tbuckley/cabot-search huggingface dataset:
Screening for Ovarian Cancer
Authors: Theodore G. Ganiats
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In his response to the question regarding screening ultrasonography for ovarian carcinoma, Dr Ferrucci<sup>1</sup>beautifully reviews the current state of the art and then concludes with erroneous recommendations. Certainly, ovarian carcinoma is a significant disease, accounting for 25% of all gynecologic cancers and over half the gynecologic cancer deaths.<sup>2</sup>As Dr Ferrucci says, "the clinical benefit of early detection of ovarian cancer" has not been shown. Dr Ferrucci's list of "high-risk" patients deserves closer attention. "Difficulties in physical examination due to obesity or vaginal stenosis" and "cancerophobia" are not risk factors for ovarian cancer. Many known risk factors (nulliparity, early menopause, type A blood, pelvic irradiation, breast cancer, high-fat diet, and others)<sup>2</sup>were omitted from the list. But this is a moot point since even in high-risk patients ultrasonography has no demonstrated benefit. Dr Ferrucci refers to the "less experienced" examiner and "difficult performance
Abstract 9965: Prediction and Diagnosis of Perioperative Myocardial Infarction with High-sensitivity troponin T
Authors: Peter Nagele, Frank Brown, Mitchell Scott, Brian F Gage, J. Philipp Miller
Journal: Circulation (2012)

Introduction The role of high-sensitivity troponin assays in the prediction and diagnosis of perioperative myocardial infarction is unknown. Methods This is an ancillary study of the Vitamins in Nitrous Oxide (VINO) Trial where 625 patients with or at risk for coronary artery disease undergoing major noncardiac surgery were studied..Plasma hsTnT (Roche) and standard troponin I (Siemens) were measured serially and 12-lead ECGs were obtained. Results At baseline 75% of patients (455/606) had a measurable preoperative hsTNT and 25% had a hsTnT &lt;3 pg/mL. The median hsTnT was 7.4 pg/mL (IQR 2.3 - 15.2). Postoperatively, 409/568 patients (72%) had an increase in hsTnT (median 2.9 pg/mL; IQR 0 - 7.4) and 159/569 (28%) had no change. The median peak hsTnT was 12.2 pg/mL (IQR 6.1 - 23.0). Peak and delta hsTnT and troponin I measurements were tightly correlated (r= 0.99 and 0.99, respectively). Eighty-two patients (13%) had a clinically relevant postoperative TnI elevation &gt;0.07 ng/mL and 30/605 (5%) had a myocardial infarction. Using the median preoperative hsTnT concentration of 7.4 pg/mL, patients above this level had a nearly 3-fold risk to develop a clinically significant postoperative troponin elevation (odds ratio 2.80, 95% CI: 1.69 - 4.63, p&lt; 0.001) and to develop postoperative myocardial infarction (odds ratio 2.94, 95% CI 1.29 - 6.71, p= 0.007). At 7.4 pg/mL, the sensitivity and specificity for postoperative troponin elevation were 71% and 54% and for postoperative myocardial infarction 73% and 52% (Figure 1). Conclusions: Preoperative hsTNT concentrations can be detected in most adult patients with or at risk for coronary artery disease before surgery and may be useful in preoperative risk-stratification for postoperative myocardial infarction. Postoperative increase in hsTnT (delta hsTnT) is common among patients with cardiovascular risk factors and may be useful as objective quantification of perioperative myocardial injury.
Unusual Gallbladder Metastasis From Non–Small-Cell Lung Cancer Detected by F-18 FDG PET/CT With Intravenous Contrast Enhancement
Authors: Hyeon Tae Jeong, Mijin Yun, Hye-Suk Hong, Jong Doo Lee, Ki Whang Kim
Journal: Clinical Nuclear Medicine (2010)

The detection of metastatic disease is important in staging and treatment of lung cancer. Metastatic lung cancer to the gallbladder is rarely reported. We report a case of an initially asymptomatic gallbladder metastasis from lung cancer detected on F-18 FDG PET/CT with intravenous contrast material enhancement. We observed elevated F-18 FDG activity in the gallbladder on PET/CT and subsequently confirmed the diagnosis of metastasis with a percutaneous needle biopsy. F-18 FDG PET/CT can be a useful tool for the detection of an unusual or unsuspected metastasis in the staging of lung cancer.
Meeting Report: Atmospheric Pollution and Human Reproduction
Authors: Rémy Slama, Lyndsey Darrow, Jennifer Parker, Tracey J. Woodruff, Matthew Strickland, Mark Nieuwenhuijsen, Svetlana Glinianaia, Katherine J. Hoggatt, Srimathi Kannan, Fintan Hurley, Jaroslaw Kalinka, Radim Šrám, Michael Brauer, Michelle Wilhelm, Joachim Heinrich, Beate Ritz
Journal: Environmental Health Perspectives (2008)

