tbuckley/cabot-search huggingface dataset:
Normal CA-125 and the Risk of Progression in Ovarian Cancer
Authors: Maurie Markman
Journal: Journal of Clinical Oncology (2006)

answer to that question is no. 8In patients who reached only partial response after six cycles, does radiotherapy reverse the odds?No randomized study is available, and the results have been yes in the EORTC experience 8 and no in the German and French experiences. 5,6 Regarding chemotherapy, we remark that the LY09 study concurs to the demonstration, made since 1975, that ABVD provides results superior to those of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and its avatars. 9We agree that, in the Hasenclever model, freedom from progression would better be correlated to actual, rather than to intended doses.In the LY09 trial, as approximately all drugs were administered at greater than 80% of intended dose (Table 3), the correlation between actual or intended dosing is probably close and could be checked.Finally, Johnson et al produced extremely valuable data, particularly on individual drug doses, with thorough analyzes.These data will contribute to designing improved trials where chemotherapy and radiation will be balanced according to the respective parts they take to cure Hodgkin's lymphoma in each different setting.
Preoperative β-Blocker Use and Mortality and Morbidity Following CABG Surgery in North America
Authors: T. Bruce Ferguson, Laura P. Coombs, Eric D. Peterson
Journal: JAMA (2002)

Context ␤-Blockade therapy has recently been shown to convey a survival benefit in preoperative noncardiac vascular surgical settings.The effect of preoperative ␤-blocker therapy on coronary artery bypass graft surgery (CABG) outcomes has not been assessed. ObjectivesTo examine patterns of use of preoperative ␤-blockers in patients undergoing isolated CABG and to determine whether use of ␤-blockers is associated with lower operative mortality and morbidity.Design, Setting, and Patients Observational study using the Society of Thoracic Surgeons National Adult Cardiac Surgery Database (NCD) to assess ␤-blocker use and outcomes among 629877 patients undergoing isolated CABG between 1996 and 1999 at 497 US and Canadian sites.Main Outcome Measure Influence of ␤-blockers on operative mortality, examined using both direct risk adjustment and a matched-pairs analysis based on propensity for preoperative ␤-blocker therapy. ResultsFrom 1996 to 1999, overall use of preoperative ␤-blockers increased from 50% to 60% in the NCD (PϽ.001 for time trend).Major predictors of use included recent myocardial infarction; hypertension; worse angina; younger age; better left ventricular systolic function; and absence of congestive heart failure, chronic lung disease, and diabetes.Patients who received ␤-blockers had lower mortality than those who did not (unadjusted 30-day mortality, 2.8% vs 3.4%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.78-0.82).Preoperative ␤-blocker use remained associated with slightly lower mortality after adjusting for patient risk and center effects using both risk adjustment (OR, 0.94; 95% CI, 0.91-0.97)and treatment propensity matching (OR, 0.97; 95% CI, 0.93-1.00).Procedural complications also tended to be lower among treated patients.This treatment advantage was seen among the majority of patient subgroups, including women; elderly persons; and those with chronic lung disease, diabetes, or moderately depressed ventricular function.Among patients with a left ventricular ejection fraction of less than 30%, however, preoperative ␤-blocker therapy was associated with a trend toward a higher mortality rate (OR, 1.13; 95% CI, 0.96-1.33;P=.23). ConclusionsIn this large North American observational analysis, preoperative ␤-blocker therapy was associated with a small but consistent survival benefit for patients undergoing CABG, except among patients with a left ventricular ejection fraction of less than 30%.This analysis further suggests that preoperative ␤-blocker therapy may be a useful process measure for CABG quality improvement assessment.
TOWARD AN UNDERSTANDING OF NKT CELL BIOLOGY: Progress and Paradoxes
Authors: Mitchell Kronenberg
Journal: Annual Review of Immunology (2005)

