tbuckley/cabot-search huggingface dataset:
Abstract 2764: Genome-wide examination of genetic variants associated with response to platinum-based chemotherapy in patients with small-cell lung cancer
Authors: Chen Wu, Binghe Xu, Peng Yuan, Jurg Ott, Yin Guan, Yu Liu, Yuanyuan Shen, Zhe Liu, Dianke Yu, Dongxin Lin
Journal: Cancer Research (2010)

Abstract Backgrounds: Small-cell lung cancer (SCLC) accounts for about 20% of total lung cancer and systemic chemotherapy is the major therapy for this cancer. Although most SCLC patients are characterized by initial chemosensitivity to the standard first-line platinum-based regimens, a significant fraction of patients are intrinsic nonresponders. Currently, no reliable biomarkers can be used to predict which patients will respond to platinum-based therapy, and this has inadvertently led to less than optimal treatment of a significant proportion of patients. Methods: We conducted a genome-wide scan of 440,093 single nucleotide polymorphisms (SNPs) using blood DNAs from 245 SCLC patients treated with the same carboplatin or cisplatin plus etoposide chemotherapy to discover variants associated with response. The results of genome-wide scan were validated in another independent set of 183 SCLC patients. Results: By Set Association analysis, 20 SNPs were identified associated with treatment response, with odds ratios (OR) ranging from 2.36 (95% confidence interval [CI]=1.56 to 3.57) to 4.38 (95% CI=2.12 to 9.29) and these results were confirmed in the replication phase. Most of these SNPs (14/20) were clustered on chromosomes 22p11.23, 6q24.3, and 20p12.2 where the BTBD3, STXBP5 and BCR genes were located. For example, 85.4% of nonresponders carried the rs41383844 (located downstream of BTBD3) AA genotype whereas 56.4% of responder carried this genotype (OR=5.24, 95% CI=2.47 to 11.13; P=1.63×10−5). Conclusion: These results suggested that germline genetic variations significantly influence the effectiveness of platinum-based chemotherapy in SCLC patients. Further studies arewarranted to test the value of these findings for personalized chemotherapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2764.
Diffusion Tensor Imaging Findings in First-Episode and Chronic Schizophrenia Patients
Authors: Joseph I. Friedman,, Cheuk Tang, David Carpenter, Monte Buchsbaum, James Schmeidler, Lauren Flanagan, Shana Golembo, Isabella Kanellopoulou, Johnny Ng, Patrick R. Hof, Philip D. Harvey, Nicholas D. Tsopelas, Daniel Stewart, Kenneth L. Davis
Journal: American Journal of Psychiatry (2008)

Comparisons of diffusion tensor imaging (DTI) data between first-episode and chronic schizophrenia patients assessed in different studies have led to the suggestion that the decreased fractional anisotropy observed in chronic schizophrenia patients is less pronounced in first-episode patients. However, such comparisons of imaging data generated across studies are susceptible to numerous confounders, which may limit the interpretation of any differences. In order to address these issues and determine whether the DTI abnormalities of chronic schizophrenia are present at illness onset, the authors conducted a DTI investigation of the largest cohort of first-episode schizophrenia patients yet reported in conjunction with a group of chronic schizophrenia patients and healthy subjects for comparison.Fractional anisotropy data generated by diffusion tensor imaging with a 3-T Siemens Allegra head-dedicated MRI system were compared between 40 first-episode schizophrenia patients and 39 age- and gender-matched healthy comparison subjects and between 40 chronic schizophrenia patients and 40 age- and gender-matched healthy comparison subjects. The following regions of interest were assessed: forceps minor (bilaterally), forceps major (bilaterally), inferior longitudinal fasciculus (bilaterally), and the genu and splenium of the corpus callosum.In most regions, chronic schizophrenia patients showed significant or trend-level lower fractional anisotropy than healthy comparison subjects, whereas the first-episode schizophrenia patients showed only trend-level lower fractional anisotropy in the inferior longitudinal fasciculus.The cross-sectional data reported here suggest less widespread changes in white matter at illness onset in schizophrenia which progress in more chronic states. More definitive conclusions will require follow-up imaging of first-episode schizophrenia patients.
Childhood Cancer Survivors' Knowledge of Their Diagnosis and Treatment
Authors: Julianne Byrne
Journal: Annals of Internal Medicine (1989)

