tbuckley/cabot-search huggingface dataset:
Analysis of advanced lung cancer patients diagnosed following emergency admission
Authors: Daichi Fujimoto, Ryoko Shimizu, Takeshi Morimoto, Ryoji Kato, Yuki Sato, Mariko Kogo, Jiro Ito, Shunsuke Teraoka, Takehiro Otoshi, Kazuma Nagata, Atsushi Nakagawa, Kojiro Otsuka, Nobuyuki Katakami, Keisuke Tomii
Journal: European Respiratory Journal (2014)

Data on prognosis and predictors of overall survival in advanced lung cancer patients diagnosed following emergency admission (DFEA) are currently lacking. We retrospectively analysed data from 771 patients with advanced nonsmall cell lung cancer between April 2004 and April 2012. Of the 771 patients, 103 (13%) were DFEA. DFEA was not an independent predictor of overall survival by multivariate Cox proportional hazard models, whereas good performance status (PS), epidermal growth factor receptor gene mutation, stage IIIB, adenocarcinoma and chemotherapy were independent predictors of overall survival (hazard ratio (95% CI) 0.36 (0.29–0.44), p&lt;0.001; 0.49 (0.38–0.63), p&lt;0.001; 0.64 (0.51–0.80), p&lt;0.001; 0.81 (0.67–0.99), p=0.044; and 0.40 (0.31–0.52), p&lt;0.001, respectively). Good PS just prior to opting for chemotherapy, but not at emergency admission, was a good independent predictor of overall survival in DFEA patients (hazard ratio (95% CI) 0.26 (0.12–0.55); p&lt;0.001). DFEA is relatively common. DFEA and PS at emergency admission were not independent predictors of overall survival, but good PS just prior to opting for chemotherapy was an independent predictor of longer overall survival. Efforts to improve patient PS after admission should be considered vital in such circumstances.
Abstract P5-10-03: Estrogen, obesity and mammary morphology in a middle-aged rat model of menopause
Authors: J Liang, JD Davis, AN Garcia, A Wolfe, AC Gore, W Yin
Journal: Cancer Research (2013)

Abstract The risk of occurrence of breast cancer changes at menopause in women. Various studies propose an association between mammographic density and adipose tissue distribution in premenopausal and post-menopausal women. There is a positive correlation between mammographic density and visceral adiposity in post-menopausal women, but an inverse correlation of the two in premenopausal women. Similar findings have also been discovered in rodent models. To model the premenopausal and post-menopausal status in women, this study used a middle-aged ovariectomized (OVX) Sprague Dawley rat model, given 17b-estradiol (E2) or vehicle (VEH) capsule, E2-deprived rats. Rats were OVX at 11 mo, and given E2 or VEH for 3 or 6 mo. A subset of rats were initially given E2 or VEH for 3 mo, then switched to the opposite treatment for another 3 mo, to evaluate the importance of E2 timing/duration. Mammary tumorigenesis was monitored through the treatment. Tumors were surgically removed upon detection. Rats were euthanized at 14 months old (3 mo of treatment) or 17 months old (6 mo of treatment). The 4th mammary gland was whole mounted for mammarographic density studies and comparisions. Serum estradiol, progesterone and prolactin concentrations were measured. Our results showed: 1) Body weight and visceral fat significantly decreased in E2 compared to VEH treated rats. 2) Following 3 or 6 mo E2 treatment, 3/54 and 5/72 rats, respectively, developed palpable mammary tumors. By contrast, 0/54 and 1/72 rats developed palpable tumors following 3 or 6 mo VEH treatment. In the group given 3 mo VEH then switched to E2 for 3 mo, 2/18 rats developed tumors. 1/18 rats developed tumors in the group given 3 mo of E2 then switched to VEH for 3 mo. 3) Mammary gland whole mounts showed increased mammographic density and decreased fat pad in E2 treated group. 4) Serum prolactin concentration significantly increased in E2 compared to VEH treated rats at euthanization. These results suggest timing and duration of hormone treatments have differing effects on mammary morphology and tumorigenesis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-10-03.
Hepatorenal Factors in Circulatory Homeostasis
Authors: EPHRAIM SHORR, BENJAMIN W. ZWEIFACH, ROBERT F. FURCHGOTT, SILVIO BAEZ
Journal: Circulation (1951)

