tbuckley/cabot-search huggingface dataset:
Nongenomic Actions of Steroid Hormones in Reproductive Tissues*
Authors: Alberto Revelli, Marco Massobrio, Jan Tesarik
Journal: Endocrine Reviews (1998)

I. Introduction II. Nongenomic Actions of Estrogens A. Granulosa cells B. Endometrial cells C. Oocytes D. Spermatozoa III. Nongenomic Actions of P A. Granulosa cells B. Oocytes C. Spermatozoa IV. Nongenomic Actions of Androgens A. Sertoli cells B. Oocytes V. Signal Transduction Pathways Involved in Nongenomic Steroid Effects A. Ca2+ signal generation and amplification B. Ca2+ signal transduction C. The PTK system D. The GABAA-like receptor/Cl− channel VI. Cross-Talk Between the Nongenomic and Genomic Responses of Cells to Steroids VII. Conclusions
Efficacy of On-Demand Asimadoline, a Peripheral κ-Opioid Agonist, in Females With Irritable Bowel Syndrome
Authors: Lawrence A. Szarka, Michael Camilleri, Duane Burton, Jean C. Fox, Sanna McKinzie, Timothy Stanislav, Julie Simonson, Nancy Sullivan, Alan R. Zinsmeister
Journal: Clinical Gastroenterology and Hepatology (2007)
A Practice Plan in a Municipal Teaching Hospital
Authors: Chester W. Schmidt, Philip D. Zieve, Burton C. D'Lugoff
Journal: New England Journal of Medicine (1981)

Academic-practice plans have become increasingly important as a source of financial support for the faculty of academic centers. We describe the planning, implementation, and development of one such plan in a municipal hospital, a major affiliate of a medical school. The incorporated practice plan is nonprofit and is owned and governed by physicians. Its success during the eight years of its existence has resulted in growth of the faculty, the development of innovative ambulatory-care programs, and increased financial stability of the hospital. Although such problems as payment for teaching costs and academic advancement for primary-care physicians remain, it is clear that academic-practice plans can support the clinical, teaching, and research goals of academic physicians.
Magnetic Resonance Imaging Assessment of the Severity of Mitral Regurgitation
Authors: W. Gregory Hundley, Hong F. Li, John E. Willard, Charles Landau, Richard A. Lange, Benjamin M. Meshack, L. David Hillis, Ronald M. Peshock
Journal: Circulation (1995)

Background In the patient with mitral regurgitation who is being considered for valvular surgery, cardiac catheterization is usually performed to quantify the severity of regurgitation and to determine its influence on left ventricular volumes and systolic function. Magnetic resonance imaging (MRI) potentially provides a rapid, noninvasive method of acquiring these data. Thus, this study was done to determine whether MRI can reliably measure the magnitude of mitral regurgitation and evaluate the effect of regurgitation on left ventricular volumes and systolic function. Methods and Results Twenty-three subjects (14 women and 9 men 15 to 72 years of age) with (n=17) or without (n=6) mitral regurgitation underwent MRI scanning followed immediately by cardiac catheterization. The presence (or absence) of valvular regurgitation was determined, and left ventricular volumes and regurgitant fraction were quantified during each procedure. There was excellent correlation between invasive and MRI assessments of left ventricular end-diastolic ( r =.95) and end-systolic ( r =.95) volumes and regurgitant fraction ( r =.96). All MRI examinations were completed in &lt;28 minutes. Conclusions In the patient with mitral regurgitation, MRI compares favorably with cardiac catheterization for assessment of the magnitude of regurgitation and its influence on left ventricular volumes and systolic function.
Racial Disparities in Adoption of Axillary Sentinel Lymph Node Biopsy and Lymphedema Risk in Women With Breast Cancer
Authors: Dalliah M. Black, Jing Jiang, Henry M. Kuerer, Thomas A. Buchholz, Benjamin D. Smith
Journal: JAMA Surgery (2014)

