tbuckley/cabot-search huggingface dataset:
Abstract P2-14-01: Breast cancer patients with HER2 low-expression: An under-recognized group at significant risk for recurrence
Authors: TJ Vreeland, BS John, AF Trappey, EJ Schneble, DF Hale, GT Clifton, NM Shumway, SA Perez, M Papamichail, S Ponniah, GE Peoples, EA Mittendorf
Journal: Cancer Research (2013)

Abstract Background: HER2 over-expression is associated with more aggressive malignant disease. The introduction of trastuzumab and other HER2-directed therapies, however, has led to improved prognosis for patients (pts) with HER2 over-expressing (OE) tumors. Currently, no HER2-targeted therapies are available for patients with HER2 low-expressing (LE) (1+, 2+ by IHC) tumors. We are conducting a randomized, controlled Phase II trial of multiple peptide vaccines enrolling patients with any level of HER2 expression (1+, 2+ and 3+). Here, we report survival data based on levels of HER2 expression in our unvaccinated, control pts. Methods: After standard of care therapy, disease-free, high-risk BCa pts were randomized to receive either peptide+GM-CSF (Vaccine Group, VG) or GM-CSF alone (Control Group, CG) in six, monthly doses followed by four boosters every six months. Pts were prospectively followed for recurrence. Demographic information was available for all pts and was compared between groups using chi square or fisher exact tests. Disease-Free Survival (DFS) was compared using log rank. Results: To date, we have enrolled 196 pts in the CG. 96 pts had HER2 OE tumors, 100 had LE tumors. The only significant demographic difference between the CG OE and LE groups was more ER/PR positive patients in LE (LE 72% vs OE 51%, p = 0.008). 83% of CG OE pts received trastuzumab, 3% of CG LE pts received trastuzumab. At a median f/u of 30 mo, DFS was significantly higher for CG OE vs CG LE (92.5% v 65.5%, p = 0.001). Conclusions: In the cohort of control pts from our ongoing vaccine trial, conducted in an era when Tz has been standard of care therapy for patients with HER2 OE tumors, we have shown that HER2 LE pts are at higher risk of recurrence than OE pts, despite having more ER/PR positive. This calls for increased efforts to develop novel therapies for patients with HER2 LE disease. We have previously shown a trend towards increased DFS with the HER2 vaccines, AE37 (p = 0.13, median f/u 22 mo) and E75 (p = 0.16, median f/u 60mo) in HER2 LE pts, suggesting that these vaccines may represent one such novel therapeutic approach. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-14-01.
Benzodiazepine-induced protein tyrosine nitration in rat astrocytes
Authors: Boris Görg, Natalie Foster, Roland Reinehr, Hans J. Bidmon, Andrea Höngen, Dieter Häussinger, Freimut Schliess
Journal: Hepatology (2003)

Recent studies indicate that ammonia and hypoosmotic astrocyte swelling can induce protein tyrosine nitration (PTN) in astrocytes with potential pathogenetic relevance for hepatic encephalopathy (HE). Because HE episodes are known to be precipitated also by sedatives, the effects of benzodiazepines on PTN in cultured rat astrocytes and rat brain in vivo were studied. In cultured rat astrocytes, diazepam, PK11195, Ro5-4864, and the benzodiazepine binding inhibitor (DBI), which acts on peripheral-type benzodiazepine receptors, induced PTN. Clonazepam, a specific ligand of the central benzodiazepine receptor, failed to induce PTN. Nanomolar concentrations of DBI and PK11195 were sufficient to increase PTN, and diazepam effects were already observed at concentrations of 1 μmol/L. Diazepam-induced PTN was insensitive to NOS inhibition and uric acid but was blunted by MK-801, BAPTA-AM, W13, and catalase, suggesting an involvement of NMDA-receptor activation, elevation of the cytosolic Ca2+ concentration [Ca2+]i, and hydrogen peroxide. Diazepam induced a plateau-like increase in [Ca2+]i and the generation of reactive oxygen intermediates (ROIs), which are both blunted by MK-801 and BAPTA-AM. The expression of functional N-methyl-D-aspartate (NMDA) receptors on cultured rat astrocytes was confirmed by reverse transcriptase polymerase chain reaction, Western blot analysis, immunhistochemistry, and receptor autoradiography. Astroglial PTN is also found in brains from rats challenged with diazepam, indicating the in vivo relevance of the present findings. In conclusion, production of ROIs and increased PTN by benzodiazepines may alter astrocyte function and thereby contribute to the precipitation of HE episodes.
The Sick Kidney and Sex
Authors: George L. Bailey
Journal: New England Journal of Medicine (1977)

