tbuckley/cabot-search huggingface dataset:
Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study
Authors: Elahe A. Mostaghel, Peter S. Nelson, Paul Lange, Daniel W. Lin, Mary Ellen Taplin, Steven Balk, William Ellis, Philip Kantoff, Brett Marck, Daniel Tamae, Alvin M. Matsumoto, Lawrence D. True, Robert Vessella, Trevor Penning, Rachel Hunter Merrill, Roman Gulati, Bruce Montgomery
Journal: Journal of Clinical Oncology (2013)

Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes.Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration.Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm(3) of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group.Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer.
Diagnosing pulmonary embolism
Authors: J R. Harding
Journal: BMJ (1995)

explained on analytical grounds as lipid analyses performed in different laboratories give consistent results."3Also, the men in the present study served as an internal control.The influence of diet and parity cannot be excluded as major contributors to this phenomenon, but Gupta and colleagues do not provide good data on these points.The endocrine control of plasma high density lipoprotein choles- terol concentrations has been widely studied, and the effect of insulin resistance in this group may be important.4Gupta and colleagues' study adds weight to the increasing body of evidence that Asian women are at increased risk of coronary heart disease.We may expect an increase in the incidence of coronary heart disease in the British Asian population in the next decade, and further studies are urgently required.
Codon optimization of human factor VIII cDNAs leads to high-level expression
Authors: Natalie J. Ward, Suzanne M. K. Buckley, Simon N. Waddington, Thierry VandenDriessche, Marinee K. L. Chuah, Amit C. Nathwani, Jenny McIntosh, Edward G. D. Tuddenham, Christine Kinnon, Adrian J. Thrasher, John H. McVey
Journal: Blood (2010)
Strategies for Flipping the Script on Opioid Overprescribing
Authors: Aileen P. Wright, William C. Becker, Gordon D. Schiff
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
The Group Treatment of Male Exhibitionists
Authors: JAMES S. WITZIG
Journal: American Journal of Psychiatry (1968)

The author describes the results of group therapy for male genital exhibitionists in a community mental health clinic. Group treatment in an open setting was found to be an efficient and effective program if certain diagnostic considerations were observed. On the basis of his own experience as well as reports in the literature, the author identifies the majority of male exhibitionists as obsessive-compulsive neurotics rather than true sexual deviates.
Hospice Benefits and Phase I Cancer Trials
Authors: Ira Byock, Steven H. Miles
Journal: Annals of Internal Medicine (2003)

Medicare denies hospice coverage to patients with terminal illnesses who enroll as participants in phase I studies, which assess the toxicity and dosing of potential treatments for incurable diseases. Federal regulations require patients to forgo curative therapies, and they interpret phase I agents as treatment for the terminal condition for which hospice care was elected. Thus, by enrolling as a participant in a phase I trial, a patient otherwise eligible for hospice is rendered ineligible. Private insurers have similar provisions for children and adults younger than 65 years of age. Such exclusions are not defensible on ethical or clinical grounds. Policymakers, insurers, and institutional review boards all have a role in resolving this problem.
Why Is the Developed World Obese?
Authors: Sara N. Bleich, David Cutler, Christopher Murray, Alyce Adams
Journal: Annual Review of Public Health (2008)

