tbuckley/cabot-search huggingface dataset:
Hyperpolarized <sup>13</sup>C magnetic resonance reveals early‐ and late‐onset changes to <i>in vivo</i> pyruvate metabolism in the failing heart
Authors: Marie A. Schroeder, Angus Z. Lau, Albert P. Chen, Yiping Gu, Jeevan Nagendran, Jennifer Barry, Xudong Hu, Jason R.B. Dyck, Damian J. Tyler, Kieran Clarke, Kim A. Connelly, Graham A. Wright, Charles H. Cunningham
Journal: European Journal of Heart Failure (2012)

Aims Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized 13 C magnetic resonance (MR), in which 13 C‐labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non‐invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non‐invasive hyperpolarized [ 13 C]pyruvate with MR, the profile of in vivo pyruvate oxidation would change throughout the course of the disease. Methods and results Dilated cardiomyopathy (DCM) was induced in pigs ( n = 5) by rapid pacing. Pigs were examined using MR at weekly time points: cine‐MRI assessed cardiac structure and function; hyperpolarized [2‐ 13 C]pyruvate was administered intravenously, and 13 C MRS monitored [ 13 C]glutamate production; 31 P MRS assessed cardiac energetics [phosphocreatine (PCr)/ATP]; and hyperpolarized [1‐ 13 C]pyruvate was administered for MRI of pyruvate dehydrogenase complex (PDC)‐mediated pyruvate oxidation via [ 13 C]bicarbonate production. Early in pacing, the cardiac index decreased by 25%, PCr/ATP decreased by 26%, and [ 13 C]glutamate production decreased by 51%. After clinical features of DCM appeared, end‐diastolic volume increased by 40% and [ 13 C]bicarbonate production decreased by 67%. Pyruvate dehydrogenase kinase 4 protein increased by two‐fold, and phosphorylated Akt decreased by half. Peroxisome proliferator‐activated receptor‐α and carnitine palmitoyltransferase‐1 gene expression decreased by a half and a third, respectively. Conclusion Despite early changes associated with cardiac energetics and 13 C incorporation into the Krebs cycle, pyruvate oxidation was maintained until DCM developed, when the heart's capacity to oxidize both pyruvate and fats was reduced. Hyperpolarized 13 C MR may be important to characterize metabolic changes that occur during heart failure progression.
MicroRNA Expression Profile of Primary Prostate Cancer Stem Cells as a Source of Biomarkers and Therapeutic Targets
Authors: Jayant K. Rane, Mauro Scaravilli, Antti Ylipää, Davide Pellacani, Vincent M. Mann, Matthew S. Simms, Matti Nykter, Anne T. Collins, Tapio Visakorpi, Norman J. Maitland
Journal: European Urology (2014)
Treating Multidrug-Resistant TB
Authors: Joan Stephenson
Journal: JAMA (2009)

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
Developing countries should have a greater say in local research agendas
Authors: R. Walgate
Journal: BMJ (2008)

Developing countries should have more say in the research that takes place in their territories, an international meeting has concluded.

The conclusion of the Global Ministerial Forum on Research for Health also recommended that health research in developing countries should be broadened to cover social and other determinants. The forum was held in Bamako, Mali, last week and was attended by representatives from 59 countries.

The forum also endorsed the four recommendations of the high level task force on scaling up research and learning on health systems of the director general of the World Health Organization, a draft of which was in circulation at Bamako.

Ok Pannenborg, senior health adviser for the World Bank’s …
Risks and Benefits of Antihypertensive Medications in Older Adults
Authors: Karen L. Margolis, Joshua I. Barzilay, Ann V. Schwartz
Journal: JAMA Internal Medicine (2014)

To the Editor The recent observational study by Tinetti et al 1 reported that treatment with antihypertensive medications is associated with an increased risk of serious fall injuries among community-living older adults with a mean age of 80 years. One reason for this study was to examine a population that may be less healthy than those enrolled in clinical trials and who may have had a higher risk of serious injuries from falls. Approximately 9% of the cohort experienced a serious injury over the follow-up period, most of which were fractures. Although the mean follow-up time is not stated, the annual rate of fractures appears to have been approximately 1.5% to 2.0%. In the Hypertension in the Very Elderly Trial (HYVET), among 3845 participants (mean age, 83 years) followed up for 2.1 years, the annual fracture rate was roughly similar at approximately 1.3%. 2 In HYVET, the risk of fractures was not higher in the group randomized to receive antihypertensive treatment (42 fractures) compared with the group randomized to receive placebo (60 fractures [hazard ratio, 0.69; 95% CI, 0.46-1.05; P = .086). In contrast to the null findings for fractures, the trial was stopped early because of a significant reduction in stroke, total mortality, and other serious cardiovascular events in the actively treated group. 3 The number of cardiovascular events (n = 331) was more than triple the number of fractures (n = 102). Likewise, the Systolic Hypertension in the Elderly Trial, which compared the thiazide-like diuretic chlorthalidone vs placebo, found a reduction in the risk of stroke and other serious cardiovascular events in the actively treated group, but no difference in falls and fractures. 4,5
Abstract 4712: Personalized ovarian cancer surveillance and detection of a therapeutic drug target in circulating tumor DNA
Authors: John A. Martignetti, Olga Camacho-Vanegas, Nolan Priedigkeit, Catalina Camacho-Vanegas, Elena Pereira, Li Lin, Bojan Losic, hardik Shah, Jun Liao, Jian Ma, Pratik Lahiri, Mark Chee, Eric Schadt, Peter Dottino
Journal: Cancer Research (2014)