▪ Abstract Natural killer T (NKT) cells constitute a conserved T cell sublineage with unique properties, including reactivity for a synthetic glycolipid presented by CD1d, expression of an invariant T cell antigen receptor (TCR) α chain, and unusual requirements for thymic selection. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes. Because of intensive research effort, we have learned much about factors promoting the development and survival of NKT cells, regulation of their cytokine production, and the means by which they influence dendritic cells and other cell types. Despite this progress, knowledge of the natural antigen(s) they recognize and their physiologic role remain incomplete. The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and we cannot predict which will occur. Despite this uncertainty, many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
Changes in Regional Cerebral Blood Flow Elicited by Craving Memories in Abstinent Opiate-Dependent Subjects
Authors: Mark R.C. Daglish, Aviv Weinstein, Andrea L. Malizia, Susan Wilson, Jan K. Melichar, Simon Britten, Colin Brewer, Anne Lingford-Hughes, Judith S. Myles, Paul Grasby, David J. Nutt
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The brain circuitry of opiate craving was investigated with positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF). METHOD: Twelve abstinent opiate-dependent subjects listened to audiotaped autobiographical scripts of an episode of craving and a neutral episode while undergoing a PET scan with the tracer [15O]H2O. Statistical parametric mapping was used to analyze the PET images of rCBF changes. RESULTS: Comparison of the drug-related and neutral stimulus conditions revealed activation of rCBF in the left medial prefrontal and left anterior cingulate cortices and deactivation in the occipital cortex in response to the drug-related stimulus. A further statistical parametric mapping analysis with a subjective rating of craving as a covariate showed a positive association of between craving and rCBF in the left orbitofrontal cortex. CONCLUSIONS: The patterns of cerebral activation reflect the different brain regions mediating the salience of opiate-related stimuli and the subjective experience of craving for opiates.
Monitoring Primary Systemic Therapy of Large and Locally Advanced Breast Cancer by Using Sequential Positron Emission Tomography Imaging With [<sup>18</sup>F]Fluorodeoxyglucose
Authors: Jörg Schwarz-Dose, Michael Untch, Reinhold Tiling, Stefanie Sassen, Sven Mahner, Steffen Kahlert, Nadia Harbeck, Annette Lebeau, Winfried Brenner, Markus Schwaiger, Fritz Jaenicke, Norbert Avril
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate positron emission tomography (PET) using [ 18 F]fluorodeoxyglucose (FDG) for prediction of histopathologic response early during primary systemic therapy of large or locally advanced breast cancer. Patients and Methods In a prospective multicenter trial, 272 FDG-PET scans were performed in 104 patients at baseline (n = 104) and after the first (n = 87) and second cycle (n = 81) of chemotherapy. The level and relative changes in standardized uptake value (SUV) of FDG uptake were assessed regarding their ability to predict histopathologic response. All patients underwent surgery after chemotherapy, and histopathologic response defined as minimal residual disease or gross residual disease served as the reference standard. Results Seventeen (16%) of 104 patients were histopathologic responders and 87 were (84%) nonresponders. All patients for whom baseline SUV was less than 3.0 (n = 24) did not achieve a histopathologic response. SUV decreased by 51% ± 18% after the first cycle of chemotherapy in histopathologic responders (n = 15), compared with 37% ± 21% in nonresponders (n = 54; P = .01). A threshold of 45% decrease in SUV correctly identified 11 of 15 responders, and histopathologic nonresponders were identified with a negative predictive value of 90%. Similar results were found after the second cycle when using a threshold of 55% relative decrease in SUV. Conclusion FDG-PET allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after each cycle of chemotherapy. Moreover, relative changes in SUV after the first and second cycle are a strong predictor of response. Thus, FDG-PET may be helpful for individual treatment stratification in breast cancer patients.
Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients
Authors: Wilma Barcellini, Bruno Fattizzo, Anna Zaninoni, Tommaso Radice, Ilaria Nichele, Eros Di Bona, Monia Lunghi, Cristina Tassinari, Fiorella Alfinito, Antonella Ferrari, Anna Paola Leporace, Pasquale Niscola, Monica Carpenedo, Carla Boschetti, Nicoletta Revelli, Maria Antonietta Villa, Dario Consonni, Laura Scaramucci, Paolo De Fabritiis, Giuseppe Tagariello, Gianluca Gaidano, Francesco Rodeghiero, Agostino Cortelezzi, Alberto Zanella
Journal: Blood (2014)
Immunosuppression minimization vs. complete drug withdrawal in liver transplantation
Authors: Maria-Carlota Londoño, Antoni Rimola, John O’Grady, Alberto Sanchez-Fueyo
Journal: Journal of Hepatology (2013)

