tbuckley/cabot-search huggingface dataset:
Abstract ES04-1: Basic science 101 – Targeting cell signaling in breast cancer
Authors: D Yee
Journal: Cancer Research (2013)

Abstract Since normal cells require extracellular signals to proliferate, it seems likely that some transformed breast cancer cells can still respond to these signals. This premise is now well established; disruption of estrogen receptor function, important in normal mammary gland biology, by estrogen deprivation (ovarian suppression or aromatase inhibition) or selective estrogen receptor modulators demonstrated the clinical value of interrupting these key signaling pathways. Further advances have included the disruption of the human epidermal growth factor 2 (HER2) by monoclonal antibodies and tyrosine kinases. These successes have generated greater enthusiasm for identifying mechanism of action of cell signaling with the hope of identifying new therapeutic targets. The intracellular signaling pathways that transduce proliferative signals is becoming better understood. Activation of the phosphatidyl 3-kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are required for normal and malignant cell growth. Multiple strategies and drugs have been developed to target these pathways and are in clinical trial. It is also evident that co-targeting of new or established pathways also have utility over targeting only one molecule. For example, the demonstration that estrogen receptor targeting and mTOR inhibition has clinical value has revealed the potential for the inhibition of multiple pathways. Similar advances have been made in targeting HER2 by both trastuzumab and pertuzumab. These clinical strategies have value as combination therapy may more fully suppress cell signaling than single agent therapy. Additional concepts and strategies will be discussed based on the established targets of estrogen receptor and HER2. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES04-1.
Effects of pressure and volume of the receiving chamber on the spatial distribution of regurgitant jets as imaged by color Doppler flow mapping. An in vitro study.
Authors: B C Maciel, V A Moises, R Shandas, I A Simpson, M Beltran, L Valdes-Cruz, D J Sahn
Journal: Circulation (1991)

Regurgitant jet dimensions imaged by color Doppler flow mapping have been used to evaluate the severity of valvular insufficiency in clinical studies. To study the effect of pressure and volume within the receiving chamber on the magnitude of spatial distribution of regurgitant jets assessed by color Doppler techniques, we designed a simple constant-flow model in which a jet was driven through a known orifice (1.5 mm2) into a compliant receiving chamber by a steady-flow pump. A distal tube at the outflow closed the system and maintained the volume of the chamber constant during pump operation. We varied flow rate from 60 to 270 ml/min into elastic balloons with different static compliances of 1, 2, 4.5, and 9 ml/mm Hg (pressures of 57, 28, 18, and 8 mm Hg, respectively); the balloons served as receiving chambers at the constant volume of 150 ml. We also evaluated the effect of different volumes of a receiving chamber (110, 130, and 150 ml and pressures of 5, 15, and 24 mm Hg) with a static compliance of 2 ml/mm Hg over the same range of flow rates. For each of the different balloons, jet area correlated linearly with the jet velocity across the orifice (r = 0.98, 0.99, 0.98, and 0.97) and also with flow rate (r = 0.97, 0.99, 0.98, and 0.99). At the same flow rate and volume of receiving chamber, however, the jet area imaged by color Doppler decreased as the pressure in the receiving chamber increased, although receiving-chamber volume was constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Perinatal Deaths Associated with Mepivacaine Paracervical-Block Anesthesia in Labor
Authors: Jonathan B. Rosefsky, Mel E. Petersiel
Journal: New England Journal of Medicine (1968)