Purpose: To determine what factors correlated with the failure of the survivors of childhood cancer to acknowledge their diagnosis. Study Design: A follow-up interview with 1928 adults who survived childhood cancer to evaluate the late effects of cancer and its treatment. Cancer was diagnosed in these survivors between 1945 and 1974 before they reached age 20; subjects had to have survived for at least 5 years and to have reached age 21. Results: Fourteen percent of the survivors of malignancies at sites other than the central nervous system said that they had not had cancer. This proportion differed according to the survivors' race, the type of tumor and its treatment, the level of their father's education, the year of diagnosis, and the center where the tumor was diagnosed. Among survivors who knew that they had cancer previously, however, most (81%) correctly identified the type of treatment they had received. Conclusions: Physicians should be aware that a substan tial proportion of long-term survivors of childhood cancer may not reveal their past history of cancer and its treatment, and possible clues to the cause of the presenting condition may thus be missed.
Diagnosis of Salmonella Infections
Authors: K. Froome, J. P. S. Whitehead
Journal: BMJ (1955)

The time-dependent effects of ethanol (EtOH) intoxication on GABA<sub>A</sub> receptor (GABA<sub>A</sub>R) composition and function were studied in rats. A cross-linking assay and Western blot analysis of microdissected CA1 area of hippocampal slices obtained 1 h after EtOH intoxication (5 g/kg, gavage), revealed decreases in the cell-surface fraction of α4 and δ, but not α1, α5, or γ2 GABA<sub>A</sub>R subunits, without changes in their total content. This was accompanied (in CA1 neuron recordings) by decreased magnitude of the picrotoxin-sensitive tonic current (<i>I</i><sub>tonic</sub>), but not miniature IPSCs (mIPSCs), and by reduced enhancement of <i>I</i><sub>tonic</sub> by EtOH, but not by diazepam. By 48 h after EtOH dosing, cell-surface α4 (80%) and γ2 (82%) subunit content increased, and cell-surface α1 (−50%) and δ (−79%) and overall content were decreased. This was paralleled by faster decay of mIPSCs, decreased diazepam enhancement of both mIPSCs and <i>I</i><sub>tonic</sub>, and paradoxically increased mIPSC responsiveness to EtOH (10–100 mm). Sensitivity to isoflurane- or diazepam-induced loss of righting reflex was decreased at 12 and 24 h after EtOH intoxication, respectively, suggesting functional GABA<sub>A</sub>R tolerance. The plastic GABA<sub>A</sub>R changes were gradually and fully reversible by 2 weeks after single EtOH dosing, but unexplainably persisted long after withdrawal from chronic intermittent ethanol treatment, which leads to signs of alcohol dependence. Our data suggest that early tolerance to EtOH may result from excessive activation and subsequent internalization of α4βδ extrasynaptic GABA<sub>A</sub>Rs. This leads to transcriptionally regulated increases in α4 and γ2 and decreases in α1 subunits, with preferential insertion of the newly formed α4βγ2 GABA<sub>A</sub>Rs at synapses.
Long-term Chelation Therapy in Thalassaemia Major: Effect on Liver Iron Concentration, Liver Histology, and Clinical Progress
Authors: M. Barry, D. M. Flynn, E. A. Letsky, R. A. Risdon
Journal: BMJ (1974)