BackgroundThere is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration.ObjectivesThe objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research.DiscussionParticipants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time–activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case–control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed.ConclusionsTo make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies.
Galium Aparine as a Remedy for Chronic Ulcers
Authors: F. J. B. Quinlan
Journal: BMJ (1883)

rysm,"-" dilatations either in the form-of pouching, or distinct cir- cumscribed sacculated projections "-the proportion of syphilitic subjects rose in 49 cases to 67 per ceht.The relative frequency of the regional site of aortic aneurysm he gives as embracing the arch, 03.3, the descending thoracic, 16.6, and the abdominal, 20 per cent.His conclusions as to causa- tion are, that the lesion of -the aortic walls, characterised by a specific fibroid growth, which, disintegrating, tends to produce dila- tation and aneurysm, is, in the majority of cases, dependent upon syphilis, and, in a minor number of cases, on rheumatism and alcoholism, as exciting agencies; while, on the other hand, simple
Soft drink that claims to burn 200 calories a can is referred to trading standards
Authors: J. Wise
Journal: BMJ (2014)

The Advertising Standards Authority (ASA) has referred two companies to Trading Standards in a bid to tackle advertisers who persistently make misleading health claims.

Critics have previously accused the independent regulator of being toothless and incapable of punishing advertisers. This is the first time that it has used its new legal backstop regime and referred advertisers to Trading Standards. The ASA said that these two cases were a clear warning to others in breach of the code that they could face legal sanctions.

In 2012 the drinks manufacturer Fahrenheit60 was investigated by the ASA and was …
Lack of Concordance Between the F-18 Fluoromisonidazole PET and the F-18 FDG PET in Human Glioblastoma
Authors: Henri De Clermont, Aymeri Huchet, Frédéric Lamare, Annalisa Rivière, Philippe Fernandez
Journal: Clinical Nuclear Medicine (2011)

A 57-year-old man with an unresectable glioblastoma had both F-18 fluorodeoxyglucose and F-18 fluoromisonidazole positron emission tomography coupled with computerized tomography before radiotherapy. Positron emission tomography images were fused with magnetic resonance imaging through computerized tomography images. Important discrepancies were observed in the spatial distribution of the F-18 fluorodeoxyglucose and the F-18 fluoromisonidazole uptake, reflecting the lack of concordance between glucose metabolism and tumor hypoxia. Although tumor hypoxia, through the HIF-1 pathway, increases the expression of GLUT-1 and hexokinase, other factors can increase glucose metabolism. Although there is often correlation between glucose metabolism and hypoxia, they do not completely agree.
Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock
Authors: Tarek Sharshar, Francoise Gray, Geoffrey Lorin de la Grandmaison, Nicholas S Hopklnson, Ewen Ross, Anne Dorandeu, David Orlikowski, Jean-Claude Raphael, Philippe Gajdos, Djillali Annane
Journal: The Lancet (2003)
Abstract 5425: Potent curcumin analogue FLLL-22, but not natural curcumin, targets the DNA damage pathway for apoptosis in lung and head and neck cancer cells
Authors: A.R.M. Ruhul Amin, Michelle Lee, Mohammad A. Rahman, James R. Fuchs, Zhuo G. Chen, Dong M. Shin
Journal: Cancer Research (2011)

Abstract Curcumin, 1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadien-3, 5-dione, is the major bioactive compound isolated from the rhizome of Curcuma longa (turmeric). Despite its high margin of safety (no dose-limiting toxicity at doses up to 10 g/day in human) and efficacy against various types of cancers, the potential utility of curcumin as a chemopreventive/chemotherapeutic drug is compromised by its low bioavailability and poor selectivity. To circumvent these problems, more potent and selective curcumin analogues have been introduced. In the current study, we investigated one such synthetic analogue, (1E, 4E)-1, 5-bis (2, 4, 6-trimethoxyphenyl) penta-1, 4-dien-3-one (FLLL-22), against the head and neck cancer cell line Tu212 and lung cancer cell line H460. We conducted an SRB assay to determine IC50 values which showed that FLLL-12 was 24.6-fold and 31.6-fold more potent than natural curcumin against Tu212 and H460 cells, respectively. FLLL-22 also more strongly inhibited colony formation in both cell lines than that of natural curcumin. FLLL-22 at 1 μM was sufficient to completely inhibit colony formation, whereas up to 5 μM of curcumin had only minimal effects on colony formation. FLLL-22 also induced apoptosis more strongly (∼10-fold) than natural curcumin as evidenced by annexin V-PE staining and cleavage of PARP. Interestingly, FLLL-22, but not natural curcumin, activates DNA double strand breaks as evidenced by phosphorylation of H2AX and activation of p53 pathway. Although FLLL-22 strongly phosphorylated H2AX at doses of 3 and 5 μM, no H2AX phosphorylation was observed after curcumin treatment with doses 20 and 30 μM. At these doses, both compounds induced comparable apoptosis. FLLL-22 increased the protein level of p53, its phosphorylation at Ser15 and Ser392, and downstream target p21. A slight increase in p53 expression was observed with 20 μM curcumin, but not with 30 μM. Ablation of p53 by shRNA inhibited FLLL-22-induced p21, suggesting that FLLL-22 activates p53-dependent transcription. We also found that treatment with both FLLL-22 and curcumin inhibited phosphorylation of AKT, S6 and expression of Bcl-2. Taken together, our data strongly suggest that FLLL-22 is a potent curcumin analogue which activates the DNA damage pathway to induce apoptosis and might be a suitable anti-cancer drug for further preclinical and clinical development (supported by U01CA101244, R01CA112643, and P50CA128613 to DMS). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5425. doi:10.1158/1538-7445.AM2011-5425
Fluticasone propionate reduces oral prednisone use while it improves asthma control and quality of life.
Authors: M Noonan, P Chervinsky, W W Busse, S C Weisberg, J Pinnas, B P de Boisblanc, H Boltansky, D Pearlman, L Repsher, D Kellerman
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