Fetal bradycardia and depression at birth have previously been reported with varying frequency after paracervical block given for the relief of pain in the first stage of labor. This report concerns the death of two infants occurring after mepivacaine paracervical block. The first experienced prolonged bradycardia and was stillborn. Bradycardia in the second coincided with maternal analgesia. This infant subsequently had convulsions and died. Mepivacaine was found in the urine. Other investigators have detected mepivacaine in depressed infants born after caudal and lumbar epidural anesthesia. Rapid passage of mepivacaine into the fetal circulation, impaired detoxification in the newborn period and increased acidosis in the perinatal period have been noted. Further study of the obstetric use of local anesthetics, and especially their paracervical administration, is imperative.
Deaths Attributable to Methadone vs Buprenorphine in France
Authors: M. Auriacombe
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials
Authors: Darren M Ashcroft, Paul Dimmock, Ruth Garside, Ken Stein, Hywel C Williams
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine the efficacy and tolerability of topical pimecrolimus and tacrolimus compared with other treatments for atopic dermatitis. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Electronic searches of the Cochrane Library, Medline, and Embase. <b>Study selection</b> Randomised controlled trials of topical pimecrolimus or tacrolimus reporting efficacy outcomes or tolerability. <b>Data extraction</b> Efficacy: investigators9 global assessment of response; patients9 global assessment of response; proportions of patients with flares of atopic dermatitis; and improvements in quality of life. Tolerability: overall rates of withdrawal; withdrawal due to adverse events; and proportions of patients with burning of the skin and skin infections. <b>Data synthesis</b> 4186 of 6897 participants in 25 randomised controlled trials received pimecrolimus or tacrolimus. Both drugs were significantly more effective than a vehicle control. Tacrolimus 0.1% was as effective as potent topical corticosteroids at three weeks and more effective than combined treatment with hydrocortisone butyrate 0.1% (potent used on trunk) plus hydrocortisone acetate 1% (weak used on face) at 12 weeks (number needed to treat (NNT) = 6). Tacrolimus 0.1% was also more effective than hydrocortisone acetate 1% (NNT = 4). In comparison, tacrolimus 0.03% was more effective than hydrocortisone acetate 1% (NNT = 5) but less effective than hydrocortisone butyrate 0.1% (NNT = −8). Direct comparisons of tacrolimus 0.03% and tacrolimus 0.1% consistently favoured the higher strength formulation, but efficacy differed significantly between the two strengths only after 12 weeks9 treatment (rate ratio 0.80, 95% confidence interval 0.65 to 0.99). Pimecrolimus was far less effective than betamethasone valerate 0.1% (NNT = −3 at three weeks). Pimecrolimus and tacrolimus caused significantly more skin burning than topical corticosteroids. Rates of skin infections in any of the comparisons did not differ. <b>Conclusions</b> Both topical pimecrolimus and topical tacrolimus are more effective than placebo treatments for atopic dermatitis, but in the absence of studies that show long term safety gains, any advantage over topical corticosteroids is unclear. Topical tacrolimus is similar to potent topical corticosteroids and may have a place for long term use in patients with resistant atopic dermatitis on sites where side effects from topical corticosteroids might develop quickly. In the absence of key comparisons with mild corticosteroids, the clinical need for topical pimecrolimus is unclear. The usefulness of either treatment in patients who have failed to respond adequately to topical corticosteroids is also unclear.
Misleading meta-analysis
Authors: M. Egger, G. D. Smith
Journal: BMJ (1995)

A meta-analysis of treatments in myocardial infarction published in 1992 retrospectively showed that streptokinase was associated with a highly significant fall in mortality by 1977, after inclusion of 15 trials.1 Thrombolysis was, however, not widely recommended until 10 years later—after the effect was confirmed in two mega trials.1 2 3 In the case of magnesium, a substantial fall in mortality was evident by 1990, after inclusion of seven trials. In 1993, based on an updated meta-analysis it was argued that magnesium treatment represented an “effective, safe, simple and inexpensive” intervention that should be introduced into clinical practice without further delay.4 The negative results of ISIS 4 (the fourth international study of infarct survival), published in last week's Lancet,5 have dealt a blow to enthusiasm for both magnesium and meta-analysis.6 As the findings of meta-analyses and systematic reviews are generally not tested in mega trials the situation regarding magnesium represents an opportunity to examine a false positive meta-analysis.

The table compares the meta-analyses of trials of magnesium and streptokinase after myocardial infarction. Trials were cumulatively included until the treatment effect was significant at P<0.001. For magnesium, seven small trials whose results were published in the 1980s were sufficient to establish the effect. Although trials were larger in the case of fibrinolytic treatment, twice as many studies and two decades were necessary to reach the same level of significance. Until recently it could …
Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience
Authors: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Hope S. Rugo, Beverly Moy, Lori J. Goldstein, Keith Stockerl-Goldstein, Leigh Neumayer, Terry S. Langbaum, Richard L. Theriault, Melissa E. Hughes, Jane C. Weeks, Judith E. Karp
Journal: Journal of Clinical Oncology (2014)

Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.
La valeur prédictive négative de la ponction sous echoendoscopie est-elle ameliorée par la cytologie monocouche?
Authors: C Menard, M Gasmi, V Vitton, S Garcia, A Desjeux, JC Grimaud, M Barthet
Journal: Endoscopy (2008)