Studies were carried out in dogs and rabbits subjected to hemorrhagic and tourniquet shock to determine the tissue origins of two newly described vasotropic principles, VEM and VDM. The vasoexcitor principle, VEM, predominates in the blood during the initial compensatory stage and was traced to the kidney. The vasodepressor principle, VDM, prevails during the decompensatory phase and was found to originate in the liver, skeletal muscle and spleen. During the decompensatory phase, there was a progressive deterioration of the hepatic mechanisms for inactivating VDM. Sequential tissue hypoxia during shock is probably responsible for the formation of these vasotropic principles and for the deterioration of the hepatic VDM inactivation system. Special emphasis is placed on the effects of local concentrations of VDM within the liver and on the resultant diversion of blood from the general circulation into the splanchnic viscera.
Placebo Therapy
Authors: Tomas J. Silber
Journal: JAMA (1979)

IN REQUESTING A MEDLINE search on the subject of placebos in English, German, and Spanish (1976 to 1978), I was surprised by the existence of 1,500 articles. When I looked at the number of articles dealing with the ethics of placebo administration, I was surprised again—only 18 of those articles dealt with that issue. There is incongruity between the richness of the pharmacologic, therapeutic, psychiatric, and research literature on this subject in general and the scant attention paid to the moral issues involved. The understanding of the ethical dimension of the diagnostic and therapeutic use of placebos would benefit from more precise examination. <h3>Definitions</h3> First, what is meant by placebo, impure placebo, and placebo effect? "Placebo" (Latin for "I shall please") is defined in<i>Webster's New Collegiate Dictionary</i>(1977) as "a medication prescribed more for the mental relief of the patient than for its actual effect on his disorders."<i>Dorland's</i>
Calnuc plays a role in dynamic distribution of Gαi but not Gβ subunits and modulates ACTH secretion in AtT-20 neuroendocrine secretory cells
Authors: Ping Lin, Thierry Fischer, Christine Lavoie, Haining Huang, Marilyn Farquhar
Journal: Molecular Neurodegeneration (2009)

In AtT-20 cells ACTH secretion is regulated by both Ca2+ and G proteins. We previously demonstrated that calnuc, an EF-hand Ca2+ binding protein which regulates Alzheimer's beta-amyloid precursor protein (APP) biogenesis, binds both Ca2+ as well as Galpha subunits. Here we investigate calnuc's role in G protein-mediated regulation of ACTH secretion in AtT-20 neuroendocrine secretory cells stably overexpressing calnuc-GFP. Similar to endogenous calnuc, calnuc-GFP is mainly found in the Golgi, on the plasma membrane (PM), and associated with regulated secretion granules (RSG). By deconvolution immunofluorescence, calnuc-GFP partially colocalizes with Galphai1/2 and Galphai3 at the PM and on RSG. Cytosolic calnuc(DeltaSS)-CFP with the signal sequence deleted also partially colocalizes with RSG and partially cosediments with Galphai1/2 in fractions enriched in RSG. Overexpression of calnuc-GFP specifically increases the distribution of Galphai1/2 on the PM whereas the distribution of Gbeta subunits and synaptobrevin 2 (Vamp 2) is unchanged. Overexpression of calnuc-GFP or cytosolic calnuc(DeltaSS)-CFP enhances ACTH secretion two-fold triggered by mastoparan or GTPgammaS but does not significantly affect glycosaminoglycan (GAG) chain secretion along the constitutive pathway or basal secretion of ACTH. Calnuc's facilitating effects on ACTH secretion are decreased after introducing anti-Galphai1/2, Galphai3, Gbeta or calnuc IgG into permeabilized cells but not when Galpha12 or preimmune IgG is introduced. The results suggest that calnuc binds to Galpha subunits on the Golgi and on RSG and that overexpression of calnuc causes redistribution of Galphai subunits to the PM and RSG, indicating that calnuc plays a role in dynamic distribution of only Galpha but not Gbeta subunits. Thus calnuc may connect G protein signaling and calcium signaling during regulated secretion.
In vitro toxicity of polymorphonuclear neutrophils to rat hepatocytes: Evidence for a proteinase-mediated mechanism
Authors: Philippe Mavier, Anne-Marie Preaux, Bernard Guigui, Marie-Claude Lescs, Elie-Serge Zafrani, Daniel Dhumeaux
Journal: Hepatology (1988)

