tbuckley/cabot-search huggingface dataset:
Minority Status and Diabetes Screening in an Ambulatory Population
Authors: Ann Sheehy, Nancy Pandhi, Douglas B. Coursin, Grace E. Flood, Sally A. Kraft, Heather M. Johnson, Maureen A. Smith
Journal: Diabetes Care (2011)

Ethnicity has been identified as a risk factor not only for having type 2 diabetes but for increased morbidity and mortality with the disease. Current American Diabetes Association (ADA) guidelines advocate screening high-risk minorities for diabetes. This study investigates the effect of minority status on diabetes screening practices in an ambulatory, insured population presenting for yearly health care.This is a retrospective population-based study of patients in a large, Midwestern, academic group practice. Included patients were insured, had ≥1 primary care visit yearly from 2003 to 2007, and did not have diabetes but met ADA criteria for screening. Odds ratios (ORs), 95% confidence intervals (CI), and predicted probabilities were calculated to determine the relationship between screening with fasting glucose, glucose tolerance test, or hemoglobin A(1c) and patient and visit characteristics.Of the 15,557 eligible patients, 607 (4%) were of high-risk ethnicity, 61% were female, and 86% were ≥45 years of age. Of the eight high-risk factors studied, after adjustment, ethnicity was the only factor not associated with higher diabetes screening (OR = 0.90 [95% CI 0.76-1.08]) despite more primary care visits in this group. In overweight patients <45 years, where screening eligibility is based on having an additional risk factor, high-risk ethnicity (OR 1.01 [0.70-1.44]) was not associated with increased screening frequency.In an insured population presenting for routine care, high-risk minority status did not independently lead to diabetes screening as recommended by ADA guidelines. Factors other than insurance or access to care appear to affect minority-preventive care.
A Model for a Smallpox-Vaccination Policy
Authors: Samuel A. Bozzette, Rob Boer, Vibha Bhatnagar, Jennifer L. Brower, Emmett B. Keeler, Sally C. Morton, Michael A. Stoto
Journal: New England Journal of Medicine (2003)

The new reality of biologic terrorism and warfare has ignited a debate about whether to reintroduce smallpox vaccination.We developed scenarios of smallpox attacks and built a stochastic model of outcomes under various control policies. We conducted a systematic literature review and estimated model parameters on the basis of European and North American outbreaks since World War II. We assessed the trade-offs between vaccine-related harms and benefits.Nations or terrorists possessing a smallpox weapon could feasibly mount attacks that vary with respect to tactical complexity and target size, and patterns of spread can be expected to vary according to whether index patients are hospitalized early. For acceptable results, vaccination of contacts must be accompanied by effective isolation. Vaccination of contacts plus isolation is expected to result in 7 deaths (from vaccine or smallpox) in a scenario involving the release of variola virus from a laboratory, 19 deaths in a human-vector scenario, 300 deaths in a building-attack scenario, 2735 deaths in a scenario involving a low-impact airport attack, and 54,729 deaths in a scenario involving a high-impact airport attack. Immediate vaccination of the public in an attacked region would provide little additional benefit. Prior vaccination of health care workers, who would be disproportionately affected, would save lives in large local or national attacks but would cause 25 deaths nationally. Prior vaccination of health care workers and the public would save lives in a national attack but would cause 482 deaths nationally. The expected net benefits of vaccination depend on the assessed probability of an attack. Prior vaccination of health care workers would be expected to save lives if the probability of a building attack exceeded 0.22 or if the probability of a high-impact airport attack exceeded 0.002. The probability would have to be much higher to make vaccination of the public life-saving.The analysis favors prior vaccination of health care workers unless the likelihood of any attack is very low, but it favors vaccination of the public only if the likelihood of a national attack or of multiple attacks is high.
Notch Pathway Inhibition Depletes Stem-like Cells and Blocks Engraftment in Embryonal Brain Tumors
Authors: Xing Fan, William Matsui, Leila Khaki, Duncan Stearns, Jiong Chun, Yue-Ming Li, Charles G. Eberhart
Journal: Cancer Research (2006)