Clinically, the severity of uremia is inversely proportional to sexual desire and activity in patients with chronic renal failure. Men and women alike are affected, the deficiency being generally more obvious in men because of requirements for performance and psychologic adjustment. However, in my own unpublished studies, I have noted that the sexes are equally affected. With progressive azotemia the woman ceases ovulation and thence menstruation; libido diminishes, and she may actually be repulsed by sex. There is further suggestion that a girl in whom uremia develops before puberty, and who then receives conservative treatment through what would have otherwise . . .
Parent warned to curb rise in measles cases by vaccinating their children
Authors: Roger Dobson
Journal: BMJ (2007)

Parents are being urged to have their children fully immunised with the combined vaccine against measles, mumps, and rubella (MMR) before school starts this month, after warnings that cases of measles are rising.

The latest figures from the Health Protection Agency show 480 confirmed cases of measles in the United Kingdom so far this year, compared with a provisional total of 756 cases for the whole of last year, which was the highest number recorded for at least 20 years.

Most of the cases reported this …
Fluorescent vs. radioactive microsphere measurement of regional myocardial blood flow
Authors: G. L. Chien, C. G. Anselone, R. F. Davis, D. M. Van Winkle
Journal: Cardiovascular Research (1995)

Objectives: This study compared simultaneous regional myocardial blood flow (RMBF) measurements using fluorescent microspheres (FM) and radiolabeled microspheres (RM). The utility of an internal standard during processing was also examined. Methods: Paired FM and RM were injected into the left atrium of 9 anaesthetised rabbits. RMBF was altered by use of either regional ischaemia or (−)-N6-(2-phenylisopropyl)-adenosine. Radioactivity of blood reference and tissue samples was quantitated using standard methods. Samples were then digested with potassium hydroxide and microspheres recovered by vacuum filtration, with an additional label of FM as the internal standard. FM labels were extracted using Carbitol® acetate and quantitated using fluorescence spectroscopy. Agreement between the fluorescent and radioactive methods was assessed using both orthogonal regression and difference-against-mean analyses. Results: Using recovery-uncorrected data, the slope of the orthogonal regression of RM and FM-determined RMBF was not statistically different from 1, but the intercept was statistically different from 0 [−0.03(0.01), P = 0.005] and the mean RMBF by each method differed from one another [1.24(0.08) vs. 1.17(0.08) ml · min−1 · g−1, P = 0.0002]. The mean ±2 s.d. of the differences of RMBF (RM minus FM) was +0.07 ± 0.30 ml · min−1 · g−1. Although recovery of FM from tissue averaged 97.6(1.2)%, use of the internal standard to correct for losses substantially improved the agreement between RM and FM-determined RMBF: the orthogonal regression slope was not statistically different from 1, the intercept was not statistically different from 0, and the means of the flows were not different. The mean ±2 s.d. of the differences of RMBF was −0.01 ± 0.22 ml · min−1 · g−1. The internal standard also improved RMBF estimates from samples with simulated large spillage during processing. Conclusion: Fluorescent microspheres are an equivalent alternative to radiolabeled microspheres for the estimation of RMBF. Although the overall recovery of microspheres using this technique was high, use of an internal standard is recommended for correction of random losses.
Use of Recombinant Antihemophilic Factor in the Treatment of Two Patients with Classic Hemophilia
Authors: Gilbert C. White, Campbell W. McMillan, Henry S. Kingdon, Charles B. Shoemaker
Journal: New England Journal of Medicine (1989)

COMMERCIAL concentrates of human antihemophilic factor (factor VIII) have been available for nearly 20 years and have resulted in dramatic changes in the treatment of classic hemophilia. Home therapy, surgical intervention, and prolonged treatment of hospitalized patients with hemophilia have all been facilitated by the availability of lyophilized factor VIII preparations.Although factor VIII concentrates have improved the ease and effectiveness of treatment, transfusion-associated complications have also increased. Patients with hemophilia have a high frequency of seropositivity for human immunodeficiency virus type 1 (HIV-1) and are at risk for the acquisition of the acquired immunodeficiency syndrome (AIDS). Most reports indicate . . .
Circulating Nonesterified Fatty Acid Level as a Predictive Risk Factor for Sudden Death in the Population
Authors: Xavier Jouven, Marie-Aline Charles, Michel Desnos, Pierre Ducimetière
Journal: Circulation (2001)