Human polymorphonuclear neutrophils, when exposed to soluble or particulate stimuli, can destroy various types of cells. The aim of this study was to investigate their toxicity against hepatocytes. Human polymorphonuclear neutrophils were incubated in basal conditions and after stimulation with 5 mg per ml opsonized zymosan in the presence of rat hepatocytes isolated by collagenase digestion. Cytotoxicity was quantified by the percentage of ALT activity released by hepatocytes in culture medium. Whereas unstimulated neutrophils exhibited only minor effects, opsonized zymosan-stimulated neutrophils induced, after 16 hr incubation, a 24.0 ± 4.1% (mean ± 1 S.E.) ALT activity release at a neutrophil/hepatocyte ratio of 5, and a 51.7 ± 6.8% ALT activity release at a ratio of 20. At this ratio of 20, the ALT activity release was 9.0% at 1 hr and 24.0% at 4 hr. Three proteinase inhibitors (i.e., soybean trypsin inhibitor, α1-proteinase inhibitor and fetal calf serum) decrease cytotoxicity by 78, 76 and 78%, respectively. The protective effect of proteinase inhibitors was not due to a nonspecific effect of proteins, since bovine serum albumin did not decrease the toxicity of stimulated polymorphonuclear cells. The supernatant of stimulated neutrophils was also found to be toxic against hepatocytes, and again, this effect was inhibited by soybean trypsin inhibitor, α1-proteinase inhibitor and fetal calf serum. Finally, the role of proteinases was supported by the demonstration of a cytotoxic effect of two purified proteinases: porcine pancreatic elastase and human neutrophil cathepsin G. The toxicity of these proteinases was also markedly reduced by the specific inhibitors used in the study. These results show that human polymorphonuclear neutrophils stimulated with opsonized zymosan may destroy hepatocytes through the release of proteinases. This might have important path-ophysiological implications, especially in alcoholic hepatitis in which polymorphonuclear neutrophils regularly infiltrate the liver and could therefore participate in the hepatocellular injury.
An Increase in Plasma Cholesterol Independent of Thyroid Function during Long-Term Amiodarone Therapy
Authors: Wilmar M. Wiersinga, Mieke D. Trip, Mieke H. van Beeren, Theo A. Plomp, Hans Oosting
Journal: Annals of Internal Medicine (1991)

Objective: To determine whether long-term amiodarone treatment is associated with a rise in plasma cholesterol, and, if so, to analyze its relation with thyroid function. Design: Consecutive entry trial, including cardiac patients who initiated amiodarone medication but excluding those with abnormal thyroid function (defined as peak thyroid-stimulating hormone [TSH] response to thyrotropin-releasing hormone [TRH] < 2.8 or > 22.0 mU/L) either before or during amiodarone treatment. Patients: Twenty-three patients who remained euthyroid were studied. Intervention: Oral administration of amiodarone (mean duration of treatment, 17 months; range, 6 to 30 months). Measurements: Fasting plasma lipids, thyroid hormones, and peak TSH to TRH values were recorded before and every 6 months during amiodarone treatment. Results: Plasma cholesterol gradually increased from 5.1 ± 0.2 mmol/L before treatment to 6.9 ± 0.8 mmol/L after 30 months of amiodarone medication (P < 0.001); the peak TSH response to TRH did not change. When age- and sex-specific reference values were applied, 30% of the patients had cholesterol values above the 75th percentile before treatment; this number rose to 69% after 2 years of treatment. The rise in plasma cholesterol was associated with an equal increase in apoprotein B. Plasma cholesterol was not related to the daily dose of amiodarone or to plasma concentrations of amiodarone, desethylamiodarone, thyroxine (T4), triiodothyronine (T3), or reverse triiodothyronine (rT3). Linear regression analysis indicated a positive relation between plasma cholesterol and the cumulative dose of amiodarone (r = 0.25, P < 0.05). Conclusion: Long-term amiodarone treatment is associated with a dose-dependent increase in plasma cholesterol that is independent of thyroid function.
Causes of blindness in schoolchildren.
Authors: B Jay
Journal: BMJ (1987)

first aid training both at work and in the community is associated with a considerable improvement in accident rates.3738Another benefit is greater appreciation among lay people of the early symptoms of heart attack and of the importance of contacting the emergency medical services early.The costs of mass training must include those of monitoring, evaluation, follow up and refresher training.Analysis of both costs and benefits is difficult, but ifmass training is to be raised from the domain of the enthusiastic amateur to that of the professional scientist the analysis must be undertaken.
Deciding to Forego Life-Sustaining Treatment: A Report on the Ethical, Medical, and Legal Issues in Treatment Decisions
Authors: Herman S. Wigodsky
Journal: JAMA (1984)

