tbuckley/cabot-search huggingface dataset:
A Prospective Study of Hemoglobin A1c Concentrations and Risk of Breast Cancer in Women
Authors: Jennifer Lin, Paul M. Ridker, Nader Rifai, I-Min Lee, JoAnn E. Manson, Julie E. Buring, Shumin M. Zhang
Journal: Cancer Research (2006)

Abstract Impaired glucose metabolism and hyperinsulinemia have been hypothesized to increase breast cancer risk. However, findings from observational studies relating blood concentrations of hyperinsulinemia markers to breast cancer risk have been inconsistent. We prospectively evaluated whether hemoglobin A1c (HbA1c) concentrations predict breast cancer risk in a large female cohort. We included 27,110 female participants of the Women's Health Study who were, at baseline, free of cancer and had usable blood specimens as well as sufficient information on potential risk factors for breast cancer. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazards regression models. All Ps were two sided. During an average of 10 years of follow-up, 790 incident cases of invasive breast cancer were confirmed. Higher baseline HbA1c levels were not associated with an increased risk of breast cancer. The multivariate RR for the highest relative to the lowest quintile of HbA1c levels was 0.87 (95% CI, 0.69-1.10; Ptrend = 0.22). Higher HbA1c levels were also not associated with an increased risk of breast cancer according to alternative clinical cutoff points for HbA1c or in the analyses stratified by body mass index or according to certain tumor characteristics. However, a weakly inverse association was noted among postmenopausal women, especially among those who had never used hormone therapy. There was also a weakly inverse association between HbA1c levels and estrogen receptor–negative breast tumors. These data suggest that higher HbA1c concentrations do not seem to increase risk of breast cancer among apparently healthy women. (Cancer Res 2006; 66(5): 2869-75)
756. The Use of Immune Cell Trafficking to Deliver an Oncolytic Virus to Tumors
Authors: Steve H. Thorne, Robert Negrin, Christopher H. Contag
Journal: Molecular Therapy (2005)

Cytokine Induced Killer (CIK) cells are a population of ex vivo-expanded PBMC's that have been found to target and destroy tumors following systemic delivery. However their effective clinical use is typically limited to residual disease. Oncolytic viruses, modified such that their replication is restricted to tumor cells, have demonstrated antitumor effects in the clinic, even against large primary tumors. It was found that an oncolytic strain of vaccinia virus displayed unusual replication kinetics within CIK cells, with an extended eclipse phase. This period of time between viral infection and lysis correlates well with the time required for CIK cells to traffic to the tumor in vivo. Additionally, CIK cells were found to maintain their killer phenotype while infected, and vaccinia-infected tumor cells were shown to become more susceptible to CIK cell killing (possibly due to NKG2D ligand up-regulation). In vivo studies used whole body bioluminescent and fluorescent imaging to track viral distribution, CIK cell trafficking and tumor size in immunocompetent mouse models. It was found that pre-infected CIK cells could be used to deliver virus systemically to tumors, with minimal infection at other sites in the body. Furthermore, it was shown that pre-infected CIK cells demonstrated significantly increased antitumor effects compared to either therapy alone, or compared to both therapies used in combination. This represents a new approach to combining two biological therapies in order to best harness the benefits of both and to increase their individual potency. This method could potentially further be used to deliver any gene-based therapy to a tumor with subsequent selective replication at the target site.
The Myc Target Gene <i>JPO1/CDCA7</i> Is Frequently Overexpressed in Human Tumors and Has Limited Transforming Activity <i>In vivo</i>
Authors: Rebecca C. Osthus, Baktiar Karim, Julia E. Prescott, B. Douglas Smith, Michael McDevitt, David L. Huso, Chi V. Dang
Journal: Cancer Research (2005)