A prospective trial of continuous chelation therapy in children with homozygous thalassaemia on a high transfusion regimen was started in April 1966. The effect of treatment on iron concentration in the liver and on hepatic histology was examined in 49 biopsy specimens obtained from nine chelator-treated patients and nine control patients between April 1966 and April 1973. Chelation therapy was associated with a significant reduction in liver iron concentration, and by the end of the trial the values for the two groups showed no overlap. A similar difference was seen in the amount of hepatic fibrosis, which showed little or no change in the chelator-treated patients but was progressive in the controls. No major clinical differences were seen, probably because both groups included several older children who were heavily loaded with iron at the start of the trial. Among the younger patients, however, puberty was delayed in four of five controls but in only one of four chelator-treated children. Prepubertal growth rate was significantly greater in the chelator-treated patients than in the controls.
Clinician’s Guide to Cardiopulmonary Exercise Testing in Adults
Authors: Gary J. Balady, Ross Arena, Kathy Sietsema, Jonathan Myers, Lola Coke, Gerald F. Fletcher, Daniel Forman, Barry Franklin, Marco Guazzi, Martha Gulati, Steven J. Keteyian, Carl J. Lavie, Richard Macko, Donna Mancini, Richard V. Milani
Journal: Circulation (2010)
Psychological and social evaluation in cases of deliberate self-poisoning admitted to a general hospital.
Authors: R Gardner, R Hanka, V C O'Brien, A J Page, R Rees
Journal: BMJ (1977)

In a prospective clinical trial 312 cases of self-poisoning (276 patients) consecutively admitted to hospital were randomly allocated to medical teams or to psychiatrists for an initial psychiatric assessment and a decision as to "disposal." Junior doctors and nurses received some instruction in this work. Both groups of assessors asked for help from social workers when necessary. Once the medical teams had completed their assessments, psychiatrists provided most of the hospital treatment. Follow-up at one year showed no significant difference between the two groups of patients in the numbers who repeated their self-poisoning or self-injury (or both), or committed suicide. Provided junior doctors and nurses are taught to assess self-poisoned patients, we think medical teams can evaluate the suicidal risk and identify patients requiring psychiatric treatment or help from social workers, or both. Contrary to the Department of Health9s recommendation that all cases of deliberate self-poisoning should be seen by psychiatrists, we have reached the conclusion that physicians should decide for each of their patients if specialist psychiatric advice is necessary.
IL2 cytotoxic responding cells infiltrating the liver of patients affected by hepatocellular carcinoma (HCC)
Authors: G.F. Stefanini, A. D'Errico, G. Piccinini, C. Fortuna, S. Caoelli, A. Cassiva, P. Amorati, P. Baccarini, G. Gasbarrini
Journal: Journal of Hepatology (1989)
Patient perception of the effect of treatment with candesartan in heart failure. Results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme
Authors: Eileen O'Meara, Eldrin Lewis, Chris Granger, Mark E. Dunlap, Robert S. McKelvie, Jeffrey L. Probstfield, James B. Young, Eric L. Michelson, Jan Ostergren, Jonas Carlsson, Bertil Olofsson, John McMurray, Salim Yusuf, Karl Swedberg, Marc A. Pfeffer
Journal: European Journal of Heart Failure (2005)
Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1
Authors: Dineke E. Folmer, Vincent A. van der Mark, Kam S. Ho-Mok, Ronald P.J. Oude Elferink, Coen C. Paulusma
Journal: Hepatology (2009)

Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1), forming a spectrum of cholestatic disease. Whereas PFIC1 is a progressive, endstage liver disease, BRIC1 patients suffer from episodic periods of cholestasis that resolve spontaneously. At present it is not clear how the type and location of the mutations relate to the clinical manifestations of PFIC1 and BRIC1. ATP8B1 localizes to the canalicular membrane of hepatocytes where it mediates the inward translocation of phosphatidylserine. ATP8B1 interacts with CDC50A, which is required for endoplasmic reticulum exit and plasma membrane localization. In this study we analyzed a panel of missense mutations causing PFIC1 (G308V, D554N, G1040R) or BRIC1 (D70N, I661T). In addition, we included two mutations that have been associated with intrahepatic cholestasis of pregnancy (ICP) (D70N, R867C). We examined the effect of these mutations on protein stability and interaction with CDC50A in Chinese hamster ovary cells, and studied the subcellular localization in WIF-B9 cells. Protein stability was reduced for three out of six mutations studied. Two out of three PFIC1 mutant proteins did not interact with CDC50A, whereas BRIC1/ICP mutants displayed reduced interaction. Importantly, none of the PFIC1 mutants were detectable in the canalicular membrane of WIF-B9 cells, whereas all BRIC1/ICP mutants displayed the same cellular staining pattern as wild-type ATP8B1. Our data indicate that PFIC1 mutations lead to the complete absence of canalicular expression, whereas in BRIC1/ICP residual protein is expressed in the canalicular membrane.These data provide an explanation for the difference in severity between the phenotypes of PFIC1 and BRIC1.
ROENTGEN RAYS INPULMONARY DISEASE.
Authors: ALBERT ABRAMS
Journal: JAMA (1902)

