tbuckley/cabot-search huggingface dataset:
Response to [90Yttrium-DOTA]-TOC Treatment is Associated with Long-term Survival Benefit in Metastasized Medullary Thyroid Cancer: A Phase II Clinical Trial
Authors: Fabienne Iten, Beat Müller, Christian Schindler, Christoph Rochlitz, Daniel Oertli, Helmut R. Mäcke, Jan Müller-Brand, Martin A. Walter
Journal: Clinical Cancer Research (2007)

We aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N-'''-tetraacetic acid ((90)Y-DOTA)-Tyr(3)-octreotide (TOC) therapy in advanced medullary thyroid cancer.In a phase II trial, we investigated the response, survival, and long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized medullary thyroid cancer. Adverse events were assessed according to the criteria of the National Cancer Institute. Survival analyses were done using multiple regression models.Thirty-one patients were enrolled. A median cumulative activity of 12.6 GBq (range, 1.7-29.6 GBq) of [(90)Y-DOTA]-TOC was administered. Response was found in nine patients (29.0%). Four patients (12.9%) developed hematologic toxicities and seven patients (22.6%) developed renal toxicities. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio, 0.20; 95% confidence interval, 0.05-0.81; P = 0.02) and from time of first [(90)Y-DOTA]-TOC therapy (hazard ratio, 0.16; 95% confidence interval, 0.04-0.63; P = 0.009). The visual grade of scintigraphic tumor uptake was not associated with treatment response or survival.Response to [(90)Y-DOTA]-TOC therapy in metastasized medullary thyroid cancer is associated with a long-term survival benefit. Treatment should be considered independently from the result of the pretherapeutic scintigraphy.
Treatment of Multidrug-Resistant Tuberculosis
Authors: Alastair J.J. Wood, Michael D. Iseman
Journal: New England Journal of Medicine (1993)

The era of modern, predictably effective tuberculosis chemotherapy began in 1952. Since then, strains of Mycobacterium tuberculosis have acquired resistance to various drugs, thus compromising both treatment and control programs. Most ominously, the rising prevalence of multidrug-resistant strains (defined here as M. tuberculosis resistant to isoniazid and rifampin, with or without resistance to other drugs) has resulted in many cases of marginally treatable, often fatal, disease. The care of patients with documented multidrug-resistant tuberculosis will be the focus of this report. I shall also examine briefly the origins, biologic mechanisms, and epidemiology of drug resistance, its impact on the outcome . . .
Use of risk adjustment in setting budgets and measuring performance in primary care II: advantages, disadvantages, and practicalities
Authors: A. Majeed, A. B Bindman, J. P Weiner
Journal: BMJ (2001)

Risk adjustment could help to improve decisions about budgets as well as help measure the performance of doctors. In the first of these two articles we discussed why risk adjustment could become more important in the United Kingdom and how it works in the United States.1 In this article we consider the benefits and problems of risk adjustment and assess how one US system would perform in the United Kingdom. #### Summary points Use of risk adjustment in the United Kingdom could help ensure that general practices and primary care trusts are not penalised for taking on patients with complex health needs Risk adjustment methods may also help ensure that computerised clinical records in primary care are complete and accurate Risk adjustment could add to the administrative complexity of healthcare systems It may draw attention away from the overall level of healthcare spending There is no gold standard method of risk adjustment Use of risk adjustment in setting budgets and monitoring performance should be explored further In the United States, risk adjustment is starting to be used to adjust capitation or other types of payments to healthcare providers such as family practices, multispecialty medical groups, or consortiums of physicians and hospitals (integrated delivery systems).2 For large populations (such as that of a broad geographical area), age, sex, and ecological measures may be adequate for this purpose. But for smaller populations, such as those managed by one family practice or a small consortium of physicians, risk adjustment helps ensure that providers who manage patients with more complex medical problems have their budgets adjusted to take this into account (box). The use of risk adjustment systems has also given doctors and health maintenance organisations a powerful incentive to provide more accurate and complete diagnostic data.1 #### Potential advantages of risk adjustment
Rapamycin Prevents Early Onset of Tumorigenesis in an Oral-Specific K-<i>ras</i> and <i>p53</i> Two-Hit Carcinogenesis Model
Authors: Ana R. Raimondi, Alfredo Molinolo, J. Silvio Gutkind
Journal: Cancer Research (2009)