In ischemic conditions, concentration of circulating nonesterified fatty acids (NEFA) is increased and has a proarrhythmic effect that is responsible for ventricular tachyarrhythmias. In nonischemic patients, high NEFA plasma concentration has been shown to be associated with frequent premature ventricular complexes and increased familial risk of cardiovascular disease, but its relation to sudden death has not been studied. We assessed the role of circulating NEFA in sudden death in asymptomatic men in a long-term cohort study.A total of 5250 men employed by the city of Paris, aged 42 to 53 in 1967 to 1972, free of known ischemic cardiac disease, and included in the Paris Prospective Study I, completed a second annual examination and had fasting plasma circulating NEFA measured. Each subject underwent a physical examination and ECG, provided blood for laboratory tests, and answered questionnaires administered by trained interviewers. Vital status was obtained for each subject from specific inquiries until he retired; after retirement, it was obtained from death certificates. Body mass index, systolic and diastolic blood pressures, tobacco consumption, parental history of sudden death, fasting cholesterol level, and circulating NEFA concentration were independent factors associated with sudden death during follow up (average, 22 years). When adjusted for confounding factors, circulating NEFA concentration remained an independent risk factor for sudden death (relative risk, 1.70; 95% confidence interval, 1.21 to 2.13) but not for fatal myocardial infarction.Circulating NEFA concentration is an independent risk factor for sudden death in middle-aged men. Some form of primary prevention could be envisaged in subjects at high risk of sudden death.
Eyelid, conjunctival, and corneal findings in sleep apnea syndrome
Authors: Daniel S Mojon, David Goldblum, Johannes Fleischhauer, Auguste G.Y Chiou, Beatrice E Frueh, Christian W Hess, Matthias Gugger, Claudio Bassetti, Matthias Boehnke, Johannes Mathis
Journal: Ophthalmology (1999)
Prerequisite for Cardiac Aldosterone Action
Authors: Marc Lombès, Nadia Alfaidy, Emmanuel Eugene, Alessandro Lessana, Nicolette Farman, Jean-Pierre Bonvalet
Journal: Circulation (1995)

Background It has been proposed that aldosterone exerts direct effects on heart function, most notably on the development of myocardial fibrosis during ventricular hypertrophy in rat. Initial events in aldosterone action entail its binding to mineralocorticoid receptor (MR). Because MR displays similar affinities for aldosterone and glucocorticoids, the in vivo aldosterone selectivity of MR requires the presence of an enzyme, 11β-hydroxysteroid dehydrogenase (11-HSD), which metabolizes glucocorticoids into inactive derivatives. Although evidence exists for the presence of MR in rodent heart, no data are available for humans; moreover, the existence of cardiac 11-HSD is controversial. Methods and Results The heart samples used originated from tissue removed during cardiac surgery in nontransplant patients or from endocavitary biopsies done for the follow-up of heart transplantation. The expression of MR was examined at the mRNA and protein level by in situ hybridization with cRNA probes specific for human MR mRNA and by immunodetection with two specific anti-MR antibodies. 11-HSD catalytic activity was determined by measurement of the metabolic rate of tritiated corticosteroids by cardiac samples. In nontransplanted hearts, an in situ hybridization signal equivalent to that found in the whole kidney was present on cardiomyocytes. Specific immunolabeling of cardiomyocytes with anti-MR antibodies demonstrated the presence of the MR protein. Cardiac 11-HSD activity was detected (243±26 fmol · 30 min −1 · mg protein −1 ) and was dependent on the cofactor NAD, not NADP, suggesting that it corresponds to the form of the enzyme specifically responsible for MR protection. In transplanted hearts that presented severe alterations, MR immunodetection was weaker and irregular, with no specific hybridization signal. Conclusions Our results demonstrate that MR is coexpressed with 11-HSD in human heart, which thus possesses the cellular machinery required for direct aldosterone action.
Does it matter who does ultrasound examination of the gall bladder?
Authors: T G Allen-Mersh, R W Motson, W Hately
Journal: BMJ (1985)

The high level of accuracy achieved by some ultrasonographers in the diagnosis of gall stones' 2 has resulted in a general acceptance of ultrasound as the primary investigation for gall stones.3 These excellent results, however, were obtained by strongly motivated and highly experienced ultrasonographers conducting clinical trials.4 The knowledge that the result of an ultrasound examination will be included in a prospective study may improve performance. We have sought to establish whether the same level of accuracy can be achieved when ultrasound is performed outside the confines of a prospective trial by ultrasonographers with varying degrees of experience. The purposes of this study were, firstly, to assess the performance of gall bladder ultrasound in a busy radiology department where gall bladder ultrasound is routinely performed by different radiologists and, secondly, to see whether there was operator variability between the ultrasonographers performing the scans. The results were examined retrospectively and represent a record of what occurred in our department without the possible bias which would be introduced by a prospective study.
Control of Food Intake in Older Men
Authors: Susan B. Roberts
Journal: JAMA (1994)