Abstract Retrospective studies have demonstrated that nearly 50% of ovarian cancer patients with normal CA125 levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here we demonstrate that for one patient, with the first reported FGFR2 fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125 and it can also inform on a candidate therapeutic. Over a four year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences and multiple chemotherapeutic regimens, blood samples were longitudinally-collected and stored. Whereas post-surgical CA125 levels were elevated only three times over 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by qtRT-PCR in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and other with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhbitor treatment. Using the same overall approach, ctDNA is demonstrated in other patients and the results compared to CA125. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease. To our knowledge, this use of a personalized biomarker represents the first example in ovarian cancer demonstrating the presence of continuous occult disease in the face of negative clinical, radiologic and biochemical examination. Moreover, the recent identification of FGFR fusions in other solid cancers suggests a broader application of this strategy beyond ovarian cancer. Citation Format: John A. Martignetti, Olga Camacho-Vanegas, Nolan Priedigkeit, Catalina Camacho-Vanegas, Elena Pereira, Li Lin, Bojan Losic, hardik Shah, Jun Liao, Jian Ma, Pratik Lahiri, Mark Chee, Eric Schadt, Peter Dottino. Personalized ovarian cancer surveillance and detection of a therapeutic drug target in circulating tumor DNA. [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 4712. doi:10.1158/1538-7445.AM2014-4712
Pathway Analysis Shows Association between FGFBP1 and Hypertension
Authors: Maciej Tomaszewski, Fadi J. Charchar, Christopher P. Nelson, Timothy Barnes, Matthew Denniff, Michael Kaiser, Radoslaw Debiec, Paraskevi Christofidou, Suzanne Rafelt, Pim van der Harst, William Y. S. Wang, Christine Maric, Ewa Zukowska-Szczechowska, Nilesh J. Samani
Journal: Journal of the American Society of Nephrology (2011)

Variants in the gene encoding fibroblast growth factor 1 (FGF1) co-segregate with familial susceptibility to hypertension, and glomerular upregulation of FGF1 associates with hypertension. To investigate whether variants in other members of the FGF signaling pathway may also associate with hypertension, we genotyped 629 subjects from 207 Polish families with hypertension for 79 single nucleotide polymorphisms in eight genes of this network. Family-based analysis showed that parents transmitted the major allele of the rs16892645 polymorphism in the gene encoding FGF binding protein 1 (FGFBP1) to hypertensive offspring more frequently than expected by chance (P=0.005). An independent cohort of 807 unrelated Polish subjects validated this association. Furthermore, compared with normotensive subjects, hypertensive subjects had approximately 1.5- and 1.4-fold higher expression of renal FGFBP1 mRNA and protein (P=0.04 and P=0.001), respectively. By immunohistochemistry, hypertension-related upregulation of FGFBP1 was most apparent in the glomerulus and juxtaglomerular space. Taken together, these data suggest that FGFBP1 associates with hypertension and that systematic analysis of signaling pathways can identify previously undescribed genetic associations.
Serum 7?-hydroxycholesterol as a new parameter of liver function in patients with chronic liver diseases*1
Authors: S KUROKI
Journal: Hepatology (1995)

