tbuckley/cabot-search huggingface dataset:
The Etiology of Pigment Gallstones
Authors: Donald J. Ostrow
Journal: Hepatology (1984)

Pigment gallstones are of two major types, black and earthy brown, each consisting of calcium salts of bilirubin and other anions, along with an unmeasured residue that is largely mucin glycoproteins. Studies in model systems indicate that the small proportion of unconjugated bilirubin in bile is solubilized by bile salts and that the ionized bilirubin is more soluble than the protonated diacid. Solubility is decreased by added lecithin but is unaffected by cholesterol. At the pH of bile, unconjugated bilirubin exists mainly as a monoanion with sufficient solubility in mixed micelles not to precipitate, were it not for the presence of calcium, which forms highly insoluble salts with unconjugated bilirubin anions. Supersaturation of bile with calcium bilirubinates is inhibited by bile salts, which bind calcium, reducing the activity of free calcium ions. When supersaturation occurs, usually due to increased concentrations of bilirubinate anion, nucleation may be initiated by binding of calcium bilirubinate to mucin glycoproteins in bile. In earthy brown stones, which form mainly in the bile ducts, the pigment is mostly calcium bilirubinate, combined with calcium palmitate. These components form due to hydrolysis, by enzymes in infecting bacteria, of conjugated bilirubin and lecithin, respectively. In black stones, which form mainly in the gallbladder, the pigment is mostly a highly cross-linked network polymer of bilirubin, which is insoluble in all solvents. Concomitant polymerization and oxidation of calcium bilirubinate probably occur in the solid state, after precipitation of the pigment due to hydrolysis of conjugated bilirubin by endogenous β-glucuronidase from the biliary tract and/or liver. This may result from a diet-related decrease in inhibitors of β-glucuronidase in bile. In hemolytic states, increased concentrations of conjugated bilirubin in bile, providing more substrate for hydrolysis, may contribute also to black stone formation. Black stones also contain coprecipitated calcium phosphate and/or carbonate, but the insoluble polymer renders them resistant to physical dissolution therapy.
Randomized Phase II Trial Comparing Amrubicin With Topotecan in Patients With Previously Treated Small-Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 0402
Authors: Akira Inoue, Shunichi Sugawara, Koichi Yamazaki, Makoto Maemondo, Toshiro Suzuki, Kazunori Gomi, Shingo Takanashi, Chieko Inoue, Minoru Inage, Hiroshi Yokouchi, Hiroshi Watanabe, Toumei Tsukamoto, Yasuo Saijo, Osamu Ishimoto, Fumihiro Hommura, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2008)

Amrubicin, a new anthracycline agent, and topotecan are both active for previously treated small-cell lung cancer (SCLC). No comparative study of these agents has been reported. This randomized phase II study was conducted to select amrubicin or topotecan for future evaluation.Patients with SCLC previously treated with platinum-containing chemotherapy were randomly assigned to receive amrubicin (40 mg/m(2) on days 1 through 3) or topotecan (1.0 mg/m(2) on days 1 through 5). Patients were stratified by Eastern Cooperative Oncology Group performance status (0, 1, or 2) and type of relapse (chemotherapy sensitive or refractory). The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival, and toxicity profile.From February 2004 to July 2007, 60 patients were enrolled, and 59 patients (36 patients with sensitive and 23 patients with refractory relapse) were assessable for efficacy and safety evaluation. Neutropenia was severe, and one treatment-related death owing to infection was observed in the amrubicin arm. ORRs were 38% (95% CI, 20% to 56%) for the amrubicin arm and 13% (95% CI, 1% to 25%) for the topotecan arm. In sensitive relapse, ORRs were 53% for the amrubicin arm and 21% for the topotecan arm. In refractory relapse, ORRs were 17% for the amrubicin arm and 0% for the topotecan arm. Median PFS was 3.5 months for patients in the amrubicin arm and 2.2 months for patients in the topotecan arm. Multivariate analysis revealed that amrubicin has more influence than topotecan on overall survival.Amrubicin may be superior to topotecan with acceptable toxicity for previously treated patients with SCLC. Further evaluation of amrubicin for relapsed SCLC is warranted.
Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study
Authors: TuomasO. Kilpeläinen, TimoA. Lakka, DavidE. Laaksonen, Ursula Mager, Titta Salopuro, Agata Kubaszek, Boryana Todorova, Olli Laukkanen, Jaana Lindström, JohanG. Eriksson, Helena Hämäläinen, Sirkka Aunola, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi, Jaako Tuomilehto, Markku Laakso, Matti Uusitupa
Journal: Metabolism (2008)
Mechanism of coronary vasodilation produced by bradykinin.
Authors: L R Pelc, G J Gross, D C Warltier
Journal: Circulation (1991)

