tbuckley/cabot-search huggingface dataset:
Docetaxel and Doxorubicin Compared With Doxorubicin and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer: Results of a Randomized, Multicenter, Phase III Trial
Authors: Jean-Marc Nabholtz, Carla Falkson, Daniel Campos, Janos Szanto, Miguel Martin, Stephen Chan, Tadeuz Pienkowski, Jerzy Zaluski, Tamas Pinter, Maciej Krzakowski, Daniel Vorobiof, Robert Leonard, Ian Kennedy, Nacer Azli, Michael Murawsky, Alessandro Riva, Pierre Pouillart
Journal: Journal of Clinical Oncology (2003)

This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC).Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m(2) plus docetaxel 75 mg/m(2) (n = 214) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (n = 215) on day 1, every 3 weeks for up to eight cycles.Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank P =.014; median TTF, 25.6 v 23.7 weeks; log-rank P =.048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P =.009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v 41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P <.001; 8% v 2%, P =.01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%).AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.
Bone mineral density in adults with cystic fibrosis
Authors: S P CONWAY
Journal: Thorax (1999)

We have known of the increased risk of prematurely reduced bone mineral density (BMD) in children and young adults with cystic fibrosis since Mischler’s work of 20 years ago1 which documented significant deficiency in 44% of 27 patients. Bone metabolism, however, remained until recently an under-researched area of cystic fibrosis care, perhaps because patients were not expected to live long enough for osteoporosis to become a clinical problem. The average age at death is now over 30 years. Today’s young children with cystic fibrosis are expected to live into middle age. Long term survival after lung transplantation is creating a cohort of patients who enter their new lives with a low bone mineral content which is then subjected to a further damaging assault by immunosuppressive therapy. The threat of osteoporosis with all its attendant complications is a problem for all involved in the care …
USE OF RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR IN THE BRAZIL RADIATION ACCIDENT
Authors: Anna Butturini, RobertPeter Gale, DouglasM. Lopes, ClaudiaB. Cunha, WinstonG. Ho, JoseM. Sanpai, PauloCezar De Souza, JoseMarcos Cordiero, Carlos Neto, CarlosEduardoP. De Souza, DanielG. Tabak, Amihay Burla, None The Navy Hospital Radiation Team
Journal: The Lancet (1988)
Screening for Prostate Cancer — The Controversy That Refuses to Die
Authors: Michael J. Barry
Journal: New England Journal of Medicine (2009)

In the United States, most men over the age of 50 years have had a prostate-specific–antigen (PSA) test,1 despite the absence of evidence from large, randomized trials of a net benefit. Moreover, about 95% of male urologists and 78% of primary care physicians who are 50 years of age or older report that they have had a PSA test themselves,2 a finding that suggests they are practicing what they preach. And indeed, U.S. death rates from prostate cancer have fallen about 4% per year since 1992, five years after the introduction of PSA testing.3 Perhaps the answer to the PSA . . .
Abiraterone in Prostate Cancer: A New Angle to an Old Problem
Authors: Mark N. Stein, Susan Goodin, Robert S. DiPaola
Journal: Clinical Cancer Research (2012)

Abstract Abiraterone acetate is an orally administered potent inhibitor of cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17), which is essential for synthesis of testosterone from cholesterol. Although decreasing serum testosterone through inhibition of testicular function is the first line of treatment for men with metastatic prostate cancer, residual androgens may still be detected in patients treated with luteinizing hormone-releasing hormone agonists or antagonists. Treatment with abiraterone results in rapid, and complete, inhibition of androgen synthesis in the adrenal glands and potentially within the tumor itself. An overall survival benefit of maximal androgen suppression was recently shown in a randomized placebo-controlled phase III clinical trial of abiraterone with prednisone versus prednisone in men with metastatic castrate-resistant prostate cancer previously treated with docetaxel chemotherapy. Abiraterone's efficacy shows the importance of androgen signaling in patients with castrate-resistant metastatic disease, with additional confirmation from recent studies of other novel agents such as MDV3100, an androgen receptor signaling inhibitor. These promising results now pose a new angle to an old problem about hormonal therapy and raise new questions about how resistance develops, how to best sequence therapy, and how to optimize combinations with other emerging novel agents. Clin Cancer Res; 18(7); 1848–54. ©2012 AACR.
Packaging Health Services When Resources Are Limited: The Example of a Cervical Cancer Screening Visit
Authors: Jane J Kim, Joshua A Salomon, Milton C Weinstein, Sue J Goldie
Journal: PLoS Medicine (2006)

