tbuckley/cabot-search huggingface dataset:
Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival.
Authors: H J Jarvinen
Journal: Gut (1992)

The incidence and prevalence rates of familial adenomatous polyposis (FAP) in Finland between 1961 and 1990 were estimated from Finnish polyposis registry data comprising 81 FAP families, including 251 affected patients. In addition, the effect of family screening on the occurrence of colorectal carcinoma was evaluated by comparing the call up and proband groups and calculating the proportion of FAP among all patients with colorectal carcinoma. The incidence of FAP was 0.62 to 2.38 per million and the prevalence increased steadily from 0.88 to 26.3 million during the study period suggesting improving prognosis. Altogether 76 of 116 probands (65.5%) had colorectal carcinoma compared with only five of 76 call up patients (6.6%). Consequently, the life expectancy of the call up patients was significantly better than that of the probands from the age of 31 years and above. However, at most, 0.53% of all colorectal carcinomas were associated with FAP in 1966-70, and the diminishing frequency of this proportion was more a result of an increase in sporadic colorectal carcinomas in Finland than of family screening for FAP. Family screening is very effective in FAP and must always be undertaken when a new proband is diagnosed.
Smoking and metabolic syndrome
Authors: Lizia Fontes, Hanns Moshammer, Ibrahim Elmadfa
Journal: European Respiratory Journal (2012)

Background: Smoking causes inflammation and chronic systemic inflammation predisposes to a range of metabolic disorders usually described as metabolic syndrome. This might likely be one pathway leading to cardiovascular disease. Nicotine reduces appetite. Therefore exact control of caloric uptake (and physical activity) is necessary when studying the association between smoking and metabolic syndrome.  Methods: We used data collected during preventive check-ups among 987 employees of a large bank. Health data including routine laboratory parameters were enhanced by a detailed nutritional recall protocol and a standardised physical activity questionnaire. Physical activity and calories uptake were indeed significant predictors of several metabolic outcomes thus proving the data reliability. Associations were investigated using linear regression.  Results: Current smoking (number of cigarettes currently smoked) showed a non-linear association with most outcomes including waist circumference, high density lipids, fasting glucose, and triglycerides: While moderate smoking did not differ significantly from non-smoking the daily consumption of more than 20 cigarettes lead to significantly adverse effects on all these parameters. Adverse effects were more pronounced and roughly linear when cumulative smoking (pack years) was considered. Smoking also lead to an increase in white blood cell counts indicating an inflammatory response.
Quality of life and everyday activities in patients with primary biliary cirrhosis
Authors: Carlo Selmi, M. Eric Gershwin, Keith D. Lindor, Howard J. Worman, Ellen B. Gold, Mitchell Watnik, Jessica Utts, Pietro Invernizzi, Marshall M. Kaplan, John M. Vierling, Christopher L. Bowlus, Marina G. Silveira, Ilaria Bossi
Journal: Hepatology (2007)

Primary biliary cirrhosis (PBC) is generally a slowly progressive disease that may lead to cirrhosis and liver failure. However, patients with PBC often suffer from a variety of symptoms long before the development of cirrhosis that include issues of daily living that have an impact on their work environment and their individual quality of life. We therefore examined multiple parameters by taking advantage of the database of our cohort of 1032 patients with PBC and 1041 matched controls. The data were obtained from patients from 23 tertiary referral centers throughout the United States and from rigorously matched controls by age, sex, ethnicity, and random-digit dialing. The data showed that patients with PBC were more likely than controls to have significant articular symptoms, a reduced ability to perform household chores, and the need for help with routine activities. Patients with PBC rated their overall activity similar or superior to that of controls; however, more of them reported limitations in their ability to carry out activities at work or at home and difficulties in everyday activities. PBC cases also more frequently reported limitations in participating in certain sports or exercises and pursuing various hobbies; however, they did not report significant limitations in social activities. In a multivariable analysis, household income, a diagnosis of systemic lupus erythematosus, limitations in work activities, a reduction in work secondary to disability, and church attendance were independently increased in PBC cases with respect to controls. Conclusion: Our data indicate that the quality of life of patients with PBC in the United States is generally well preserved. Nevertheless, patients with PBC suffer significantly more than controls from a variety of symptoms that are beyond the immediate impact of liver failure and affect their lifestyle, personal relationships, and work activities. (Hepatology 2008.)
Emergence of West Nile virus infections in humans in Turkey, 2010 to 2011
Authors: H Kalaycioglu, G Korukluoglu, A Ozkul, O Oncul, S Tosun, O Karabay, A Gozalan, Y Uyar, D Y Caglayık, G Atasoylu, A B Altas, S Yolbakan, T N Ozden, F Bayrakdar, N Sezak, T S Pelıtlı, Z O Kurtcebe, E Aydın, M Ertek
Journal: Eurosurveillance (2012)

