tbuckley/cabot-search huggingface dataset:
Abstract OT1-1-03: A phase 3 randomized, double-blind trial comparing PF-05280014 + paclitaxel vs. trastuzumab + paclitaxel for treatment of HER2+ metastatic breast cancer patients
Authors: R Ewesuedo, KB Barker, CT Taylor, I Jacobs
Journal: Cancer Research (2013)

Abstract Background: PF05280014 is being developed as a potential biosimilar to trastuzumab. PF-05280014 demonstrated similarity to trastuzumab in nonclinical evaluations. In a Phase I trial in healthy volunteers, PF-05280014 pharmacokinetic characteristics and safety profile were shown to be similar to those of trastuzumab. The goal of this Phase 3 trial is to demonstrate that the efficacy and safety of PF-05280014 + paclitaxel are similar to those of trastuzumab sourced from the EU (trastuzumab-EU) + paclitaxel in women with HER2-positive metastatic breast cancer. Trial design: In this randomized, double-blind trial, patients will be randomized 1:1 into 2 arms: PF-05280014 + paclitaxel and trastuzumab-EU + paclitaxel. Randomization will be stratified by prior adjuvant trastuzumab exposure and estrogen receptor status. The order of infusion will be PF-05280014 or trastuzumab (4 mg/kg in Cycle 1; 2 mg/kg thereafter over 90 min) first followed by paclitaxel (80 mg/m2). Eligibility: Female patients, aged ≥18 y with confirmed HER-2 overexpressing metastatic breast cancer, ≥1measurable lesion (RECIST), Eastern Cooperative Oncology Group status 0–2, normal left ventricular ejection fraction, and normal laboratory values are eligible. Key exclusion criteria are prior systemic therapy for metastatic disease, prior cumulative dose of anthracyclines &amp;gt;400 mg/m2, and major surgery, radiotherapy or investigational agents within 4 weeks. All subjects must provide informed consent. Aims: The primary objective is to demonstrate the similarity in objective response rate (ORR) of PF-05280014 + paclitaxel treatment to that of trastuzumab-EU + paclitaxel. Secondary objectives include evaluating 1-year progression-free survival, safety, pharmacokinetics, and immunogenicity of these combination treatments. Statistical methods: This study tests whether the ORR of PF-05280014 is similar to that of trastuzumab-EU, using a margin of 13%, i.e., 5% alpha for non-inferiority. Assuming 60% ORR in both arms, 600 patients (300/arm) will be needed to achieve 90% power. Assuming 10% attrition, a total of 660 patients will be randomized. The intent-to-treat (ITT) population is defined as all subjects who are randomized to receive treatment. The per-protocol population is defined as all subjects who are randomized to and receive treatment and do not have any major protocol violations and will be used for evaluation efficacy endpoints. Accrual: The target accrual of this global trial is 660 patients. Contact information: For further information, please contact the Director, Clinical Trials Disclosure Group, Pfizer Inc. (marla.brickman@pfizer.com). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-03.
Effect of sex on preactivation of the gastrocnemius and hamstring muscles: Table 1
Authors: R G DeMont, S M Lephart
Journal: British Journal of Sports Medicine (2004)

