tbuckley/cabot-search huggingface dataset:
Association Between Statin Use and Risk for Keratinocyte Carcinoma in the Veterans Affairs Topical Tretinoin Chemoprevention Trial
Authors: David D. Dore
Journal: Annals of Internal Medicine (2009)

Background: Recent evidence suggests that statins may prevent cancer. Objective: To quantify the association between statin use and the occurrence of keratinocyte carcinoma in high-risk veterans. Design: Cohort study. Setting: 6 Veterans Affairs medical centers. Participants: 1037 participants of the Veterans Affairs Topical Tretinoin Chemoprevention Trial, a randomized, multicenter, double-blind, vehicle-controlled trial of topical tretinoin, 0.1%, for prevention of keratinocyte carcinoma conducted from November 1998 to November 2004. Measurements: Time to first occurrence of keratinocyte carcinoma on the face or ears. Participants using a statin at randomization, according to the Veterans Affairs Pharmacy Benefits Management database, were considered exposed. Study dermatologists conducted physical examinations at baseline and every 6 months during follow-up. The association between statin use at randomization and the outcome was evaluated by using propensity score matching (n = 608) and Cox proportional hazards regression (n = 1037). Results: Among the 1037 participants, 37% used a statin at randomization (n = 397) for a median duration of at least 900 days over a median follow-up of 3.5 years. In the propensity score–matched analysis, statin use at randomization was not associated with keratinocyte carcinoma (rate ratio, 0.92 [95% CI, 0.73 to 1.16]), a finding that was consistent with the estimates derived from the Cox proportional hazards regression (rate ratio, 0.84 [CI, 0.70 to 1.02]). Limitations: The extent of residual confounding is unknown, and the confidence bounds around the measures of association were wide. These data may not be generalizable to lower-risk populations. Conclusion: These data show no conclusive or consistent relationship between long-term statin use and risk for keratinocyte carcinoma. Funding: Department of Veterans Affairs, Agency for Healthcare Research and Quality, American Cancer Society, and National Institutes of Health.
Chemotherapy for non-small cell lung cancer
Authors: D. P Carbone, J. D Minna
Journal: BMJ (1995)

A meta-analysis suggests that the benefits are small

For some cancers, treatments are so effective that the question of whether to treat does not arise. For many others, however, while gratifying responses sometimes occur, there are also substantial toxicities related to treatment, and benefits of any kind may be small. The toxicities, inconvenience, and expense of chemotherapy are endured by both patients whose tumours do and do not respond. When faced with such imperfect treatments, clinical trialists must determine, within the limitations of biological variability, whether these treatments result in statistically significant benefits and at what cost. Doctors thenhave to decide whether these benefits are clinically important and whether they outweigh potential risks for a particular patient.

With the relatively small absolute survival benefits observed for chemotherapy of non-small cell lung cancer, large numbers of patients are required to draw conclusions with confidence. In this issue of the Journal Albertini et al report the results of a meta-analysis of updated data from 9387 patients participating in 52 randomised clinical trials comparing chemotherapy with no chemotherapy …
CHADS2 SCORE PREDICTS THE OCCURRENCE OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH ATRIAL FIBRILLATION: A SINGLE-CENTER COHORT STUDY
Authors: Sylvie LANG, Stephane EDERHY, Louise BOYER-CHATENET, Ghislaine DUFAITRE, Emanuele Di ANGELANTONIO, Catherine MEULEMAN, Nabila HADDOUR, Emmanuelle BERTHELOT, Fanny DOUNA, Nadia AISSAOUI, Franck BOCCARA, Ariel COHEN
Journal: Journal of the American College of Cardiology (2010)
Abstract B76: CD8+FoxP3+ T cells: A new player in the immune response to ovarian cancer.
Authors: Sara E.F. Kost, Ronald J. deLeeuw, Brad H. Nelson
Journal: Cancer Research (2013)