Abstract MYC is frequently overexpressed in human cancers, but the downstream events contributing to tumorigenesis remain incompletely understood. MYC encodes an oncogenic transcription factor, of which target genes presumably contribute to cellular transformation. Although Myc regulates about 15% of genes and combinations of target genes are likely required for tumorigenesis, we studied in depth the expression of the Myc target gene, JPO1/CDCA7, in human cancers and its ability to provoke tumorigenesis in transgenic mice. JPO1/CDCA7 is frequently overexpressed in human cancers, and in particular, its expression is highly elevated in chronic myelogenous leukemia blast crisis as compared with the chronic phase. In murine lymphoid tissues, ectopic human JPO1/CDCA7 expression resulted in a 2-fold increased risk of lymphoid malignancies at 1 year. The transgene, which was driven by the H2-K promoter, exhibited leaky expression in nonlymphoid tissues such as kidney. We observed a significant increased incidence of transgenic animal solid tumors, which were not seen in littermate controls. These observations suggest that JPO1/CDCA7 may contribute to Myc-mediated tumorigenesis.
Markedly enhanced susceptibility to experimental autoimmune myasthenia gravis in the absence of decay-accelerating factor protection
Authors: Feng Lin, Henry J. Kaminski, Bianca M. Conti-Fine, Wei Wang, Chelliah Richmonds, M. Edward Medof
Journal: Journal of Clinical Investigation (2002)

Myasthenia gravis (MG) is an autoimmune neuromuscular transmission disorder characterized by loss of acetylcholine receptors (AChR's) due primarily to the production of anti-AChR autoantibodies. In this study we investigated whether the presence of decay-accelerating factor (DAF or CD55), an intrinsic complement regulator, protects against the development of disease. Experimental autoimmune MG was induced in Daf1(-/-) mice (devoid of neuromuscular DAF protein) and their Daf1(+/+) littermates by injection of rat anti-AChR mAb McAb-3. After twenty-four hours, grip strength assessment revealed that Daf1(-/-) mice exhibited hold times of less than 30 seconds, compared with more than 8 minutes for the Daf1(+/+) controls. The weakness was reversed by edrophonium, consistent with a myasthenic disorder. Immunohistochemistry revealed greatly augmented C3b deposition localized at postsynaptic junctions, and radioimmunoassays showed more profound reductions in AChR levels. Electron microscopy demonstrated markedly greater junctional damage in the Daf1(-/-) mice compared with the Daf1(+/+) littermates. Control studies showed equivalent levels of other cell surface regulators, i.e., Crry and CD59. The results demonstrate that mice that lack DAF are markedly more susceptible to anti-AChR-induced MG, which simulates the primary mechanism in the human disease, and strongly suggest that in disease flares complement inhibitors might have therapeutic value.
Doctors demand national screening for chlamydia
Authors: Rebecca Coombes
Journal: BMJ (2004)

Public health doctors have derided the slow progress towards a national screening programme for chlamydia as “disgraceful.”

The BMA's annual conference of public health medicine called on the government to roll out screening across the United Kingdom as a matter of urgency.

Dr Howard Barnes, who proposed the motion, said the absence of a national programme had led to a high volume of uncoordinated testing.

“In a district near me in Yorkshire 14 000 people have been tested. That is out …
Acute medical beds could be cut.
Authors: C. J. Williams, J. D. Yeomans
Journal: BMJ (1992)

infarction in 1988.For the 109 patients whose patients' health status or their satisfaction with SIR,-Those responsible for medical and surgical notes were available (less than half the number of their care.-emergencies will have read with astonishment and patients identified from the coronary care unit'sWe believe that audit is important and that its dismay the Audit Commission's recommendations records), the median delay in attending the accident lessons should be viewed primarily in a clinical to reduce the numbers of acute hospital beds.'" and emergency department was 240 minutes.The rather than a financial light.The complexities of
Smoke hoods in aeroplanes.
Authors: I. R. Hill
Journal: BMJ (1992)

European Joint Aviation Authority inevitably introduces further delay.As far back as 1976 the Snyder report concluded that state of the art technology was not being sufficiently applied to cabin safety,'°and reports since then have concurred.51'As a survivor of the Kegworth crash asked, why does it take so long to do so little?
P214 SPECIFIC MUTATIONS (L5P; L7P; L15S) IN THE IMMUNODOMINANT EPITOPE HCV-NS3 (AA 1253–1272) AGAINST HLA-DQB1*0301, PROVOKE NON-RESPONSE TO ANTIVIRAL TREATMENT WITH PEGIFN/RBV IN PATIENTS WITH CHC-1
Authors: P. Muñoz de Rueda, R. Quiles, A. Gila, M.A. Lopez Nevot, J. Casado, A. Carazo, A.B. Martín Álvarez, S. Jimenez Ruíz, J.A. Muñoz Gámez, E.J. Pavón Castillero, L. Sanjuan Núñez, A. Ruíz Extremera, J. Salmerón
Journal: Journal of Hepatology (2014)
Clinical Lectures Delivered in the Out-Patient Department of the Hospital for Sick Children, Great Ormond Street
Authors: W. B. Cheadle
Journal: BMJ (1872)

