tbuckley/cabot-search huggingface dataset:
Atopy, lung function, and obstructive airways disease after prenatal exposure to famine
Authors: C E Lopuhaa
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944–5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. <h3>METHODS</h3> Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). <h3>RESULTS</h3> Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0.9 to 2.6). <h3>CONCLUSIONS</h3> The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.
Prognostic value of indocyanine green and lidocaine kinetics for survival and chronic hepatic encephalopathy in cirrhotic patients following elective end-to-side portacaval shunt
Authors: Gilles Pomier-Layrargues, Pierre-Michel Huet, Claire Infante-Rivard, Jean-Pierre Villeneuve, Denis Marleau, Lester Duguay, Serge Tanguay, Pierre Lavoie
Journal: Hepatology (1988)

The objective of this study was to assess the prognostic value of spontaneous portosystemic shunting and liver function for survival and spontaneous hepatic encephalopathy after end-to-side portacaval shunt in cirrhotic patients. One hundred ninety-eight patients with variceal hemorrhage as shown by endoscopy were evaluated. Forty-five were excluded because of uncontrollable hemorrhage; 84 were rejected because they were poor operative risk, had portal vein thrombosis or had been previously treated with β-blockers, sclerotherapy or surgery. The remaining 69 patients were enrolled in this prospective study. There were 43 patients with alcoholic cirrhosis, 23 with cryptogenic cirrhosis and three with primary biliary cirrhosis. The severity of liver disease was assessed according to the Pugh classification: 37 patients (54%) had Pugh's score 5 to 7, 26 (38%) had 8 to 10 and six (8%) had 11 to 12. Indocyanine green intrinsic clearance was used as a probe of preoperative liver function and lidocaine systemic availability as an index of spontaneous preoperative shunting. All the patients underwent an elective end-to-side portacaval shunt. The length of minimal follow-up was 40 months. One-year survival was 76% and 5-year survival was 46%. During follow-up, 25 patients died from their liver disease and 11 patients died from various causes unrelated to their liver disease. Spontaneous chronic encephalopathy occurred in 16 patients (23%). Age, Pugh's score, active alcoholism, indocyanine green intrinsic clearance and lidocaine systemic availability were tested as prognostic factors in a multivariate analysis. A stepwise analysis using the Cox proportional hazard demonstrated that, in this population of cirrhotic patients, the Pugh score was the only variable significantly related to survival (β = 0.3; S.E. = 0.12, p < 0.05). A stepwise multiple logistic regression analysis showed that none of the studied parameters was significantly related to the onset of postoperative spontaneous encephalopathy. These findings suggest that in this population of cirrhotic patients the Pugh score remains the best predictive variable for survival and that pharmacokinetic parameters have no role in the prediction of postoperative outcome after end-to-side portacaval shunt.
A regional prospective study of in-hospital mortality associated with coronary artery bypass grafting. The Northern New England Cardiovascular Disease Study Group
Authors: G. T. O'Connor
Journal: JAMA (1991)

A prospective regional study was conducted to determine if the observed differences in in-hospital mortality rates associated with coronary artery bypass grafting (CABG) are solely the result of differences in patient case mix. DESIGN-Regional prospective cohort study. Data including patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected. This study presents data for 3055 CABG patients between July 1, 1987, and April 15, 1989.This study includes data from all surgeons performing cardiothoracic surgery in Maine, New Hampshire, and Vermont; the data were collected from five regional medical centers.Data were collected from all consecutive isolated CABG surgery patients during the study period.Crude and adjusted in-hospital mortality rates associated with CABG.The overall crude in-hospital mortality rate for isolated CABG was 4.3%. The rate varied among centers (range, 3.1% to 6.3%) and among surgeons (range, 1.9% to 9.2%). Predictors of in-hospital mortality included increased age, female gender, small body surface area, greater comorbidity, reoperation, poorer cardiac function as indicated by a lower ejection fraction, increased left ventricular end diastolic pressure and emergent or urgent surgery. After adjusting for the effects of potentially confounding variables, substantial and statistically significant variability was observed among medical centers (P = .021) and among surgeons (P = .025).We conclude that the observed differences in in-hospital mortality rates among institutions and among surgeons in northern New England are not solely the result of differences in case mix as described by these variables and may reflect differences in currently unknown aspects of patient care. Understanding this variation requires a detailed understanding of the processes of care.
Prevalence of gastroschisis at birth: retrospective study
Authors: G. L. Di Tanna
Journal: BMJ (2002)