In 2010, 47 human cases of West Nile virus (WNV)infection, including 12 laboratory-confirmed and 35 probable cases, were identified in Turkey. These were the first cases detected during routine surveillance.The patients were from 15 provinces, mainly located in the western part of the country. Incidence was 0.19/100,000 with a maximum of 1.39 in Sakarya province.Forty of the total 47 cases showed neuroinvasive manifestation. Median age was 58 years with a range of four to 86. Ten of the patients died. Enhanced surveillance in humans and animals and mosquito control measures were implemented. The WNV infections were included in the national notifiable diseases list as of April 2011. In 2011, three probable and two confirmed cases of WNV infection were diagnosed in provinces where infections had been detected in the previous year, supporting a lower activity than 2010. However,detection of WNV infections in humans in 2010 and 2011 consecutively, may indicate that WNV has become endemic in the western part of Turkey. Field epidemiological studies were undertaken to understand more about the nature of infection in Turkey.
Impact of Cranial Radiotherapy on Central Nervous System Prophylaxis in Children and Adolescents With Central Nervous System–Negative Stage III or IV Lymphoblastic Lymphoma
Authors: Birgit Burkhardt, Wilhelm Woessmann, Martin Zimmermann, Udo Kontny, Josef Vormoor, Wolfgang Doerffel, Georg Mann, Guenter Henze, Felix Niggli, Wolf-Dieter Ludwig, Dirk Janssen, Hansjoerg Riehm, Martin Schrappe, Alfred Reiter
Journal: Journal of Clinical Oncology (2006)

In the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) 95 trial, we tested, against the historical control of the combined trials NHL-BFM90 and NHL-BFM86, whether prophylactic cranial radiotherapy (PCRT) can be omitted for CNS-negative patients with stage III or IV lymphoblastic lymphoma (LBL) with sufficient early response.Apart from the removal of PCRT in NHL-BFM95, the chemotherapy of the three trials was identical except for the amount of l-asparaginase and daunorubicin during induction. The therapy in NHL-BFM95 was accepted to be noninferior when compared with trials NHL-BFM90/86 if the lower limit of the one-sided 95% CI for the difference in the 2-year probability of event-free-survival (pEFS) between target patients of NHL-BFM95 and the historical controls of NHL-BFM90/86 did not exceed -14%. The target patient group consisted of stage III and IV patients who were CNS negative and responded well to induction therapy.The number of target patients was 156 in NHL-BFM95 (median age, 8.6 years; range, 0.2 to 19.5 years) and 163 in NHL-BFM90/86 (median age, 8.4 years; range, 0.6 to 16.6 years). For the target group, the pEFS rates at 2 and 5 years were 86% +/- 3% and 82% +/- 3%, respectively, in NHL-BFM95 (median follow-up time, 5.1 years; range, 2.1 to 9.1 years) compared with 91% +/- 2% and 88% +/- 3%, respectively in NHL-BFM90/86 (median follow-up time, 10.7 years; range, 5 to 15.4 years). The lower limit of the one-sided 95% CI for the difference in pEFS was -11% at 2 years and -13% at 5 years. In NHL-BFM95, one isolated and two combined CNS relapses occurred compared with one combined CNS relapse in NHL-BFM90/86. Five-year disease-free-survival rate was 88% +/- 3% in NHL-BFM95 compared with 91% +/- 2% in NHL-BFM90/86.For CNS-negative patients with stage III or IV LBL and sufficient response to induction therapy, treatment without PCRT may be noninferior to treatment including PCRT.
Applying Diabetes-Related Prevention Quality Indicators to a National Cohort of Veterans With Diabetes
Authors: Drew A. Helmer, Chin-Lin Tseng, Michael Brimacombe, Mangala Rajan, Nikolay Stiptzarov, Leonard Pogach
Journal: Diabetes Care (2003)