Although not included originally in the legislative mandate establishing the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, the study Deciding to Forego Life-Sustaining Treatment was undertaken as a natural outgrowth of our studies on informed consent, the `definition' of death, and access to health care and because it seemed to us to involve some of the most important and troubling ethical and legal questions in modern medicine. In his letter of transmittal to the President, the Commission's chairman goes on to state:  Although our study has done nothing to decrease our estimation of the importance of this subject to physicians, patients and their families, we have concluded that the cases that involve true ethical difficulties are many fewer than commonly believed and that the perception of difficulties occurs primarily because of misunderstandings about the dictates of law and ethics. Neither criminal nor
UK Supreme Court abolishes immunity for expert witnesses
Authors: C. Dyer
Journal: BMJ (2011)

The United Kingdom Supreme Court has abolished the longstanding immunity expert witnesses have enjoyed from being sued for negligence, in a landmark judgment.

By a five-two majority, the UK’s highest court has swept away the rule that negligence claims cannot be brought against expert witnesses over anything said in court or in the preparation of reports for court proceedings.

The case was brought against a consultant clinical psychologist but will apply to all sorts of experts, including medical experts. Those who give expert evidence in court cases will now be well advised to carry insurance against negligence claims.

Paul Wynne Jones sued psychologist Sue Kaney, his own expert witness in a …
Secular Trends in Cardiac Transplant Recipient and Donor Management in the United States, 1990 to 1994
Authors: Richard J. Rodeheffer, David C. Naftel, Lynne Warner Stevenson, Charles B. Porter, James B. Young, Leslie W. Miller, Joseph L. Kenzora, Garrie J. Haas, James K. Kirklin, Robert C. Bourge
Journal: Circulation (1996)

Background The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. Methods and Results At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months ( P &lt;.0001), and the proportion of recipients whose status was urgent at transplantation increased from 41% to 60% ( P &lt;.0001). Donor ischemic time increased from 150 to 166 minutes ( P &lt;.0001), and the proportion of donors requiring pressor support increased from 68% to 85% ( P &lt;.0001). Despite these changes in practice, the 1-year survival rate remained constant at 84% during this 4.5-year interval. There was no significant difference in 1-year survival rate between urgent status patients (83%) and nonurgent status patients (85%) ( P =.08). Conclusions The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.
Prospective Validation for Prediction of Gefitinib Sensitivity by Epidermal Growth Factor Receptor Gene Mutation in Patients with Non-Small Cell Lung Cancer
Authors: Kimihide Yoshida, Yasushi Yatabe, Ji Young Park, Junichi Shimizu, Yoshitsugu Horio, Keitaro Matsuo, Takayuki Kosaka, Tetsuya Mitsudomi, Toyoaki Hida
Journal: Journal of Thoracic Oncology (2007)
Embolus Location Affects the Sensitivity of a Rapid Quantitative <scp>d</scp>-dimer Assay in the Diagnosis of Pulmonary Embolism
Authors: WOUTER DE MONYÉ, BERND-JAN SANSON, MELVIN R. MAC GILLAVRY, PETER M. T. PATTYNAMA, HARRY R. BÜLLER, ANNETTE A. VAN DEN BERG-HUYSMANS, MENNO V. HUISMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