BACKGROUND Bradykinin has been demonstrated to be an endothelium-dependent vasodilator in the cerebral circulation of the mouse, but the actions of bradykinin on regional tissue perfusion in the canine coronary circulation have not been studied. METHODS AND RESULTS The mechanism of coronary vasodilation by bradykinin was studied in open-chest, anesthetized dogs. The role of cyclooxygenase stimulation, bradykinin B2 receptor activation, and endothelium-derived relaxing factor in bradykinin-mediated vasodilation was studied in separate groups of dogs. Bradykinin was infused intracoronarily so as to avoid changes in systemic hemodynamics capable of altering the regional distribution of coronary blood flow (radioactive microspheres). Bradykinin produced a preferential increase in subendocardial blood flow. Pretreatment with indomethacin had no effect on bradykinin-mediated increases in total left ventricular flow or the transmural distribution of coronary blood flow. Blockade of bradykinin B2 receptors with the competitive antagonist [Thi5,8, D-Phe7]-bradykinin attenuated both the increase in total flow and redistribution of perfusion to the subendocardium produced by bradykinin. Inhibition of endothelium-derived relaxing factor with quinacrine, occlusion/reperfusion, or NG-monomethyl L-arginine attenuated the total increase in left ventricular flow and blocked the redistribution of flow to the subendocardium produced by bradykinin. CONCLUSIONS The present results demonstrate that intracoronary infusion of bradykinin produces a preferential increase in blood flow to the subendocardium via stimulation of B2 receptors and the release of an endothelium-dependent relaxing factor that may be nitric oxide.
Biological quality control for exercise testing
Authors: S M Revill
Journal: Thorax (2000)

<h3>BACKGROUND</h3> A study was undertaken to evaluate the use of a biological quality control programme for a computer controlled, breath-by-breath exercise test system over a 2.5 year period. <h3>METHODS</h3> One healthy volunteer performed a regular progressive treadmill test with breath-by-breath measurements of oxygen uptake (V˙o<sub>2</sub>), carbon dioxide output (V˙co<sub>2</sub>), ventilation (V˙e), and the ECG heart rate (HR). Following a familiarisation period, five consecutive tests were performed and the measurements at peak exercise were averaged to give baseline values. All tests were compared with these values. <h3>RESULTS</h3> A total of 35 tests were recorded. The within subject standard deviation for measurements at peak exercise were 52 ml/min forV˙o<sub>2</sub>, 74 ml/min forV˙co<sub>2</sub>, 3.1 l/min forV˙e, and 3 beats/min for HR. The mean (SE) percentage variation in measurements at peak exercise compared with the baseline values was +0.37 (0.30)% for V˙o<sub>2</sub>, –0.10 (0.39)% for V˙co<sub>2</sub>, –0.88 (0.52)% forV˙e, and +1.2 (0.26)% for HR. The variability present in measurements made during high and moderate intensity exercise (73%V˙o<sub>2</sub>peak) was not significantly different (p&gt;0.05). During the study period the quality control detected a fault on the oxygen analyser which was not apparent from the automatic calibration. <h3>CONCLUSIONS</h3> Regular quality control using a healthy volunteer allows all components of the breath-by-breath system to be checked simultaneously and in a manner which is consistent with its clinical use. This practice can highlight faults not detected by automatic calibration.
Nonalcoholic Steatohepatitis Is Associated With Increased Mortality in Obese Patients Undergoing Bariatric Surgery
Authors: Nicolas Goossens, Yujin Hoshida, Won Min Song, Minoa Jung, Philippe Morel, Shigeki Nakagawa, Bin Zhang, Jean-Louis Frossard, Laurent Spahr, Scott L. Friedman, Francesco Negro, Laura Rubbia-Brandt, Emiliano Giostra
Journal: Clinical Gastroenterology and Hepatology (2015)
A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients with Solid Malignancies
Authors: Howard A. Burris, Charles W. Taylor, Suzanne F. Jones, Kevin M. Koch, Melissa J. Versola, Niki Arya, Ronald A. Fleming, Deborah A. Smith, Lini Pandite, Neil Spector, George Wilding
Journal: Clinical Cancer Research (2009)