Abstract Introduction: Tumor-infiltrating lymphocytes (TIL) are an important prognostic indicator in high-grade serous ovarian carcinoma (HGSC). Certain types of TIL (in particular CD8+ effector T cells) predict better outcomes, whereas others (most notably CD4+CD25+FoxP3+ regulatory T cells or Tregs) predict worse outcomes. An unconventional subset of CD8+FoxP3+ T cells has been widely reported in autoimmunity. While the functional significance of CD8+FoxP3+ TIL remains poorly understood, in a murine tumor model they were associated with effective anti-tumor responses. Hypothesis: CD8+FoxP3+ TIL are present in HGSC and correlate with effector TIL and increased patient survival. Experimental Design: Multi-parameter flow cytometry and immunohistochemistry (IHC) were performed on cohorts of 12 and 45 primary HGSC specimens, respectively, to enumerate and locate CD8+FoxP3+ TIL. For IHC, intraepithelial versus stromal location was determined by staining adjacent sections for the epithelial marker cytokeratin. Multi-color staining was resolved using the Nuance™ multispectral imaging system in conjunction with Metamorph software. Survival analysis will be performed by staining a cohort of 200 cases of HGSC. Results: By flow cytometry, CD8+FoxP3+ cells were found in variable proportions between HGSC cases, representing 1.3 - 7.9% of CD8+ TIL and 1.3 - 25.8% of FoxP3+ TIL. By IHC, CD8+FoxP3+ TIL were found together with CD8+FoxP3- and CD4+FoxP3+ TIL in epithelial and stromal tumor regions and represented up to 19% of the FoxP3+ population. Interestingly, the majority of CD8+FoxP3+ TIL were also found to be TIA-1+KI67-, consistent with an active role in the anti-tumor response. Conclusions: CD8+FoxP3+ TIL are a component of the host immune response to HGSC. Survival analysis is ongoing and will determine whether CD8+FoxP3+ T cells enhance or inhibit tumor immunity. Improved understanding of this new TIL subset will inform future immunotherapy strategies for this challenging malignancy. Citation Format: Sara E.F. Kost, Ronald J. deLeeuw, Brad H. Nelson. CD8+FoxP3+ T cells: A new player in the immune response to ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B76.
Abstract C9: An <i>in vitro</i> model of osteoblastic bone metastasis in prostate cancer
Authors: Reynald M. Lescarbeau, David L. Kaplan
Journal: Cancer Research (2009)

Abstract Prostate cancer progression is characterized by a striking affinity to spread to bone, where it forms metastases predominately of an osteoblastic phenotype, resulting in a significant source of morbidity. Currently, animal models for studying the development of these osteoblastic metastases are limited due to a lack of spontaneous osteoblastic metastasis development. In order to recapitulate osteoblastic metastasis development, an in vitro, three dimensional culture system was created utilizing silk fibroin scaffolds. LNCaP cells were seeded to silk scaffolds with human bone marrow derived mesenchymal stem cells (hMSCs) and cultured for 6 weeks. Examination after co-culture revealed through histological analysis that hMSCs underwent osteogenic differentiation in response to LNCaP paracrine signals. Paracrine interactions between hMSCs and LNCaPs were studied and IL-6, known to promote androgen independent growth, was found to be transiently expressed by hMSCs over the first two weeks of co-culture. In addition to secreted soluble signaling factors, the effect of extracellular matrix signals on the LNCaP cells was examined. LNCaP cells grown in a decellularized matrix, derived from hMSCs having undergone osteogenic differentiation, showed a 12 fold survival advantage in androgen depleted conditions over controls. This data indicates the ability of the co-culture system to stimulate differentiation of hMSCs towards an osteogenic linage and release soluble and extracellular matrix cues which stimulate androgen independent disease progression. The in vitro co-culture system presents a scalable and high throughput method for studying the molecular mechanisms underlying the osteoblastic component of prostate cancer bone metastasis. Citation Information: Cancer Res 2009;69(23 Suppl):C9.
Predicting Response to Recombinant Human Erythropoietin
Authors: Moshe Mittelman
Journal: Annals of Internal Medicine (1993)

