, regulatory incompatibilities are not widespread in hybrids.
“The only thing I know is that I know nothing”: 5-fluorouracil in human milk
Authors: F.A. Peccatori, E. Giovannetti, B. Pistilli, G. Bellettini, G. Codacci-Pisanelli, N. Losekoot, G. Curigliano, H.A. Azim, A. Goldhirsch, G.J. Peters
Journal: Annals of Oncology (2012)
Endovascular Repair of Abdominal Aortic Aneurysm
Authors: Roger M. Greenhalgh, Janet T. Powell
Journal: New England Journal of Medicine (2008)

A 72-year-old man is found to have an abdominal aortic aneurysm that is 5.7 cm in diameter, and endovascular repair is considered. The use of an abdominal aortic stent–graft for repair of an abdominal aortic aneurysm is associated with lower early mortality than open surgical repair but also with a higher risk of subsequent need for reintervention and with a less certain long-term outcome.
Anthrax toxin blocks priming of neutrophils by lipopolysaccharide and by muramyl dipeptide.
Authors: G G Wright, G L Mandell
Journal: The Journal of Experimental Medicine (1986)

We studied the pretreatment of human polymorphonuclear neutrophils (PMN) with purified preparations of the anthrax toxin components--protective antigen (PA), edema factor (EF), and lethal factor (LF)--and their effects on release of superoxide anion (O-2) after stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). PMN isolated in the absence of lipopolysaccharide (LPS) (less than 0.1 ng/ml) released only small amounts of O-2 after FMLP stimulation; pretreatment with anthrax toxin had little effect. The release of O-2 was increased fivefold by prior treatment with 3 ng/ml LPS for 1 h at 37 degrees C, an effect referred to as priming. PMN were primed to an equivalent extent by treatment with 100 ng/ml N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide [MDP]). Pretreatment of PMN with anthrax toxin components PA plus EF or PA plus LF inhibited priming by LPS or MDP, as shown by the reduction in the release of O-2 up to 90% relative to controls not treated with toxin; single toxin components were inactive. The inhibition was markedly reduced when priming with LPS or MDP was carried out before exposure to toxin. O-2 release after stimulation by phorbol myristate acetate was not increased by priming, and pretreatment with toxin did not inhibit O-2 release after this stimulus. Evidently, anthrax toxin inhibits the priming that is normally induced in PMN by bacterial products and is necessary for the full expression of antimicrobial effects.
Preventing necrotising enterocolitis with amniotic fluid stem cells
Authors: William F Stenson
Journal: Gut (2013)

Necrotising enterolcolitis (NEC) is a common and devastating disease in preterm infants.1 The prevention of NEC has become a high research priority. NEC is precipitated by the exposure of the immature intestine to bacteria after birth. Studies in animal models and xenografts suggest that the preterm infant mounts an excessive inflammatory response to luminal bacteria.2–4 In the term infant, the intestine adapts to luminal microbes by downregulating the immune system, whereas, in the preterm infant, it does not. Intestinal epithelial cell toll-like receptor (TLR)4 responses appear to be much more active in the preterm intestine than in the term intestine.3 ,4 Intestinal epithelial TLR4 activation, driven by exposure to luminal Gram-negative bacteria, leads to increased mucosal injury through accelerated enterocyte apoptosis as well as reduced healing through impaired intestinal restitution and proliferation.3 Mice deficient in TLR4 show reduced severity in models of NEC. Apoptosis of epithelial cells is seen in histologic specimens collected at the time of small bowel resection in patients with NEC. Apoptosis usually precedes other signs of tissue damage. Animal models of NEC also demonstrate epithelial apoptosis. Clinical trials with breast milk feeding and probiotics (including Lactobacillus acidophilus and Bifidobacterium bifidum ) have shown efficacy in preventing NEC.5 ,6

Zani et al 7 demonstrate that amniotic fluid stem (AFS) cells given intraperitoneally improve survival and enhance repair of damaged intestine in a rat model of NEC. …
T cell receptor (TCR) structure of autologous melanoma-reactive cytotoxic T lymphocyte (CTL) clones: tumor-infiltrating lymphocytes overexpress in vivo the TCR beta chain sequence used by an HLA-A2-restricted and melanocyte-lineage-specific CTL clone.
Authors: M Sensi, S Salvi, C Castelli, C Maccalli, A Mazzocchi, R Mortarini, G Nicolini, M Herlyn, G Parmiani, A Anichini
Journal: The Journal of Experimental Medicine (1993)

HLA-A2+ melanomas express common melanoma-associated antigens (Ags) recognized in vitro by autologous cytotoxic T lymphocytes (CTL). However, it is not known whether tumor Ags can drive in vivo a selective accumulation/expansion of Ag-specific, tumor-infiltrating T lymphocytes (TIL). Therefore, to evaluate this possibility, 39 CTL clones isolated from several independent mixed lymphocyte tumor cultures (MLTC) of TIL and peripheral blood lymphocytes (PBL) of an HLA-A2+ melanoma patient and selected for T cell receptor (TCR)-dependent, HLA-restricted tumor lysis, were used for analysis of TCR alpha and beta chain structure by the cDNA polymerase chain reaction (PCR) technique with variable gene-specific primers followed by sequencing. Despite absence of oligoclonality in fresh TIL and PBL, as well as in T cells of day 28 MLTC (day of cloning), sequence analysis of TCR alpha and beta chains of TIL clones revealed a dominance of a major category of melanoma-specific, HLA-A2-restricted T cells expressing a V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1 TCR. The same TCR was also found in 2 out of 14 PBL clones. The other PBL clones employed a V alpha 2.1 gene segment associated with either V beta 13.2, 14, or w22. Clones A81 (V alpha 2.1/J alpha IGRJ alpha 04/C alpha and V beta 14/D beta 1/J beta 1.2/C beta 1) and A21 (V alpha 8.2/J alpha AP511/C alpha and V beta 2.1/D beta 1/J beta 1.1/C beta 1), representative of the two most frequent TCR of PBL and TIL, respectively, expressed different lytic patterns, but both were HLA-A2 restricted and lysed only HLA-A2+ melanomas and normal melanocytes, thus indicating recognition of two distinct HLA-A2-associated and tissue-related Ags. Finally, by the inverse PCR technique, the specific TCR beta chain (V beta 2.1/D beta 1/J beta 1.1/C beta 1) expressed by the dominant TIL clone was found to represent 19 and 18.4% of all V beta 2 sequences expressed in the fresh tumor sample and in the purified TIL, respectively, but &amp;lt; 0.19% of V beta 2+ sequences expressed in PBL. These results are consistent with the hypothesis that a clonal expansion/accumulation of a melanocyte-lineage-specific and HLA-A2-restricted T cell clone occurred in vivo at the site of tumor growth.