Gastroschisis is a congenital defect of the abdominal wall, characterised by herniation of abdominal viscera outside the abdominal cavity through a defect in the abdominal wall to the side of the umbilicus.1 Recent studies showed an increase in the prevalence of gastroschisis at birth but gave no convincing explanation. 2 3 We describe the temporal and geographical variation in this prevalence, using data from the International Clearinghouse For Birth Defects Monitoring Systems, founded in 1974, which fosters sharing information and collaboration among the programmes that monitor birth defects worldwide. Currently, 36 programmes from Europe, the Americas, Asia, Australia, and South Africa participate in the clearinghouse and cumulatively monitor 3.3 million births each year. The head office of the clearinghouse, the International Centre for …
Chemoradiation With and Without Surgery in Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus
Authors: Michael Stahl, Martin Stuschke, Nils Lehmann, Hans-Joachim Meyer, Martin K. Walz, Siegfried Seeber, Bodo Klump, Wilfried Budach, Reinhard Teichmann, Marcus Schmitt, Gerd Schmitt, Claus Franke, Hansjochen Wilke
Journal: Journal of Clinical Oncology (2005)

Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown.Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time.The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001).Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.
Acetyl-CoA Carboxylase α Is Essential to Breast Cancer Cell Survival
Authors: Véronique Chajès, Marie Cambot, Karen Moreau, Gilbert M. Lenoir, Virginie Joulin
Journal: Cancer Research (2006)

Abstract Activation of de novo fatty acid synthesis is a characteristic feature of cancer cells. We have recently described an interaction between acetyl-CoA carboxylase α (ACCα), a key enzyme in fatty acid synthesis, and BRCA1, which indicates a possible connection between lipid synthesis and genetic factors involved in susceptibility to breast and ovarian cancers. For this reason, we explored the role of ACCα in breast cancer cell survival using an RNA interference (RNAi) approach. We show that specific silencing of either the ACCα or the fatty acid synthase (FAS) genes in cancer cells results in a major decrease in palmitic acid synthesis. Depletion of the cellular pool of palmitic acid is associated with induction of apoptosis concomitant with the formation of reactive oxygen species (ROS) and mitochondrial impairment. Expression of a small interfering RNA (siRNA)–resistant form of ACCα mRNA prevented the effect of ACCα-RNAi but failed to prevent the effect of FAS gene silencing. Furthermore, supplementation of the culture medium with palmitate or with the antioxidant vitamin E resulted in the complete rescue of cells from both ACCα and FAS siRNA–induced apoptosis. Finally, human mammary epithelial cells are resistant to RNAi against either ACCα or FAS. These data confirm the importance of lipogenesis in cancer cell survival and indicate that this pathway represents a key target for antineoplastic therapy that, however, might require specific dietary recommendation for full efficacy. (Cancer Res 2006; 66(10): 5287-94)
Health of Previously Uninsured Adults After Acquiring Medicare Coverage
Authors: J. Michael McWilliams, Ellen Meara, Alan M. Zaslavsky, John Z. Ayanian
Journal: JAMA (2007)

Uninsured near-elderly adults, particularly those with cardiovascular disease or diabetes, experience worse health outcomes than insured adults. However, the health benefits of providing insurance coverage for uninsured adults have not been clearly demonstrated.To assess the effect of acquiring Medicare coverage on the health of previously uninsured adults.We conducted quasi-experimental analyses of longitudinal survey data from 1992 through 2004 from the nationally representative Health and Retirement Study. We compared changes in health trends reported by previously uninsured and insured adults after they acquired Medicare coverage at age 65 years.Five thousand six adults who were continuously insured and 2227 adults who were persistently or intermittently uninsured from ages 55 to 64 years.Differential changes in self-reported trends after age 65 years in general health, change in general health, mobility, agility, pain, depressive symptoms, and a summary measure of these 6 domains; and adverse cardiovascular outcomes (all trend changes reported in health scores per year).Compared with previously insured adults, previously uninsured adults reported significantly improved health trends after age 65 years for the summary measure (differential change in annual trend, +0.20; P = .002) and several component measures. Relative to previously insured adults with cardiovascular disease or diabetes, previously uninsured adults with these conditions reported significantly improved trends in summary health (differential change in annual trend, +0.26; P = .006), change in general health (+0.02; P = .03), mobility (+0.04; P = .05), agility (+0.08; P = .003), and adverse cardiovascular outcomes (-0.015; P = .02) but not in depressive symptoms (+0.04; P = .32). Previously uninsured adults without these conditions reported differential improvement in depressive symptoms (+0.08; P = .002) but not in summary health (+0.10; P = .17) or any other measure. By age 70 years, the expected difference in summary health between previously uninsured and insured adults with cardiovascular disease or diabetes was reduced by 50%.In this study, acquisition of Medicare coverage was associated with improved trends in self-reported health for previously uninsured adults, particularly those with cardiovascular disease or diabetes.
Function and mechanism of tumor suppressor gene LRRC4/NGL-2
Authors: Peiyao Li, Gang Xu, Guiyuan Li, Minghua Wu
Journal: Molecular Cancer (2014)