Letters1 July 1993Predicting Response to Recombinant Human ErythropoietinMoshe Mittelman, MD and Sharon Floru, MDMoshe Mittelman, MDHasharon Hospital, Tel Aviv University; Petah-Tikva 49372, IsraelSearch for more papers by this author and Sharon Floru, MDHasharon Hospital, Tel Aviv University; Petah-Tikva 49372, IsraelSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-1-199307010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest the recent article by Henry and colleagues [1], summarizing four clinical trials of recombinant human erythropoietin (r-HuEPO). They conclude that therapy with r-HuEPO can increase the mean hematocrit value and decrease the mean transfusion requirement in anemic patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine and have low endogenous erythropoietin levels (<500 IU/L).Given the expanding indications for and the high price of r-HuEPO therapy, predicting the response to therapy is important. Response to r-HuEPO appears not to be related to age, gender, time since diagnosis, time since initiation of ...References1. Henry DH, Beall GN, Benson CA, Carey J, Cone LA, Eron LJ, et al. Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials. Ann Intern Med. 1992; 117:739-48. Google Scholar2. Stein RS, Abels RI, Krantz SB. Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes. Blood. 1991; 78:1658-63. Google Scholar3. Adamson JW, Schuster M, Allen S, Haley NR. Effectiveness of recombinant human erythropoietin therapy in myelodysplastic syndromes. Acta Haematol. 1992; 87(Suppl 1):20-4. Google Scholar4. Mittelman M, Floru S, Djaldetti M. Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders (Letter). Blood. 1992; 80:841-3. Google Scholar5. Cazzola M, Ponchio L, Beguin Y, Bergamaschi G, Liberato NL, Fregoni V, et al. Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial. Blood. 1992; 79:29-37. Google Scholar Author, Article, and Disclosure InformationAffiliations: Hasharon Hospital, Tel Aviv University; Petah-Tikva 49372, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1993Volume 119, Issue 1Page: 91-92KeywordsAIDSAttentionBlood plasmaClinical trialsErythropoietinHematocritPlasma proteinsSexual identityStem cells Issue Published: 1 July 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pulmonary Alveolar Proteinosis in Four Siblings
Authors: Kuldeep Teja, Philip H. Cooper, Jerry E. Squires, Patricia T. Schnatterly
Journal: New England Journal of Medicine (1981)

PULMONARY alveolar proteinosis (PAP) is a distinctive pathologic lesion in which alveoli are filled with periodic acid–Schiffpositive proteinaceous material. It is usually idiopathic, but it has been reported in association with a variety of other conditions.1 2 3 4 5 6 7 8 PAP is usually seen in adults, although the first description of cases included a young child.9 Since then, there have been several reports of PAP in infants and children, and the condition has been found at birth.8 This report describes four siblings in whom PAP developed during infancy. Our review of the literature disclosed several other affected sibships, yet the familial aspect of PAP . . .
Ireland announces compensation for hepatitis C
Authors: K. Wilson-Davis
Journal: BMJ (1995)

The Irish government has announced a package of compensation and treatment for people infected with hepatitis C virus after they were given blood transfusions or anti-D immunoglobulin. Blood donations were not tested for the virus before 1991, and some 500 people are estimated to have been infected by blood products, while about 1000 women were infected after being given anti-D immunoglobulin during pregnancy.

In a press release issued last week the minister of health, Mr Michael Noonan, said, “I am very hopeful that all those …
726 GENOTYPE OF THE TRANSCRIPTION FACTOR FOXO1 MEDIANTING INSULIN SIGNALING INFLUENCES THE SUSCEPTIBILITY TO AND SEVERITY OF NONALCOHOLIC FATTY LIVER DISEASE BY MODULATING FOXO1 MRNA LEVELS
Authors: L. Valenti, P. Dongiovanni, R. Rametta, A.L. Fracanzani, S. Fargion
Journal: Journal of Hepatology (2009)
STRUCTURE OF CEREBRUM
Authors: T. P. S. Powell
Journal: BMJ (1960)

<h3>Background</h3> Testicular dysgenesis syndrome (TDS) is a common disease that links testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis. The incidence of these disorders has increased over the last few decades, and testicular cancer now affects 1% of the Danish and Norwegian male population. <h3>Methods</h3> To identify genetic variants that span the four TDS phenotypes, the authors performed a genome-wide association study (GWAS) using Affymetrix Human SNP Array 6.0 to screen 488 patients with symptoms of TDS and 439 selected controls with excellent reproductive health. Furthermore, they developed a novel integrative method that combines GWAS data with other TDS-relevant data types and identified additional TDS markers. The most significant findings were replicated in an independent cohort of 671 Nordic men. <h3>Results</h3> Markers located in the region of <i>TGFBR3</i> and <i>BMP7</i> showed association with all TDS phenotypes in both the discovery and replication cohorts. An immunohistochemistry investigation confirmed the presence of transforming growth factor β receptor type III (TGFBR3) in peritubular and Leydig cells, in both fetal and adult testis. Single-nucleotide polymorphisms in the <i>KITLG</i> gene showed significant associations, but only with testicular cancer. <h3>Conclusions</h3> The association of single-nucleotide polymorphisms in the <i>TGFBR3</i> and <i>BMP7</i> genes, which belong to the transforming growth factor β signalling pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating data from multiple layers can highlight findings in GWAS that are biologically relevant despite having border significance at currently accepted statistical levels.
Abstract 5145: KDM2B expression regulates ribosome biogenesis and cancer cell growth in a p53-dependent manner
Authors: Marianna Penzo, Lucia Casoli, Laura Sicuro, Alice Galibiati, Daniela Pollutri, Marzia Govoni, Claudio Ceccarelli, Donatella Santini, Mario Taffurelli, Davide Treré, Lorenzo Montanaro
Journal: Cancer Research (2014)