Abstract The Notch signaling pathway is required in both nonneoplastic neural stem cells and embryonal brain tumors, such as medulloblastoma, which are derived from such cells. We investigated the effects of Notch pathway inhibition on medulloblastoma growth using pharmacologic inhibitors of γ-secretase. Notch blockade suppressed expression of the pathway target Hes1 and caused cell cycle exit, apoptosis, and differentiation in medulloblastoma cell lines. Interestingly, viable populations of better-differentiated cells continued to grow when Notch activation was inhibited but were unable to efficiently form soft-agar colonies or tumor xenografts, suggesting that a cell fraction required for tumor propagation had been depleted. It has recently been hypothesized that a small population of stem-like cells within brain tumors is required for the long-term propagation of neoplastic growth and that CD133 expression and Hoechst dye exclusion (side population) can be used to prospectively identify such tumor-forming cells. We found that Notch blockade reduced the CD133-positive cell fraction almost 5-fold and totally abolished the side population, suggesting that the loss of tumor-forming capacity could be due to the depletion of stem-like cells. Notch signaling levels were higher in the stem-like cell fraction, providing a potential mechanism for their increased sensitivity to inhibition of this pathway. We also observed that apoptotic rates following Notch blockade were almost 10-fold higher in primitive nestin-positive cells as compared with nestin-negative ones. Stem-like cells in brain tumors thus seem to be selectively vulnerable to agents inhibiting the Notch pathway. (Cancer Res 2006; 66(15): 7445-52)
The Dispersal of Replication Proteins after Etoposide Treatment Requires the Cooperation of Nbs1 with the Ataxia Telangiectasia Rad3-Related/Chk1 Pathway
Authors: Rossella Rossi, Maria Rosa Lidonnici, Samuela Soza, Giuseppe Biamonti, Alessandra Montecucco
Journal: Cancer Research (2006)

Abstract In mammalian cells, DNA replication takes place in functional subnuclear compartments, called replication factories, where replicative factors accumulate. The distribution pattern of replication factories is diagnostic of the different moments (early, mid, and late) of the S phase. This dynamic organization is affected by different agents that induce cell cycle checkpoint activation via DNA damage or stalling of replication forks. Here, we explore the cell response to etoposide, an anticancer drug belonging to the topoisomerase II poisons. Etoposide does not induce an immediate block of DNA synthesis and progressively affects the distribution of replication proteins in S phase. First, it triggers the formation of large nuclear foci that contain the single-strand DNA binding protein replication protein A (RPA), suggesting that lesions produced by the drug are processed into extended single-stranded regions. These RPA foci colocalize with DNA replicated at the beginning of the treatment. Etoposide also triggers the dispersal of replicative proteins, proliferating cell nuclear antigen and DNA ligase I, from replication factories. This event requires the activity of the ataxia telangiectasia Rad3-related (ATR) checkpoint kinase. By comparing the effect of the drug in cell lines defective in different DNA repair and checkpoint pathways, we show that, along with the downstream kinase Chk1, the Nbs1 protein, mutated in the Nijmegen breakage syndrome, is also relevant for this response and for ATR-dependent phosphorylation. Finally, our analysis evidences a critical role of Nbs1 in the etoposide-induced inhibition of DNA replication in early S phase. (Cancer Res 2006; 66(3): 1675-83)
Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment
Authors: Suzanne M de la Monte, Ming Tong, Margot Lawton, Lisa Longato
Journal: Molecular Neurodegeneration (2009)

The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. NDEA and HFD ± NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics.
A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children.
Authors: K V Lieberman, A Tejani
Journal: Journal of the American Society of Nephrology (1996)

There is no generally accepted treatment for primary focal segmental glomerulosclerosis (FSGS). Steroids alone and steroids plus cyclophosphamide can be expected to induce a remission of the proteinuria in only 27% of patients. Probably the majority of FSGS patients will reach ESRD over the extended course of their disease. In addition to the work presented in this study, there have been many reports of the potential effectiveness of cyclosporine (CSA) on reducing the proteinuria of FSGS. This study was undertaken to test the efficacy and safety of a 6-month course of CSA in a double-blinded, prospectively randomized, placebo-controlled trial in children with corticosteroid-resistant FSGS. The potential inhibitory effect of hypercholesterolemia on the proteinuria-reducing actions of CSA was also assessed. Twenty-five patients with FSGS were randomized to receive either placebo or CSA for 6 months. Twelve of the 12 patients that received CSA experienced a diminution of their proteinuria as opposed to only two of the 12 placebo-treated patients. Proteinuria was significantly reduced from 151.7 +/- 162.4 mg/kg per 24 h at Week 0 to 36.9 +/- 42.3 at the end of the study in the group that received CSA (P < 0.05). There was no significant change in the proteinuria of the patients in the placebo group. A significant correlation between the percentage change of proteinuria over the 6 months of the study and the prestudy serum cholesterol levels (r = 0.79, P < 0.05) was seen in the CSA group. A partial correlation analysis controlling for the effects of serum cholesterol uncovered a significant relationship between average CSA level and proteinuria change (r = -0.76, P < 0.05). The fractional decline in GFR over the course of the study was not significantly different between the CSA and placebo-treated groups. In conclusion, CSA reduces proteinuria, increases serum albumin levels, and can be expected, therefore, to reduce the symptoms of nephrotic syndrome. Hypercholesterolemia antagonizes this effect of CSA.
Structure and Expression of the Variant Melanin-Concentrating Hormone Genes: Only PMCHL1 Is Transcribed in the Developing Human Brain and Encodes a Putative Protein
Authors: Agnès Viale, Anouk Courseaux, Françoise Presse, Christine Ortola, Christophe Breton, Daniel Jordan, Jean-Louis Nahon
Journal: Molecular Biology and Evolution (2000)