The reason for the higher incidence of anterior cruciate ligament injury from non-contact mechanisms in female athletes is not known. Stability of the joint from dynamic restraints occurs through proprioceptive and kinaesthetic mechanisms providing a flexion moment. Reflexive muscle activation is different between the sexes, but it is unclear if sex differences exist in the ability to dynamically stabilise joints through a neuromuscular feed forward process as measured by preactivation of the muscles.To determine if the level of preactivation of the gastrocnemius and hamstring muscles during dynamic activity is affected by sex.Thirty four healthy active subjects, evenly grouped by sex, participated in the study. Maximum voluntary contraction normalised electromyographic (EMG) activity of the quadriceps, hamstrings, and gastrocnemius muscles was recorded during downhill walking (0.92 m/s) and running (2.08 m/s) on a 15 degrees declined treadmill. Preactivation of the EMG signal was calculated by setting a mark 150 milliseconds before foot strike, as indicated by a footswitch. Multiple t tests for sex differences of preactivity mean percentage (M-EMG%) during the downhill activities were performed.The female subjects had a higher M-EMG% for the medial hamstrings than the male subjects (31.73 (9.89) and 23.04 (8.59) respectively; t((2,32)) = 2.732, p = 0.01) during walking. No other muscles exhibited a sex difference in M-EMG% during either activity.The female subjects in this study showed higher medial hamstring preactivation. However, this may be because they were not injured, indicating their propensity for joint stabilisation. A long term prospective study is required to eliminate this potential explanation. No sex difference in gastrocnemius preactivation was seen, adding to the controversy about whether this muscle contributes to feed forward joint stability. Further research of preactivation of the musculature of the leg is required.
Follow-up Testing of Blood Donors Found to Be Enzyme Immunoassay Positive/Western Blot Negative for HTLV-III Antibody
Authors: Ritchard G. Cable
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The human T-cell lymphotropic virus type III antibody enzyme immunoassay (EIA) has now been used for approximately eight months in blood centers. Early experience with the test nationwide shows 0.25% of the normal blood donor population to be positive.<sup>1</sup>Of EIA positives, 23% are subsequently found to be Western blot (WB) positive.<sup>2</sup> The EIA is a spectrophotometric assay that is interpreted based on optical density values compared with a positive cutoff. Studies have correlated optical density values of EIA-positive blood samples with WB positivity and with positive viral cultures; most lowoptical density EIA-positive blood samples (close to the cutoff) are false-positives, ie, WB negative and viral culture negative.<sup>3</sup>Enzyme immunoassay-positive/WB-negative donors are equally likely to be female as male, whereas most EIA-positive/WB-positive donors are males and many are members of high-risk groups for acquired immunodeficiency syndrome (AIDS).<sup>2</sup> Blood centers are currently discarding EIA-positive/WB-negative
Issues in reporting epidemiological studies: Authors' reply
Authors: Stuart J Pocock, Timothy J Collier, Kimberley J Dandreo
Journal: BMJ (2005)

Users' guide to detecting misleading claims in researchMisleading claims may be symptom of even more serious flaws Editor-Montori et al justifiably draw attention to misleading claims in published clinical trials. 1 This is a serious and common problem. 2 3 However, I object to their radical proposal that only the methods and results sections should be read, while the remainder of the paper should be ignored.The proposal is inconsistent with the title of their paper, "Users' guide to detecting misleading claims in clinical research reports." 1 How are these misleading claims to be identified if the sections containing them are omitted?Furthermore, anyone capable of critically appraising a trial solely on the basis of the methods and results is unlikely to be fooled by misleading claims in the discussion.But, more importantly, the proposal would deprive the discerning reader of witnessing the conflict between the results and the unwarranted conclusions.If researchers are willing to disseminate misleading claims then their integrity is brought into question.But if so, then all aspects of the trial-including the methods and results sections-are also brought into question.Misleading claims should be identified and broadcast loudly for they signal doubts about the entire study.Large scale randomised trials create the ideal conditions for data manipulation.Yet this is merely one of a multitude of problems stemming from a flawed method. 3 The remedy?When reading a study, ignore everything except the number of patients recruited.If this is large proceed no further as there is little prospect of encountering any data of genuine benefit to patients.
Global Gene Expression Analysis in the Livers of Rat Offspring Perinatally Exposed to Low Doses of 2,2′,4,4′-Tetrabromodiphenyl Ether
Authors: Alexander Suvorov, Larissa Takser
Journal: Environmental Health Perspectives (2009)

