tbuckley/cabot-search huggingface dataset:
Relations of Lipid Concentrations to Heart Failure Incidence
Authors: Raghava S. Velagaleti, Joseph Massaro, Ramachandran S. Vasan, Sander J. Robins, William B. Kannel, Daniel Levy
Journal: Circulation (2009)

Background— The relations of lipid concentrations to heart failure (HF) risk have not been elucidated comprehensively. Methods and Results— In 6860 Framingham Heart Study participants (mean age, 44 years; 54% women) free of baseline coronary heart disease, we related high-density lipoprotein cholesterol (HDL-C) and non-HDL-C to HF incidence during long-term follow-up, adjusting for clinical covariates and myocardial infarction at baseline and updating these at follow-up examinations. We evaluated dyslipidemia-specific population burden of HF by calculating population attributable risks. During follow-up (mean of 26 years), 680 participants (49% women) developed HF. Unadjusted HF incidence in the low (&lt;160 mg/dL) versus high (≥190 mg/dL) non-HDL-C groups was 7.9% and 13.8%, respectively, whereas incidence in the high (≥55 [men], ≥65 [women] mg/dL) versus low (&lt;40 [men], &lt;50 [women] mg/dL) HDL-C groups was 6.1% and 12.8%, respectively. In multivariable models, baseline non-HDL-C and HDL-C, modeled as continuous measures, carried HF hazards (confidence intervals) of 1.19 (1.11 to 1.27) and 0.82 (0.75 to 0.90), respectively, per SD increment. In models updating lipid concentrations every 8 years, the corresponding hazards (confidence intervals) were 1.23 (1.16 to 1.31) and 0.77 (0.70 to 0.85). Participants with high baseline non-HDL-C and those with low HDL-C experienced a 29% and 40% higher HF risk, respectively, compared with those in the desirable categories; the population attributable risks for high non-HDL-C and low HDL-C were 7.5% and 15%, respectively. Hazards associated with non-HDL-C and HDL-C remained statistically significant after additional adjustment for interim myocardial infarction. Conclusions— Dyslipidemia carries HF risk independent of its association with myocardial infarction, suggesting that lipid modification may be a means for reducing HF risk.
Chronic vomiting in a case of citrullinaemia detected after treatment by total parenteral nutrition.
Authors: A Benque, G Bommelaer, G Rozental, P Cales, L Cathelineau, D Pham Dinh, A Ribet
Journal: Gut (1984)

We report a case of a 56 year old woman who presented with a long history of chronic attacks of vomiting. On admission to hospital she was cachectic, and attempted parenteral nutrition induced coma. The illness was found to be due to citrullinaemia, a metabolic disorder of the urea cycle. Our patient is the oldest with this disorder so far described in the literature. The main points of the case and its investigation are outlined: hyperammonaemia, amino acid chromatogram, measurement of enzyme activity in skin and liver biopsy material. The therapeutic measures which led to cure are of particular interest.
The Metabolic Syndrome as a Predictor of Nonalcoholic Fatty Liver Disease
Authors: Masahide Hamaguchi, Takao Kojima, Noriyuki Takeda, Takayuki Nakagawa, Hiroya Taniguchi, Kota Fujii, Tatsushi Omatsu, Tomoaki Nakajima, Hiroshi Sarui, Makoto Shimazaki, Takahiro Kato, Junichi Okuda, Kazunori Ida
Journal: Annals of Internal Medicine (2005)