Increasing evidence supporting the value of screening women for cervical cancer once in their lifetime, coupled with mounting interest in scaling up successful screening demonstration projects, present challenges to public health decision makers seeking to take full advantage of the single-visit opportunity to provide additional services. We present an analytic framework for packaging multiple interventions during a single point of contact, explicitly taking into account a budget and scarce human resources, constraints acknowledged as significant obstacles for provision of health services in poor countries.
Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis
Authors: David Tarussio, Salima Metref, Pascal Seyer, Lourdes Mounien, David Vallois, Christophe Magnan, Marc Foretz, Bernard Thorens
Journal: Journal of Clinical Investigation (2013)

How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice was reduced compared with that of WT mice due to lower β cell proliferation rates in NG2KO mice during the early postnatal period. The difference in proliferation between NG2KO and control islets was abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat diet. Electrophysiological recordings showed reduced parasympathetic nerve activity in the basal state and no stimulation by glucose. Furthermore, sympathetic activity was also insensitive to glucose. Collectively, our data show that GLUT2-dependent control of parasympathetic activity defines a nervous system/endocrine pancreas axis that is critical for β cell mass establishment in the postnatal period and for long-term maintenance of β cell function.
Toenail onychomycosis in patients with acquired immune deficiency syndrome: treatment with terbinafine
Authors: P. HERRANZ, J. GARCÍA, R. DE LUCAS, J. GONZÁLEZ, J.M. PEÑA, R. DÍAZ, M. CASADO
Journal: British Journal of Dermatology (1997)

Skin infections caused by dermatophytes are one of the most frequent dermatological complications in patients with acquired immunodeficiency syndrome (AIDS) resulting from infection with human immunodeficiency virus (HIV). Tinea unguium associated with AIDS is characterized by being clinically more aggressive and therapeutically more difficult to treat than in the general population. Terbinafine is considered to be a first-choice option for the treatment of dermatophyte onychomycosis in immunocompetent individuals. This drug has been used in a series of 21 HIV-positive patients diagnosed with tinea unguium for 1 year in the University Hospital La Paz, Madrid. All patients underwent a subsequent clinical follow-up for 6 months. The results showed a high percentage of clinical and mycological cures, as well as maintenance of the response after follow-up; no drug interactions or significant adverse effects related to the drug under study were recorded.
Development of the anticitrullinated peptide antibody repertoire prior to the onset of rheumatoid arthritis
Authors: L. A. van de Stadt, M. H. M. T. de Koning, R. J. van de Stadt, G. Wolbink, B. A. C. Dijkmans, D. Hamann, D. van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Anticitrullinated protein antibodies (ACPA) probably play a pathogenic role in rheumatoid arthritis (RA). The ACPA response is already expanded before the first symptoms of RA and hardly changes thereafter. <h3>Objectives</h3> To explore the degree of ACPA epitope spreading prior to onset of clinical RA and the pattern of auto-antigen reactivity at the beginning of the immune response. <h3>Methods</h3> Multiple serial serum samples of 79 RA patients who had donated blood before disease onset were available for analysis. 47 patients tested ACPA (anti-CCP2) positive prior to the onset of clinical RA. Of these patients a median of 6 (IQR 4–9) sequential pre-RA sera spaced 1–2 years apart were tested for reactivity to five distinct citrullinated peptides in an ELISA. Two fibrinogen peptides, 1 vimentin, 1 α-enolase and 1 cyclic citrullinated peptide (CCP1) were tested. <h3>Results</h3> Four out of 47 ACPA positive patients (9%) did not show reactivity to any peptide. In 23 ACPA positive patients seroconversion from ACPA absence to ACPA presence was observed. In 16 (70%) of these patients, the immune response started with reactivity towards one peptide, without preference for a particular peptide. In two patients (9%) it started with two peptides, in three (13%) it started with three peptides and in two (9%) it started with four peptides. The number of recognised peptides increased over time, without a dominant epitope spreading pattern. Median titres of all measured ACPA increased over time in a biphasic manner. <h3>Conclusion</h3> ACPA epitope spreading occurs over several years prior to onset of clinical RA. None of the tested auto-antigens is solely responsible for the initial auto-immune response. ACPA epitope spreading is a random process. ACPA titers increase in a biphasic way, suggesting a 'second event' a few years before diagnosis of RA.
Isoproterenol to Evaluate Resumption of Conduction After Right Atrial Isthmus Ablation in Type I Atrial Flutter
Authors: Ashish Nabar, Luz-Maria Rodriguez, Carl Timmermans, Joep L. R. M. Smeets, Hein J. J. Wellens
Journal: Circulation (1999)