CASE. -Dropsy after Sczrlatina.-Hydirolthorax.-Treat,nentfby Digi.Ia?is.-CopiousDiuresis.-Coliapse of thte Chest-Wall.-Com.pieeRe..oz'ewy.-Remarks.-FrederickC., a large healthy looking child, two years old, first came here three months ago.His appearance at that time presented a great contrast to his present condition, for his lips were bloodless, his face pale and bloated, and his whole body swollen: he was suffering, in fact, from general anasarca.The history given by tlle mother was, that the child had had scarlatina three months pre- viously, and when recovering from this was again laid up with what the doctor in attendance called congestion of the lungs.The boy had never been well since, and had lately become more pale and puffy in the face.The urine was examined and found to be albuminous.There was stated to be some dyspnoea, but not of any distressing kind, and
A Different Peer Review
Authors: Irvine H. Page
Journal: JAMA (1973)

Peer review means different things to different people. To most American physicians it means PSRO, to the British House of Lords it means Peers examining other Peers for moral turpitude, and to the scientific community, it means Study Sections and Councils that determine a grantee's financial and possibly research future. I shall prudently leave discussion of the first two to<i>my</i>peers. But as an ancient peer reviewer (ad 1949) I feel impelled, by my desire to have all physicians understand the threat to biomedical research, to challenge Secretary Weinberger's quoted statement (UPI) that, "There is too much emphasis on investigator-initiated research and not enough on directed research." Further, the Bureau of Management and Budget let it be known by way of a position paper released by Senator Kennedy, that the peer review groups of the National Institutes of Health (NIH) are self-serving, too numerous and costly, allow government administrators
Lack of Evidence of Upper Gastrointestinal Endoscopy as a Risk Factor for Transmission of Hepatitis B Virus
Authors: A. P. Ferrari, S. Geocze, M. L. G. Ferraz, A. E. B. Silva, M. P. Vilela
Journal: Endoscopy (1991)

See also: Methods of Disinfecting Endoscopic Material: Results of an International SurveyEndoscopy 1989; 21(06): 247-250DOI: 10.1055/s-2007-1012962
Firearm Training and Storage
Authors: David Hemenway
Journal: JAMA (1995)

To determine the extent of firearm training among gun owners, how gun owners currently store their weapons, and the relationship between gun training and gun storage.A national random telephone survey of gun owners conducted from May through June 1994.A total of 800 adult gun owners residing in the United States.Number of gun owners who received firearm training and number who store a firearm loaded and unlocked. Logistic regression analyses were conducted to examine factors associated with firearm training and gun storage practices.A total of 451 (56%) of gun owners have received firearm training. A total of 170 (21%) of gun owners keep a firearm both loaded and unlocked in the home. Factors associated with an increased likelihood of storing guns loaded and unlocked included owning a gun for protection (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.62 to 3.54), owning a handgun (OR, 3.31; 95% CI, 1.85 to 5.95), and having received firearm training (OR, 1.71; 95% CI, 1.10 to 2.67). Length of firearm training and how recently training was received have little effect on storage practices.It has been suggested that many homicide, suicide, and accidental firearm injuries might be prevented if ready access to lethal weapons was reduced, in part through appropriate storage of guns. Although increased training has been advocated as the prime method to improve gun storage practices, our results cast doubt on whether firearm training, at least as currently provided, will substantially reduce the inappropriate storage of firearms.
Endoscopic ultrasound rendezvous for bile duct access using a transduodenal approach: cumulative experience at a single center. A case series
Authors: Y. Kim, K. Gupta, S. Mallery, R. Li, T. Kinney, M. Freeman
Journal: Endoscopy (2010)