d-dimer blood tests have been suggested to rule out pulmonary embolism. Despite evidence of the safety of withholding anticoagulant treatment in patients with suspected pulmonary embolism and a normal d-dimer assay result, clinicians remain reluctant to use a d-dimer assay as a sole diagnostic test. This prospective study in 314 consecutive inpatients and outpatients investigates the relation between the diagnostic accuracy of d-dimer plasma concentration and pulmonary embolus location. Plasma d-dimer levels were measured using a quantitative immunoturbidimetric method. A strict protocol of ventilation–perfusion scintigraphy, pulmonary angiography, and spiral computed tomography was used to arrive at a final diagnosis and to assess the largest pulmonary artery in which embolus was visible. The influence of embolus location on the diagnostic accuracy was evaluated using the Kruskal-Wallis test and receiver operator characteristics (ROC) analysis. There was a strong correlation between plasma d-dimer concentration and embolus location (Kruskal-Wallis, p < 0.001). Thus, the assay showed greater accuracy in excluding segmental or larger emboli (sensitivity = 93%) than subsegmental emboli (sensitivity = 50%). d-dimer concentration and the accuracy of d-dimer assays are clearly dependent on embolus location and smaller, subsegmental emboli may be missed when d-dimer assays are used as a sole test to exclude pulmonary embolism.
Long-term outcome of cryopreserved bone-derived osteoblasts for bone regeneration in vivo
Authors: Shaoyi Wang, Wenjie Zhang, Jun Zhao, Dongxia Ye, Chao Zhu, Yunhao Yang, Xiuli Zhang, Xiaojuan Sun, Chi Yang, Xinquan Jiang, Zhiyuan Zhang
Journal: Biomaterials (2011)
Controversies in Oncology
Authors: Richard J. Ugoretz
Journal: JAMA (1982)

In 26 paired chapters, opposing views on 13 issues in medical oncology are presented. No attempt is made to be all inclusive (breast cancer, small cell lung cancer, and osteosarcoma are the only solid tumors covered), and the editor does not discuss the criteria used to select the subjects to be included. These range from the current and practical (combined radiation and chemotherapy for early Hodgkin's disease) to the well worn (efficacy of high-dose methotrexate) to the philosophical (euthanasia). Adjuvant radiation therapy for breast cancer and adjuvant chemotherapy for osteosarcoma and brain tumors are discussed. Adjuvant chemotherapy for breast cancer and issues in surgical oncology generally are omitted. All of the authors use review article format, with heavy emphasis on reference to the current literature rather than a subjective synthesis of broader concepts. Most chapters are thoroughly referenced, and it is notable how often opposing authors draw different conclusions from
Cross-National Comparisons of Seafood Consumption and Rates of Bipolar Disorders
Authors: Simona Noaghiul, Joseph R. Hibbeln
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors sought to determine if greater seafood consumption, a measure of omega-3 fatty acid intake, is associated with lower prevalence rates of bipolar disorder in community samples. METHOD: Lifetime prevalence rates in various countries for bipolar I disorder, bipolar II disorder, bipolar spectrum disorder, and schizophrenia were identified from population-based epidemiological studies that used similar methods. These epidemiological studies used structured diagnostic interviews with similar diagnostic criteria and were population based with large sample sizes. Simple linear and nonlinear regression analyses were used to compare these prevalence data to differences in apparent seafood consumption, an economic measure of disappearance of seafood from the economy. RESULTS: Simple exponential decay regressions showed that greater seafood consumption predicted lower lifetime prevalence rates of bipolar I disorder, bipolar II disorder, and bipolar spectrum disorder. Bipolar II disorder and bipolar spectrum disorder had an apparent vulnerability threshold below 50 lb of seafood/person/year. The absence of a correlation between lifetime prevalence rates of schizophrenia and seafood consumption suggests a specificity to affective disorders. CONCLUSIONS: These data describe a robust correlational relationship between greater seafood consumption and lower prevalence rates of bipolar disorders. These data provide a cross-national context for understanding ongoing clinical intervention trials of omega-3 fatty acids in bipolar disorders.
Effects of self-induced starvation on cardiac size and function in anorexia nervosa.
Authors: J S Gottdiener, H A Gross, W L Henry, J S Borer, M H Ebert
Journal: Circulation (1978)

Cardiac size, function and rhythm were examined in 11 patients with anorexia nervosa. Mean left ventricular, left atrial and aortic dimensions on echocardiogram were below normal adult values at baseline. In addition to decreased cardiac dimensions--ventricular ectopy, relative hypotension, bradycardia and blunted heart rate--response to exercise were noted. Left ventricular systolic function, however, was unimpaired as indicated by normal echocardiographic fractional shortening, and by normal exercise augmentation of ejection fraction determined by radionuclide cineangiography. Eight of the patients responded to treatment with a mean weight gain of 32%. In these eight, cardiac dimensions increased toward normal: left ventricular dimension increased by 13%; left atrial dimension by 20%; aortic dimension by 15% and estimated left ventricular mass by 20%. We conclude that abnormalities of heart size and rhythm occur in patients with anorexia nervosa. However, cardiac dimensions, including left ventricular mass, may increase following nutritional rehabilitation, accompanied by an increase in heart rate and blood pressure.