<h3>Objective.</h3> —To investigate the effects of aging on mechanisms of body energy regulation and thereby determine the causes of unexplained weight loss in older persons, a factor predisposing to premature death and disability. <h3>Design.</h3> —Dietary intervention study. <h3>Setting.</h3> —Metabolic ward and outpatient. <h3>Participants.</h3> —The subjects were 35 healthy younger and older men of normal body weight consuming a diet of typical composition and performing usual activities. <h3>Main Outcome Measures.</h3> —Subjects were either overfed by a mean (±SD) of 4.09 (±0.26) MJ/d (n=17) or underfed by 3.17 (±0.68) MJ/d (n=18) for 21 days. Measurements were made of changes in body weight, body composition, and energy expenditure during overfeeding or underfeeding, and of subsequent voluntary nutrient intakes and changes in body weight. <h3>Results.</h3> —There was no significant effect of aging on changes in body composition, body weight, or energy expenditure with overfeeding or underfeeding. However, following overfeeding, younger men exhibited spontaneous hypophagia, whereas the older men did not (mean [±SD] changes in energy intake relative to control values were -2.11 [±2.18] and 1.55 [±2.11] MJ/d, respectively;<i>P</i>=.006). As a result, the younger men lost the excess body weight gained during overfeeding but the older men did not. Similarly, following underfeeding, the younger men exhibited hyperphagia while the older men did not (mean [±SD] changes in energy intake relative to control values were 1.88 [±2.31]and -0.52 [±1.54] MJ/d, respectively;<i>P</i>=.02), and as a result the older men failed to regain the weight lost during underfeeding. <h3>Conclusions.</h3> —These results in 35 men suggest that aging may be associated with a significant impairment in the ability to control food intake following overeating or undereating. Since overeating and undereating occur routinely as part of the normal pattern of energy regulation, the findings reported herein may help to explain the vulnerability of older persons to unexplained weight gain and weight loss. (<i>JAMA</i>. 1994;272:1601-1606)
Quinine as Drug Adulterant, And Malaria Transmission
Authors: Arthur S. Dover
Journal: JAMA (1971)

To the Editor.—  Malaria transmission by contaminated injection equipment is a well-documented phenomenon among heroin users in the United States.1An epidemic of falciparum malaria among heroin addicts in New York City began during the 1930s and persisted for nearly ten years, and there were more than 200 documented deaths. During the course of this epidemic, crime laboratories began to detect quinine as a common diluent or adulterant of confiscated heroin,2,3and by 1943, no further cases of needle-induced malaria were reported in the United States until the recent outbreaks associated with heroin-using Vietnam returnees (R.R. Roberto, et al, unpublished data).4  These outbreaks have been confined almost exclusively to California, where more than 50 cases have been reported since December 1970, and where, as we learned during the epidemiologic investigations, recently confiscated heroin when analyzed rarely has been found adulterated with quinine.*In contrast, only three induced
Insulin-Resistant Heart Exhibits a Mitochondrial Biogenic Response Driven by the Peroxisome Proliferator-Activated Receptor-α/PGC-1α Gene Regulatory Pathway
Authors: Jennifer G. Duncan, Juliet L. Fong, Denis M. Medeiros, Brian N. Finck, Daniel P. Kelly
Journal: Circulation (2007)

Obesity and diabetes mellitus are complex metabolic problems of pandemic proportion, contributing to significant cardiovascular mortality. Recent studies have shown altered mitochondrial function in the hearts of diabetic animals. We hypothesized that regulatory events involved in the control of mitochondrial function are activated in the prediabetic, insulin-resistant stage.
Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes
Authors: Delphine Ducoulombier, Anne-Marie Roque-Afonso, Gaëtana Di Liberto, François Penin, Rachid Kara, Yolande Richard, Elisabeth Dussaix, Cyrille Féray
Journal: Hepatology (2004)