Endoscopic ultrasound (EUS)-assisted biliary access is utilized when conventional endoscopic retrograde cholangiopancreatography (ERCP) fails. We report a 10-year experience utilizing a transduodenal EUS rendezvous via a transpapillary route without dilation of the transduodenal tract, followed by immediate ERCP access. Patients included all EUS-guided rendezvous procedures for biliary access that were performed following ERCP failure. EUS-assisted bile duct puncture was performed via a transduodenal approach and a guide wire was advanced through the papilla without any dilation or bougienage of the tract; ERCP was performed immediately afterwards. EUS-assisted biliary rendezvous was attempted in 15 patients (mean age 66 +/- 18.2 years; malignant = 10, benign = 5). Mean diameter of measured bile ducts was 14.3 +/- 5.17 mm (range 4-23 mm). The reasons for initial ERCP failure were tumor infiltration or edema (n = 9), intradiverticular papilla (n = 2), pre-existing duodenal stent (n = 1), and anatomic anomalies (n = 3). Successful EUS-guided bile duct puncture and wire passage were achieved in all 15 patients (100 %), with drainage being successful in 12 / 15 (80 %). Failures occurred in three patients due to inability to traverse the biliary stricture (n = 2) or dissection of a choledochocele with the guide wire (n = 1); all were subsequently drained via percutaneous methods. Stents placed were metallic in eight patients and plastic in four. Complications consisted of moderate pancreatitis after a difficult ERCP attempt in one patient, and bacteremia after percutaneous biliary drainage in another. There were no instances of perforation, extraluminal air or fluid collections. EUS-assisted biliary drainage utilizing a transduodenal rendezvous approach demonstated a high success rate without any complications directly attributable to the EUS access. Advantages over percutaneous biliary and other methods of EUS biliary access include performance under the same anesthesia, and a very small-caliber needle puncture similar to EUS/fine-needle aspiration.
Temporary blood flow stasis with degradable starch microspheres (DSM) for liver metastases in a rat model.
Authors: A D Flowerdew, H K Richards, I Taylor
Journal: Gut (1987)

A reliable liver metastasis model using intraportal injections of sarcoma cells was established in syngeneic hooded Lister rats to study the blood supply of the tumours and to evaluate the role of degradable starch microspheres (DSM) in conjunction with selective hepatic arterial and portal venous chemotherapy. The tumour/normal liver (T/L) ratio after intra-arterial and intraportal injection of 113Sn microspheres was 1.04 (range: 0.38-1.15) and 0.03 (range: 0.006-0.22), respectively. After intravenous 14C-iodoantipyrine quantitative autoradiography of tumour and normal regions demonstrated a mean T/L ratio of 0.74 +/- 0.05. After hepatic artery ligation (HAL) and portal vein ligation (PVL) the values were 0.32 +/- 0.05 and 0.42 +/- 0.05, respectively. These results confirm that the vascularity of the tumours in this model is similar to human colorectal cancer metastases. Radiolabelled 14C 5-Fluorouracil (5-FU) was given intravenously, via the hepatic artery and via the portal vein (the latter two routes with and without DSM). Quantitative autoradiography of tumour regions showed that selective hepatic arterial administration with DSM resulted in a significantly increased concentration of 14C-5-FU within the tumours. These results suggest that DSM may enhance the therapeutic benefit of hepatic arterial 5-FU by increasing its uptake into tumours.
THE BILIARY OBSTRUCTION REQUIRED TO PRODUCE JAUNDICE
Authors: Philip D. McMaster, Peyton Rous
Journal: The Journal of Experimental Medicine (1921)

The bile ducts from three-quarters of the liver substance in dogs and monkeys can be obstructed without any clinical evidence developing of pigment or cholate accumulation in the organism. And in the dog nineteen-twentieths of the liver substance can be placed in stasis without the occurrence of tissue icterus such as regularly follows total obstruction in this animal. There is no reason to suppose that this will not be found true in the monkey as well. Always a local obstruction results sooner or later in atrophy of the affected tissue with compensatory hypertrophy elsewhere. Thus as time passes the derangement of function produced by the sudden stasis is progressively lessened. The plasma of the dog and monkey, unlike that of man, is normally free from bilirubin, and this pigment so readily escapes from the blood into the urine that bilirubinuria is often to be found in the dog in the absence of bilirubinemia, while the latter is never met with alone in either animal. It follows that in both species the renal threshold for bilirubin is much lower than in man,-if indeed one can be said to exist at all. The amount of biliary obstruction required to produce jaundice in human beings is probably as great as in the experimental animals with which we have dealt. The clinical jaundice encountered in association with local liver lesions should be viewed not as the result of local bile resorption, but as due to a general injury to the hepatic parenchyma or ducts, or to blood destruction.
Cancer Risk Disparities between Hispanic and Non-Hispanic White Populations: The Role of Exposure to Indoor Air Pollution
Authors: Diana E. Hun, Jeffrey A. Siegel, Maria T. Morandi, Thomas H. Stock, Richard L. Corsi
Journal: Environmental Health Perspectives (2009)