This study examined the ability of fluticasone propionate aerosol to reduce oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated for 16 wk with placebo or fluticasone propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral prednisone was adjusted weekly according to predetermined criteria. A total of 69% and 88% of patients treated with fluticasone propionate 750 and 1,000 micrograms twice daily, respectively, compared with 3% of placebo-treated patients used no prednisone by the end of the study. In the fluticasone propionate groups, FEV1 and peak expiratory flow rates at the last evaluable visit/date improved and the number of night awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms improved in the groups receiving fluticasone propionate but not in the placebo group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it improved some dimensions of health-related quality of life measured using a standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms twice daily) effectively and safely allowed most asthmatics dependent on oral corticosteroids to reduce or eliminate oral prednisone use while improving pulmonary function and quality of life.
Loss of intestinal core 1–derived O-glycans causes spontaneous colitis in mice
Authors: Jianxin Fu, Bo Wei, Tao Wen, Malin E.V. Johansson, Xiaowei Liu, Emily Bradford, Kristina A. Thomsson, Samuel McGee, Lilah Mansour, Maomeng Tong, J. Michael McDaniel, Thomas J. Sferra, Jerrold R. Turner, Hong Chen, Gunnar C. Hansson, Jonathan Braun, Lijun Xia
Journal: Journal of Clinical Investigation (2011)

Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell–specific deficiency of core 1–derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1–derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1–derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase–specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.
P1015 COMBINATION OF BLOOD MARKERS TARGETED FOR DIFFERENT FIBROSIS STAGES OUTPERFORMS LIVER BIOPSY FOR PROGNOSTICATION IN HEPATITIS C
Authors: J. Boursier, C. Brochard, S. Bertrais, S. Michalak, Y. Gallois, I. Fouchard-Hubert, F. Oberti, M.-C. Rousselet, P. Cales
Journal: Journal of Hepatology (2014)
The FDA Does Not Approve Uses of Drugs
Authors: John D. Archer
Journal: JAMA (1984)

As a reviewer of medical manuscripts and reader of published articles, I find it frustrating to continue to find reference to "Food and Drug Administration (FDA)—approved uses of drugs"—or worse, allegations that certain uses are "not approved." For nearly two decades, through published articles, speeches, and personal communications, I have cautioned the medical profession against such diction. Perhaps the most definitive article was "Instrument or Impediment? The Regulatory Monograph in Medical Communications."<sup>1</sup>The FDA cannot approve or disapprove of how a legally marketed drug is used by a physician in his practice. The agency approves of what the manufacturer may<i>recommend</i>about uses in its labeling (package insert) and advertising. Failure to recognize this distinction can have various harmful results. Many valid uses of drugs become recognized long before they are included in manufacturers' literature—provided they ever are. Such uses may range from the unstudied (but reasonable) to the
Abstract P5-10-04: Metformin mediated upregulation of microRNA-193 triggers apoptosis by decreasing fatty acid synthase
Authors: DR Cochrane, RS Wahdan-Alaswad, SM Edgerton, KL Terrell, NS Spoelstra, AD Thor, SM Anderson, JK Richer
Journal: Cancer Research (2012)