Abstract Head and neck squamous cell carcinomas (HNSCC), the majority of which occur in the oral cavity, remain a significant cause of morbidity and mortality worldwide. A major limitation in HNSCC research has been the paucity of animal models to test the validity of current genetic paradigms of tumorigenesis and to explore the effectiveness of new treatment modalities and chemopreventive strategies. Here, we have developed an inducible oral-specific animal tumor model system, which consists in the expression of a tamoxifen-inducible Cre recombinase (CreERtam) under the control of the cytokeratin 14 (K14) promoter (K14-CreERtam) and mice in which the endogenous K-ras locus is targeted (LSL-K-rasG12D), thereby causing the expression of endogenous levels of oncogenic K-rasG12D following removal of a stop element. Surprisingly, whereas K14-CreERtam can also target the skin, K14-CreERtam/LSL-K-rasG12D mice developed papillomas exclusively in the oral mucosa within 1 month after tamoxifen treatment. These lesions were highly proliferative but never progressed to carcinoma. However, when crossed with p53 conditional knockout (p53flox/flox) mice, mice developed SCCs exclusively on the tongue as early as 2 weeks after tamoxifen induction, concomitant with a remarkable activation of the mammalian target of rapamycin (mTOR) signaling pathway. The availability of this ras and p53 two-hit animal model system recapitulating HNSCC progression may provide a suitable platform for exploring novel molecular targeted approaches for the treatment of this devastating disease. Indeed, we show here that mTOR inhibition by the use of rapamycin is sufficient to halt tumor progression in this genetically defined oral cancer model system, thereby prolonging animal survival. [Cancer Res 2009;69(10):4159–66]
Ischaemic colitis associated with JAK2<sup>V617F</sup>mutation: Table 1
Authors: J Barbieri, H Duboc, F Teillet, J M Sabate, E Peynaud, P Jouet, B Coffin
Journal: Gut (2011)

<h3></h3> Tumor immunosurveillance plays a crucial role in cancer prevention. Transplant recipients have a 3 to 4 times higher risk of developing skin cancer than the general population, often with multiple aggressive tumors, even in sun-protected areas. They also show a reversal of the ratio of squamous to basal cell carcinomas seen in the general population, from 1:4 to 4:1. Long-term immunosuppressive therapy likely plays a major role in making transplant recipients more susceptible to developing tumors. We reasoned that immune cell numbers might be different in transplant vs nontransplant patients with skin cancer. We examined frequencies of adaptive and innate immune cells in lesions of cutaneous squamous cell carcinoma (SCC) from both patient populations and detected no differences. We therefore hypothesized that the function of innate immune cells might be compromised in transplant recipients, leading to impaired tumor immunosurveillance. We designed an in vitro model to investigate functional differences between macrophages (MACs) and dendritic cells (DCs) in response to SCC. Tumor cells induced release of both interleukin-12 (IL-12) and tumor necrosis factor (TNF)-α from innate immune cells, although IL-12 production was higher in DCs than in MACs. Conversely, TNF-α production was higher in MACs than in DCs. Vascular endothelial growth factor (VEGF), a potent angiogenic factor and an immunosuppressive cytokine, was produced spontaneously and abundantly by tumor cells. DCs exposed to SCC inhibited VEGF production by ≈ 35%, whereas MACs had little effect (only 8.6% decrease). Angiogenesis and immunosuppression are the main mechanisms by which tumors grow and metastasize. Therefore, DCs may play a critical role in anti-tumor immunity by releasing IL-12 and inhibiting VEGF expression by tumor cells, while TNF-α production by MACs may increase VEGF, promoting tumor neovascularization and growth. It is possible that immunosuppressive therapy in transplant patients may impair the immunosurveillance function of DCs and other innate immune cells.
High resolution manometry during a standardised test meal and free drinking
Authors: R. Sweis, A. Anggiansah, T. Wong, M. Fox
Journal: Gut (2011)