Abstract Ribosome biogenesis is a cellular process requiring a fine-tuned control, as its deregulation is linked to cancer progression. Indeed, tumors characterized by an intense ribosome biogenesis often display a more aggressive biological and clinical behavior. Ribosomal RNA (rRNA) synthesis is controlled at several levels, the higher one being the epigenetic regulation of chromatin portions containing rRNA genes. KDM2B (Lysine (K)-specific demethylase 2B) is a histone demethylase modulating the accessibility of rRNA genes, thereby repressing their transcription. In particular KDM2B is known to specifically act on trimethylated K4 of histone H3 (H3K4) associated with rDNA. In this study we aimed to define the contribution of KDM2B expression to the biological features of breast cancer, a tumor type whose clinical behavior is known to be related to the rate of ribosome biogenesis. We show that, in primary breast carcinomas, lower KDM2B expression correlates with an increased size of specifically stained nucleolar organizer regions, a morphological parameter directly related to the rate of ribosome biogenesis, and with a poorer prognosis. In vitro, in breast cancer-derived cell lines, siRNA mediated KDM2B knock-down (KD) induced an increase in H3K4 trimethylation and in rRNA transcription. However, this is mirrored by an augmented cell proliferation only in p53 compromised cells, while p53 competent cells undergo cellular senescence and death. The latter effect, appears to be mediated by a p38-mediated phosphorylation of p53, inducing the expression of p15Ink4b and p21Waf1, and is not linked to p53 stabilization. In the long term, stable KDM2B KD in p53-compromised breast cancer cells induced a series of additional biological features including their augmented cellular clonogenic potential and invasive capability. Altogether our data indicate that abnormal JHDM1B-mediated epigenetic activation of rDNA genes elicits a p53-mediated growth arrest, but may promote cancer cell growth when p53 is lacking. Citation Format: Marianna Penzo, Lucia Casoli, Laura Sicuro, Alice Galibiati, Daniela Pollutri, Marzia Govoni, Claudio Ceccarelli, Donatella Santini, Mario Taffurelli, Davide Treré, Lorenzo Montanaro. KDM2B expression regulates ribosome biogenesis and cancer cell growth in a p53-dependent manner. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5145. doi:10.1158/1538-7445.AM2014-5145
SELENIUM DEFICIENCY IN PATIENTS WITH HEART FAILURE ENHANCES THE OXIDATIVE STRESS AND AGGRAVATES THE IMPAIRMENT OF CARDIAC FUNCTION
Authors: Yuji Hiraoka, Akihiro Nakayama, Yutaka Iida, Hiroyuki Yasui, Tadashi Matsumura, Masatoshi Fujita
Journal: Journal of the American College of Cardiology (2011)
Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry in lipid and phospholipid research
Authors: J. Schiller, R. Süß, J. Arnhold, B. Fuchs, J. Leßig, M. Müller, M. Petković, H. Spalteholz, O. Zschörnig, K. Arnold
Journal: Progress in Lipid Research (2004)
Formative Care: defining the purpose and clinical practice of care for the frail
Authors: Clive Bowman, Julienne Meyer
Journal: Journal of the Royal Society of Medicine (2013)

The emerging population of older people with chronic, progressive degenerative diseases pose the greatest challenge to the sustainability of health and care systems but services are not well developed for their needs1,2 and robust metrics of experience lacking. Modern Medicine generally can be described in terms of prevention, diagnosis and the evidenced treatment of acute and long-term conditions. Additionally, and particularly, for older people needs assessment, rehabilitation, palliative and end of life care are well established. These clinical domains are broadly mirrored in social care where prevention, personalisation, enablement, empowerment and risk management are commonly cited.