Background —After radiofrequency (RF) ablation of atrial flutter (AFL), the demonstration of bidirectional isthmus conduction (BIC) block is considered the hallmark of a successful procedure. The purpose of our study was to test the persistence of BIC block after isoproterenol administration and to evaluate the importance of this finding with regard to AFL recurrences. Methods and Results —RF ablation of AFL was performed in 44 consecutive patients with type I AFL by linear ablation of the posterior isthmus (n=29 patients), septal isthmus (n=4 patients), or both right atrial (RA) isthmi (n=11 patients). The procedural end point was complete BIC block and noninducibility of AFL. In case of noninducibility and apparent BIC block, the pacing protocol was repeated under isoproterenol infusion (1 to 3 μg/min). Reversal of apparent BIC block occurred in 7 (15.9%) of 44 patients. Six patients had bidirectional and 1 had unidirectional resumption of isthmus conduction. Counterclockwise AFL could be reinduced in 4 of these patients. Two to 24 (median, 4) additional RF applications were required to achieve permanent BIC block. At a mean follow-up of 7.3±7.6 months (range, 2 to 31 months), 2 (4.5%) of 44 patients had AFL recurrences. Conclusions —Partial linear RF ablation could possibly aggravate preexisting nonuniform anisotropic conduction in the RA isthmus, resulting in profound conduction slowing and apparent BIC block. Isoproterenol can unmask apparent BIC block, thus providing an opportunity to assess the possibility of reversal of BIC block and completeness of isthmus ablation during the same procedure. The low incidence (4.5%) of AFL recurrences at follow-up suggests that noninducibility and BIC block under isoproterenol infusion may be a better end point for successful AFL ablation.
Bromocriptine: A Sympatholytic, D2-Dopamine Agonist for the Treatment of Type 2 Diabetes
Authors: Ralph A. DeFronzo
Journal: Diabetes Care (2011)

Bromocriptine: A Sympatholytic, D2-Dopamine Agonist for the Treatment of Type 2 Diabetes B romocriptine is a sympatholytic D2-dopamine agonist that has been approved for the treatment of type 2 diabetes.Based on animal and human studies, timed bromocriptine administration within 2 h of awakening is believed to augment low hypothalamic dopamine levels and inhibit excessive sympathetic tone within the central nervous system (CNS), resulting in a reduction in postmeal plasma glucose levels due to enhanced suppression of hepatic glucose production.Bromocriptine has not been shown to augment insulin secretion or enhance insulin sensitivity in peripheral tissues (muscle).Addition of bromocriptine to poorly controlled type 2 diabetic patients treated with diet alone, metformin, sulfonylureas, or thiazolidinediones produces a 0.5-0.7 decrement in HbA 1c .Bromocriptine also reduces fasting and postmeal plasma free fatty acid (FFA) and triglyceride levels.In a 52 doubleblind, placebo-controlled study in type 2 diabetic patients, bromocriptine reduced the composite cardiovascular end point by 40%.The mechanism of the drug's beneficial effect on cardiovascular disease remains to be determined.
Study on the effects of nylon–chitosan-blended membranes on the spheroid-forming activity of human melanocytes
Authors: Sung-Jan Lin, Wen-Chu Hsiao, Shiou-Hwa Jee, Hsin-Su Yu, Tsen-Fang Tsai, Juin-Yih Lai, Tai-Horng Young
Journal: Biomaterials (2006)
Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero
Authors: Yoshiaki Kubota, Keiyo Takubo, Masanori Hirashima, Narihito Nagoshi, Kazuo Kishi, Yuji Okuno, Ayako Nakamura-Ishizu, Keigo Sano, Masato Murakami, Masatsugu Ema, Yoshiki Omatsu, Satoru Takahashi, Takashi Nagasawa, Masabumi Shibuya, Hideyuki Okano, Toshio Suda
Journal: The Journal of Experimental Medicine (2011)