Hispanics are the fastest growing minority group in the United States; however, minimal information is available on their cancer risks from exposures to hazardous air pollutants (HAPs) and how these risks compare to risks to non-Hispanic whites.We estimated the personal exposure and cancer risk of Hispanic and white adults who participated in the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study. We evaluated 12 of the sampled volatile organic compounds and carbonyls and identified the HAPs of most concern and their possible sources. Furthermore, we examined sociodemographic factors and building characteristics.Cumulative cancer risks (CCRs) estimated for Hispanics (median = 519 x 10(-6), 90th percentile = 3,968 x 10(-6)) and for whites (median = 443 x 10(-6), 90th percentile = 751 x 10(-6)) were much greater than the U.S. Environmental Protection Agency (EPA) benchmark of 10(-6). Cumulative risks were dominated by formaldehyde and p-dichlorobenzene (p-DCB) and, to a lesser extent, by acetaldehyde, chloroform, and benzene. Exposure to all of these compounds except benzene was primarily due to indoor residential sources. Hispanics had statistically higher CCRs than did whites (p </= 0.05) because of differences in exposure to p-DCB, chloroform, and benzene. Formaldehyde was the largest contributor to CCR for 69% of Hispanics and 88% of whites. Cancer risks for pollutants emitted indoors increased in houses with lower ventilation rates.Hispanics appear to be disproportionately affected by certain HAPs from indoor and outdoor sources. Policies that aim to reduce risk from exposure to HAPs for the entire population and population subgroups should consider indoor air pollution.
Adjuvant UK: A UK Prognostic Model for Early Breast Cancer That Includes Mode of Detection.
Authors: G. Wishart, E. Azzato, P. Pharoah, D. Greenberg, J. Rashbass, O. Kearins, G. Lawrence, C. Caldas, P. Ravdin
Journal: Cancer Research (2009)

Abstract AIM: To develop and validate a prognostication model to predict overall survival for women treated for early breast cancer in the UK based on cancer registry data. Unlike SEER, this dataset includes accurate information on mode of detection as well as systemic therapy.METHOD: Using the Eastern Cancer Registration &amp; Information Centre (ECRIC) dataset, information was collated for 5818 women diagnosed with invasive breast cancer in East Anglia from 1999-2003. All patients underwent surgery, had records of pathological staging (tumour size, grade, lymph node status, ER status), systemic treatment (chemotherapy, hormone therapy, both), mode of detection (screen-detected, symptomatic) and follow up, censored on 31 December 2007. A model was derived from these data using Cox proportional hazards, with ER positive and ER negative tumours modelled separately, and this was subsequently validated in an external dataset of 5468 patients from the West Midlands Cancer Intelligence Unit (WMCIU). Validation was performed by comparing (a) observed and expected mortality (overall &amp; breast cancer specific) at 5 &amp; 8 years and (b) receiver operating characteristic (ROC) curves in both ECRIC &amp; WMCIU datasets.RESULTS:ECRIC datasetDifference in overall observed/expected mortality &amp;lt;1% at 5 years (14.8% vs 14.9%) and 8 years (18.9% vs 18.9%). Area under ROC curve (AUC) was 0.81.Difference in breast cancer specific observed/expected mortality &amp;lt;1% at 5 years (10.6% vs 11.0%) and 8 years (12.9% vs 13.5%). AUC was 0.84.WMCIU dataset:Difference in overall observed/expected mortality &amp;lt; 1% at 5 years (15.8% vs 16.5%) and 8 years (17.5% vs 17.8%). AUC was 0.79.Difference in breast cancer specific observed/expected mortality &amp;lt;2% at 5 years (11.0% vs 12.6%) and 8 years (12.2% vs 13.6%). AUC was 0.82.Overall model fit was good across all subgroups although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). There was no significant difference between the ROC curves generated with ECRIC and WMCIU data (ER positive X2 = 0.17, p=0.68; ER negative X2 =0.00, P=0.95).CONCLUSION: We have developed a prognostication model for early breast cancer based on data from a UK cancer registry that has included mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second patient cohort. This model will underpin a new web-based prognostication and treatment benefit tool for early breast cancer based on UK data (Adjuvant UK). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4033.
Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin
Authors: Toshiaki Iba, Akio Kidokoro, Masaki Fukunaga, Kunihiko Nagakari, Masaru Suda, Seiichiro Yoshikawa, Yukiko Ida
Journal: Intensive Care Medicine (2005)