The early phase of Geriatric Medicine highlighted the importance of Comprehensive Geriatric Assessment, treatment and rehabilitation in reducing care needs3 and the improvement of living conditions and general support.4 Collectively, these have successfully limited avoidable dependency. In recent years, development has focused on improving end of life care. However, ageing populations feature a growing number of older dependent people who are increasingly unresponsive to traditional treatment(s) but for whom dying and death is not imminently anticipated.

This emerging dependent population is increasingly recognized5 as is the complexity of managing multiple morbidities.6 However, there is little coherence to the purpose of medicine for this population in spite of frequent public, professional and political concerns with common themes of dignity, quality of life and affordability.7,8 The continued major failures of care9 and inadequate clarity over life status10 or monitoring measures to assess experience11 all point to a need for new thinking in this ‘clinical space’.
Letter: Disclosure of medical records.
Authors: J Patterson, J L Taylor, J W Barnett
Journal: BMJ (1975)

18 (2-1%) 56 (8 0%) 2 (0 7%) Minor difference (B) 41 (4 7%) 77 (11-0%)12 (4-1%)Total A + B 59 (6-8%) 133 (19-0%)14 (4-8%)
The police surgeon's view Medical paternalism is unacceptable
Authors: M A Knight
Journal: BMJ (1995)

Police surgeons (otherwise known as forensic medical examiners in metropolitan London and forensic medical officers in Northern Ireland) are mostly general practitioners, and they may see both the victims and the perpetrators of violent and sexual assaults. They may be asked to attend accident and emergency departments and sometimes paediatric wards in order to assist with the documentation of injuries, the compilation of police statements, and to conduct joint examinations with paediatricians in cases of alleged physical and sexual child abuse.

Police surgeons may also see those accused of such assaults, who may themselves be injured, with a view to establishing their …
Sulfonylurea derivatives in cardiovascular research and in cardiovascular patients
Authors: Carl E Schotborgh, Arthur A.M Wilde
Journal: Cardiovascular Research (1997)

Sulfonylurea derivatives are hypoglycemic drugs frequently used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). In the β-cell sulfonylureas act by blocking ATP-sensitive potassium channels (K.ATP channels). In several organ systems, including the cardiovascular system, sulfonylurea receptors and functional K.ATP channels have been identified. In the heart their role is not clear; an endogenous cardioprotective effect has been suggested. There is no doubt that K.ATP channels are effectively blocked by sulfonylureas. In the last decade sulfonylureas have been widely used as a pharmacological tool in experimental (cardiac) research. Blockade of K.ATP channels is the proposed cellular mechanism of action for all sulfonylurea-related effects. However, other membrane currents are affected as well. In addition, myocardial metabolism is modified by sulfonylurea pretreatment. Hence, it should seriously be questioned whether these drugs are suitable in assessing involvement of cardiac K.ATP channels in, for example, ischemia-related events. The detrimental effects of sulfonylureas in experimental studies on myocardial ischemia have led to speculation whether the widespread use of these drugs in patients with NIDDM, most often suffering from accompanying ischemic heart disease, should be reconsidered. However, a review of the clinical literature reveals that the most consistent finding is a lower incidence of ventricular arrhythmias associated with the use of glibenclamide, while no excess mortality has been shown for this agent in NIDDM with ischemic heart disease. Despite some direct effects on systemic and coronary vasculature, there are, at present, no firm clinical data on the basis of which sulfonylurea derivatives should be withheld from the cardiac patient.
The Treatment of Persons Exposed to Rabies
Authors: Jonathan B. Rosefsky
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The article by Drs Corey and Hattwick (232:272, 1975) presents a dilemma because of the prophylaxis algorithm. If a normally behaving but unvaccinated dog, such as a pup under 1 year of age, licks a child on the mouth or on a skinned knee, then the "no" arrow drops to box number 8 that indicates killing the animal for flourescent antibody examination of the brain! Whereas I recognize the intent and value of this article, there may soon be many unnecessarily dead dogs around. Would Drs Corey and Hattwick wish to make some additional modifications to the prophylaxis algorithm?