BackgroundPolybrominated diphenyl ethers are a group of flame-retardant chemicals appearing increasingly in the environment. Their health effects and mechanisms of toxicity are poorly understood.ObjectivesWe screened for the sensitive effects and mechanisms of toxicity of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) by analyzing the gene expression profile in rats exposed to doses comparable to human exposure.MethodsWistar dams were exposed to vehicle or BDE-47 (0.002 and 0.2 mg/kg body weight) every fifth day from gestation day 15 to postnatal day 20 by injections to caudal vein. Total RNA was extracted from the livers of pups and hybridized to the whole-genome RNA expression microarrays. The list of genes 2-fold differentially expressed was exported to PANTHER and Ingenuity Systems for analysis of enriched ontology groups and molecular pathways.ResultsOxidoreductase and transferase protein families were enriched in exposed rats as were these biological process categories: carbohydrate metabolism; electron transport; and lipid, fatty acid, and steroid metabolism. Four signaling pathways (cascades of activation of drug-metabolizing enzymes) and 10 metabolic pathways were significantly enriched. Drug-metabolizing enzymes appear to be regulated by BDE-47 through an aryl hydrocarbon receptor–independent mechanism. Direct interaction with retinoid X receptor or its upstream cascade may be involved. The main metabolic effects consisted of activation of metabolic pathways: α- and ω-oxidation of fatty acids, glycolysis, and starch hydrolysis.ConclusionsAltered expression of genes involved in metabolic and signaling pathways and functions of the organism occurs after perinatal exposure of rat offspring to BDE-47 at doses relevant for the general population.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Walther F. Goebel, Francis Binkley, Ely Perlman
Journal: The Journal of Experimental Medicine (1945)

1. Methods for the isolation of the specific antigens of Types V, W, Z, and Newcastle Shigella paradysenteriae are given. 2. The physical, chemical, toxic, and immunological properties of these substances are described.
Synthesis and degradation of ribosomal RNA in regenerating liver.
Authors: J N Loeb, L L Yeung
Journal: The Journal of Experimental Medicine (1975)

A simple double-isotope method is described which permits precise determination of both synthetic and degradative rates of liver cell constituents during the course of regeneration after partial hepatectomy. By employing animals which have previously received both tritiated thymidine and an appropriate 14C-labeled precursor it is possible to obtain precise turnover data in individual animals by comparing the concentration and the total isotope content of the 14C-labeled component in the initially excised and regenerating portions of liver. The presence of a 3H marker in the liver DNA makes it possible in addition to calculate the exact size of the initial liver remnant and hence to interpret the observed 14C turnover data in terms of specific rates of synthesis and degradation. As an illustration of its usefulness this method has been employed to study changes in cell proliferation rate after partial hepatectomy, and to determine the day-to-day rates of synthesis and degradation of ribosomal RNA, the major component of rat liver RNA. It is shown that during the first 24 h after a 70% hepatectomy ribosomal RNA synthesis undergoes a nearly fourfold stimulation to a rate of approximately 53% per unit mass per day. This accelerated rate of synthesis is sustained for an additional 2 days and is accompanied by exponential DNA synthesis until the hepatic remnant has more than tripled its initial DNA and ribosomal RNA content to attain values identical to those in the initial intact liver; the rates of DNA and RNA synthesis then fall abruptly. In striking contrast to the marked fluctuations in its rate of synthesis, ribosomal RNA continues to be degraded throughout the course of regeneration at a constant rate of 12% per day, a rate virtually identical to that observed in normal liver. The approach described here permits the accurate determination of turnover rates over intervals considerably shorter than even one half-life, and should be applicable to the study of the specific rates of synthesis and degradation of other cell components as well.
TCT-453 Serial Angiographic Follow-Up after Successful Implantation of Sirolimus, Paclitaxel, Everolimus and Zotarolimus-Eluting Stent for Chronic Total Occlusions: Multicenter Registry in Asia
Authors: Sunao Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Journal of the American College of Cardiology (2012)
Lessons for doctors from Jewish philosophy
Authors: Naomi Lear
Journal: BMJ (2006)

I became active in the Jewish community and interested in medicine at about the same time. I was in high school, and I became involved in my synagogue's youth group. I loved the friends I made and the programmes I attended. And although there were no formal educational sessions, over time I learnt by example the values of social activism, leadership, community, personal growth, and ethical development.