Vasculogenesis describes the process of de novo vessel formation from vascular precursor cells. Although formation of the first major vessels, such as the dorsal aorta and cardinal veins, occurs during embryonic vasculogenesis, the contribution of precursor cell populations to postnatal vessel development is not well understood. Here, we identified a novel population of postnatal vascular precursor cells in mice. These cells express the Schwann cell protein myelin protein zero (Po) and exhibit a CD45−CD31−VEcad−c-kit+CXCR4+ surface phenotype. Po+ vascular precursors (PVPs) are recruited into the growing vasculature, and comprise a minor population of arterial endothelial cells in adult mice. Recruitment of PVPs into growing vessels is mediated by CXCL12–CXCR4 signaling, and is enhanced during vascular expansion induced by Notch inhibition. Po-specific ablation of Flk1, a receptor for VEGF, results in branching defects and insufficient arterial patterning in the retina, as well as reduced neovascularization of tumors and ischemic tissues. Thus, in postnatal mice, although growing vessels are formed primarily by angiogenesis from preexisting vessels, a minor population of arterial endothelia may be derived from tissue-resident vascular precursor cells.
Low-Dose Nitric Oxide Inhibition Produces a Negative Sodium Balance in Conscious Dogs
Authors: ERDMANN SEELIGER, PONTUS B. PERSSON, WILLEHAD BOEMKE, GO[Combining Diaeresis]TZ MOLLENHAUER, BENNO NAFZ, H. WOLFGANG REINHARDT
Journal: Journal of the American Society of Nephrology (2001)

Nitric oxide modulates renal hemodynamics and salt and water handling. Studies on the latter have provided conflicting results, however. Electrolyte and water balances were therefore studied in 28 beagles for 4 d, to determine the various effects of nitric oxide synthase (NOS) inhibition on renal function. The dogs were chronically equipped with aortic occluders to reduce renal perfusion pressure (RPP), bladder catheters, and catheters for measurements of RPP and mean arterial BP. A swivel system allowed free movement within the kennels. In a first set of experiments, a nonpressor dose of L-Nomega-nitroarginine (LN) (3 microg/min per kg body wt) was administered, to prevent increases in mean arterial BP and thus pressure effects on renin release and natriuresis. Remarkably, the nonpressor dose of LN caused a negative sodium balance. The natriuretic effect may involve reduced plasma renin activity, reduced aldosterone concentrations, and increased atrial natriuretic peptide concentrations. Changes in aldosterone levels, however, were the only parameters to parallel the time course of sodium excretion. In a second set of experiments, a sodium-retaining challenge was elicited by reduction of RPP. Dogs without NOS inhibition escaped sodium retention during RPP reduction after 2 d ("pressure escape"). LN neither ameliorated nor aggravated the sodium-retaining effect of reduced RPP, nor did it compromise the accomplishment of pressure escape. In conclusion, inhibition of NOS with a low dose of LN results in a reduction of total-body sodium. This effect mainly relies on reduced aldosterone concentrations. Furthermore, LN does not change the regulatory response to long-term RPP reduction.
EVALUATION OF TREATMENT WITH RECORDED INTERVIEWS
Authors: MURRAY ALPERT, LEON J. HEKIMIAN, WILLIAM A. FROSCH
Journal: American Journal of Psychiatry (1966)