OBJECTIVE—The Prevention Quality Indicators (PQIs) are measures of hospitalizations that reflect quality of ambulatory care. We applied the PQIs of metabolic decompensation to Veterans Health Administration (VHA) utilizers with diabetes. We identified patient-level characteristics associated with hospitalization for metabolic decompensation, developed a risk-adjustment model for the measures, and compared regional network performance using these PQIs. RESEARCH DESIGN AND METHODS—This was a retrospective cohort study of 406,575 veterans with diabetes who used the VHA between 1997 and 1999. The outcomes were the PQIs of uncontrolled diabetes, short-term complications, or a combined measure. Patient-level variables were identified from administrative databases. Variation in performance of the networks was compared between full risk adjustment and age and sex adjustment only. RESULTS—In fiscal year 1999, there were 1,719 VHA discharges (4.2 per 1,000 cohort members) for uncontrolled and short-term complications of diabetes. A logistic regression model including age, sex, marital status, Charlson Comorbidity Index, mental health condition, insulin use, and oral antiglycemic medication use was developed for risk adjustment of the combined PQI. Full risk adjustment changed performance ranks of the networks using the combined PQI outcome relative to age and sex adjustment only. Ten networks remained in the same quartile of performance, five moved one quartile, and seven moved two or more quartiles. CONCLUSIONS—The PQIs of uncontrolled and short-term complications of diabetes are uncommon outcomes among veterans with diabetes and should be used only as a combined outcome. More complete risk adjustment should be used when comparing systems of care using the combined measure.
Improved Survival of Children With Isolated CNS Relapse of Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: A. Kim Ritchey, Brad H. Pollock, Stephen J. Lauer, Yvonne Andejeski, George R. Buchanan
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Isolated meningeal relapse in children with acute lymphoblastic leukemia (ALL) usually has been followed by bone marrow relapse and limited survival. The purpose of this study was to prevent marrow relapse by administering intensive therapy before delayed craniospinal radiation. PATIENTS AND METHODS: Eighty-three patients with ALL in first bone marrow remission with an isolated CNS relapse were treated with systemic chemotherapy known to enter into the CSF and intrathecal chemotherapy for 6 months. Craniospinal irradiation (24 Gy cranial/15 Gy spinal) was then administered, followed by 1.5 years of maintenance chemotherapy. RESULTS: All 83 patients achieved a second remission. The 4-year event-free survival (EFS) rate was 71.1% ± 5.3%. There was a fourfold increased risk of relapse for children whose initial remission was less than 18 months. The 4-year EFS rate for patients with a first complete remission ≥ 18 months was 83.3% ± 5.3%, and for those with a first complete remission less than 18 months, it was 46.2% ± 10.2% (P = .0002.) There was a low incidence of neurologic toxicity and an unexpectedly high rate of allergic reactions to l-asparaginase. Five patients developed secondary malignancies: two with acute nonlymphoblastic leukemia during therapy, one with myelodysplasia after therapy, and two with brain tumors 1.5 to 2 years after cessation of therapy. CONCLUSION: For children with ALL and an isolated CNS relapse, treatment that delays definitive craniospinal irradiation by 6 months to allow for more intensive systemic and intrathecal chemotherapy results in better EFS than has been previously reported. Using this approach, the long-term prognosis for children with first complete remission ≥ 18 months is comparable to that at the time of original diagnosis of ALL.
Enhancing the T-cell Stimulatory Capacity of Human Dendritic Cells by Co-electroporation With CD40L, CD70 and Constitutively Active TLR4 Encoding mRNA
Authors: Aude Bonehill, Sandra Tuyaerts, An MT Van Nuffel, Carlo Heirman, Tomas J Bos, Karel Fostier, Bart Neyns, Kris Thielemans
Journal: Molecular Therapy (2008)