PMCHL1 and PMCHL2 are two copies of the so-called variant melanin-concentrating hormone (MCH) gene that are located, respectively, on human chromosome 5p14 and 5q13 and that emerged recently during primate evolution. They correspond to a 5′-end truncated version of the MCH gene mapped on chromosome 12q23 and encoding a neuropeptide precursor. The gene organization and regulation of the expression of the variant MCH genes in the human brain are the central issues we investigated. First, the structure and fine chromosomal mapping of the 5p and 5q variant MCH genes were established. These revealed several point mutations and length variations of one CA/TA repeat which allow discrimination between each copy. Using a combination of RACE-PCR, RT-PCR, and sequencing analysis, we provided strong evidence for the expression of the PMCHL1 gene but not the PMCHL2 gene in the human fetal, newborn, and adult brains. Sense, potentially coding, RNAs, as well as noncoding antisense RNAs, were identified and displayed a region-specific expression in the human brain. Strikingly, sense unspliced RNAs of the PMCHL1 gene carried a novel open reading frame and may produce an NLS-containing protein of 8 kDa named VMCH-p8. These transcripts were translated in vitro and in transfected COS cells. Therefore, the PMCHL1 gene provides a unique example of the generation of a gene in the Hominoidae lineage which is specifically transcribed in the developing human brain and has the capacity to be translated into a putative novel protein.
Brown adipose tissue volume in healthy lean south Asian adults compared with white Caucasians: a prospective, case-controlled observational study
Authors: Leontine E H Bakker, Mariëtte R Boon, Rianne A D van der Linden, Lenka Pereira Arias-Bouda, Jan B van Klinken, Frits Smit, Hein J Verberne, J Wouter Jukema, Jouke T Tamsma, Louis M Havekes, Wouter D van Marken Lichtenbelt, Ingrid M Jazet, Patrick C N Rensen
Journal: The Lancet Diabetes & Endocrinology (2013)
<i>JAMA</i>Theme Issues Grow to Fruition
Authors: Jody W. Zylke
Journal: JAMA (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 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
Target to start clinical trials within 70 days of approval will take time to achieve, admits minister
Authors: A. O'Dowd
Journal: BMJ (2013)

A nationally set target in England to have all clinical trials begin within 70 days of being approved is achievable but would take some time to become a reality across the country, a government minister has told MPs.

Appearing before the House of Commons Science and Technology Committee on 3 June as part of its inquiry into clinical trials, Earl Howe, the undersecretary of state for quality at the Department of Health, told MPs that universally speedy trials would not happen everywhere overnight.

The committee’s inquiry is in the context of the European Commission’s current proposals to revise the clinical trials directive, which regulates trials in the United Kingdom, and follows concerns about transparency and …
Light and Heavy Chain Components of Gamma Globulins in Urines of Normal Persons and Patients with Agammaglobulinemia*
Authors: John H. Vaughan, Ralph F. Jacox, Barry A. Gray
Journal: Journal of Clinical Investigation (1967)

A heavy chain component of gammaG-globulins in normal urines has the characteristics of the proteolytic digestion product, Fc-fragment. This fragment is estimated to compose up to 15% of the gamma globulins present in urines. In contrast to urinary light chains, the urinary Fc-like fragment probably represents a catabolic component in normal gammaG-globulin metabolism. The light chains of the urine constitute more than half the total gamma globulin present. The calculated kappa/lambda ratio of light chains averaged 1.9 in ten urines, but the ratio in individual urines varied widely to either side of this figure. In two adult patients with agammaglobulinemia whose sera contained less than one-hundredth the normal gamma globulin levels, the urinary Fc-like fragment was absent, whereas the light chain levels were only one-tenth the average normal level. Treatment with exogenous gamma globulins resulted in normal or near normal Fc-like fragment excretion, whereas light chain excretion was only modestly affected.
Metabolic equivalents during the 10-m shuttle walking test for post-myocardial infarction patients
Authors: K Woolf-May, D Ferrett
Journal: British Journal of Sports Medicine (2007)