<h3>Introduction</h3> Published reference values for oesophageal High Resolution Manometry (HRM) are available only for 5 ml water swallows in the supine position; however this is not representative of normal behaviour and rarely triggers symptoms. Analysis during and after eating a solid meal or drinking larger volumes is likely to increase the sensitivity of manometric studies to symptomatic oesophageal dysmotility and dysfunction. However this increases the complexity of pressure activity and, if it is to be applied in clinical practice, normal values for oesophageal motility and function are required. <h3>Methods</h3> 10 healthy volunteers (6M:4F, age 20–45) underwent HRM (Manoscan 360, SSI; 36 sensors). After baseline measurements of the oesophago-gastric junction (OGJ) and standard 5 ml water swallows, volunteers were observed eating a test meal (cheese and onion pie; 500 Kcal, 34 g fat) followed by drinking a 200 ml fruit-smoothie (9/10 subjects) and for 10 min afterwards. Physiologic measurements from HRM topographic plots focused on parameters that predict the success of solid bolus transport. <h3>Results</h3> No subject had hiatus hernia or primary oesophageal dysmotility. All completed liquid swallows and standard meal (consumption time median 6:15 min (range 3:30–13:30 min)). A mean of 1.5 pharyngeal swallows (range 1–3) was required to propel each mouthful into the oesophagus. 20 swallows (range 13–34) were required to ingest the meal of which 89% were successful, 3% were simultaneous (focal spasm) and 5% failed. The median (IQR) for intrabolus pressure (IBP) increased from 8.9 (6.7–13.8) mm Hg for 5 ml water to 18.9 (16.8–24.0) mm Hg for solid meal swallows (p&lt;0.001). Normal values for key parameters are presented in the table 1. A mean of 20 swallows (range 13–34) was required to drink the smoothie. Complete suppression of oesophageal contractility was achieved in 7/9 subjects. A powerful postcontraction was observed in 8/9 subjects. Apart from postprandial belching, no volunteer reported symptoms during or after the study. <h3>Conclusion</h3> Peristaltic coordination and pressure increased in response to resistance to bolus passage (raised IBP) with solid compared to liquid swallows. Complete oesophageal relaxation and LOS opening was observed on free drinking. Reference values for future studies are presented to assess the clinical utility of including a standardised meal and free drinking in HRM investigation of patients with oesophageal symptoms.
Sequential administration of temozolomide and fotemustine: Depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours
Authors: M. Gander, S. Leyvraz, L. Decosterd, M. Bonfanti, C. Marzolini, F. Shen, D. Liénard, L. Perey, G. Colella, J. Biollaz, F. Lejeune, D. Yarosh, M. Belanich, M. D'Incalci
Journal: Annals of Oncology (1999)
Codon Volatility As an Indicator of Positive Selection: Data from Eukaryotic Genome Comparisons
Authors: Robert Friedman, Austin L. Hughes
Journal: Molecular Biology and Evolution (2004)

It has been suggested that codon volatility (the proportion of the point-mutation neighbors of a codon that encode different amino acids) can be used as an index of past positive selection. We compared codon volatility with patterns of synonymous and nonsynonymous nucleotide substitution in genome-wide comparisons of orthologous genes between three pairs of related genomes: (1) the protists Plasmodium falciparum and P. yoelii, (2) the fungi Saccharomyces cerevisiae and S. paradoxus, and (3) the mammals mouse and rat. Codon volatility was not consistently associated with an elevated rate of nonsynonymous substitution, as would be expected under positive selection. Rather, the most consistent and powerful correlate of elevated codon volatility was nucleotide content at the second codon position, as expected, given the nature of the genetic code.
LSC 2013 abstract - Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and COPD
Authors: Ken Bracke, Fien Verhamme, Mootoosamy Cunoosamy, Ronald Herbst, Hamida Hammad, Bart Lambrecht, Guy Joos, Guy Brusselle
Journal: European Respiratory Journal (2013)

Rationale: The B-cell attracting chemokine CXCL13 is an important mediator in the formation of tertiary lymphoid organs (TLOs). Increased numbers of ectopic lymphoid follicles have been observed in lungs of patients with severe COPD. However, the role of these TLOs in the pathogenesis of COPD remains unknown.

Objectives: By neutralizing CXCL13 in a mouse model of chronic cigarette smoke (CS)-exposure, we aimed at interrogating the link between lymphoid follicles and development of pulmonary inflammation, emphysema and airway wall remodelling.