Obesity has risen dramatically in the past few decades. However, the relative contribution of energy intake and energy expenditure to rising obesity is not known. Moreover, the extent to which social and economic factors tip the energy balance is not well understood. This exploratory study estimates the relative contribution of increased caloric intake and reduced physical activity to obesity in developed countries using two methods of energy accounting. Results show that rising obesity is primarily the result of consuming more calories. We estimate multivariate regression models and use simulation analysis to explore technological and sociodemographic determinants of this dietary excess. Results indicate that the increase in caloric intake is associated with technological innovations as well as changing sociodemographic factors. This review offers useful insights to future research concerned with the etiology of obesity and suggests that obesity-related policies should focus on encouraging lower caloric intake.
Clinical and laboratory manifestations of elderly onset psoriatic arthritis: a comparison with younger onset disease
Authors: L. Punzi, M. Pianon, P. Rossini, F. Schiavon, P. F. Gambari
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Although the influence of age on clinical and laboratory features has been widely demonstrated in many arthropathies, studies on elderly onset (&gt; 60 years) psoriatic arthritis (EOPsA) are rare. This study compares manifestations at onset and two year outcome of EOPsA with those of younger onset PsA (YOPsA). <h3>PATIENTS AND METHODS</h3> Sixty six consecutive PsA patients with disease duration &lt; 1 year, 16 EOPsA (&gt;60 years) and 50 YOPsA (⩽60 years) were admitted to a prospective study. Clinical, laboratory, and radiographic assessment were carried out at admission and after two years. HLA class I and bone scintigraphy were also recorded. In 10 patients with EOPsA and 24 with YOPsA it was possible to obtain synovial fluid, which was subsequently analysed for local inflammatory indices, including interleukin (IL) 1β, IL6, and IL8. <h3>RESULTS</h3> Presenting manifestations of EOPsA differed from YOPsA in number of active joints (mean (SD)) (12.2 (6.3) <i>v</i> 6.7 (4.6), p&lt;0.001), foot bone erosions (2.7 (1.2) <i>v</i>1.1 (1.1), p&lt;0.001), erythrocyte sedimentation rate (64.2 (35.3)<i>v</i> 30.5 (30.0) mm 1st h, p&lt;0.001), C reactive protein (3.9 (2.0) <i>v</i> 1.3 (1.3) mg/dl, p&lt;0.001) and synovial fluid IL1β (8.0 (4.7)<i>v</i> 3.0 (3.0) pg/ml, p&lt;0.001) and IL6 (828.2 (492.6) <i>v</i> 469.3 (201.4) pg/ml, p&lt;0.005). No differences were found in the number of subjects with dactylitis, pitting oedema, HLA-B27, or signs of sacroiliac and sternoclavicular joint involvement at bone scintigraphy. After two years, progression was more evident in EOPsA than in YOPsA, as the number of new erosions in the hands and also the C reactive protein were higher in EOPsA patients. <h3>CONCLUSION</h3> PsA has a more severe onset and a more destructive outcome in elderly people (onset &gt;60 years) than in younger subjects. This behaviour may be influenced by immune changes associated with aging, as suggested by the higher concentrations of IL1β and IL6 found in the synovial fluid of EOPsA than in YOPsA.
Chronic Critical Illness
Authors: Daniela Lamas
Journal: New England Journal of Medicine (2014)

Early in my intern year, I admitted an 80-year-old man with pneumonia to the intensive care unit (ICU). He had hypotension and was struggling to breathe, and my senior resident and I told his family that it was touch and go. Their response: Do everything. He had repaired cars for a living, and he was a tough guy, a fighter.Ten days later, his condition had stabilized, but he was delirious and unable to breathe on his own. We told his family that if we were to continue, he'd need a tracheotomy and feeding tube. They agreed without question. We . . .
Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells
Authors: Bastian Zimmer, Gabsang Lee, Nina V Balmer, Kesavan Meganathan, Agapios Sachinidis, Lorenz Studer, Marcel Leist
Journal: Environmental Health Perspectives (2012)

Background: Information on the potential developmental toxicity (DT) of the majority of chemicals is scarce, and test capacities for further animal-based testing are limited. Therefore, new approaches with higher throughput are required. A screening strategy based on the use of relevant human cell types has been proposed by the U.S. Environmental Protection Agency and others. Because impaired neural crest (NC) function is one of the known causes for teratologic effects, testing of toxicant effects on NC cells is desirable for a DT test battery.Objective: We developed a robust and widely applicable human-relevant NC function assay that would allow for sensitive screening of environmental toxicants and defining toxicity pathways.Methods: We generated NC cells from human embryonic stem cells, and after establishing a migration assay of NC cells (MINC assay), we tested environmental toxicants as well as inhibitors of physiological signal transduction pathways.Results: Methylmercury (50 nM), valproic acid (> 10 µM), and lead-acetate [Pb(CH3CO2)4] (1 µM) affected the migration of NC cells more potently than migration of other cell types. The MINC assay correctly identified the NC toxicants triadimefon and triadimenol. Additionally, it showed different sensitivities to various organic and inorganic mercury compounds. Using the MINC assay and applying classic pharmacologic inhibitors and large-scale microarray gene expression profiling, we found several signaling pathways that are relevant for the migration of NC cells.Conclusions: The MINC assay faithfully models human NC cell migration, and it reveals impairment of this function by developmental toxicants with good sensitivity and specificity.
Richard Mead, Thomas Guy, the South Sea Bubble and the founding of Guy's Hospital
Authors: Roger Jones
Journal: Journal of the Royal Society of Medicine (2010)