LRRC4/NGL-2 (Leucine rich repeat containing 4/Netrin-G ligand-2), a relatively specific expressed gene in brain tissue, is a member of the LRRC4/ NGL (netrin-G ligand) family and belongs to the superfamily of LRR proteins. LRRC4/NGL-2 regulates neurite outgrowth and lamina-specific dendritic segmentation, suggesting that LRRC4/NGL-2 is important for the development of the nervous system. In addition, LRRC4/NGL-2 has been identified as a tumor suppressor gene. The overexpression of LRRC4/NGL-2 suppresses glioma cell growth, angiogenesis and invasion through complicated signaling regulation networks. LRRC4/NGL-2 also has the ability to form multiphase loops with miRNA, transcription factors and gene methylation modification; the loss of LRRC4/NGL-2 function may be an important event in multiple biological processes in gliomas. In summary, LRRC4/NGL-2 is a critical gene in the normal development and tumorigenesis of the nervous system.
Understanding the Complexity of <i>Trans</i> Fatty Acid Reduction in the American Diet
Authors: Robert H. Eckel, Susan Borra, Alice H. Lichtenstein, Shirley Y. Yin-Piazza
Journal: Circulation (2007)

A 2-day forum was convened to discuss the current status and future implications of reducing trans fatty acids without increasing saturated fats in the food supply while maintaining functionality and consumer acceptance of packaged, processed, and prepared foods. Attendees represented the agriculture and oilseed industry and oil processing, food manufacturing, food service, government, food technology, and health and nutrition disciplines. Presentations included food science behind fatty acid technology, the health science of dietary fatty acids, alternatives to trans fatty acids, and the use of alternatives in food manufacturing and food service. The reduction of trans fatty acids in the food supply is a complex issue involving interdependent and interrelated stakeholders. Actions to reduce trans fatty acids need to carefully consider both intended and unintended consequences related to nutrition and public health. The unintended consequence of greatest concern is that fats and oils high in saturated fats, instead of the healthier unsaturated fats, might be used to replace fats and oils with trans fatty acids. Many different options of alternative oils and fats to replace trans fatty acids are available or in development. Decisions on the use of these alternatives need to consider availability, health effects, research and development investments, reformulated food quality and taste, supply-chain management, operational modifications, consumer acceptance, and cost. The conference demonstrated the value of collaboration between the food industry and health and nutrition professionals, and this conference model should be used to address other food development, processing, and/or technology issues.
Oral Capecitabine Compared With Intravenous Fluorouracil Plus Leucovorin in Patients With Metastatic Colorectal Cancer: Results of a Large Phase III Study
Authors: Eric Van Cutsem, Chris Twelves, Jim Cassidy, David Allman, Emilio Bajetta, Michael Boyer, Roland Bugat, Mike Findlay, Stefan Frings, Michaela Jahn, Joe McKendrick, Bruno Osterwalder, Gumersindo Perez-Manga, Riccardo Rosso, Philippe Rougier, Wolff H. Schmiegel, Jean-Francois Seitz, Paul Thompson, Jose Maria Vieitez, Christof Weitzel, Peter Harper
Journal: Journal of Clinical Oncology (2001)

To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m(2) administered twice daily days 1 to 14 every 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/LV) until disease progression or unacceptable toxicity.The primary objective, to demonstrate at least equivalent response rates in the two treatment groups, was met. The overall response rate was 18.9% for capecitabine and 15.0% for 5-FU/LV. In the capecitabine and 5-FU/LV groups, respectively, median time to disease progression was 5.2 and 4.7 months (log-rank P =.65); median time to treatment failure was 4.2 and 4.0 months (log-rank P =.89); and median overall survival was 13.2 and 12.1 months (log-rank P =.33). The toxicity profiles of both treatments were typical of fluoropyrimidines. However, capecitabine led to significantly lower incidences (P <.00001) of stomatitis and alopecia, but a higher incidence of cutaneous hand-foot syndrome (P <.00001). Capecitabine also resulted in lower incidences (P <.00001) of grade 3/4 stomatitis and neutropenia, leading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 hand-foot syndrome (P <.00001) and uncomplicated grade 3/4 hyperbilirubinemia (P <.0001) were reported more frequently with capecitabine.Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent.
Beneficial Effect of the Central Nervous System β-Adrenoceptor Blockade on the Failing Heart
Authors: Andrey Gourine, Svetlana I. Bondar, K. Michael Spyer, Alexander V. Gourine
Journal: Circulation Research (2008)

Heart failure patients are routinely given beta-adrenoceptor antagonists (beta-blockers), although the mechanism(s) underlying their beneficial effects is not fully resolved. It is not entirely clear how long-term application of negative inotropic compounds improves cardiac performance, slows remodeling processes, and decreases mortality. All beta-blockers, which produce a beneficial effect in heart failure, have in common a high degree of lipophilicity and, therefore, have the ability to cross the blood-brain barrier. Here, we show that blockade of beta-adrenoceptors directly in the brain (chronic intracerebroventricular administration of metoprolol) attenuates the progression of left ventricular remodeling in a rat model of myocardial infarction-induced heart failure. These results provide the first direct evidence that the action of certain beta-blockers in the brain could contribute to their beneficial effect on the failing heart.
Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.
Authors: T Sornasse, P V Larenas, K A Davis, J E de Vries, H Yssel
Journal: The Journal of Experimental Medicine (1996)

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.