Racial disparities exist in many aspects of breast cancer care. Sentinel lymph node biopsy (SLNB) was developed to replace axillary lymph node dissection (ALND) for staging early breast cancer to minimize complications. Racial disparities in the use of SLNB remain incompletely characterized, and their effect on lymphedema risk is not known.To determine racial differences in SLNB use among patients with pathologically node-negative breast cancer during the period when SLNB became the preferred method for axillary staging as well as whether such differences affect lymphedema risk.A retrospective study was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 through 2007 to identify cases of incident, nonmetastatic, pathologically node-negative breast cancer in women aged 66 years or older.Sentinel lymph node biopsy use and 5-year cumulative incidence of lymphedema by race.Of 31 274 women identified, 1767 (5.6%) were black, 27 856 (89.1%) were white, and 1651 (5.3%) were of other or unknown race. Sentinel lymph node biopsy was performed in 73.7% of white patients and 62.4% of black patients (P < .001). The use of SLNB increased by year for both black and white patients (P < .001); however, a fixed disparity of approximately 12 percentage points in SLNB use persisted through 2007. In adjusted analysis, black patients were significantly less likely than white patients to undergo SLNB (odds ratio, 0.67; 95% CI, 0.60-0.75; P < .001). Overall, the 5-year cumulative lymphedema risk was 8.2% in whites and 12.3% in blacks (hazard ratio [HR], 1.43; 95% CI, 1.23-1.67; P < .001). When stratified by type of axillary surgery, 5-year lymphedema risk was 6.8% in whites undergoing SLNB (HR, 1 [reference]), 8.8% in blacks undergoing SLNB (HR, 1.28; 95% CI, 1.02-1.60; P = .03), 12.2% in whites undergoing ALND (1.79; 1.63-1.96; P < .001), and 18.0% in blacks undergoing ALND (2.76; 2.25-3.39; P < .001).Although SLNB use increased in both black and white patients with pathologically node-negative breast cancer from 2002 through 2007, the rates of SLNB remained lower in black than white patients during this entire period by approximately 12 percentage points. This racial disparity in SLNB use contributed to racial disparities in lymphedema risk. Improvements in the dissemination of new techniques are needed to avoid disparities in breast cancer care and patient outcomes, particularly in disadvantaged groups.
How Common Is Resistance to Treatment in Recurrent, Nonpsychotic Geriatric Depression?
Authors: John T. Little, Charles F. Reynolds, Mary Amanda Dew, Ellen Frank, Amy E. Begley, Mark D. Miller, Cleon Cornes, Sati Mazumdar, James M. Perel, David J. Kupfer
Journal: American Journal of Psychiatry (1998)

Effective treatments are available for major depressive disorder in later life. The purpose of this study was to elucidate the frequency of treatment resistance among the elderly.Treatment resistance, defined as lack of recovery despite combined pharmacotherapy and psychotherapy, was prospectively examined in 180 elderly patients in an episode of recurrent, nonpsychotic major depression who were referred to a university medical center for treatment. They received open acute and continuation treatment with nortriptyline and interpersonal psychotherapy.Among the 159 patients who completed acute treatment, 19 (11.9%) did not experience a remission of depression. In addition, nine patients who had achieved remission relapsed during continuation therapy and did not recover despite vigorous treatment. Hence, excluding dropouts, 18.4% of the patients met the criteria for treatment resistance by their lack of response to acute treatment or by relapsing during continuation therapy and not recovering subsequently despite further vigorous treatment.The study suggests a relatively low rate of resistance to treatment among depressed geriatric patients referred to a university tertiary care setting.
Lack of Comparability Between Binding of Monoclonal Antibodies to Melanoma Cells In Vitro and Localization In Vivo
Authors: D. R. McCready, C. M. Balch, I. J. Fidler, J. L. Murray
Journal: JNCI Journal of the National Cancer Institute (1989)

The affinity and specificity of monoclonal antibodies (MAbs) to tumor-associated antigens are often determined by in vitro assays. The specific binding of two anti-human melanoma antibodies (96.5 and ZME-018) and a control antibody (ZCE-025) to three human melanoma cell lines (DX3, A375-M, and Hs294t) was examined under in vitro conditions and compared to in vivo localization of 111In-labeled antibodies to the same cells growing as solid tumors in the subcutis of nude mice. The in vitro binding of the specific MAbs to the tumor cells did not predict in vivo localization. Under in vitro conditions, MAb ZME-018 bound to all three cell lines at levels exceeding that of 96.5, yet ZME-018 did not show superior localization to subcutaneous tumors. MAb 96.5 bound to cultured DX3 cells at levels exceeding those observed with A375-M cells. Yet, 96.5 localized better to A375-M xenografts in nude mice than to DX3 or Hs294t xenografts. Antigen expression differed between in vitro and in vivo growing cells, as evidenced by alteration in binding of 96.5 to tumor cells dissociated from solid subcutaneous tumors. Collectively, the data suggest that in vitro parameters do not predict the clinically relevant localization of MAbs to tumors. [J Natl Cancer Inst 81: 682–687, 1989]
Disseminated Varicella Complicating Ulcerative Colitis
Authors: Jack K. Keene
Journal: JAMA (1978)