Several of London's major hospitals were founded in the first half of the 18th century. The Westminster Hospital was built in Petty France in 1719, St George's at Hyde Park Corner in 1732, the Royal London at Moorfields in 1740 and the Middlesex Hospital in Windmill Street, Soho in 1745. Guy's Hospital, founded in 1721, was a product of this voluntary hospital movement, in which charity hospitals, supported by individual contributions, but not by the State, were established in response to a range of scientific, social and humanitarian motives, some of them at a time of austerity following the war against France.
Capture-recapture method in the epidemiology of type 2 diabetes: a contribution from the Verona Diabetes Study.
Authors: G Verlato, M Muggeo
Journal: Diabetes Care (2000)

OBJECTIVE: The present investigation used data from the Verona Diabetes Study to verify a main assumption of the capture-recapture method (source independence) and to characterize the subgroup of known diabetic patients missed by all sources whose number is estimated by the capture-recapture method. RESEARCH DESIGN AND METHODS: The Verona Diabetes Study identified 7,148 type 2 diabetic patients on 31 December 1986 using 3 different sources: family physicians, a diabetes center, and a drug prescription database. Completeness of ascertainment was estimated with traditional methods based on the hypergeometric distribution and with a log-linear model. RESULTS: Identification sources were not independent because the drug prescription database was positively related to family physicians and negatively related to the diabetes center (P &amp;lt; 0.001). Thus, completeness of ascertainment was overestimated (87.5% [95% CI 86.3-88.8]) when using only family physicians and the drug prescription database and underestimated (45.9% [43.9-48.1]) when using only the diabetes center and the drug prescription database. Because of characteristics contributing to variable "catchability" (probability of ascertainment), the estimated proportion of ascertainment increased with increasing time since diagnosis from 65.6% in the first tertile (&amp;lt;6 years) to 91.5% in the third tertile (&amp;gt;12 years); moreover, the ascertainment was estimated to be nearly complete (97.9%) for insulin-treated patients and scanty (28.9%) for diet-treated patients. CONCLUSIONS: Because identification sources are likely to be dependent, the capture-recapture method should be used with caution in diabetes epidemiology and possibly when at least 3 sources are available. The subgroup of diabetic patients whose existence is inferred by this technique likely consists of newly diagnosed patients with mild disease severity.
Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection
Authors: R Rad
Journal: Gut (2004)

<b>Background and aims:</b> Recent studies linked cytokine gene polymorphisms to <i>H pylori</i> related gastric cancer development. The current study evaluated the role of cytokine gene polymorphisms for mucosal cytokine expression, the gastric inflammatory response, and bacterial colonisation during <i>H pylori</i> infection. <b>Patients and methods:</b> In 207 <i>H pylori</i> infected patients with chronic gastritis, polymorphisms at different loci of the interleukin (<i>IL</i>)<i>-10</i>,<i> IL-1B</i>,<i> IL-1 receptor antagonist </i>(<i>IL-1RN</i>), tumour necrosis factor <i>(TNF)-A</i>, and interferon <i>(IFN)-G</i> genes were genotyped by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR. Mucosal cytokine mRNA copy numbers were determined by real time quantitative PCR. Presence of bacterial virulence factors was investigated by <i>cagA</i>, <i>vacAs1/2</i>, and <i>babA2</i> PCR. Biopsies were assessed with regard to the degrees of granulocytic/lymphocytic infiltration and the presence of intestinal metaplasia (IM) and atrophic gastritis (AG). <b>Results:</b> Proinflammatory <i>IL-1</i> polymorphisms (<i>IL-1RN*2<sup>+</sup>/IL-1B−511T/−31C<sup>+</sup></i>) were associated with increased IL-1β expression, more severe degrees of inflammation, and an increased prevalence of IM and AG. Carriers of the <i>IL-10−1082G/−819C/−592C</i> alleles (GCC haplotype) had higher mucosal IL-10 mRNA levels than ATA haplotype carriers and were associated with colonisation by more virulent cagA<sup>+</sup>, vacAs1<sup>+</sup>, and babA2<sup>+</sup> H pylori strains. The <i>TNF-A−307(G/A)</i> and <i>IFN-G+874(A/T)</i> polymorphisms did not influence mucosal cytokine expression or the inflammatory response to <i>H pylori</i>. <b>Conclusions:</b> Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and the long term development of precancerous lesions in <i>H pylori</i> infection. Host polymorphisms are associated with certain bacterial strain types, suggesting host specific colonisation or adaptation. These findings contribute to the understanding of the complex interplay between host and bacterial factors involved in the development of gastric pathology.
Regulation of taurine transporter activity in LLC-PK1 cells
Authors: D P Jones, L A Miller, C Dowling, R W Chesney
Journal: Journal of the American Society of Nephrology (1991)