In the same year that I became president of my youth group I met Dr Ipp. I used to run Dr Ipp's office when he was working on call on the weekends. One Saturday he took me to a movie after work. Just before Hamlet's major monologue he was paged. A woman's baby had fallen and lost consciousness for a moment. Dr Ipp insisted that she take the baby to the hospital, but the woman refused, saying that she didn't want to drive on the Sabbath. Although in Judaism the saving of a life takes precedence over the customs of Shabbat, the woman continued to refuse. “Come on,” Dr Ipp said to me, “it's not a child's …
Abstract B60: Prostate-derived factor/macrophage inhibitory cytokine-1/nonsteroidal anti-inflammatory drug activated gene: A mediator of prostatic inflammation
Authors: Ramon J. Whitson, Erin Genova, Kathleen Torkko, Francisco G. La Rosa, Julie Kelly, Storey Wilson, James R. Lambert, Marshall Scott Lucia
Journal: Cancer Research (2012)

Abstract Prostatic inflammation is recognized as a potential initiating and potentiating factor in the development of prostate cancer. Prostate derived factor (PDF), also known as macrophage inhibitory cytokine-1 (MIC-1) and nonsteroidal anti-inflammatory drug activated gene (NAG-1), was first cloned in a screen for genes involved in macrophage activation and as a gene induced by nonsteroidal anti-inflammatory drugs in colorectal carcinoma cells. These findings suggested that PDF may play a role in inflammatory processes. Previously, we identified an inverse relationship between PDF staining and inflammation severity using immunohistochemical (IHC) analysis in human prostatectomy samples suggesting a role for PDF in prostatic inflammation. Here, we extended these findings by examining the histologic compartment and inflammatory cell types that are potentially affected by PDF in the prostate. We found that a significant inverse relationship exists between PDF staining and CD3+ (T cells), CD4+ (T helper cells), CD8+ (cytotoxic T cells), and CD68+ (macrophages) cells in both the epithelial and periglandular compartments of the prostate. Linear correlation analysis using PDF and inflammatory cell marker staining showed moderate negative correlations with r values ranging from −0.47 to −0.52 and −0.43 to -0.46 in the epithelial and periglandular regions respectively (p &amp;lt; 0.006). To identify a potential mechanism for the role of PDF during inflammation, we studied the effect of PDF on NF-kappaB activity in PC3 prostate cancer cells. Increased expression of PDF was accompanied by a decrease in NF-kappaB minimal promoter activation. In addition, increased PDF expression resulted in decreased activation of the NF-kappaB-regulated promoters for COX2 and IL8. These findings suggest that PDF may suppress prostatic inflammatory responses by inhibiting expression of key genes mediating inflammatory responses in human prostate. Citation Format: Ramon J. Whitson, Erin Genova, Kathleen Torkko, Francisco G. La Rosa, Julie Kelly, Storey Wilson, James R. Lambert, Marshall Scott Lucia. Prostate-derived factor/macrophage inhibitory cytokine-1/nonsteroidal anti-inflammatory drug activated gene: A mediator of prostatic inflammation [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B60.
Atopy and intolerance of antimicrobial drugs increase the risk of reactions to acetaminophen and nimesulide in patients allergic to nonsteroidal anti‐inflammatory drugs
Authors: E. A. Pastorello, C. Zara, G. G. Riario‐Sforza, V. Pravettoni, C. Incorvaia
Journal: Allergy (1998)

This study evaluated the risk factors for developing allergic reactions to alternative drugs such as acetaminophen and nimesulide in 367 patients intolerant of nonsteroidal anti-inflammatory drugs (NSAID) compared to 243 healthy controls. All subjects were given test doses (TD) of acetaminophen and nimesulide, and age, sex, atopy, and history of reactions also to unrelated drugs were compared in those who reacted and those who were tolerant of the challenge. TD was positive in 49 of 367 (14%) NSAID-allergic patients and in one (0.4%) of the controls (P<0.001). No difference was found in age and sex between the TD-positive and TD-negative subjects, although a significantly larger number of females were NSAID allergic (P<0.01). Of the 367 patients, 208 had a history of reactions only to NSAID, and 148 to NSAID and antimicrobial drugs (AMD). TD with acetaminophen or nimesulide was positive in 6% of patients intolerant only of NSAID and in 24% of those intolerant of both NSAID and AMD, with an odds ratio of 4.82. Atopy was more frequent among patients (36%) than controls (23%) (P=0.004), among TD-positive (51%) than TD-negative patients (33.5%) (P<0.02), and among patients intolerant of NSAID and AMD (48%) than those intolerant only of NSAID (P=0.006). The odds ratios were, respectively, 1.87, 2.57, and 3.16. This study provides evidence that atopy and history of allergic reactions to AMD increase the likelihood of intolerance of usually well-tolerated alternative drugs such as acetaminophen and nimesulide in subjects allergic to NSAID.
Insiders criticise FDA's decision not to withdraw rosiglitazone
Authors: D. Cohen
Journal: BMJ (2010)

The decision of the US Food and Drug Administration to place more restrictions on GlaxoSmithKline’s diabetes drug rosiglitazone (Avandia) rather than withdraw it has drawn criticism from senior officials within the agency.