Disseminated varicella is an uncommon complication of ulcerative colitis, despite the frequent use of steroid therapy in this disorder. Fatal varicella infection occurred in a patient with ulcerative colitis who was receiving steroid therapy. This observation suggests that zoster-immunoglobulin should be administered to patients exposed to varicella with ulcerative colitis who are receiving steroid therapy. (<i>JAMA</i>239:45-46, 1978)
The use of SI units in cardiovascular studies
Authors: C. T. KAPPAGODA, R. J. LINDEN
Journal: Cardiovascular Research (1976)

Journal Article The use of SI units in cardiovascular studies Get access C. T. KAPPAGODA, C. T. KAPPAGODA From the Department of Cardiovascular Studies, University of Leeds, Leeds LS2 9JT Search for other works by this author on: Oxford Academic PubMed Google Scholar R. J. LINDEN R. J. LINDEN From the Department of Cardiovascular Studies, University of Leeds, Leeds LS2 9JT Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 10, Issue 2, March 1976, Pages 141–148, https://doi.org/10.1093/cvr/10.2.141 Published: 01 March 1976
Assessing the Excitable Gap in Reentry by Resetting
Authors: Hailing Fei, Michael S. Hanna, Lawrence H. Frame
Journal: Circulation (1996)

Background The shortest excitable gap during reentry may determine responses to pacing and antiarrhythmic drugs. The resetting response has been used clinically to assess the excitable gap, but it cannot directly indicate the shortest excitable gap. Methods and Results We studied resetting in the in vitro canine atrial tricuspid ring using an adjustable reentry preparation in which the ring was cut and reconnected electronically with an adjustable delay to vary the cycle length and excitable gap. We reset the tachycardias using 31 delays in 12 experiments. Tachycardias were terminated by premature stimuli in 16 delays. The reset window overestimated the shortest excitable gap by 25±14 ms, and the maximum degree of advancement of tachycardia underestimated the shortest excitable gap by 22±11 ms. The slope of the increasing portion of the resetting response curve was steeper in tachycardias terminated by premature stimuli than in those not terminated (−0.69±0.2 versus −0.37±0.2, P &lt;.01). The effective refractory period difference between the sites of pacing and of block correlated with the slope of the resetting response curve. Damped cycle length oscillation after a long return cycle during resetting was always present when there was a partially excitable gap. Conclusions The reset window during pacing within the circuit and the maximum degree of advancement provided equally good estimates bracketing the shortest excitable gap. The slope of the resetting response curve predicted the likelihood of termination by premature stimuli. Damped cycle length oscillation after resetting detected a partially excitable gap.
DISCHARGE MEDICATION USE IN PATIENTS WHO EXPERIENCE BLEEDING COMPLICATIONS AFTER PRIMARY PCI: ANALYSIS FROM HORIZONS-AMI
Authors: Roxana Mehran, Bimmer E. Claessen, George D. Dangas, Jung Woh Suh, Helen Parise, Alexandra J. Lansky, Bernhard Witzenbichler, Cindy L. Grines, Giulio Guagliumi, Ran Kornowski, Jochen Wöhrle, Dariusz Dudek, Giora Weisz, Jeffrey W. Moses, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2011)
The Kansas Statute on Death — An Appraisal
Authors: Ian McColl Kennedy
Journal: New England Journal of Medicine (1971)