Taurine transporter activity increases after exposure of cultured renal epithelial cells to taurine-free medium for 24 h and decreases after incubation in high (500 microM) taurine. This adaptive response mimics that observed in rat kidney after manipulation of dietary taurine. In order to elucidate potential mechanisms involved in the regulation of beta-amino acid transporter activity, the role of RNA transcription, protein synthesis, and protein import (trafficking), as well as protein kinase C activation, on the control of taurine transport was examined in the continuous proximally derived LLC-PK1 renal cell line. Inhibition of RNA transcription with actinomycin D did not alter the up-regulatory and down-regulatory adaptive responses. Inhibition of protein synthesis with cycloheximide prevented the increased taurine transport in response to taurine-free medium as well as the decrease in taurine transport after exposure to high taurine. Colchicine prevented the response to taurine-free medium but had no effect on the response to high-taurine medium. Exposure of confluent cell monolayers to the active phorbol esters, phorbol 12-myristate 13-acetate and phorbol 12,13 dibutyrate, resulted in a reduction in taurine uptake. The effect was seen within minutes of exposure but was not observed in the presence of the inactive phorbol 4-alpha. This inhibitory action was blocked by staurosporin, an inhibitor of protein kinase C (PKC). Treatment of cells with the diacylglycerol kinase inhibitor R59022, which results in increased intracellular diacylglycerol, a natural stimulant of PKC, also inhibited taurine uptake, providing further evidence for a specific effect of PKC activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Dissociated Functional Brain Abnormalities of Inhibition in Boys With Pure Conduct Disorder and in Boys With Pure Attention Deficit Hyperactivity Disorder
Authors: Katya Rubia, Rozmin Halari, Anna B. Smith, Majeed Mohammed, Steven Scott, Vincent Giampietro, Eric Taylor, Michael J. Brammer
Journal: American Journal of Psychiatry (2008)

Inhibitory dysfunction may be a transdiagnostic etiopathophysiology of disruptive behavior disorders. Functional magnetic resonance imaging (fMRI) of inhibitory control has only been investigated in patients with attention deficit hyperactivity disorder (ADHD), including comorbidity with conduct disorder, showing frontal-striatal dysfunction. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between medication-naive adolescents with pure conduct disorder and those with pure ADHD to identify biological markers that distinguish these clinically overlapping disorders.Event-related fMRI was used to compare brain activation of 13 boys with noncomorbid conduct disorder, 20 with noncomorbid ADHD, and 20 normal boys during an individually adjusted tracking stop task that measures the neural substrates of inhibition and stopping failure.During successful inhibition, only patients with ADHD showed reduced activation in the left dorsolateral prefrontal cortex in relation to comparison subjects and patients with conduct disorder. During inhibition failures compared to go responses, both patient groups shared underactivation in the posterior cingulate gyrus in relation to comparison subjects. Patients with conduct disorder showed reduced activation in bilateral temporal-parietal regions compared to the other groups, which did not differ in this measure.Patients with pure ADHD or pure conduct disorder show qualitative differences in their brain abnormality patterns during inhibitory control. Inhibition-mediating prefrontal regions appear to be specifically reduced in ADHD, whereas posterior temporal-parietal, performance monitoring networks are specifically dysfunctional in conduct disorder. The findings provide pioneering evidence that distinct neurobiological abnormalities may be underlying the overlapping behavioral phenotype of the two disruptive disorders.
Ultrastructural aspects of pemphigoid
Authors: F. GUERRA RODRIGO
Journal: British Journal of Dermatology (2006)

Biopsies of skin lesions in different stages of evolution were taken from two patients with pemphigoid and studied by electron microscopy. Early cytoplasmic changes in the basal keratinocytes and supralaminar cleavage were seen. In the germinative cells of the regenerating skin of the blister floor in the older lesions, an inversion of the polarity of the Golgi apparatus was observed. The findings are discussed and compared with those observed in dermatitis herpetiformis. It is suggested that the pathomechanism of the early dermo‐epidermal cleavage may be similar in both diseases.