The effectiveness of the dendritic cell (DC) vaccination protocols that are currently in use could be improved by providing the DCs with a more potent maturation signal. We therefore investigated whether the T-cell stimulatory capacity of human monocyte-derived DCs could be increased by co-electroporation with different combinations of CD40L, CD70, and constitutively active toll-like receptor 4 (caTLR4) encoding mRNA. We show that immature DCs electroporated with CD40L and/or caTLR4 mRNA, but not those electroporated with CD70 mRNA, acquire a mature phenotype along with an enhanced secretion of several cytokines/chemokines. Moreover, these DCs are very potent in inducing naive CD4(+) T cells to differentiate into interferon-gamma (IFN-gamma)-secreting type 1 T helper (Th1) cells. Further, we assessed the capacity of the electroporated DCs to activate naive HLA-A2-restricted MelanA-specific CD8(+) T cells without the addition of any exogenous cytokines. When all three molecules were combined, a >500-fold increase in MelanA-specific CD8(+) T cells was observed when compared with immature DCs, and a >200-fold increase when compared with cytokine cocktail-matured DCs. In correlation, we found a marked increase in cytolytic and IFN-gamma/tumor necrosis factor-alpha (TNF-alpha) secreting CD8(+) T cells. Our data indicate that immature DCs genetically modified to express stimulating molecules can induce tumor antigen-specific T cells in vitro and could prove to be a significant improvement over DCs matured with the methods currently in use.
Immune evasion in acute myeloid leukemia: current concepts and future directions
Authors: Ryan M Teague, Justin Kline
Journal: Journal for ImmunoTherapy of Cancer (2013)

Immune responses generated against malignant cells have the potential to inhibit tumor growth, or even eliminate transformed cells before a tumor forms. However, immune tolerance mechanisms that normally protect healthy tissues from autoimmune damage pose a formidable barrier to the development of effective anti-tumor immunity. Because malignant cells are derived from self-tissues, the majority of defined tumor antigens are either shared or aberrantly expressed self-proteins. Eliciting productive T cell responses against such proteins is challenging, as most high-affinity, self-reactive T cells are purged during thymic selection. Some T cells capable of tumor antigen recognition escape thymic deletion, but are functionally inhibited by peripheral tolerance mechanisms which limit their ability to attack a developing malignancy. Alternatively, some tumors express antigens derived from mutated self-proteins, viral proteins or self proteins expressed only during embryonic development. These antigens are recognized by the immune system as foreign and could be recognized by a relatively large number of peripheral T cells. Even in this scenario, tumors evade otherwise effective T cell responses by employing potent immunosuppressive mechanisms within their local environment. In the setting for solid malignancies, such as melanoma, a growing number of putative immune evasion mechanisms have been characterized. However, acute myeloid leukemia (AML) is a systemic disease, and the pathways it exploits to subvert the host immune response may be quite different than those of a solid tumor. Much remains unknown regarding the immune escape mechanisms promoted by AML, and whether efforts to thwart tolerance may influence the progression of this disease. Here, we review current concepts of immune evasion in AML, and speculate how potentially effective immunotherapeutic strategies might be developed to reverse immune tolerance in leukemia patients in the future.
Immunoregulatory role of maternal idiotypes. Ontogeny of immune networks.
Authors: M Wikler, C Demeur, G Dewasme, J Urbain
Journal: The Journal of Experimental Medicine (1980)

Specific idiotypie can be induced in randomly chosen rabbits by preimmunization with anti-idiotypic antibodies (Ab2). Rabbits that synthesize anti-anti-idiotypic antibodies (Ab3) when injected with antigen produce antibodies that display idiotypic specificities that are also found on the starting idiotype. When female rabbits actively producing Ab3 are crossed with naive males, a significant proportion of the offsprings (approximately 40%) produce antibodies that were idiotypically cross-reactive with the starting idiotype, as compared to 3% of the controls. This conclusion was obtained using 5 female rabbits and their 32 surviving offspring. Maternal idiotypes have therefore strong immunoregulatory properties and influence the emergence of the available idiotypic repertoire.
Diastolic Heart Failure — Abnormalities in Active Relaxation and Passive Stiffness of the Left Ventricle
Authors: Michael R. Zile, Catalin F. Baicu, William H. Gaasch
Journal: New England Journal of Medicine (2004)