Despite the increase in long-term survival, liver transplant recipients still exhibit higher morbidity and mortality than the general population. This is in part attributed to the lifelong administration of immunosuppression and its associated side effects. Several studies reported in the last decades have evaluated the impact of immunosuppression minimization in liver transplant recipients, but results have been inconsistent due to the heterogeneity of study designs and insufficient sample sizes. On the other hand, complete immunosuppression withdrawal has proven to be feasible in approximately 20% of carefully selected liver transplant recipients, especially in older patients and those with longer duration after transplantation. The long-term risks and clinical benefits of this strategy, however, also need to be clarified. As a consequence, and despite the general perception that a large proportion of liver recipients are over-immunosuppressed, it is currently not possible to derive evidence-based guidelines on how to manage long-term immunosuppression to improve clinical outcomes. Large clinical trials of drug minimization and/or withdrawal focused on clinically-relevant long-term outcomes are required. Development of personalized medicine tools and a deeper understanding of the pathogenesis of idiopathic inflammatory graft lesions will be pre-requisites to achieve these goals.
Modulation of conductive elements by Pitx2 and their impact on atrial arrhythmogenesis
Authors: D. Franco, A. Chinchilla, H. Daimi, J. N. Dominguez, A. Aranega
Journal: Cardiovascular Research (2011)

The development of the heart is a complex process during which different cell types progressively contribute to shape a four-chambered pumping organ. Over the last decades, our understanding of the specification and transcriptional regulation of cardiac development has been greatly augmented as has our understanding of the functional bases of cardiac electrophysiology during embryogenesis. The nascent heart gradually acquires distinct cellular and functional characteristics, such as the formation of contractile structures, the development of conductive capabilities, and soon thereafter the co-ordinated conduction of the electrical impulse, in order to fulfil its functional properties. Over the last decade, we have learnt about the consequences of impairing cardiac morphogenesis, which in many cases leads to congenital heart defects; however, we are not yet aware of the consequences of impairing electrical function during cardiogenesis. The most prevalent cardiac arrhythmia is atrial fibrillation (AF), although its genetic aetiology remains rather elusive. Recent genome-wide association studies have identified several genetic variants highly associated with AF. Among them are genetic variants located on chromosome 4q25 adjacent to PITX2, a transcription factor known to play a critical role in left–right asymmetry and cardiogenesis. Here, we review new insights into the cellular and molecular links between PITX2 and AF.
The Trichoplax PaxB Gene: A Putative Proto-PaxA/B/C Gene Predating the Origin of Nerve and Sensory Cells
Authors: Thorsten Hadrys, Rob DeSalle, Sven Sagasser, Nina Fischer, Bernd Schierwater
Journal: Molecular Biology and Evolution (2005)

Pax genes play key regulatory roles in embryonic and sensory organ development in metazoans but their evolution and ancestral functions remain widely unresolved. We have isolated a Pax gene from Placozoa, beside Porifera the only metazoan phylum that completely lacks nerve and sensory cells or organs. These simplest known metazoans also lack any kind of symmetry, organs, extracellular matrix, basal lamina, muscle cells, and main body axis. The isolated Pax gene from Trichoplax adhaerens harbors a paired domain, an octapeptide, and a full-length homeodomain. It displays structural features not only of PaxB and Pax2/5/8-like genes but also of PaxC and Pax6 genes. Conserved splice sites between Placozoa, Cnidaria, and triploblasts, mark the ancient origin of intron structures. Phylogenetic analyses demonstrate that the Trichoplax PaxB gene, TriPaxB, is basal not only to all other known PaxB genes but also to PaxA and PaxC genes and their relatives in triploblasts (namely Pax2/5/8, Pax4/6, and Poxneuro). TriPaxB is expressed in distinct cell patches near the outer edge of the animal body, where undifferentiated and possibly multipotent cells are found. This expression pattern indicates a developmental role in cell-type specification and/or differentiation, probably in specifying-determining fiber cells, which are regarded as proto-neural/muscle cells in Trichoplax. While PaxB, Pax2/5/8, and Pax6 genes have been linked to nerve cell and sensory system/organ development in virtually all animals investigated so far, our study suggests that Pax genes predate the origin of nerve and sensory cells.
Evolution and Diversification of the CYC/TB1 Gene Family in Asteraceae--A Comparative Study in Gerbera (Mutisieae) and Sunflower (Heliantheae)
Authors: S. Tahtiharju, A. S. Rijpkema, A. Vetterli, V. A. Albert, T. H. Teeri, P. Elomaa
Journal: Molecular Biology and Evolution (2011)

Plant-specific TCP domain transcription factors have been shown to regulate morphological novelties during plant evolution, including the complex architecture of the Asteraceae inflorescence that involves different types of flowers. We conducted comparative analysis of the CYCLOIDEA/TEOSINTE BRANCHED1 (CYC/TB1) gene family in Gerbera hybrida (gerbera) and Helianthus annuus (sunflower), two species that represent distant tribes within Asteraceae. Our data confirm that the CYC/TB1 gene family has expanded in Asteraceae, a condition that appears to be connected with the increased developmental complexity and evolutionary success of this large plant family. Phylogenetic analysis of the CYC/TB1 gene family revealed both shared and lineage-specific duplications in gerbera and sunflower, corresponding to the three gene lineages previously identified as specific to core eudicots: CYC1, CYC2, and CYC3. Expression analyses of early stages of flower primordia development indicated that especially within the CYC2 clade, with the greatest number of secondary gene duplications, gene expression patterns are conserved between the species and associated with flower and inflorescence development. All sunflower and gerbera CYC2 clade genes showed differential expression between developing flower types, being upregulated in marginal ray (and trans) flowers. One gene in gerbera (GhCYC3) and two in sunflower (HaCYC2d and HaCYC2c) were indicated to be strong candidates as regulators of ray flower identity, a function that is specific for Asteraceae. Our data further showed that other CYC2 clade genes are likely to have more specialized functions at the level of single flowers, including the late functions in floral reproductive organs that may be more conserved across plant families. The expression patterns of CYC1 and CYC3 clade genes showed more differences between the two species but still pointed to possible conserved functions during vegetative plant development. Pairwise protein–protein interaction assays gave the first molecular evidence that CYC/TB1-like proteins function in complexes. Compared with sunflower, the gerbera proteins showed higher capacity for dimerization, between as well as within CYC clades. Our data from two distant species within the Asteraceae suggest that the expansion and the apparent conservation of especially the CYC2 clade CYC/TB1-like genes are associated with the evolution of the increased complexity of the Asteraceae inflorescence architecture.
Blue limbs (the importance of history and examination)
Authors: Oana Predescu
Journal: BMJ (2004)

I have come across an unusual hospital presentation of “blue limbs” three times in my years of practice, though the incidence in the population is likely to be high.

As a surgical house officer, I encountered the condition twice within a couple of weeks. On the first occasion I was covering the wards when I was bleeped regarding a patient who had developed blue hands. A rare problem, I thought, and a number of possible medical and severe scenarios ran through my head. As I approached the ward, I expected to find a case of either Raynaud's syndrome or a rather ill patient, perhaps cyanosed or with superior vena cava …
Comparison of Glycemic and Metabolic Control in Youth With Type 1 Diabetes With and Without Antipsychotic Medication: Analysis From the Nationwide German/Austrian Diabetes Survey (DPV)
Authors: Angela Galler, Esther Bollow, Michael Meusers, Bela Bartus, Andrea Näke, Holger Haberland, Edith Schober, Reinhard W. Holl
Journal: Diabetes Care (2015)