Fourteen psychiatric patients were evaluated by two psychiatrists before and after treatment with either chlorpromazine or placebo. The rating interviews were tape-recorded and the recordings were rated by two other psychiatrists who did not see the patients. There was significant agreement between and among ratings based on the face-to-face interviews and those based on the tape-recorded interviews with regard to global ratings of severity of illness, incapacitation, clinical change following treatment and the "nonvisual" elements of a 26-item symptom scale. Tape recording of clinical interviews is a promising tool for the evaluation of treatments and for attempts to objectify and quantify clinical impressions. With tape recordings the investigator gains control of the interview situation without distorting it beyond recognition. He can repeat fleeting events as often as necessary, immediately contrast events separated widely in time and space and eliminate some of the factors which presently appear as "error" in his investigations. Further, since the information on a tape recording can be described physically, the use of tapes may make it possible to isolate and characterize the cues which subserve clinical impressions.
Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients
Authors: Sherrill J. Slichter, Kathryn Davis, Helen Enright, Hayden Braine, Terry Gernsheimer, Kuo Jang Kao, Thomas Kickler, Edward Lee, Janice McFarland, Jeffrey McCullough, Glenn Rodey, Charles A. Schiffer, Robert Woodson
Journal: Blood (2005)
Factitious urticaria (dermographism): treatment by cimetidine and chlorpheniramine in a randomized double-blind study
Authors: SURRINDER KAUR, MALCOLM GREAVES, NAHID EFTEKHARI
Journal: British Journal of Dermatology (1981)

The HI-antihistamine chlorpheniramine and the H2-antihistamine cimetidine, given alone and in combination, have been compared with placebo in twenty patients with factitious urticaria (dermographism), in a double-blind, randomized cross-over trial. Of these regimes, the combination was the only treatment which significantly reduced weal size, flare size and duration of weal, compared with placebo, although other treatments approached statistical significance. Continuation of the most effective of the four treatments in nineteen of the patients for a further 3 months without breaking the randomization code provided further evidence of the great effectivness of combined cimetidine and chlorpheniramine. No significant side effects were note.
Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function
Authors: M Pizarro, N Balasubramaniyan, N Solís, A Solar, I Duarte, J F Miquel, F J Suchy, M Trauner, L Accatino, M Ananthanarayanan, M Arrese
Journal: Gut (2004)

Obese Zucker rats (ZR) have been used as an experimental model for non-alcoholic fatty liver disease and are particularly susceptible to various types of liver injury. Bile secretory function has not been assessed in ZR.To study bile secretion and expression of the main hepatobiliary transporters in ZR.Bile flow and biliary secretion of lipids and glutathione were determined in eight and 14 week old obese ZR and their lean controls. Protein mass and mRNA of the Na(+)/taurocholate cotransporting polypeptide (Ntcp), the bile salt export pump (Bsep), and the multidrug resistant associated protein 2 (Mrp2) were assessed by western and northern blot, respectively. The effects of administration of a tumour necrosis factor alpha inactivator (etanercept) and an insulin sensitiser (rosiglitazone) were assessed in obese ZR while leptin was given to non-obese rats to study its effect on Mrp2 expression.ZR exhibited increased body weight and hyperlipidaemia. Only 14 week old obese ZR has fatty liver. Decreased bile flow and biliary lipid and glutathione secretion as well as reduced hepatic transport of both taurocholate and bromosulphthalein were found in obese ZR. Hepatic Mrp2 protein mass was markedly reduced (-70%) in obese rats while Ntcp and Bsep protein levels were similar to lean rats. Downregulation of Mrp2 seems to involve both transcriptional and post-transcriptional mechanisms probably related to insulin and leptin resistance.Obese ZR exhibit an impaired bile secretory function with significant functional and molecular alterations consistent with mild cholestasis. A defective hepatobiliary transport capacity may be a contributory factor in rendering the obese ZR more susceptible to liver injury.