Methods: We first quantified and localized CXCL13 in lungs of air- or CS-exposed mice and in lungs of never smokers, smokers without airflow obstruction and patients with COPD by RT-PCR, ELISA and immunohistochemistry. Next, CXCL13 signaling was blocked by prophylactic or therapeutic administration of anti-CXCL13 antibodies in mice exposed to air or CS for 24 weeks (chronic exposure) and several hallmarks of COPD were evaluated. Results: Both mRNA and protein levels of CXCL13 were increased in lungs of CS-exposed mice and patients with COPD. Importantly, expression of CXCL13 was observed in CD20+ B-lymphocytes within lymphoid follicles. Prophylactic and therapeutic administration of anti-CXCL13 antibodies completely prevented the CS-induced formation of pulmonary lymphoid follicles in mice. Interestingly, absence of these TLOs attenuated inflammation in bronchoalveolar lavage, but did not influence the development of emphysema and airway wall remodelling.

Conclusion: CXCL13 is produced by B-lymphocytes within lymphoid follicles of patients with COPD and is crucial for the formation of TLOs and for inflammatory responses in bronchoalveolar lavage of CS-exposed mice.
Gastric bypass surgery in NASH: a major modulator of hepatic mitochondrial dysfunction
Authors: Floriane Baraille, Sandra Guilmeau, Catherine Postic
Journal: Gut (2014)

Non-alcoholic fatty liver disease (NAFLD), the hepatic counterpart of metabolic syndrome, has gained increasing recognition worldwide as a component of the obesity and type 2 diabetes pandemic. The spectrum of NAFLD ranges from simple fatty liver with benign prognosis, to non-alcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis, thereby increasing morbidity and mortality. According to the traditional view, hepatic fat accumulation represents the prerequisite for hepatocyte injury to develop, whereas cytokines, adipokines, bacterial endotoxin, mitochondrial dysfunction and/or endoplasmic reticulum stress are described as aggravating factors involved in NASH progression. It is believed that approximately 1%–5% of the Western population exhibit NASH. However, no therapeutic approaches are currently effective in slowing or reversing NASH, and the most promising treatments remain weight loss and exercise. Generating rodent models for preclinical investigations on NASH has been quite challenging over the past years for several laboratories.1–3 The current study of Verbeek et al ,4 elegantly validates the long-term use of a high-fat high-sucrose diet (HF-HSD: 40% of saturated fat and 45% of sucrose), also known as Western diet, as a relevant NASH mouse model. Indeed, 12 weeks of HF-HSD diet feeding triggers obesity and insulin resistance in mice, and also leads to liver steatosis accompanied with all clinical features of NASH, namely inflammation, fibrosis, oxidative stress and mitochondrial dysfunction (figure …
Brain allometry: Correlated variation in cytoarchitectonics and neurochemistry?
Authors: Walter Wilczynski
Journal: Behavioral and Brain Sciences (2001)

Brains vary in characters other than size. We should consider whether Finlay et al.'s argument, that developmental shifts responding to selection for change in one area yield correlated changes across the brain, must be extended from size differences to other neural characters responsible for the circuitry or physiological differences distinguishing vertebrate brains.
Estimates of familial risks from family data are biased when ascertainment of families is not independent of family history
Authors: A. K. Win, J. L. Hopper, M. A. Jenkins
Journal: Gut (2010)

In estimating familial risks from family data one must be careful that ascertainment of families does not depend on family history, otherwise the estimates might not be applicable even to the setting from which the families were ascertained. In this regard, Boparai et al 1 reported the largest study to date examining the risk of colorectal cancer (CRC) and hyperplastic polyposis syndrome (HPS) for first-degree relatives (FDRs) of HPS patients. They found that the FDRs of the studied HPS patients had five times the incidence of CRC (relative risk, RR=5.4; 95% CI 3.7 to 7.8), and 39 times the incidence of HPS (RR=39; 95% CI 13 to 121) compared to people from the general population. They interpreted the RR estimates as applying to relatives of …
Coevolution of neocortical size, group size and language in humans
Authors: R. I. M. Dunbar
Journal: Behavioral and Brain Sciences (1993)

