tbuckley/cabot-search huggingface dataset:
Efficacy of Inhaled Insulin in Patients With Type 2 Diabetes not Controlled With Diet and Exercise
Authors: Ralph A. DeFronzo, Richard M. Bergenstal, William T. Cefalu, John Pullman, Sam Lerman, Bruce W. Bode, Lawrence S. Phillips
Journal: Diabetes Care (2005)

Effective type 2 diabetes management requires prompt intervention if glycemic control is not achieved by nonpharmacological means. This study investigates whether inhaled insulin (INH; Exubera) can achieve target glycemic control in patients failing on diet and exercise.Patients with suboptimal control on diet and exercise (HbA(1c) [A1C] 8-11%) were randomized to 3 months' treatment with either INH before meals (n = 76) or rosiglitazone 4 mg twice a day (n = 69), in conjunction with a diet and exercise regimen. The primary end point was percentage of patients achieving A1C <8.0%.The INH and rosiglitazone groups had comparable baseline A1C values (9.5 vs. 9.4%, respectively). Significantly more patients achieved A1C <8.0% (83 vs. 58%, adjusted odds ratio 7.14 [95% CI 2.48-20.58], P = 0.0003), A1C <7.0% (44 vs. 18%, 4.43 [1.94-10.12]), and A1C < or = 6.5% (28 vs. 7.5% 5.34 [1.83-15.57]) with INH. A1C decrease was greater with INH (-2.3% vs. -1.4%, adjusted treatment group difference: -0.89% [95% CI -1.23 to -0.55]) with final mean A1C values of 7.2 and 8.0% for INH and rosiglitazone, respectively. Hypoglycemia (episodes per subject-month) was higher with INH (0.7 vs. 0.05, risk ratio 14.72 [95% CI 7.51-28.83]), with no severe hypoglycemic episodes. Pulmonary function changes were small and comparable between groups.INH could be an effective therapy for people with type 2 diabetes early in the course of their disease.
MOLECULAR MOTORS AS NOVEL TARGETS TO BLOCK GLIOMA DISPERSION AND PROLIFERATION
Authors: S. S. Rosenfeld, M. Venere, J. Lammerding, S. Ivkovic, B. Amendolara, J. Crish, H. Picariello, J. Rich, P. Canoll
Journal: Neuro-Oncology (2014)

BACKGROUND: Two of the defining features of glioblastoma are their ability to invade brain and to proliferate. While both processes are stimulated by the multiple signaling cascades that are activated in GBM, the redundancy present in these pathways has limited the clinical efficacy of kinase inhibitors. An alternative would be to directly target the cellular machinery that drives dispersion and proliferation. This machinery includes “molecular motors”—a superfamily of enzymes that generate the forces needed for a wide variety of cellular physiologies. In this study, we have examined two members from this family that can be targeted with clinically available drugs—cytoplasmic myosin II, which drives cellular motility, and Eg5, which drives the separation of the chromosomes during mitosis. METHODS: Rodent proneural glioblastomas were generated by intracranial injection of PDGF-expressing bi-cistronic retroviruses, and tumor cell invasion in vitro and ex vivo was examined as described (Ivkovic et al., Mol. Biol. