tbuckley/cabot-search huggingface dataset:
Huntingtons Disease
Authors: Jeffrey S. Flier, Lisa H. Underhill, Joseph B. Martin, James F. Gusella
Journal: New England Journal of Medicine (1986)

HUNTINGTON'S disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by a progression of involuntary choreiform movements, psychological change, and dementia.1 George Huntington and his father and grandfather first studied the illness in families in East Hampton, Long Island, New York. The ancestry of some cases has been traced to immigrants from Bures, England, in 1649.2 , 3 Other evidence also suggests that the disease is of European origin; cases in South Africa have been traced to Dutch settlers who emigrated there in 1658,4 and cases in Tasmania have been traced to ancestors from Somerset, England.3 These . . .
Abstract 13888: Critical Role of Hyaluronan in Neointimal Formation after Vascular Injury in Mice
Authors: Yuichiro Kashima, Masafumi Takahashi, Yuji Shiba, Naoki Itano, Koji Kimata, Atsushi Izawa, Uichi Ikeda
Journal: Circulation (2012)

Background: Hyaluronan (HA), a non-sulfated glycosaminoglycan, is a primary component of extracellular matrix that accumulates in the lesions of atherosclerosis and restenosis after percutaneous coronary intervention. However, the role of HA in these lesions remains unclear. The purpose of this study is to investigate the role of HA in neointimal formation after vascular injury and its tissue-specific role in vascular smooth muscle cells (VSMCs) by using a cre-lox conditional transgenic (cTg) strategy. Methods and Results: HA was expressed in neointimal lesion in human atherosclerosis. We produced 2 types of vascular injury, cuff-mediated and wire-mediated injury, in femoral artery and found that marked HA expression in the injury-induced neointimal lesion of wild-type (C57BL/6) mice. We further examined the effect of 4-methylumbelliferone (4-MU), a specific inhibitor of HA production, on neointimal formation after wire-mediated injury. Neointimal formation was significantly attenuated by the oral treatme...
How well do standard prognostic criteria predict oncotype DX (ODX) scores?
Authors: A. H. Kamal, C. L. Loprinzi, C. Reynolds, A. C. Dueck, X. J. Geiger, J. N. Ingle, R. W. Carlson, T. J. Hobday, E. P. Winer, E. A. Perez, M. P. Goetz
Journal: Journal of Clinical Oncology (2007)

576 Background: In node-negative, ER + breast cancer, gene expression profiling can identify level of risk and, in the case of ODX, may also identify pts with a higher chance of benefiting from adjuvant chemotherapy. Because the gene profile in ODX includes an assessment of ER, HER2, and proliferation, we hypothesized that clinicians using standardized criteria could discriminate risk (high versus low/intermediate) as specified by ODX. Methods: We identified Mayo Clinic patients with node-negative, ER + breast cancer, for whom ODX scores were available. Tumor slides were reviewed by an expert breast pathologist to confirm tumor size, histology, and tumor grade. Both ER and PR were quantitated; HER-2 was determined by IHC (FISH, if 2+). These clinical cases were presented to six academic oncologists, blinded to the ODX score, to predict ODX risk (low, intermediate, or high) and give their recommendation for chemotherapy (CTX) (yes/no). Afterwards, they were presented with the same cases with the actual ODX score, to give recommendations regarding CTX. Results: ODX scores in tumors from 31 patients were low in 18 pts, intermediate in 10 pts, and high in 3 pts. Concordance between predicted and actual ODX scores being low/intermediate vs high exceeded 87% for each oncologist. The most frequent discrepancies were actual low scores predicted as intermediate (31/80 discordant) and actual intermediate scores predicted as low (29/80 discordant). Overall agreement of predicted scores (high vs low/intermediate) among the oncologists was substantial (kappa=0.75, p&lt;0.0001). CTX recommendations following provision of the ODX scores changed on average 18.2% (range 12.9%-25.8%) of the time, with slightly fewer changing for, versus against, a CTX recommendation. Conclusions: Our findings suggest that the proper evaluation and interpretation of traditional prognostic criteria will identify most node negative, ER + patients at high risk of recurrence (as predicted by ODX) but poorly discriminate low versus intermediate risk. The provision of ODX data changed the recommendation for CTX in approximately 20% of cases. No significant financial relationships to disclose.
The true predictive value of the human tumor stem cell assay: does a workable assay select for treatment responders?
Authors: V Hug, H Thames, D Johnston, G Blumenschein, B Drewinko, G Spitzer
Journal: Journal of Clinical Oncology (1984)

In practice, the human tumor clonogenic assay is workable for less than half of the patient population to which it is applied, since the remainder of the specimens fail to produce sufficient numbers of colonies. Thereby a bias may be introduced which could result in a false predictive value positive of the test. It is therefore necessary to compare the responses to treatment of patients whose tumors could be assayed in vitro to those whose tumors failed to grow adequately, to assure that the prevalence of treatment responders has not changed within the group of patients for which the assay worked. From an analysis of the treatment response of 70 patients with stage III and IV ovarian carcinomas and 70 patients with stage IV breast cancer, no selection bias did occur and no preferential in vitro growth of tumor samples from patients with treatment response was found.
High-dose cytosine arabinoside in the treatment of acute myelogenous leukemia: contributions to outcome of clinical and laboratory attributes.
Authors: J E Curtis, H A Messner, M D Minden, S Minkin, E A McCulloch
Journal: Journal of Clinical Oncology (1987)

High-dose cytosine arabinoside (HDAra-C) has been used for remission induction, and in conventional doses for maintenance in a trial of single-agent therapy in 43 previously untreated patients with acute myelogenous leukemia (AML). Rationale for the trial was provided by the observed decrease in leukemic blast cell self-renewal in culture following exposure to Ara-C. Compared with a previous trial of 57 patients treated with multidrug therapy, single-drug Ara-C was associated with a significantly improved complete remission rate (P = .010), although the survival time was not increased. All patients with low self-renewal responded to HDAra-C in contrast to the previous trial where some patients with this phenotype failed remission induction. The clinical observations are consistent with the view that the antileukemic effect of Ara-C has some specificity for cellular events required for self-renewal of blast cells. Exposure in vivo to Ara-C was associated with an increase in blast stem cell renewal at relapse, indicating that maintenance with other drugs should be tested. The study demonstrates the importance of biological attributes in design and analysis of clinical trials.
Letrozole for advanced breast cancer.
Authors: G Hoctin-Boes, R Yates, M Steinberg
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.8.2892 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9704745 Letrozole for advanced breast cancer. G Hoctin-BoesxG Hoctin-BoesSearch for articles by this author , R YatesxR YatesSearch for articles by this author , M SteinbergxM SteinbergSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.8.2892 PDF "Letrozole for advanced breast cancer.." Journal of Clinical Oncology, 16(8), pp. 2892–2893© 1998 by American Society of Clinical Oncology
Abstract 186: The Cardiac Specific Splicing Regulator Rbm20 decreases in Specific Forms of Acquired Heart Disease
Authors: Maarten van den Hoogenhof, Abdelaziz Beqqali, Inge van der Made, Dirk Duncker, Jolanda van der Velden, Yigal Pinto, Esther Creemers
Journal: Circulation Research (2013)

Introduction: Rbm20 is a RNA-binding protein enriched in heart- and skeletal muscle. Mutations in Rbm20 have been described to cause heart failure. Furthermore, Rbm20 has been shown to regulate alternative splicing of titin (Ttn). This demonstrates that RBM20 has a major role in cardiac biology. However, it is unknown how Rbm20 expression changes in acquired heart disease. Therefore, we investigated expression of Rbm20 on mRNA and protein level and the degree of alternative splicing of Ttn in various forms of heart disease. Methods: We measured mRNA expression and protein levels of Rbm20 by western blotting and qPCR in transverse aorta constrictions (TAC) in mice and pigs, and in human heart disease including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), aortic stenosis (AoS) and pulmonary artery hypertension (PAH). We measured cardiac function in mice with echocardiography, and measured stress markers with qPCR. Furthermore, we analyzed Ttn splicing using qPCR and RT-PCR. Results: Real-time PCR and western blotting revealed that Rbm20 is selectively downregulated in mice after TAC and in patients with aortic stenosis. In contrast, we did not observe a difference in Rbm20 levels in patients with DCM, HCM and PAH. Furthermore, we measured functional parameters such as ejection fraction (EF), systolic left ventricular internal diameter (LVIDsys), and fractional shortening (FS), as well as ANF level in TAC mice, and correlated these to Rbm20 level. We found that the level of downregulation of Rbm20 is correlated with heart failure severity in mice after TAC. Also, we found that Ttn is differentially spliced after loss of Rbm20. Conclusions: Here we show for the first time that Rbm20 decreases in acquired forms of heart failure such as TAC in mice and pigs, and AoS in men. Furthermore, in experimental HF in mice, Rbm20 levels correlate to HF severity. Moreover, loss of Rbm20 leads to skipping of intron retention in Ttn in the region between exon 50-70. However, the biological effect of this event remains unclear. Given its major role in the heart, loss of Rbm20 may play an important role in the development of heart disease.
Abstract P147: Hemoglobin A1c Cut Points to Define Various Glucose Intolerance Groups in a South Asian Population
Authors: Mohan Thanikachalam, Vijaykumar Harivanzan, Vijay Nambi, Sadagopan Thanikachalam
Journal: Circulation (2015)

Objective: American Diabetes Association (ADA) has proposed a hemoglobin A1c cut point of 6.5% as a diagnostic test for diabetes (DM). It is important to know whether this cut point applies to populations worldwide. Here we determine the A1c cut points for various levels of glycemia in South Asian population, a ethnic group with high susceptibility to type-2 DM. Methodology: We conducted a cross-sectional analysis in 6965 South Indians without history of DM. All had fasting plasma glucose (FPG) and 2-hour post-prandial plasma glucose (PPG) measurements after a 75-g glucose load and were classified to have Impaired Fasting Glucose (IFG; FPG ≥100 & ≤125 & PPG ≤139), Impaired Glucose Tolerance (IGT; FPG ≤99 & PPG ≥140 & ≤199), DM (FPG ≥126 or PPG ≥200) and normal glucose tolerance (NGT; FPG ≤99 & PPG ≤139) according to ADA criteria. A1c was measured using BIORAD D-10 A1c analyzer. Based on receiver operating characteristic curves, optimum sensitivity and specificity were derived for defining A1c cut points f...
Health status, medical care, preventive screening, and risk behaviors in adult survivors of cancer diagnosed during adolescence: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: A. Termuhlen, J. Tersak, M. Hudson, A. Mertens, N. Gimpel, W. Bleyer, Y. Yasui, L. Robison, K. Oeffinger
Journal: Journal of Clinical Oncology (2004)

6023 Background: Adolescence (AD) and pre-adolescence (PRE-AD) are critical physical and psychological developmental periods. The purpose of this study was to determine if the health status, health care utilization, or risk behaviors were different in survivors diagnosed in their AD and PRE-AD years in comparison with those diagnosed in their childhood years. Methods. The CCSS is a 26 institution cohort study of 5 year survivors of pediatric cancer diagnosed 1970–1986. Self-reported data were analyzed in 9535 adult survivors (≥ 18 years of age) grouped into three categories based on age at cancer diagnosis: 0–9 years old (CH, N=4768), 10–12 years old (PRE-AD, N=1438), and 13–20 years old (AD, N=3329). Logistic regression was used to estimate odds ratio and 95% confidence levels for outcomes in survivors diagnosed in PRE-AD and AD in comparison to the CH group. Results: CH, PRE-AD, and AD had similar health status outcomes and cancer-related health care. AD females were more likely to report a pap smear or a clinical breast exam than CH females. PRE-AD females were more likely to be current smokers, physically inactive, or binge drink in comparison with CH females. PRE-AD males were more likely to binge drink in comparison with CH males. In contrast, AD males who were 26 years or older at the time of interview were less likely to binge drink in comparison with CH males of the same age at interview strata. Conclusion: The diagnosis of cancer during the teens does not produce more adverse general or mental health outcomes than diagnosis as a younger child. Survivors of adolescent cancer seek cancer-related visits, general medical care and perform health screenings equally or better than do survivors who are younger at diagnosis. Survivors diagnosed during pre-adolescence report an excess of risk behaviors as young adults and could benefit from targeted interventions. No significant financial relationships to disclose.
Inversion of emergency pyramid
Authors: B. J Finlayson
Journal: BMJ (2003)

Editor—I do not think the sentiments in the letter by Cooke and Castile reflect the views of most consultants in emergency medicine.1 The “see and treat” concept was developed at a single hospital and worked well there. It has not been subjected to critical appraisal or peer review.

I have serious concerns that diverting senior clinicians from treating ill patients will be detrimental. It is a waste of years of training and expertise to concentrate the most experienced medical resources of an emergency department on patients who have the least serious conditions—some of whom, one could argue, should not be there at all. I find the term “the faded idea of inappropriate attendance” inappropriate in itself. I think this is an expression of political correctness.

I tested a similar scheme in my own department in 1999, as a run-up to Millennium Eve. I abandoned the idea when I found that I was reassuring a patient that he would come to no harm from a house spider bite while my registrar struggled with the case of a critically ill patient in the resuscitation room, reluctant to disturb the “great experiment.”

NHS Direct, despite its much trumpeted development, has not reduced the numbers of patients attending emergency departments; neither has the opening of walk-in centres—at least not in my area. Emergency departments, in common with the rest of the NHS, remain underresourced, and such schemes as see and treat, while laudable in the big picture, are methods of massaging the figures towards achieving the government's four hour emergency targets without adequately addressing the real problems.
The prognostic significance of donor dendritic cells in allogeneic hematopoietic progenitor cell transplant
Authors: N. Dejoubner, Z. Ali, M. Grasier, E. Hamilton, C. Flowers, S. Lonial, A. Langston, E. K. Waller
Journal: Journal of Clinical Oncology (2008)

7044 Background: We tested whether numbers of donor dendritic cells (DC) are correlated with GvHD, relapse and survival following allogeneic blood hematopoietic progenitor (HPC) transplantation. Methods: Analysis of 251 patients with blood cancers who received non- manipulated allogeneic HPC transplants from HLA matched related (N=134) and unrelated donors (N=117). 86 patients had low-risk and 165 had high-risk cancer. Numbers of donor cells were measured by flow cytometry. Results: 21 patients, average age 34 + 9 yrs, underwent myeloablative BM transplants, 162 patients, average age of 43 +17 yrs underwent myeloablative conditioning and blood HPC transplants, and 65 patients, average age 54 + 10 yrs underwent non-myeloablative blood HPC transplants. Overall survival at 4 years was 46% for recipients of myeloablative blood HPC transplants, 28% for recipients of myeloablative BM transplants, and 34% following non-myeloablative blood HPC transplants. High-risk was associated a HR for death of 1.9 (95% CI 1.2–3.1, p=0.01) in myeloablative blood HPC transplants, but not with other transplant groups. For all transplant recipients, grafts with >90 x 106 CD8+ T-cells/kg (median) was the only covariate significantly associated with improved survival (HR for death of 0.6, 95% CI 0.4–0.8, p=0.007). Consistent with our previous observation, recipients of BM grafts with >1 x 106 pDC/kg had worse post-transplant survival (HR for death of 3.6, 95% CI 1.2–10.8, p=0.02) and a lower incidence of chronic GvHD (18% vs 45%, p=0.17). Using quartiles or median values, the numbers of CD34+ cells, CD4+ T- cells and mDC were not significantly associated with post-transplant survival in any patient group, and neither DC subset were associated with acute GvHD, chronic GvHD, relapse or overall survival in blood HPC transplant recipients. Conclusions: More donor CD8+ T-cells in the graft were associated with improved survival in this population of predominately high-risk patients. The content of pDC in allogeneic BM HPC grafts was associated with increased frequency of post-transplant death, supporting the hypothesis that donor pDC may modulate graft versus leukemia effects in allogeneic BMT. A similar association was not seen in recipients of cytokine-mobilized blood HPC grafts. No significant financial relationships to disclose.
IL-10 resolves the neutrophilic inflammation in mice exposed to cigarette smoke
Authors: Manabu Higaki, Hiroo Wada, Tetsuo Yasutake, Shinichiro Mikura, Kojiro Honda, Masuo Nakamura, Mamoru Niikura, Fumie Kobayashi, Shigeru Kamiya, Hajime Goto
Journal: European Respiratory Journal (2011)

Introduction:  IL-10 plays a suppressive role in the inflammation. In order to elucidate the role of IL-10 in the inflammation caused by cigarette smoke, mice exposed to cigarette smoke were investigated.   Materials & methods:  Mice (C57BL/6J) were exposed either to cigarette smoke or to environmental air for 5, 8 or 12 days. To characterize the inflammation, cellularity in bronchoalveolar lavage (BAL) fluid was investigated. The levels of inflammation-associated cytokines, such as IL-10, KC, MIP-2, TNF-a and GM-CSF, were further determined by measuring both mRNA levels in the lung tissues and the protein levels in BAL fluid. Then, a group of mice was intranasally treated either with recombinant murine IL-10 or with vehicle and exposed to cigarette smoke, before the same analysis was performed.   Results:  Cigarette smoke exposure provoked pulmonary inflammation in mice, as neutrophil and macrophage counts in BAL fluid were increased (p   Conclusion:  Our results suggested that IL-10 potentiates the suppression of the neutrophil-associated inflammatory reactions caused by cigarette smoke exposure.
Making regulation responsive to commercial interests: streamlining drug industry watchdogs * Commentary: Concern over drug industry's influence on regulatory policy in Europe * Commentary: Much ado about a good thing * Commentary: The freedom of informed choice
Authors: J. Abraham
Journal: BMJ (2002)

# Making regulation responsive to commercial interests: streamlining drug industry watchdogs {#article-title-2} Has the pharmaceutical industry skilfully managed to achieve an unhealthy influence over European drug regulatory agencies? New prescription drugs are developed and tested for quality, safety, and efficacy by the pharmaceutical industry, and little or no drug testing is conducted by governments in modern industrialised countries. Governments have regulatory authorities which have a legal duty to protect public health by ensuring that new drugs are not licensed unless they are of adequate quality, safety, and efficacy (box 1). The thousands of birth deformities and deaths caused by thalidomide focused public and professional concerns on how the commercial interests of pharmaceutical companies may diverge from, or conflict with, the interests of patients and public health. The reasoning behind the creation of new government regulatory authorities in the post-thalidomide era was therefore that they should be "entirely independent" of the commercial interests of the pharmaceutical industry and should act on behalf of the public interest by checking the adequacy of the test data produced by the industry.1–3 I explain how these government regulatory authorities in the European Union, which were initially established to provide independent scrutiny of pharmaceutical firms in the interests of public health, have become increasingly responsive to the commercial interests of the industry (box 2). ### Summary points After the thalidomide disaster the public expected drug regulation would be independent of the interests of the pharmaceutical industry In the past 15 years the regulatory agencies have been overly influenced by the industry's desire for rapid drug approvals Regulatory agencies have become heavily dependent on industry fees for their survival National agencies now find themselves competing with each other for industry fees for regulatory work The arguments in this paper are derived from electronic searches of the medical and pharmaceutical literature, combined with interviews with industry, regulators, and other professionals … Correspondence to: Christophe Kopp
A Treatise on Hygiene and Public Health. With Special Reference to the Tropics.
Journal: JAMA (1925)

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