Abstract Background: We have previously shown that the anti-diabetic drug metformin kills triple negative (TN) breast cancer cells lines via apoptosis, at lower IC50 than luminal and HER2 subtypes (presented at ENDO, manuscript in preparation). Metformin reportedly shows greater efficacy against stem cells than differentiated cells, reducing mammosphere formation in in non-adherent culture. Fatty acid synthase (FASN) is an enzyme critical for de novo fatty acid synthesis that is overexpressed in breast cancer. Hypothesis: We hypothesized that miRNAs might be involved in the ability of metformin to preferentially kill TN cell lines at a lower IC50 than luminal A lines. Methods: TN and luminal A (LA) breast cancer cell lines (MDA-468, HCC70 and MCF7, T47D, respectively) were used to study the effects of 10mM metformin action in vitro, at physiological and hyperglycemic culture conditions. Affymetrix chips Human Gene 1.1 and the miRNA 2.0 were utilized to profile gene and miRNA expression at 6 and 24 hrs. Mimics and lentiviral expression vectors were utilized to manipulate miRNA expression and a luciferase reporter was used to confirm miR-193 direct targeting of the FASN 3′ UTR. Results: miR-193 is significantly higher in untreated LA as compared to TN cells. MiR-193 increases 2–4 fold within 6 hrs of metformin treatment in both TN, but not LA cell lines. A predicted target of miR-193, fatty acid synthase (FASN), is decreased by 8 fold following 24 hrs 10mM metformin treatment of the TN breast cancer cells. miR-193 directly targets FASN via a binding site in the 3′ UTR, downregulating gene expression. Restoration of miR-193 to TN lines, causes a dramatic decrease in FASN protein in a dose dependent fashion. Conclusions and future directions: Metformin stimulates an increase in mature miR-193, which mediates the dramatic downregulation of FASN. This occurs coincident with apoptotic cell death. It remains to be determined if FASN is the only relevant direct target of miR-193 in TN cell lines. The addition of exogenous non-targetable FASN, lacking its 3′ UTR, will demonstrate whether this pathway is a primary mechanism of metformin action in TN cells. Future studies will investigate the ability of metformin to inhibit FASN in non-adherent mammosphere (stem cell-like) subpopulations, the role of fatty acid metabolism in mammosphere maintenance and anoikis resistance. Supported by Komen Breast Cancer Foundation Grants KG100575 (ADT, JKR, SME, NSS) and KG090415 (JKR, DRC) Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-04.
Why is gout so poorly managed?
Authors: E. Pascual, F. Sivera
Journal: Annals of the Rheumatic Diseases (2007)

Gout has been recognised since ancient times, and we currently have a deep understanding of its pathophysiology. The disease results from a deposit of monosodium urate (MSU) crystals in joint structures and in other, generally periarticular, sites in the form of tophi. High serum uric acid (SUA) is required for the formation of these crystals. The most characteristic features of gout are acute attacks of joint inflammation, which frequently occur at the first metatarsophalangeal joint, although their occurrence in other joints and in bursae is also very common. Oligoarticular, polyarticular, and more protracted and lingering forms of the disease occur, and if untreated or poorly managed, the disease can become very persistent and disabling. Fortunately, we now have highly effective drugs enabling us to deal with gouty joint inflammation and to prevent their recurrence.1 An unequivocal diagnosis can be obtained by identifying MSU crystals in joint fluid obtained either during the attacks2 or at intercritical periods from previously inflamed asymptomatic joints of untreated subjects,3,4 or from a tophus. This procedure requires only skill in performing arthrocentesis and familiarity with the use of the polarised microscope, both a part of the core curriculum in rheumatology. The deposited crystals responsible for the disease dissolve when SUA levels are brought back to normal,3,5 and the time for total dissolution relates to the duration of the disease; after 1 year of adequate hypouricaemic treatment, crystals have usually disappeared from the joints if the disease duration has not been too long.6 In the absence of MSU crystals, attacks of gout are impossible, and the disease can be considered cured. Patients who have formed MSU crystals on one occasion appear to easily form them anew if SUA levels are allowed to rise again, prompting the return of the disease.7,8 To avoid this, lifelong hypouricaemic drug treatment is necessary after the crystals have dissolved, although for some patients dietary and lifestyle modifications may suffice. Finally, in an important proportion of patients with gout, hyperuricaemia is a part of metabolic syndrome and the presence of gout should make clinicians aware of associated morbidities, which are reversible, at least to some extent, by modifying dietary and lifestyle habits. The recent publication of guidelines on gout diagnosis9 and management10 by the European League Against Rheumatism (EULAR), the quality of care indicators from the US,11 and outcome measures for clinical trials12 outline the current interest in gout.
Universities have a vital role
Authors: Sally C Davies
Journal: BMJ (2005)

Academic medicine has a key role in health systems, and the definition of the International Campaign to Revitalise Academic Medicine (ICRAM) captures the issues well. 1 In the United Kingdom, the number of clinical academics continues to fall, particularly at the clinical lecturer grade (42% lower in 2004 than in 2000). 2 At the same time, the numbers of students and young doctors are rising, creating an unstable situation.NHS staff already do most of the training for both postgraduates and undergraduates, and this is increasingly occurring outside university centres, including in primary care.The NHS funds some 40% of the academic posts.