Objective: Comorbidities are found to affect metabolic equivalents (METs). Therefore the main objective of this study was to compare METs (1 MET: oxygen uptake (V o 2 ) 3.5 ml/kg/min) during an incremental shuttle walking test (SWT) between non-cardiac and post-myocardial infarction (MI) men, and secondly to determine any differences in V o 2 (ml/kg/min) between flat treadmill walking and the turning during the shuttle walking in non-cardiac subjects. Design: Comparative study. Subjects: Thirty one post-MI (mean (SD) age 63.5 (6.5), range 53–77 years) from phase IV cardiac rehabilitation and 19 non-cardiac (64.6 (7.5), range 51–76 years) men participated. Methods: All subjects performed an SWT, and non-cardiac subjects a treadmill test of similar protocol. Throughout both, the subject’s V o 2 was measured. Results: Analysis comparing lines of regression showed METs at 1.12 to 4.16 mph were higher (p&lt;0.001) for post-MIs versus non-cardiac subjects. For non-cardiac subjects, there were no differences between the treadmill test and SWT (p&gt;0.9) and LoA showed acceptable agreement in METs between treadmill vs SWT, mean difference −1.1 (8.8) (1.96SD). Conclusion: It would appear that for asymptomatic individuals it is appropriate to apply established METs for flat walking to the SWT. However, the significantly higher METs for the post-MI compared with the non-cardiac subjects indicates the need for caution when using METs derived from healthy subjects in the prescription of exercise for myocardial patients.
Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data
Authors: Antonio Palumbo, Sara Bringhen, Shaji K Kumar, Giulia Lupparelli, Saad Usmani, Anders Waage, Alessandra Larocca, Bronno van der Holt, Pellegrino Musto, Massimo Offidani, Maria T Petrucci, Andrea Evangelista, Sonja Zweegman, Ajay K Nooka, Andrew Spencer, Meletios A Dimopoulos, Roman Hajek, Michele Cavo, Paul Richardson, Sagar Lonial, Giovannino Ciccone, Mario Boccadoro, Kenneth Anderson, Bart Barlogie, Pieter Sonneveld, Philip L McCarthy
Journal: The Lancet Oncology (2014)
A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients with advanced colorectal cancer
Authors: A.L. Thomas, T. Trarbach, C. Bartel, D. Laurent, A. Henry, M. Poethig, J. Wang, E. Masson, W. Steward, U. Vanhoefer, B. Wiedenmann
Journal: Annals of Oncology (2007)
Prediction of Cardiovascular Death in Men Undergoing Noninvasive Evaluation for Coronary Artery Disease
Authors: Kiernan Morrow
Journal: Annals of Internal Medicine (1993)

Objective: To develop prediction rules from clinical and exercise test data identifying patients at high and low risk for cardiovascular events among a group of male veterans. Design: Prognostic study with prospective gathering of data and routine follow-up of consecutive patients referred for exercise testing. Patients only underwent noninvasive evaluation for coronary artery disease. No validation cohort is yet available. Setting: A 1200-bed Veterans Affairs Medical Center. Patients: Of 3609 men referred for exercise testing between 1984 and 1990, 2546 patients remained evaluable after exclusion of those who underwent subsequent cardiac catheterization, those with significant valvular heart disease, and those who had previous coronary artery bypass surgery. Measurements: Evaluation included recording of clinical data on a standardized form and a standard treadmill test followed by assessment of cardiovascular events. Results: During a mean follow-up period (SD) of 2.75 ( 1.8) years, 119 cardiovascular deaths and 44 nonfatal myocardial infarctions occurred in 2546 patients. The Cox proportional-hazards model showed the following characteristics to be statistically independent predictors of time until cardiovascular death: history of congestive heart failure or digoxin use, exercise-induced ST depression, change in systolic blood pressure during exercise, and exercise capacity. Using a simple score based on one item of clinical information (history of congestive heart failure or digoxin use) and three exercise test responses (ST depression, exercise capacity, and change in systolic blood pressure), 77% of patients were categorized as low risk (annual cardiac mortality rate, less than 2%), 18% as moderate risk (annual cardiac mortality rate, 7%), and 6% as high risk (annual cardiac mortality rate, 15%; hazard ratio, 10; 95% confidence interval, 6 to 17). This model has not yet been validated. Conclusions: Variables available from the usual noninvasive work-up of patients with known or suspected coronary artery disease can be used to predict future risk for cardiovascular death.
Ovariotomy as a Prophylaxis and Cure for Insanity.
Authors: Robert A. Kitto
Journal: JAMA (1891)

<h3>To the Editor:</h3> —I wrote an article on this subject in March of this year. I further report concerning the same case. Miss Ada N., age 28, had been insane for 13 years, when on February 4, 1891, I made my first ovariotomy upon her, with the result as shown in my article of March, 1891. The young lady continues to improve mentally and physically. Hers was a case of hysterical insanity, although the case had been for 13 years pronounced a case of dementia. As stated in my first article she had had scarlet fever at 13 years of age; just at the time when the ovaria were developing into active maturity, and were consequently checked and diseased. She complained of ovarian pain for years, increased at each menstrual epoch. Now here is one of those cases wherein the sympathetic nervous system was at fault and not, as was