This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence of clinical activity following once or twice daily administration of lapatinib in patients with solid malignancies.Cancer patients (n = 81) received oral doses of lapatinib ranging from 175 to 1,800 mg once daily or 500 to 900 mg twice daily. Clinical assessments of safety and antitumor activity were recorded and blood was sampled for pharmacokinetic assessments. The effect of a low-fat meal on lapatinib pharmacokinetics was assessed in a subset of patients.Lapatinib was well tolerated, such that dose escalation was limited at 1,800 mg once daily only by pill burden. Twice-daily dosing was implemented to further explore tolerability, and was limited by diarrhea to 500 mg twice daily. The most commonly reported adverse events with once-daily dosing were diarrhea (48%), nausea (40%), rash (40%), and fatigue (38%) and with twice-daily dosing were diarrhea (85%), rash (54%), and nausea (34%). Lapatinib serum concentrations accumulated upon repeated dosing, increasing nearly in proportion with dose, and were significantly increased when dosed with food or administered twice daily. One patient with head and neck cancer achieved a confirmed complete response and 22 patients had stable disease of >or=8 weeks including three patients with stable disease of >10 months (renal, lung, and salivary gland cancers).Lapatinib was well tolerated following once and twice daily administration. Systemic exposure to lapatinib was dependent on the dose, duration and frequency of dosing, and prandial state. Clinical activity was observed.
Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine
Authors: Tsuyoshi Hatakeyama, Chiemi Noguchi, Nobuhiko Hiraga, Nami Mori, Masataka Tsuge, Michio Imamura, Shoichi Takahashi, Yoshiiku Kawakami, Yoshifumi Fujimoto, Hidenori Ochi, Hiromi Abe, Toshiro Maekawa, Hiroiku Kawakami, Hiromi Yatsuji, Yasuyuki Aisaka, Hiroshi Kohno, Shiomi Aimitsu, Kazuaki Chayama
Journal: Hepatology (2007)

Lamivudine (LAM) is a nucleoside analogue widely used for the treatment of chronic hepatitis B virus (HBV) infection. Emergence of resistant strains with amino acid substitutions in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of reverse transcriptase is a serious problem in patients on LAM therapy. The amount of covalently closed circular DNA in the serum is reported to be higher in patients who develop YMDD mutants than in those without mutants. However, there is no useful serum marker that can predict early emergence of mutants during LAM therapy. Analysis of patients who were treated with entecavir (n = 7) and LAM (n = 36) showed some patients had high serum levels of HBV RNA. Median serum levels of HBV RNA were significantly higher in patients in whom the YMDD mutant had emerged within 1 year (n = 6, 1.688 log copies/ml) than in those in whom the YMDD mutant emerged more than 1 year after treatment (n = 12, 0.456 log copies/ml, P = 0.0125) or in whom the YMDD mutant never emerged (n = 18, 0.688 log copies/ml, P = 0.039). Our results suggest that HBV RNA is a valuable predictor of early occurrence of viral mutation during LAM therapy. (HEPATOLOGY 2007;45:1179–1186.)
Religion, Spirituality, and Medicine: Psychiatrists’ and Other Physicians’ Differing Observations, Interpretations, and Clinical Approaches
Authors: Farr A. Curlin, Ryan E. Lawrence, Shaun Odell, Marshall H. Chin, John D. Lantos, Harold G. Koenig, Keith G. Meador
Journal: American Journal of Psychiatry (2007)