Abstract The State of Kansas has taken the first step in the common-law world to enact into law a definition of death. There are conflicting opinions on whether it is desirable to legislate in what is a fast moving area, particularly because legislation has a tendency to retard development in the law. A strong argument exists for leaving the matter to be developed by the courts with the co-operation of the medical profession. Given the Kansas Statute, several criticisms can be raised against it. It is too biased toward facilitating transplant surgery, ignoring the fact that most problems relate to other dying patients. Legislating for what appear to be alternative definitions of death could harm public respect for medicine. World opinion is ignored by not building into the law such safeguards as requiring two physicians to announce death, and the separation of these from the transplant team. For these reasons statutes such as the Kansas one may prove to be counter-productive.
Abstract P5-18-22: Long-term survival of patients with HER2 metastatic breast cancer treated by targeted therapies.
Authors: F Fiteni, C Villanueva, F Bazan, L Chaigneau, L Cals, E Dobi, P Montcuquet, V Nerich, S Limat, X Pivot
Journal: Cancer Research (2012)

Abstract Purpose: HER2 targeted therapies have substantially improved outcomes of patients with HER2 positive metastatic breast cancer (MBC). Medical records of patients with HER2 positive MBC achieving long survival were reviewed to describe their clinical characteristics and to assess whether curability is possible. Patients and methods: One thousand and seven hundred patients with MBC were treated between 01/01/2003 and 31/05/2012 in the 5 hospitals from the Franche-Comte region. All 217 patients with HER2 positive MBC region were retrospectively studied. Results: Among this population of HER2 positive MBC, 56 patients (26%) survived longer than 5 years. The characteristics of these long survivors were the following: median age at diagnosis was 55 years old (range, 33–87); 20 patients (35,7%) were metastatic at presentation; 20 patients (35,7%) had received adjuvant chemotherapy; the median disease-free interval was 17 months; brain, liver, lung, bone metastases were observed in 4 (7%), 19 (34%), 13 (23%), 23 (41%) in cases at occurrence of metastatic disease, respectively; tumours were hormonal receptors positive in 39 cases (70%) of these patients. A total of 16 (29%), 7 (12,5%), 7 (12,5%) and 26 (46%) cases had received 1, 2, 3 or more lines of chemotherapy at metastatic setting. The proportion of HER2 targeted treatment was 79%, 61%, 50% in first, second and third line, respectively. All patients received trastuzumab or lapatinib for their disease and 18 patients (32%) were given an anthracycline containing regimen. There were 7 complete response (CR), there were all observed after one line of chemotherapy based on trastuzumab combined with a taxane in all cases. Among these 7 patients, all continued trastuzumab after CR and all RH+ patients received hormonotherapy after CR. Among these 56 patients, 35 (62,5%) were still alive at the date cutoff in 31/05/2012. Conclusion: A significant proportion of patients with HER2 positive MBC were long survivors. Prospective clinical trials in this subset of patients should take into account this high number of patients with favorable outcome to achieve conclusion in term of survival. Can one consider the curabiblity of some MBC patients with HER2 overexpression? Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-22.
Abstract 69: Functional metabolomic profiling of human melanocyte and melanoma cells during hypoxic adaptation
Authors: Adam D. Richardson, David A. Scott, Fabian V. Filipp, Christine A. Knutzen, Gary G. Chiang, Ze'ev A. Ronai, Andrei L. Osterman, Jeffrey W. Smith
Journal: Cancer Research (2010)

Abstract Adaptation to hypoxia is an important part of the cellular progression from normal melanocyte to malignant melanoma. This adaptation can be comprised of short-term remodeling of the cellular metabolic network and/or the permanent, gene-driven development of a new metabolic program. In either case, low oxygen conditions require a unique metabolic program for continued survival and proliferation. However, beyond a general shift from respiration to glycolysis, the details of this permissive metabolic program in melanoma are generally unknown. In order to better understand the changes to both the metabolome and metabolic flux in this system, we applied functional metabolomic profiling to seven human melanoma cell lines and to two human melanocyte cell lines under both hypoxic and normoxic conditions. The melanoma panel consists of four cell lines driven by B-raf mutations (WM35, UACC903, WM793 and LU1205), two containing N-ras mutations (MEL501 and WM1346) and one p53 mutant (MeWo). These cells, along with the two melanocyte lines, were grown in media containing a 1:1 mixture of natural and [U-13C]-labeled glucose for 24 hours in either 1% oxygen or atmospheric conditions. We then employed GCMS, NMR and biochemical experiments to map flux through five metabolic hubs and quantify the abundance of 28 key metabolites for each cell line and condition. These maps of central carbon metabolism encompass glycolysis, the pentose phosphate pathway, fatty acid biosynthesis, the glutamate-glutamine-proline network, and glycine/serine de novo synthesis, along with a number of other important metabolites. Analyzing these data with unbiased hierarchical clustering and Ingenuity Pathway Analysis, we discovered a metabolite-derived signature for hypoxic adaptation in melanocytes. Furthermore, we found that certain hypoxic responses are unique to either the B-raf or N-ras of the cell line subset. Interestingly, the hypoxic response of the mutant p53 cell line is more like that of the B-raf mutant cell lines than the B-raf and N-ras sets are to each other. The information gained from this functional metabolomic profiling advances our ability to identify hypoxia-adapted melanomas and develop metabolism-based therapeutic interventions. This work was supported by P01 CA128814-01 from the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 69.
The evidence base for orthopaedics and sports medicine
Authors: L. S. Lohmander, E. M. Roos
Journal: BMJ (2015)