The frequent association of nonalcoholic fatty liver disease with components of the metabolic syndrome such as obesity, hyperglycemia, dyslipidemia, and hypertension is well known. However, no prospective study has examined the role of the metabolic syndrome in the development of this disease.To characterize the longitudinal relationship between the metabolic syndrome and nonalcoholic fatty liver disease.A prospective observational study.A medical health checkup program in a general hospital.4401 apparently healthy Japanese men and women, 21 to 80 years of age, with a mean body mass index (BMI) of 22.6 kg/m2 (SD, 3.0).Alcohol intake was assessed by using a questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome.At baseline, 812 of 4401 (18%) participants had nonalcoholic fatty liver disease. During the mean follow-up period of 414 days (SD, 128), the authors observed 308 new cases (10%) of nonalcoholic fatty liver disease among 3147 participants who were disease-free at baseline and who completed a second examination. Regression of nonalcoholic fatty liver disease was found in 113 (16%) of 704 participants who had the disease at baseline and who completed a second examination. Men and women who met the criteria for the metabolic syndrome at baseline were more likely to develop the disease during follow-up (adjusted odds ratio, 4.00 [95% CI, 2.63 to 6.08] and 11.20 [CI, 4.85 to 25.87], respectively). Nonalcoholic fatty liver disease was less likely to regress in those participants with the metabolic syndrome at baseline.Ultrasonography may lead to an incorrect diagnosis of nonalcoholic fatty liver disease in 10% to 30% of cases and cannot distinguish steatohepatitis from simple steatosis. Self-reported alcohol intake may cause bias. Because all of the participants were Japanese, generalizability to non-Japanese populations is uncertain.The metabolic syndrome is a strong predictor of nonalcoholic fatty liver disease.
Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies
Authors: L. Te Morenga, S. Mallard, J. Mann
Journal: BMJ (2012)

<b>Objective</b> To summarise evidence on the association between intake of dietary sugars and body weight in adults and children. <b>Design</b> Systematic review and meta-analysis of randomised controlled trials and prospective cohort studies. <b>Data sources</b> OVID Medline, Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Web of Science (up to December 2011). <b>Review methods</b> Eligible studies reported the intake of total sugars, intake of a component of total sugars, or intake of sugar containing foods or beverages; and at least one measure of body fatness. Minimum duration was two weeks for trials and one year for cohort studies. Trials of weight loss or confounded by additional medical or lifestyle interventions were excluded. Study selection, assessment, validity, data extraction, and analysis were undertaken as specified by the Cochrane Collaboration and the GRADE working group. For trials, we pooled data for weight change using inverse variance models with random effects. We pooled cohort study data where possible to estimate effect sizes, expressed as odds ratios for risk of obesity or β coefficients for change in adiposity per unit of intake. <b>Results</b> 30 of 7895 trials and 38 of 9445 cohort studies were eligible. In trials of adults with ad libitum diets (that is, with no strict control of food intake), reduced intake of dietary sugars was associated with a decrease in body weight (0.80 kg, 95% confidence interval 0.39 to 1.21; P&lt;0.001); increased sugars intake was associated with a comparable weight increase (0.75 kg, 0.30 to 1.19; P=0.001). Isoenergetic exchange of dietary sugars with other carbohydrates showed no change in body weight (0.04 kg, −0.04 to 0.13). Trials in children, which involved recommendations to reduce intake of sugar sweetened foods and beverages, had low participant compliance to dietary advice; these trials showed no overall change in body weight. However, in relation to intakes of sugar sweetened beverages after one year follow-up in prospective studies, the odds ratio for being overweight or obese increased was 1.55 (1.32 to 1.82) among groups with the highest intake compared with those with the lowest intake. Despite significant heterogeneity in one meta-analysis and potential bias in some trials, sensitivity analyses showed that the trends were consistent and associations remained after these studies were excluded. <b>Conclusions</b> Among free living people involving ad libitum diets, intake of free sugars or sugar sweetened beverages is a determinant of body weight. The change in body fatness that occurs with modifying intakes seems to be mediated via changes in energy intakes, since isoenergetic exchange of sugars with other carbohydrates was not associated with weight change.
Effect of Tamoxifen After Chemotherapy in Hormone Receptor–Positive, Node-Negative Breast Cancer
Authors: Lawrence C. Panasci
Journal: Journal of Clinical Oncology (2006)