Objective: This study compared the ways in which psychiatrists and nonpsychiatrists interpret the relationship between religion/spirituality and health and address religion/spirituality issues in the clinical encounter. Method: The authors mailed a survey to a stratified random sample of 2,000 practicing U.S. physicians, with an oversampling of psychiatrists. The authors asked the physicians about their beliefs and observations regarding the relationship between religion/spirituality and patient health and about the ways in which they address religion/spirituality in the clinical setting. Results: A total of 1,144 physicians completed the survey. Psychiatrists generally endorse positive influences of religion/spirituality on health, but they are more likely than other physicians to note that religion/spirituality sometimes causes negative emotions that lead to increased patient suffering (82% versus 44%). Compared to other physicians, psychiatrists are more likely to encounter religion/spirituality issues in clinical settings (92% versus 74% report their patients sometimes or often mention religion/spirituality issues), and they are more open to addressing religion/spirituality issues with patients (93% versus 53% say that it is usually or always appropriate to inquire about religion/spirituality). Conclusions: This study suggests that the vast majority of psychiatrists appreciate the importance of religion and/or spirituality at least at a functional level. Compared to other physicians, psychiatrists also appear to be more comfortable, and have more experience, addressing religion/spirituality concerns in the clinical setting.
The Evolution of Invertebrate Gene Body Methylation
Authors: S. Sarda, J. Zeng, B. G. Hunt, S. V. Yi
Journal: Molecular Biology and Evolution (2012)

DNA methylation of transcription units (gene bodies) occurs in the genomes of many animal and plant species. Phylogenetic persistence of gene body methylation implies biological significance; yet, the functional roles of gene body methylation remain elusive. In this study, we analyzed methylation levels of orthologs from four distantly related invertebrate species, including the honeybee, silkworm, sea squirt, and sea anemone. We demonstrate that in all four species, gene bodies distinctively cluster to two groups, which correspond to high and low methylation levels. This pattern resembles that of sequence composition arising from the mutagenetic effect of DNA methylation. In spite of this effect, our results show that protein sequences of genes targeted by high levels of methylation are conserved relative to genes lacking methylation. Our investigation identified many genes that either gained or lost methylation during the course of invertebrate evolution. Most of these genes appear to have lost methylation in the insect lineages we investigated, particularly in the honeybee. We found that genes that are methylated in all four invertebrate taxa are enriched for housekeeping functions related to transcription and translation, whereas the loss of DNA methylation occurred in genes whose functions include cellular signaling and reproductive processes. Overall, our study helps to illuminate the functional significance of gene body methylation and its impacts on genome evolution in diverse invertebrate taxa.
(21) Case for diagnosis—a progeria-like syndrome
Authors: K.J. Misch, E.L. Rhodes
Journal: British Journal of Dermatology (1985)

Journal Article (21) Case for diagnosis—a progeria‐like syndrome Get access K.J. Misch, K.J. Misch SL Helier Hospital, Carshalton Search for other works by this author on: Oxford Academic Google Scholar E.L. Rhodes E.L. Rhodes SL Helier Hospital, Carshalton Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 64–65, https://doi.org/10.1111/j.1365-2133.1985.tb13036.x Published: 01 July 1985
Salbutamol exhibits androgenic activity in vitro
Authors: André O von Bueren, Risheng Ma, Margret Schlumpf, Walter Lichtensteiger
Journal: British Journal of Sports Medicine (2007)