But: La ponction sous échoendoscopie de masse pancréatique solide est souvent limitée par sa valeur prédictive négative qui est proche, dans la littérature, de 50%. Le but de ce travail était d'évaluer l'amélioration des performances diagnostiques apportées par la cytologie monocouche et la répétition des ponctions.
Value of Dobutamine-Echocardiogram in Predicting Functional Recovery of Hypokinetic or Akinetic Myocardium After Coronary Revascularlsation
Authors: Rudolf Strasser, Albrecht Elsasser, Klaus D. Müiler, Hassan Bahavar, Christina Gagel, Wolf P. Klövekorn, Martin Schlepper
Journal: Journal of the American College of Cardiology (1995)
Bacterial Cytosine Deaminase Mutants Created by Molecular Engineering Show Improved 5-Fluorocytosine–Mediated Cell Killing <i>In vitro</i> and <i>In vivo</i>
Authors: Michi Fuchita, Andressa Ardiani, Lei Zhao, Kinta Serve, Barry L. Stoddard, Margaret E. Black
Journal: Cancer Research (2009)

Abstract Cytosine deaminase is used in combination with 5-fluorocytosine as an enzyme-prodrug combination for targeted genetic cancer treatment. This approach is limited by inefficient gene delivery and poor prodrug conversion activities. Previously, we reported individual point mutations within the substrate binding pocket of bacterial cytosine deaminase (bCD) that result in marginal improvements in the ability to sensitize cells to 5-fluorocytosine (5FC). Here, we describe an expanded random mutagenesis and selection experiment that yielded enzyme variants, which provide significant improvement in prodrug sensitization. Three of these mutants were evaluated using enzyme kinetic analyses and then assayed in three cancer cell lines for 5FC sensitization, bystander effects, and formation of 5-fluorouracil metabolites. All variants displayed 18- to 19-fold shifts in substrate preference toward 5FC, a significant reduction in IC50 values and improved bystander effect compared with wild-type bCD. In a xenograft tumor model, the best enzyme mutant was shown to prevent tumor growth at much lower doses of 5FC than is observed when tumor cells express wild-type bCD. Crystallographic analyses of this construct show the basis for improved activity toward 5FC, and also how two different mutagenesis strategies yield closely related but mutually exclusive mutations that each result in a significant alteration of enzyme specificity. [Cancer Res 2009;69(11):4791–9]
Malignant hyperpyrexia during anaesthesia for colectomy.
Authors: B. R. Murray, P. A. Williams
Journal: BMJ (1969)

tion which is increasingly attracting the attention of anaes- thetists and surgeons.Initially most reports came from the North American Continent (Canad.Anaesth.Soc.7., 1966;Stephen, 1967), but it now appears that a number of cases have occurred in Britain (Brit.med.7., 1968).The following report illustrates such a case. CASE REPORTThe patient, a 20-year-old man, was a routine list case for total colectomy and ileorectal anastomosis.He had a history of two severe attacks of typical ulcerative colitis which had responded adequately but not completely to medical treatment.Two squint operations at the age of 4 years had been performed without incident, and two siblings and both parents had operations under general anaesthesia quite uneventfully.Immediately before operation his temperature was normal and his resting pulse rate was 90.After premedication with papaveretum 20 mg. and hyoscine 0 4 mg. he was conscious and co-operative.Induction of anaesthesia at 8.50 a.m.(0 hours) with methohexitone 100 mg. and suxamethonium 75 mg.was normal and uneventful, and an endotracheal tube was passed.The action and duration of the suxamethonium were normal and the patient was allowed to breathe spontaneously while sigmoidoscopy was performed.At 20 minutes tubocurarine 45 mg. and pethidine 30 mg. were given, and his respirations were completely controlled on the East-Radcliffe ventilator with a mixture of oxygen 3 l., nitrous oxide 5 1., and halothane 0-25 %.Relaxation was complete and the operation was begun.The systolic blood pressure stabilized at 120 mm.Hg and the pulse rate at 120.An intravenous infusion of Ringer lactate solution was started.Operation and anaesthesia proceeded quite normally and uneventfully, and regular monitoring of pulse and blood pressure showed no change from the original measurements.The tachycardia was attributed to the nature of the patient's disease.At 1 hour 30 minutes the first bottle of blood (group Q rhesus-negative) was
EUS-guided methylene blue injection into the pancreatic duct as a guide for pancreatic stenting after ampullectomy
Authors: S. Carrara, P. Arcidiacono, A. Diellou, G. Mezzi, M. Rossi, C. Boemo, E. Masci, P. Testoni
Journal: Endoscopy (2007)