In the discussion of the article by Hutchins et al 1 it is stated that both the hazard ratios for disease-free survival and overall survival show a narrow advantage for cyclophosphamide, doxorubicin, and fluorouracil that was not as strong as had been hypothesized.Furthermore, it was stated that the two-sided statistical test was not statistically significant.Later in the discussion, it is stated that the benefit seen in hormone receptor-positive patients was dramatic.It is clear that the disease-free survival is 6% different in favor of tamoxifen in the hormone receptor-positive patients, but this difference appears to be largely due to a reduction in opposite breast recurrences.Moreover, the difference in overall survival is exactly the same as the difference between cyclophosphamide, methotrexate, and fluorouracil and cyclophosphamide, doxorubicin, and fluorouracil, which is 82% with no tamoxifen versus 85% with tamoxifen.There was a one-sided P test, which was significant, but there is no discussion of the two-sided P test.In fact, it appears that if you treat hormonepositive, node-negative breast cancer with chemotherapy the effect of tamoxifen on survival is minimal.
Monocytes give rise to mucosal, but not splenic, conventional dendritic cells
Authors: Chen Varol, Limor Landsman, Darin K. Fogg, Liat Greenshtein, Boaz Gildor, Raanan Margalit, Vyacheslav Kalchenko, Frederic Geissmann, Steffen Jung
Journal: The Journal of Experimental Medicine (2006)

The mononuclear phagocyte (MP) system is a body-wide macrophage (MΦ) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, and immune defense. The in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified MΦ/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral MΦs and DCs. We show that MDPs are in vivo precursors of BM and blood monocytes. Interestingly, grafted Gr1high “inflammatory” blood monocytes shuttle back to the BM in the absence of inflammation, convert into Gr1low monocytes, and contribute further to MP generation. The grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCs in the spleen, which develop during homeostasis from MDPs without a monocytic intermediate.
Ethnic Differences in Insulin Sensitivity and β-Cell Function in Premenopausal or Early Perimenopausal Women Without Diabetes
Authors: Javier I. Torréns, Joan Skurnick, Amy L. Davidow, Stanley G. Korenman, Nanette Santoro, Maria Soto-Greene, Norman Lasser, Gerson Weiss
Journal: Diabetes Care (2004)

OBJECTIVE—To assess differences in insulin sensitivity and β-cell function between nondiabetic premenopausal or early perimenopausal non-Hispanic white women and African American, Chinese American, Japanese American, and non–Mexican-American Latino women. RESEARCH DESIGN AND METHODS—Homeostasis model assessments (HOMAs) of insulin sensitivity (HOMA%S) and β-cell function (HOMA%β) were used. Stepwise multivariable ethnic-specific ANCOVA models were used to compare HOMA%S and HOMA%β between non-Hispanic whites and each of the four ethnic groups. RESULTS—HOMA%S was lower in African Americans, Chinese Americans, and Japanese Americans when compared with non-Hispanic white women after correcting for waist circumference, presence of impaired fasting glucose, and site. Significant differences persisted only between African Americans and non-Hispanic whites after inclusion of triglycerides in the model. Triglycerides indirectly corrected for the differences in HOMA%S in the other two groups. There were no differences in HOMA%S between the non–Mexican-American Latinos and the non-Hispanic whites. Japanese Americans and Chinese Americans had lower HOMA%β than non-Hispanic whites, whereas African Americans had higher HOMA%β than non-Hispanic whites after correcting for confounders. HOMA%β was similar between non–Mexican-American Latinos and non-Hispanic whites. CONCLUSIONS—These data suggest that type 2 diabetes prevention strategies for African-American women should initially target decreased insulin sensitivity, whereas strategies for Japanese-American and Chinese-American women may initially need to target both decreased insulin sensitivity and β-cell function. Previous studies of Mexican-American populations may not apply to non–Mexican-American Latino women.
Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip
Authors: Shilpi Arora, Yipeng Wang, Zhenyu Jia, Saynur Vardar-Sengul, Ayla Munawar, Kutbuddin S Doctor, Michael Birrer, Michael McClelland, Eileen Adamson, Dan Mercola
Journal: Genome biology (2008)