Background: Salbutamol has been shown to mediate anabolic effects after intravenous administration. However, the mechanism responsible for the anabolic actions of salbutamol remains unknown. Aim: To investigate the potential mechanism by which salbutamol mediates anabolic effects in vitro. Methods: The potential androgenic activity of salbutamol was investigated in vitro by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. Results: The assay was validated with three known androgens; methyltrienolone (R1881), 5α-dihydrotestosterone (DHT) and danazol. IC 50 values of R1881, DHT and danazol, 4.41×10 −11 , 4.44×10 −11 and 1.08×10 −8 M, respectively, were in the ranges known from earlier studies. Our results demonstrate that salbutamol exhibits androgenic activity, with an IC 50 value of 8.93×10 −6 M. Anti-estrogenic or cytotoxic effects, which might have interfered with the assay, were excluded by additional experiments on wild-type MCF7 and MCF7-AR1 cells, respectively. Conclusion: These data indicate that salbutamol exerts anabolic effects through androgen receptor agonistic activity in vitro.
Dyspepsia in England and Scotland.
Authors: R H Jones, S E Lydeard, F D Hobbs, J E Kenkre, E I Williams, S J Jones, J A Repper, J L Caldow, W M Dunwoodie, J M Bottomley
Journal: Gut (1990)

A validated postal questionnaire has been used to establish the prevalence of dyspeptic symptoms in five geographical locations from the south coast of England to the north of Scotland. The six month period prevalence of dyspepsia in the 7428 respondents to the questionnaire is 41% and equal between the sexes, with similar prevalence rates in the centres studied. There is considerable overlap between upper abdominal symptoms and symptoms of heartburn; 56% of patients with dyspepsia experience both groups of symptoms. Symptom frequency falls progressively with age in men and women, but the proportion of people seeking medical advice for dyspepsia rises with age. One quarter of the dyspeptic patients studied have consulted a general practitioner about their symptoms. This study suggests that the prevalence of dyspepsia in the community has changed little over the last 30 years, despite evidence that the frequency of peptic ulcer disease is falling. Symptom prevalence is unrelated to social class, but this factor is associated with consultation behaviour, the consultation rate rising from 17% in social class 1 to 29% in social class 4. The use of investigations--barium meal and endoscopy--is similarly related to social class; the lowest rate for ulcer diagnosis (4.7%) is found in social class 1 and the highest (17.1%) in social class 5.
Breast-Feeding and Risk of Childhood Acute Leukemia
Authors: X. O. Shu, M. S. Linet, M. Steinbuch, W. Q. Wen, J. D. Buckley, J. P. Neglia, J. D. Potter, G. H. Reaman, L. L. Robison
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.
Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study.
Authors: C C Erhardt, P A Mumford, P J Venables, R N Maini
Journal: Annals of the Rheumatic Diseases (1989)

This prospective study evaluates the usefulness of clinical features and measurements of circulating immune complexes and autoantibodies for identification of patients with rheumatoid arthritis with a poor life prognosis. One hundred and seven hospital clinic patients, 64 with extra-articular manifestations, were followed up for a mean period of eight years, during which 50 deaths occurred. Comparison with an age and sex matched control population showed an increased incidence of deaths from myocardial infarction, pneumonia, and complications of rheumatoid arthritis. Patients with cutaneous ulcers, vasculitic rash, neuropathy, and scleritis had a higher mortality than patients whose disease was confined to the joints. Positive serological tests for precipitating antibodies to soluble cellular antigens and cryoglobulinaemia also predicted a poor prognosis. Eleven out of 12 patients (92%) with antibodies to soluble cellular antigens died compared with 21 out of 64 patients (33%) without antibodies. The presence of cryoglobulinaemia was associated with almost a twofold higher mortality. The laboratory measurements may reflect immunopathogenic mechanisms which lead to the occurrence of extra-articular disease features and reduce life expectancy.