Differences in the composition of the hepatitis C virus (HCV) quasispecies between plasma and blood mononuclear cells (BMC) strongly suggest that BMCs support viral replication. We examined the frequency of such compartmentalization, the cell types involved, the constraints exerted on the different variants, and the role of immunoglobulin-complexed variants. We screened the hypervariable region (HVR1) of HCV isolates from 14 HBsAg - and HIV-seronegative patients with chronic HCV infection. HCV RNA was amplified and cloned from plasma, the immunoglobulin G (IgG)-bound fraction, and total and sorted BMCs (CD19+, CD8+, CD4+, and CD14+ cells). Compartmentalization was estimated using a matrix correlation test. The ratio of nonsynonymous/synonymous substitutions (d N /d S ratio) was calculated for each compartment. HCV RNA was detected in 3/3 BMC, 11/11 CD19+, 10/11 CD14+, 4/11 CD8+ and 0/11 CD4+ cell samples. HVR1 sequences were significantly different between plasma and at least one cellular compartment in all nine cases analyzed, and between B cells (CD19+) and monocytes (CD14+) in all five available cases. IgG-bound variants were distinct from cellular variants. D N /d S ratios were similar (n = 3) or lower (n = 6) in cellular compartments compared with plasma and the IgG-bound fraction. In conclusion, HCV compartmentalization is a common phenomenon. B cells and monocytes harbor HCV variants showing a low rate of nonsynonymous mutations, a feature that might contribute to the persistence of HCV infection. (Hepatology 2004;39:817-825.)
Treatment of Severe Lactic Acidosis with Dichloroacetate
Authors: Perry J Blackshear, Leslie S-T Fang, Lloyd Axelrod
Journal: Diabetes Care (1982)

Four patients with severe lactic acidosis associated with septic shock were treated with sodium dichloroacetate (DCA) (50 mg/kg body wt), an activator of pyruvate dehydrogenase. All patients were in a group with an expected mortality rate of 90–100%, based on previous studies. In one patient, treatment with DCA was associated with a decrease in blood lactate levels from 11.2 mM before treatment to 0.8 mM 16 h later. Markedly elevated blood pyruvate and alanine levels also decreased to normal. After treatment, the arterial blood pH rose to 7.53, and vasopressor agents were no longer needed to support blood pressure. Some degree of biochemical improvement was also noted in the other cases in whom the blood lactate levels before treatment were 15, 17, and 31 mM. However, all three patients eventually died of refractory acidosis.
Angiographic patterns of balloon inflation during percutaneous transluminal coronary angioplasty: Role of pressure-diameter curves in studying distensibility and elasticity of the stenotic lesion and the mechanism of dilation
Authors: Craig E. Hjemdahl-Monsen, John A. Ambrose, Susan Borrico, Marc Cohen, Warren Sherman, Dimitrios Alexopoulos, Richard Gorlin, Valentin Fuster
Journal: Journal of the American College of Cardiology (1990)
Mother asks court to let her brain damaged daughter die
Authors: C. Dyer
Journal: BMJ (2011)

A mother is asking the Court of Protection in London to let her brain damaged daughter die, in a case described by the judge as “unique,” raising “very important issues of principle.”

At a preliminary hearing Mr Justice Baker said the issue of public importance was that the woman was said to be in a minimally conscious state rather than a persistent vegetative state, as in previous cases involving the withdrawal of artificial nutrition and hydration. The 53 year old woman, known only as M, was healthy until she …
Half of all doctors are worse than average
Authors: K. Patel
Journal: BMJ (2009)

The General Medical Council sent me a letter last week saying that I had a licence to practise. All I had to do was to return a slip of paper to get it, but it was a bit of a relief all the same. However, it did make me think. How would you rate your competence: (1) awful, (2) below average, (3) average, (4) above average, or (5) superb?

Let me guess: most of you selected 4, with a few choosing 5 or 3. None of us really likes to think of ourselves …
Preimplantation genetic diagnosis for donor babies carries some harm
Authors: S. Turner
Journal: BMJ (2002)

EDITOR—Are the dangers in using preimplantation genetic diagnosis to create donor babies as minimal as Boyle and Savulescu claim?1 The concerns about “commodification” of donor babies are real. The fact that Kant's dictum was “never use people solely as a means” is not a reassurance, because these donor babies are solely means to an end (the successful treatment of a sick sibling).

To rebuff accusations of instrumentalism, parents have claimed that they wanted another …
Extracellular Engrailed Participates in the Topographic Guidance of Retinal Axons In Vivo
Authors: Andrea Wizenmann, Isabelle Brunet, Joyce S.Y. Lam, Laure Sonnier, Marine Beurdeley, Konstantinos Zarbalis, Daniela Weisenhorn-Vogt, Christine Weinl, Asha Dwivedy, Alain Joliot, Wolfgang Wurst, Christine Holt, Alain Prochiantz
Journal: Neuron (2009)