UV irradiation activates the epidermal growth factor receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells. UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes belongs to the epidermal growth factor receptor-signal transduction pathway. Egr1 promoter binding had a significant impact on gene expression of target genes. Conventional chromatin immunoprecipitation and quantitative real time PCR were used to validate promoter binding and expression changes. Small interfering RNA experiments were used to demonstrate the specific role of Egr1 in gene regulation. UV stimulation promotes growth arrest and apoptosis of M12 cells and our data clearly show that a downstream target of the epidermal growth factor receptor, namely Egr1, mediates this apoptotic response. Our study also identified numerous previously unknown targets of Egr1. These include FasL, MAX and RRAS2, which may play a role in the apoptotic response/growth arrest. Our results indicate that M12 cells undergo Egr1-dependent apoptotic response upon UV stimulation and led to the identification of downstream targets of Egr1, which mediate epidermal growth factor receptor function.
ABC of allergies: Asthma and allergy
Authors: A J N. Taylor
Journal: BMJ (1998)

### Asthma

Asthma is commonly defined as a narrowing of the airways that is reversible over short periods of time, either spontaneously or as a result of treatment. This clinical definition (which characterises asthma as reversible airway narrowing) distinguishes it from other predominantly irreversible causes of airway narrowing, such as chronic obstructive bronchiolitis and emphysema. Another cardinal characteristic of asthma is airway hyper-responsiveness, an exaggerated narrowing of the airways provoked by a variety of non-specific stimuli, such as exercise and cold air. The two defining characteristics of asthma—reversible airway narrowing and airway hyper-responsiveness—are manifestations of a characteristic pattern of airway inflammation (a Th2 lymphocyte dependent desquamative eosinophilic bronchitis).



Normal bronchiole



### Atopy

Atopy is the propensity to produce IgE antibody to allergens (antigens that stimulate the production of IgE antibodies) that are commonly encountered in the general environment—for example, pollens, mites, and moulds. Atopy is usually identified by the provocation of one or more immediate “weal and flare” responses in the skin to extracts of common inhalant allergens. Specific IgE antibody to common inhalant allergens can also be found in the serum samples of atopic individuals, who may also have a raised serum concentration of total IgE.



Bronchiole from asthmatic patient narrowed by eosinophilic infiltration, oedema, and increased smooth muscle



The development of atopy is influenced by both genetic and environmental factors:

•The genetic basis of atopy is debated. Twin studies have consistently shown that atopy occurs more frequently in identical than non-identical twins. The findings in different family studies, however, have not identified a consistent pattern of inheritance. Recent molecular studies have suggested an association between atopy and polymorphisms of the high affinity IgE receptor on chromosome 11q (FCΣR1-β) and linkage with the interleukin 4 gene cluster on chromosome 5. It seems likely that atopy will eventually be associated with polymorphisms of many …
Induction of Mammary Neoplasms in the ACI Rat by 430-keV Neutrons, X-Rays, and Diethylstilbestrol&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: C J Shellabarger, D Chmelevsky, A M Kellerer, J P Stone, S Holtzman
Journal: JNCI Journal of the National Cancer Institute (1982)

Mammary tumorigenesis was studied in female ACi rats after treatment with X-irradiation or neutron-irradiation, with or without diethylstilbestrol (DES) treatment. The mortality-corrected cumulative tumor rate based on all mammary neoplasms and the mortality-corrected incidence based on the first neoplasms only have been derived. In non-DES-treated animals, at the relatively high radiation doses studied, all dose-effect relationships were consistent with relative biological effectiveness (RBE) values slightly in excess of 10. In DES-treated rats definite findings were observed at neutron doses as low as 0.01 Gy (1 rad). The dose-effect relationship in DES-treated rats showed a strong sublinearly (dose exponent less than 1) at low neutron doses. RBE values in DES-treated rats increased in inverse proportion to the square root of the neutron dose, and exceeded 100 at a neutron dose of 0.01 Gy (1 rad).
Diagnostic accuracy of clinical tests of the hip: a systematic review with meta-analysis
Authors: Michael P Reiman, Adam P Goode, Eric J Hegedus, Chad E Cook, Alexis A Wright
Journal: British Journal of Sports Medicine (2012)