Patients with signs and symptoms of heart failure and a normal left ventricular ejection fraction are said to have diastolic heart failure. It has traditionally been thought that the pathophysiological cause of heart failure in these patients is an abnormality in the diastolic properties of the left ventricle; however, this hypothesis remains largely unproven.We prospectively identified 47 patients who met the diagnostic criteria for definite diastolic heart failure; all the patients had signs and symptoms of heart failure, a normal ejection fraction, and an increased left ventricular end-diastolic pressure. Ten patients who had no evidence of cardiovascular disease served as controls. Left ventricular diastolic function was assessed by means of cardiac catheterization and echocardiography.The patients with diastolic heart failure had abnormal left ventricular relaxation and increased left ventricular chamber stiffness. The mean (+/-SD) time constant for the isovolumic-pressure decline (tau) was longer in the group with diastolic heart failure than in the control group (59+/-14 msec vs. 35+/-10 msec, P=0.01). The diastolic pressure-volume relation was shifted up and to the left in the patients with diastolic heart failure as compared with the controls. The corrected left ventricular passive-stiffness constant was significantly higher in the group with diastolic heart failure than in the control group (0.03+/-0.01 vs. 0.01+/-0.01, P<0.001).Patients with heart failure and a normal ejection fraction have significant abnormalities in active relaxation and passive stiffness. In these patients, the pathophysiological cause of elevated diastolic pressures and heart failure is abnormal diastolic function.
A Population-based Survey of the Prevalence and Types of Glaucoma in Nepal: The Bhaktapur Glaucoma Study
Authors: Suman S. Thapa, Indira Paudyal, Shankar Khanal, Shankha N. Twyana, Govinda Paudyal, Reeta Gurung, Sanduk Ruit, Ger H.M.B. van Rens
Journal: Ophthalmology (2012)
Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case–control studies
Authors: E.V. Kane, L. Bernstein, P.M. Bracci, J.R. Cerhan, L. Costas, L. Dal Maso, E.A. Holly, C. La Vecchia, K. Matsuo, S. Sanjose, J.J. Spinelli, S.S. Wang, Y. Zhang, T. Zheng, E. Roman, A. Kricker
Journal: Annals of Oncology (2012)
Dramatic diurnal variation in the concentration of the human trefoil peptide TFF2 in gastric juice
Authors: J I Semple, J L Newton, B R Westley, F E B May
Journal: Gut (2001)

BACKGROUND TFF2, a member of the trefoil factor family of proteins, is a glycosylated protein of 106 amino acids. It is secreted by gastric antral and pyloric glands and by Brunner's glands of the duodenum. TFF2 is found in high concentrations around sites of ulceration. It stimulates cell motility and is probably the principal cytoprotective trefoil peptide in the stomach. AIMS To determine if production of TFF2 follows a circadian rhythm and to measure changes in secretion of TFF2 in response to food intake and during sleep. SUBJECTS Young healthy adults were recruited. They were asymptomatic and were not receiving medication. The 24 hour regimen was designed to allow normal stimulation of gastric secretion in response to food intake and sleep. Gastric juice was collected two hourly via a nasogastric tube. METHODS Glycosylated and non-glycosylated TFF2 proteins were measured by quantitative western transfer analysis. The results were analysed statistically using SPSS software. RESULTS There was a dramatic diurnal variation in the concentration of TFF2. The mean concentration was lowest in the early evening (0.29 μg/ml), increased gradually during the evening, and then sharply during the night to reach 7.9 μg/ml. The ratio of glycosylated to non-glycosylated TFF2 varied and was higher during the night than in the afternoon. pH, total protein, and pepsin concentrations in gastric juice did not vary significantly over 24 hours. CONCLUSION The data suggest that diurnal variations in TFF2 secretion occur independently of pepsin and gastric acid secretion. The concentration of glycosylated TFF2 in the gastric lumen falls in response to food intake. TFF2 secretion increases during inactivity and sleep. These results suggest that secretion of TFF2 in the stomach is highest during the night and that the cytoprotective effects of TFF2 on the gastric mucosa occur mainly during sleep.
Maximizing Human Epidermal Growth Factor Receptor 2 Inhibition: A New Oncologic Paradigm in the Era of Targeted Therapy
Authors: Erin M. Olson
Journal: Journal of Clinical Oncology (2012)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2011.40.2545 Journal of Clinical Oncology - published online before print March 5, 2012 PMID: 22393085 Maximizing Human Epidermal Growth Factor Receptor 2 Inhibition: A New Oncologic Paradigm in the Era of Targeted Therapy Erin M. OlsonxErin M. OlsonSearch for articles by this author Show More The Ohio State University Comprehensive Cancer Center, Columbus, OH https://doi.org/10.1200/JCO.2011.40.2545 First Page Full Text PDF Figures and Tables © 2012 by American Society of Clinical Oncology