The brief time allotted to me in this symposium permits only a hurried survey of the advanced data in lung skiascopy. The possession of an<i>x</i>-ray apparatus does no more in postulating a knowledge of skiascopy than the possession of a microscope, of microscopy. The errors perpetrated by the microscopist are no less grave than those of the skiascopist. Skill in the use of the Roentgen rays for purposes of diagnosis can only be attained by the elimination of errors and this requires much experience. One should be prepared at the outset of an examination to see nothing, so that the expectant mind does not transfer to the ocular sense a function which should be reserved for judgment. The<i>x</i>-rays have not supplanted the conventional physical signs of thoracic disease; on the contrary, the later signs have advanced in value since the advent of the former. It is
[645] EARLY VIRAL KINETICS IN PATIENTS WITH CHRONIC HEPATITIS C GENOTYPE 2 OR 3 TREATED WITH PEGINTERFERON o-2a AND RIBAVIRIN
Authors: Th-M. Scherzer, K. Staufer, P. Steindl-Munda, H. Holzmann, P. Ferenci
Journal: Journal of Hepatology (2007)
A Case of Spontaneous Rupture of the Heart
Authors: J. Gordon
Journal: BMJ (1899)

SPONTANEOUS rupture of the heart is by nlo means a common occurrence.That being so, I thought it would be interesting to bring together the notes of this case, which I confess I was unable, either by percussion or by auscultation, to diagnose as a ruptured heart.The true ,nature was only shown by the post-mortem examination.
Interaction between Borrelia burgdorferi and endothelium in vitro.
Authors: A Szczepanski, M B Furie, J L Benach, B P Lane, H B Fleit
Journal: Journal of Clinical Investigation (1990)

During the pathogenesis of Lyme disease, Borrelia burgdorferi spreads hematogenously from the site of a tick bite to several tissues throughout the body. The specific mechanism of spirochete emigration is presently unknown. Using cultured human umbilical vein endothelial cells, we found that Borrelia burgdorferi bound to the endothelial cells and to the subendothelial matrix. Low passage isolates adhered 22-30-fold greater than a strain maintained in culture continuously. Spirochete binding to subendothelial matrix was inhibited 48-63% by pretreatment of the matrix with anti-fibronectin antiserum. Spirochete migration across endothelial monolayers cultured on amniotic membrane was increased when the monolayers were damaged by chemical or physical means. Electron microscopic examination of spirochete-endothelial interactions demonstrated the presence of spirochetes in the intercellular junctions between endothelial cells as well as beneath the monolayers. Scanning electron microscopy identified a mechanism of transendothelial migration whereby spirochetes pass between cells into the amniotic membrane at areas where subendothelium is exposed.
New Screening Methods Offer Hope for More Accurate Breast Cancer Detection
Authors: Mike Mitka
Journal: JAMA (2008)

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Abstract B24: Establishment of human primary non-small cell lung cancer xenograft models to test anticancer drugs
Authors: Changnian Liu, Wenwei Li, Bin Li, Yong Liu, Wenpeng Huang, Boliang Lou, Hua Yang
Journal: Clinical Cancer Research (2010)