Medicine rests on an uneven evidence base.Some interventions are supported by large multicenter randomised controlled trials that have a low risk of bias and are powered for hard endpoints-a high level of evidence.Others depend on retrospective observational data that provide a lower level of evidence.Yet others were theorised and considered biologically or mechanistically plausible and are heirlooms of eminence based medicine.
Allergic inflammation: cellular aspects
Authors: S. R. Durham
Journal: Allergy (1999)

Summary Tissue eosinophilia and IgE production during allergic inflammation are under the regulation of Th2‐type T cells. In addition, mast cells, basophils, and possibly eosinophils represent alternative sources of these cytokines, particularly UL‐4, which augments Th2 T‐cell development and local IgE production by B cells. Corticosteroids act by downregulating Th2 responses, whereas immunotherapy acts either by inhibiting immune deviation in favour of Th1 responses with augmentation of IgG production by B cells, Tho/Thou by inducing T‐cell anergy with downregulation of Tho/Th2 responses. The role of the antigen‐presenting cell is pivotal in determining T‐cell differentiation. Th2 development is favoured by low‐antigen‐concentration presentation by B cells and/or dendritic cells, in the presence of IL‐4. Novel strategies directed against IL‐4, IL‐5, and IgE are currently under investigation.
Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells
Authors: Su Mi Choi, Yonghak Kim, Joong Sup Shim, Joon Tae Park, Rui-Hong Wang, Steven D. Leach, Jun O. Liu, Chuxia Deng, Zhaohui Ye, Yoon-Young Jang
Journal: Hepatology (2013)

Abstract Patient-specific induced pluripotent stem cells (iPSCs) represent a potential source for developing novel drug and cell therapies. Although increasing numbers of disease-specific iPSCs have been generated, there has been limited progress in iPSC-based drug screening/discovery for liver diseases, and the low gene-targeting efficiency in human iPSCs warrants further improvement. Using iPSC lines from patients with alpha-1 antitrypsin (AAT) deficiency, for which there is currently no drug or gene therapy available, we established a platform to discover new drug candidates and correct disease-causing mutation with a high efficiency. A high-throughput format screening assay, based on our hepatic differentiation protocol, was implemented to facilitate automated quantification of cellular AAT accumulation using a 96-well immunofluorescence reader. To expedite the eventual application of lead compounds to patients, we conducted drug screening utilizing our established library of clinical compounds (the Johns Hopkins Drug Library) with extensive safety profiles. Through a blind large-scale drug screening, five clinical drugs were identified to reduce AAT accumulation in diverse patient iPSC-derived hepatocyte-like cells. In addition, using the recently developed transcription activator-like effector nuclease technology, we achieved high gene-targeting efficiency in AAT-deficiency patient iPSCs with 25%-33% of the clones demonstrating simultaneous targeting at both diseased alleles. The hepatocyte-like cells derived from the gene-corrected iPSCs were functional without the mutant AAT accumulation. This highly efficient and cost-effective targeting technology will broadly benefit both basic and translational applications. Conclusions : Our results demonstrated the feasibility of effective large-scale drug screening using an iPSC-based disease model and highly robust gene targeting in human iPSCs, both of which are critical for translating the iPSC technology into novel therapies for untreatable diseases.