Abstract Group size covaries with relative neocortical volume in nonhuman primates. This regression equation predicts a group size for modern humans very similar to that for hunter-gatherer and traditional horticulturalist societies. Similar group sizes are found in other contemporary and historical societies. Nonhuman primates maintain group cohesion through social grooming; among the Old World monkeys and apes, social grooming time is linearly related to group size. Maintaining stability of human-sized groups by grooming alone would make intolerable time demands. It is therefore suggested (1) that the evolution of large groups in the human lineage depended on developing a more efficient method for time-sharing the processes of social bonding and (2) that language uniquely fulfills this requirement. Data on the size of conversational and other small interacting groups of humans accord with the predicted relative efficiency of conversation compared to grooming as a bonding process. In human conversations about 60% of time is spent gossiping about relationships and personal experiences. Language may accordingly have evolved to allow individuals to learn about the behavioural characteristics of other group members more rapidly than was feasible by direct observation alone.
A Multiple-Center, Randomized, Double-Blind, Placebo-Controlled Study of Oral Aripiprazole for Treatment of Adolescents With Schizophrenia
Authors: Robert L. Findling, Adelaide Robb, Margaretta Nyilas, Robert A. Forbes, Na Jin, Svetlana Ivanova, Ronald Marcus, Robert D. McQuade, Taro Iwamoto, William H. Carson
Journal: American Journal of Psychiatry (2008)

Aripiprazole is a dopamine partial agonist approved for use in adults for short- and long-term treatment of schizophrenia and bipolar disorder. This study was designed to examine the acute efficacy, safety, and tolerability of aripiprazole for adolescents with schizophrenia.This was a 6-week multicenter, double-blind, randomized, placebo-controlled trial. Subjects 13 to 17 years old with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale (PANSS) total score of 70 or more were randomly assigned (1:1:1 ratio) to placebo or 10 or 30 mg/day of aripiprazole. The primary endpoint was mean change from baseline to endpoint (last observation carried forward) in PANSS total score. Assessments of safety and tolerability included spontaneously reported adverse events, extrapyramidal symptom scores, serum prolactin concentration, body weight, and metabolic measures.Of 302 patients, 85% completed the 6-week study. The mean baseline PANSS score was 94.1. At the end of the study, both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score. Adverse events occurring in more than 5% of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder, somnolence, and tremor. Mean changes in prolactin were -8.45, -11.93, and -15.14 ng/ml for placebo and 10 mg and 30 mg of aripirazole, respectively. Mean body weight changes were -0.8, 0.0, and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole, respectively.Both 10- and 30-mg/day doses of aripiprazole were superior to placebo in the acute treatment of adolescents with schizophrenia. Aripiprazole was generally well tolerated.
Cutanous lesions in multiple myeloma.
Authors: D G Beevers
Journal: BMJ (1972)

C101,000 Shear rate Viscosity patterns (poise) for sputum from patient (1), saliva from patient (2), and sputum from "normal" chromc bronchitic (3), tested from low to high shear rates (S-i).on the expectorated material confirmed that it had the phy-sical properties expected of sputum.Saliva produced by the patient was shown to have different rheological properties (see Chart).
Clinical Trials in Peripheral Vascular Disease
Authors: Sumeet Subherwal, Manesh R. Patel, Karen Chiswell, Beth A. Tidemann-Miller, W. Schuyler Jones, Michael S. Conte, Christopher J. White, Deepak L. Bhatt, John R. Laird, William R. Hiatt, Asba Tasneem, Robert M. Califf
Journal: Circulation (2014)

Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease).
Activation of bone marrow–resident memory T cells by circulating, antigen-bearing dendritic cells
Authors: Lois L Cavanagh, Roberto Bonasio, Irina B Mazo, Cornelia Halin, Guiying Cheng, Adrianus W M van der Velden, Annaiah Cariappa, Catherine Chase, Paul Russell, Michael N Starnbach, Pandelakis A Koni, Shiv Pillai, Wolfgang Weninger, Ulrich H von Andrian
Journal: Nature Immunology (2005)
Computed Tomography of the Hepatobiliary System
Authors: M Korobkin, H I Goldberg
Journal: Annual Review of Medicine (1979)

Computed tomography (CT) has truly revolutionized the field of diagnostic radiology. In the period of six years since its introduction into clinical practice, CT scanning has become the indispensable focal point of the diagnostic evaluation of a suspected structural abnormality of the brain. During the past three years, development of CT scanners capable of com­ pleting a scan while the patient suspends respiration has led to initial experience with CT evaluation of extracranial structures, including the hepatobiliary system. This review describes and illustrates the CT images of normal and abnormal liver and biliary tract, and it addresses the more difficult question of how CT should relate to the other available diagnostic modalities.