OBJECTIVE The objective of this study was to explore metabolic risk factors and glycemic control in youth with type 1 diabetes treated with typical or atypical antipsychotics. RESEARCH DESIGN AND METHODS Data for 60,162 subjects with type 1 diabetes up to the age of 25 years registered in the nationwide German/Austrian Diabetes Survey were included in the analysis. BMI; HbA1c; treatment strategy; prevalence of hypertension, dyslipidemia, microalbuminuria, and retinopathy; frequency of hypoglycemia and diabetic ketoacidosis (DKA); and immigrant status among subjects treated with typical or atypical antipsychotics were compared with those without antipsychotic medication and analyzed by regression analysis. RESULTS A total of 291 subjects with type 1 diabetes (median diabetes duration 7.2 years) received antipsychotic medications (most commonly risperidone). Subjects treated with antipsychotics had a higher BMI (P = 0.004) and dyslipidemia was more frequent (P = 0.045) compared with subjects not receiving antipsychotic medication. Frequencies of severe hypoglycemia and DKA were significantly higher in subjects receiving antipsychotics (P &amp;lt; 0.001). The prevalences of hypertension, microalbuminuria, and retinopathy were not different. In subjects treated with typical antipsychotics, glycemic control did not differ compared with those who did not receive antipsychotic medications. By contrast, subjects treated with atypical antipsychotics had higher HbA1c levels (P = 0.022). CONCLUSIONS This analysis from a real-life survey demonstrated that subjects with antipsychotic medication had worse glycemic control and a higher rate of acute complications compared with those without antipsychotic medication. Health care teams caring for youth with type 1 diabetes taking antipsychotic medication need to know about these findings. We suggest monitoring metabolic risk factors as well as providing diabetes education about prevention of acute complications.
Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen γ′ levels
Authors: Shirley Uitte de Willige, Marieke C. H. de Visser, Jeanine J. Houwing-Duistermaat, Frits R. Rosendaal, Hans L. Vos, Rogier M. Bertina
Journal: Blood (2005)
Enhancement of Heterotransplanted Human Tumor Graft Survival in Nude Mice Treated With Antilymphocyte Serum and in Congenitally Athymic-Asplenic (lasat) Mice2
Authors: M. Eric Gershwin, Richard M. Ikeda, Kent Erickson, Robert Owens
Journal: JNCI Journal of the National Cancer Institute (1978)

The latency period, success rate, and minimal cell inoculum size required for transplantation of continuously passaged human tumor lines into congenitally athymic (nude) mice, antilymphocyte serum (ALS)-treated congenitally athymic (nude) mice, and congenitally athymic-asplenic (lasat) mice were compared. The 11 tumor lines studied included examples of breast adenocarcinoma, transitional cell carcinoma, osteosarcoma, fibrosarcoma, Hodgkin's disease, malignant melanoma, and rhabdomyosarcoma. Of these 11 tumor lines, 3 were successfully transplanted into nude mice, compared to 5 of 10 tumor lines in ALS-treated nude mice and 9 of 11 lines in lasat mice. Moreover, the latency period was shorter and the minimal cell inoculum size was lower for lasat mice than for either nude or ALS-treated nude mice. Despite this enhancement of heterotransplantation into lasat mice and despite the growth of large local masses, no evidence of distant metastases was found.
Nontypeable <i>Haemophilus influenzae</i> in the Lower Respiratory Tract of Patients with Chronic Bronchitis
Authors: VENKATA BANDI, MICHAEL A. APICELLA, EDWARD MASON, TIMOTHY F. MURPHY, ATHER SIDDIQI, ROBERT L. ATMAR, STEPHEN B. GREENBERG
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The frequency of colonization and intracellular localization of nontypeable Haemophilus influenzae (NTHi) in the lower respiratory tract was determined in healthy adults and in clinically stable and acutely ill chronic bronchitis (CB) patients. NTHi was recovered from bronchial wash or bronchial brush specimens in 6 of 23 (26%) stable CB patients and in 1 of 15 (7%) CB patients with a respiratory exacerbation. No NTHi (0 of 26) was recovered from lower tract specimens of healthy adults undergoing anesthesia for elective surgery. Molecular typing of NTHi strains revealed that five of nine patients with stable CB had different strains in upper respiratory tract and bronchial wash/brush specimens collected simultaneously. Four stable patients with CB had different strains recovered on repeat bronchoscopy. These results demonstrate the frequent colonization of the lower airways of stable CB patients with multiple strains of NTHi. Bronchial biopsies also were examined for intracellular NTHi by in situ hybridization and immunofluorescence microscopy. Intracellular NTHi were found in 0 of 7 healthy adults, 8 of 24 patients with clinically stable CB, and 13 of 15 acutely ill CB patients. This observation suggests a role for intracellular infection by NTHi in the pathogenesis of exacerbations of CB.