In simultaneous statements last week both the FDA and the European Medicines Agency (EMA) suggested that the drug was associated with important safety concerns and that data pointed to a raised risk of cardiovascular events, such as heart attack and stroke, in patients taking rosiglitazone.

Unlike the EMA—which said that the “benefits of rosiglitazone no longer outweigh its risks” and recommended its suspension from the market in Europe—the FDA has recommended a package of measures to try to determine the safety of the drug and further restrict its use.

The US drug regulator does not have the legal means to suspend a drug, although it did not rule out removing the drug from the market at a later date. In Europe suspension means that rosiglitazone’s manufacturer, GlaxoSmithKline (GSK), has scope to “provide convincing data” to identify a group of patients in whom the drug’s benefits outweigh the risks. 

The FDA will implement a risk evaluation and mitigation strategy. This will mean that rosiglitazone will be available to new …
Dissemination of resistance plasmids among gentamicin-resistant enterobacteria from hospital patients.
Authors: S Knight, M Casewell
Journal: BMJ (1981)

Out of 184 patients who were infected or colonised with gentamicin-resistant enterobacteria, 17 (9%) harboured more than one strain. Single antibiotic-resistance plasmids were common to more than one of the different organisms isolated from nine patients, strongly suggestive of in-vivo conjugation. An "epidemic" plasmid with a molecular weight of approximately 110 megadaltons was found in 11 distinct strains isolated from four patients. Seven of the organisms harbouring this plasmid were Klebsiella aerogenes. Spread of multiple-resistance plasmids among endemic gentamicin-resistant enterobacteria is not uncommon, and these organisms provide a reservoir of plasmids that may ultimately spread to more pathogenic genera.
Digitalis in Congestive Heart Failure
Authors: JEROME L. FLEG
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 December 1984Digitalis in Congestive Heart FailureJEROME L. FLEG, M.D., EDWARD G. LAKATTA, M.D.JEROME L. FLEG, M.D.Search for more papers by this author, EDWARD G. LAKATTA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-101-6-879_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editors: We read the interesting review by Mulrow and associates (1) and wish to clarify a few points, particularly with regard to our own study (2). Although we did not explicitly state so, our double-blind, placebo-controlled study of digitalis in patients with stable congestive heart failure was in fact randomized. Indeed, after designing a placebo-controlled crossover study, it would make little sense not to randomize. Randomization was done by our hospital pharmacy.We did not use phonocardiography routinely because only one patient had an S3 gallop heard on auscultation. We agree that a sample size calculation...References1. MULROWFEUSSNERVELEZ CJR. Reevaluation of digitalis efficacy: new light on an old leaf. Ann Intern Med. 1984;101:113-7. LinkGoogle Scholar2. FLEGGOTTLIEBLAKATTA JSE. Is digoxin really important in treatment of compensated heart failure? A placebo-controlled crossover trial in patients with sinus rhythm. Am J Med. 1982;73:244-50. CrossrefMedlineGoogle Scholar3. GRIFFITHSPENNYLEWISHENDERSON BWMA. Maintenance of the inotropic effect of digoxin on long-term treatment. Br Med J 1982;284:1819-22. CrossrefMedlineGoogle Scholar4. GHEORGHIADEBELLER MG. Effects of discontinuing maintenance digoxin therapy in patients with ischemic heart disease and congestive heart failure in sinus rhythm. Am J Cardiol. 1983;51:1243-50. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: National Institutes of Health Bethesda, MD 21224 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1984Volume 101, Issue 6Page: 879-880KeywordsAuscultationHeart failureLongitudinal studies Issue Published: 1 December 1984 PDF downloadLoading ...