Abstract Background: Human xenograft tumor models established by transplantation of human tumor cell lines into immunodifficient mice have been routinely used for preclinical test of anticancer agents. But such tumor models have a relatively low transplantability and limited correlation with clinical findings. Recently, we have developed human non-small lung cancer (NSCLC) xenograft models by transplanting human fresh lung cancer tissues into nude mice, which have been employed for test of clinically used chemotherapeutical drugs and are under way for new drug chemosensitivity in vivo screening. Methods: The fresh lung cancer samples were collected from local hospitals. The tumor fragments of 1–2 mm3 were subcutaneously implanted in the flanks of the Balb/c nude mice by trocar needle. Sixteen tumor fragments were grafted into four mice from one patient tumor tissue (passage 1). In the first passage, tumors derived from male patients were implanted into male mice, and tumors from women were inoculated into female mice. All therapeutic efficacy experiments used female mice. The drugs tested were clinically used drugs for NSCLC including cisplatin (4 mg/kg, q3d x 4), paclitaxel (15 mg/kg, q3d x 4), vinorelbine (2.5 mg/kg, q4d x 4), gemcitabine (120 mg/kg, q4d x 4), and the epidermal growth factor receptor (EGFR) inhibitor erlotinib (50 mg/kg/daily x 14, po). Results: A total of 42 NSCLC samples were implanted, and 13 tumor models were established (tumor taking rate 31%) for the first passage. The tumor taking rates were higher in the second and third passages (80–100%). Cisplatin, paclitaxel, vinorelbine, and gemcitatbine produced tumor growth inhibition rates of 48–55% regardless of the EGFR mutation status. While erlotinib demonstrated a significant antitumor activity only in the tumors bearing EGFR, which were consistent with their clinical findings. The tumor xenografts' architecture, the cell and histopathological morphology from the three generations mirrored the original patient cancers. Conclusions: These results suggest that human primary tumor xenograft models provide a unique renewable source of tumor material for test of novel anticancer agents. They may predict more relevant clinical response rates and higher correlation with clinical findings than use of xenograft models established from in vitro long-term cultured cancer cell lines, especially for test of target-oriented therapeutics in new drugs development programs. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B24
Aortic elastic properties and left ventricular diastolic function in patients with Adamantiades-Behcet's disease
Authors: Ignatios Ikonomidis, John Lekakis, Kimon Stamatelopoulos, Nikolaos Markomihelakis, Phaedon G Kaklamanis, Myron Mavrikakis
Journal: Journal of the American College of Cardiology (2004)
Randomized Controlled Clinical Trial of Glargine Versus Ultralente Insulin in the Treatment of Type 1 Diabetes
Authors: Yogish C. Kudva, Ananda Basu, Gregory D. Jenkins, Guillermo M. Pons, Lori L. Quandt, Julie A. Gebel, Debra A. Vogelsang, Steven A. Smith, Robert A. Rizza, William L. Isley
Journal: Diabetes Care (2005)

OBJECTIVE—Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia. We conducted a randomized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS—To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin, 22 individuals (aged 44 ± 14 years [±SD], 55% men) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of &amp;lt;7.8% were randomized in a crossover design to receive either glargine or ultralente as the basal insulin for 4 months. Aspart insulin was used as the prandial insulin. Physicians providing insulin dose adjustment advice were masked to the type of basal insulin. RESULTS—Treatment with glargine resulted in lower mean HbA1c (6.82 ± 0.13 vs. 7.02 ± 0.13, difference: 0.2 ± 0.08, P = 0.026), less nocturnal variability (plasma glucose 49.06 ± 4.74 vs. 62.36 ± 5.21 mg/dl, P = 0.04), and less hypoglycemia (24.5 ± 2.99 vs. 31.3 ± 4.04 events, P = 0.05), primarily due to less daytime hypoglycemia (P = 0.002). On the other hand, serious hypoglycemia and average glucose concentration measured with continuous subcutaneous glucose monitoring did not differ. CONCLUSIONS—We conclude that while use of either ultralente or glargine as a basal insulin can result in excellent glycemic control, treatment with glargine is associated with slightly but significantly lower HbA1c and less nocturnal glycemic variability and hypoglycemia.