Methylene blue (MB) is an intravital stain, mostly used to demonstrate specialized epithelium in Barrett’s esophagus [1], for locating the minor papilla during endoscopic retrograde cholangiopancreatography (ERCP) [2], or injected into the submucosa before endoscopic mucosal resection and polypectomy [3]. Endosonography (EUS)-guided injection of MB into the pancreatic duct (PD) has been described to identify the minor papilla after unsuccessful ERCP [4].
RELATIONSHIP BETWEEN BIOMARKERS AND SUBSEQUENT CLINICAL AND ANGIOGRAPHIC RESTENOSIS AFTER PACLITAXEL-ELUTING STENTS FOR TREATMENT OF STEMI: A HORIZONS-AMI SUBSTUDY
Authors: Bimmer E. Claessen, Gregg W. Stone, Roxana Mehran, Bernhard Witzenbichler, Bruce R. Brodie, Witold Ruzyllo, Krzysztof Zmudka, Giulio Guagliumi, Jochen Wöhrle, Kurt Huber, Janusz Kochman, Franz Hartmann, Elias Sanidas, Diaa Hakim, Vasiliki Chantziara, Selene Leon, George D. Dangas
Journal: Journal of the American College of Cardiology (2011)
Risk assessments for diabetes should be offered widely, says NICE
Authors: J. Wise
Journal: BMJ (2012)

Risk assessments for type 2 diabetes should be offered to all adults over 40 and those aged 25-39 who are of South Asian, Chinese, African-Caribbean, or Black African descent, according to new public health guidelines from the National Institute for Health and Clinical Excellence.

The first stage of this risk assessment could be carried out in GP surgeries as part of the NHS Health Check programme but equally could take place in workplaces, job centres, pharmacies, faith centres, libraries, or shops. NICE says it is not advocating a national screening programme for type 2 diabetes but wants to encourage people to identify their own personal risk and make lifestyle changes that can delay or prevent them from developing the condition.

Preventing type 2 diabetes: risk identification and interventions for individuals at high risk calls for a new accreditation body to oversee effective practice in type 2 diabetes. The proposed body would be facilitated by NICE and involve professional associations, royal colleges, academic centres, and community and voluntary sector organisations. It would conduct research …
Host innate recognition of an intestinal bacterial pathogen induces TRIF-dependent protective immunity
Authors: John Sotolongo, Cecilia España, Andrea Echeverry, David Siefker, Norman Altman, Julia Zaias, Rebeca Santaolalla, Jose Ruiz, Kurt Schesser, Becky Adkins, Masayuki Fukata
Journal: The Journal of Experimental Medicine (2011)

Toll-like receptor 4 (TLR4), which signals through the adapter molecules myeloid differentiation factor 88 (MyD88) and toll/interleukin 1 receptor domain-containing adapter inducing IFN-β (TRIF), is required for protection against Gram-negative bacteria. TRIF is known to be important in TLR3-mediated antiviral signaling, but the role of TRIF signaling against Gram-negative enteropathogens is currently unknown. We show that TRIF signaling is indispensable for establishing innate protective immunity against Gram-negative Yersinia enterocolitica. Infection of wild-type mice rapidly induced both IFN-β and IFN-γ in the mesenteric lymph nodes. In contrast, TRIF-deficient mice were defective in these IFN responses and showed impaired phagocytosis in regional macrophages, resulting in greater bacterial dissemination and mortality. TRIF signaling may be universally important for protection against Gram-negative pathogens, as TRIF-deficient macrophages were also impaired in killing both Salmonella and Escherichia coli in vitro. The mechanism of TRIF-mediated protective immunity appears to be orchestrated by macrophage-induced IFN-β and NK cell production of IFN-γ. Sequential induction of IFN-β and IFN-γ leads to amplification of macrophage bactericidal activity sufficient to eliminate the invading pathogens at the intestinal interface. Our results demonstrate a previously unknown role of TRIF in host resistance to Gram-negative enteropathogens, which may lead to effective strategies for combating enteric infections.