To examine bile acid synthesis in chronic liver diseases, serum total 7α-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry in patients with cirrhosis (n = 23), patients with chronic hepatitis (n = 21), and control subjects (n = 18). The serum α-hydroxycholesterol levels were significantly lower in patients with cirrhosis than the controls (78 ± 59 pmol/mL vs. 237 ± 97 pmol/mL; mean ± SD). However, in patients with chronic hepatitis, the level was fully retained (262 ± 102 pmol/mL). Serum 7α-hydroxycholesterol levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/mL, and all were less than the normal range (between 104 and 466 pmol/mL), however, those levels of some patients classified as Child A were within the normal range. Serum 7α-hydroxycholesterol levels significantly correlated with serum albumin, cholinesterase, total bile acid, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test, and lecithin-cholesterol acyltransferase activities. We conclude that bile acid synthesis is well preserved in patients with chronic hepatitis and that it is decreased in most patients with cirrhosis. Serum 7α-hydroxycholesterol may be a new parameter of liver function testing to assess hepatic bile acid synthesis in patients with chronic liver diseases.
The Fate of the Mentally Ill Physician
Authors: IVER F. SMALL, JOYCE G. SMALL, CLARE M. ASSUE, DONALD F. MOORE
Journal: American Journal of Psychiatry (1969)

Extensive information collected on 40 Physicians who had been hospitalized for the treatment of a psychiatric disorder revealed that more than half of these doctors were ultimately able to return to active professional lives, despite the generally poor prognoses for the disorders from which they suffered. The severity of their illnesses was emphasized, however, by the unusually high death rate, which included five suicides, during the follow-up period. The authors examine the implications of their findings for the training of young physicians, the need for early preventive efforts against mental illness, and the treatment and rehabilitation of physicians who do become ill.
The incidence-based and pathogen-based disability-adjusted life-years approach for measuring infectious disease burden in Europe: the Burden of Communicable Diseases in Europe (BCoDE) project
Authors: Dietrich Plass, Marie-Josée J Mangen, Arie H Havelaar, Cheryl Gibbons, Juanita Haagsma, Beate Jahn, Taavi Lai, Alies van Lier, Silvia Longhi, Scott A McDonald, Alexander Kraemer, Piotr Kramarz, Alessandro Cassini, Mirjam E Kretzschmar
Journal: The Lancet (2013)
A Prognostic Model for Predicting 10-Year Survival in Patients with Primary Melanoma
Authors: Lynn Schuchter
Journal: Annals of Internal Medicine (1996)

Objective: To develop a prognostic model, based on clinical and pathologic data that are routinely available to the clinician, that would estimate the chance for survival of a patient with primary cutaneous melanoma after definitive surgical therapy. Design: Cohort analytical study. Setting: University medical center. Patients: 488 patients with primary cutaneous melanoma who had no apparent metastatic disease. Patients were followed prospectively for at least 10 years. An independent validation sample of 142 patients was used to assess the stability of the model. Measurements: Six clinical and pathologic variables that predict survival and are readily available to the clinician were used to develop a prediction model. The variables were tested for their association with death by using a univariate logistic regression model. Point estimates were generated for the probability of surviving melanoma at 10 years. Variables that were statistically significantly associated with survival were retained for testing in a logistic regression model. Results: 488 patients were followed prospectively for a median of 13.5 years (minimum, 10.0 years; maximum, 20.5 years). The overall 10-year survival of the study group was 78%. Four variables were found to be independent predictors of survival. Presented as adjusted odds ratios, from strongest to weakest relative predictive strength, these variables were tumor thickness (odds ratio, 50.8), site of primary melanoma (odds ratio, 4.4), age of the patient (odds ratio, 3.0), and sex of the patient (odds ratio, 2.0). The four-variable model was significantly more accurate than tumor thickness alone, particularly for predicting death. Overall, use of the model reduced the error rate of the prediction of death by 50%. Conclusions: A prognostic model that uses four readily accessible variables more accurately predicts outcome in patients with primary melanoma than does tumor thickness alone. This four-variable model can identify patients at high risk for the recurrence of disease, an identification that becomes increasingly important as adjuvant therapies are developed for treatment of melanoma.
Community Members as Recruiters of Human Subjects: Ethical Considerations
Authors: Christian Simon, Maghboeba Mosavel
Journal: The American Journal of Bioethics (2010)

Few studies have considered in detail the ethical issues surrounding research in which investigators ask community members to engage in research subject recruitment within their own communities. Peer-driven recruitment (PDR) and its variants are useful for accessing and including certain populations in research, but also have the potential to undermine the ethical and scientific integrity of community-based research. This paper examines the ethical implications of utilizing community members as recruiters of human subjects in the context of PDR, as well as the authors' experience with a variant of PDR in a research project in South Africa. The importance of situating PDR in a comprehensive community engagement process that is responsive to the constraints of science and local needs and interests is emphasized. The paper will have relevance to bioethicists, health researchers, and research regulators concerned about the appropriate use of peer-driven recruitment strategies in health research.
Violaceous Perivulvar Nodular Eruption After Chemotherapy
Authors: Aizuri Murad, Anne Fortune, Fergal J. Moloney
Journal: JAMA Dermatology (2014)

A woman in her 60s developed fever, rigors, periorbital swelling, and a painful perivulvar eruption, 7 days after her first cycle of cytarabine and daunorubicin hydrochloride for newly diagnosed acute myeloid leukemia (AML). She had a history of type 2 diabetes mellitus, hypothyroidism, and hypercholesterolemia. Her regular medications included metformin, insulin, rosuvastatin calcium, levothyroxine sodium, and aspirin. Examination revealed edematous labia and multiple perivulvar tender nodules on violaceous and indurated plaques sparing the vaginal mucosa and inguinal creases (Figure, A). She also had bilateral injected conjunctivae with periorbital swelling. A punch biopsy of the perivulvar lesions was performed for histopathologic analysis (Figure, B and C) and tissue culture. A C
Nonadrenergic effects of isoproterenol in dogs with hypoxic pulmonary vasoconstriction. Possible role of prostaglandins.
Authors: L J Rubin, J D Lazar
Journal: Journal of Clinical Investigation (1983)

To determine whether the pulmonary vasodilation produced by isoproterenol is mediated solely by its beta adrenergic effects, we studied the hemodynamic responses to isoproterenol in three groups of dogs with pulmonary vasoconstriction produced by continuous ventilation with 10% oxygen: (a) hypoxia alone, (b) hypoxia and propranolol 0.3 mg/kg i.v. bolus followed by an infusion of 5 micrograms/kg per min, and (c) hypoxia after pretreatment with an inhibitor of cyclooxygenase, either indomethacin or meclofenamate 5 mg/kg s.c. twice daily for 2 d prior to study. All groups had similar values for mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR) during room air and hypoxic ventilation. Isoproterenol in doses of 0.0025, 0.005, and 0.05 micrograms/kg per min produced a dose-related decline in PAPm and PVR during hypoxia in group 1. Despite beta-blockade with propranolol (group 2), isoproterenol at all three doses significantly reduced PAPm and PVR. The responses to isoproterenol were comparable in the presence or absence of propranolol; at 0.05 micrograms/kg per min the effects of isoproterenol were blunted, but not abolished, by propranolol. Similar results were observed even when five times the dose of propranolol was given. Isoproterenol at all three doses had no effect, however, on PAPm and PVR in the cyclooxygenase inhibitor-pretreated group. These data suggest that the pulmonary vasodilator effects of isoproterenol are not mediated solely by pulmonary vascular beta adrenergic receptors, and that vasodilator prostaglandins may play a role in the responses to this drug.
The Role of the Thymus and Recent Thymic Migrants in the Maintenance of the Adult Peripheral Lymphocyte Pool
Authors: S.P. Berzins, R.L. Boyd, J.F.A.P. Miller
Journal: The Journal of Experimental Medicine (1998)

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.
French Abortion Drug RU 486: U.S. Research Battles Heat Up
Authors: Lou Fintor
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article French Abortion Drug RU 486: U.S. Research Battles Heat Up Get access Lou Fintor Lou Fintor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Pages 316–318, https://doi.org/10.1093/jnci/83.5.316-a Published: 06 March 1991
Factors Associated With Glucose and Insulin Levels in Healthy Postmenopausal Women
Authors: Elizabeth Barrett-Connor, Helmut G Schrott, Gail Greendale, Donna Kritz-Silverstein, Mark A Espeland, Michael P Stern, Trudy Bush, Jeffrey A Perlman
Journal: Diabetes Care (1996)

OBJECTIVE Little is known about the covariates of hyperglycemia and hyperinsulinemia. We examined candidate factors in postmenopausal women. RESEARCH DESIGN AND METHODS We determined the cross-sectional associations of sociodemographic, body-size, lifestyle, reproductive, and menopausal factors with pretrial fasting and postchallenge glucose and insulin levels in 869 postmenopausal women aged 45-65 years. Women were participants in the Postmenopausal Estrogen/Progestin Interventions study who were not taking estrogen or insulin. RESULTS Plasma glucose levels increased significantly with age; serum insulin levels did not. BMI and waist-to-hip ratio (WHR) each showed graded positive and independent associations with glucose and insulin levels. Alcohol intake, cigarette smoking, physical activity, parity, education, and income were also associated with insulin or glucose in age-adjusted models. In multivariable models, BMI and WHR explained 18% of the variability in fasting glucose, 16% in postchallenge glucose, 28% in fasting insulin, and 17% in postchallenge insulin. Age and all other factors combined accounted for &amp;lt;6% of the variance in glucose or insulin. In multiply adjusted models, African-American and Hispanic women had higher fasting and 2-h insulin levels than non-Hispanic white women. CONCLUSIONS Most of the variance in glycemia and insulin is unexplained. Measures of obesity and fat distribution account for nearly all the explained variance.