<h3>Background</h3> Hip Physical Examination (HPE) tests have long been used to diagnose a myriad of intra-and extra-articular pathologies of the hip joint. Useful clinical utility is necessary to support diagnostic imaging and subsequent surgical decision making. <h3>Objective</h3> Summarise and evaluate the current research and utility on the diagnostic accuracy of HPE tests for the hip joint germane to sports related injuries and pathology. <h3>Methods</h3> A computer-assisted literature search of MEDLINE, CINHAL and EMBASE databases (January 1966 to January 2012) using keywords related to diagnostic accuracy of the hip joint. This systematic review with meta-analysis utilised the <i>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</i> (PRISMA) guidelines for the search and reporting phases of the study. Der-Simonian and Laird random effects models were used to summarise sensitivities (SN), specificities (SP), likelihood ratios and diagnostic OR. <h3>Results</h3> The employed search strategy revealed 25 potential articles, with 10 demonstrating high quality. Fourteen articles qualified for meta-analysis. The meta-analysis demonstrated that most tests possess weak diagnostic properties with the exception of the patellar-pubic percussion test, which had excellent pooled SN 95 (95% CI 92 to 97%) and good specificity 86 (95% CI 78 to 92%). <h3>Conclusion</h3> Several studies have investigated pathology in the hip. Few of the current studies are of substantial quality to dictate clinical decision-making. Currently, only the patellar-pubic percussion test is supported by the data as a stand-alone HPE test. Further studies involving high quality designs are needed to fully assess the value of HPE tests for patients with intra- and extra-articular hip dysfunction.
Longitudinal changes in cardiac function after cisplatin-based chemotherapy for testicular cancer
Authors: R. Altena, Y.M. Hummel, J. Nuver, A.J. Smit, J.D. Lefrandt, R.A. de Boer, A.A. Voors, M.P. van den Berg, E.G.E. de Vries, H.M. Boezen, J.A. Gietema
Journal: Annals of Oncology (2011)
Pediatric-Inspired Therapy in Adults With Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia: The GRAALL-2003 Study
Authors: Françoise Huguet, Thibaut Leguay, Emmanuel Raffoux, Xavier Thomas, Kheira Beldjord, Eric Delabesse, Patrice Chevallier, Agnes Buzyn, André Delannoy, Yves Chalandon, Jean-Paul Vernant, Marina Lafage-Pochitaloff, Agnès Chassevent, Véronique Lhéritier, Elizabeth Macintyre, Marie-Christine Béné, Norbert Ifrah, Hervé Dombret
Journal: Journal of Clinical Oncology (2009)

Retrospective comparisons have suggested that adolescents or teenagers with acute lymphoblastic leukemia (ALL) benefit from pediatric rather than adult chemotherapy regimens. Thus, the aim of the present phase II study was to test a pediatric-inspired treatment, including intensified doses of nonmyelotoxic drugs, such as prednisone, vincristine, or L-asparaginase, in adult patients with ALL up to the age of 60 years.Between 2003 and 2005, 225 adult patients (median age, 31 years; range, 15 to 60 years) with Philadelphia chromosome-negative ALL were enrolled onto the Group for Research on Adult Acute Lymphoblastic Leukemia 2003 protocol, which included several pediatric options. Some adult options, such as allogeneic stem-cell transplantation for patients with high-risk ALL, were nevertheless retained.were retrospectively compared with the historical France-Belgium Group for Lymphoblastic Acute Leukemia in Adults 94 (LALA-94) trial experience in 712 patients age 15 to 55 years. Results Complete remission rate was 93.5%. At 42 months, event-free survival (EFS) and overall survival (OS) rates were 55% (95% CI, 48% to 52%) and 60% (95% CI, 53% to 66%), respectively. Age remained an important bad prognostic factor, with 45 years of age as best cutoff. In older versus younger patients, there was a higher cumulative incidence of chemotherapy-related deaths (23% v 5%, respectively; P < .001) and deaths in first CR (22% v 5%, respectively; P < .001), whereas the incidence of relapse remained stable (30% v 32%, respectively). Complete remission rate (P = .02), EFS (P < .001), and OS (P < .001) compared favorably with the previous LALA-94 experience.These results suggest that pediatric-inspired therapy markedly improves the outcome of adult patients with ALL, at least until the age of 45 years.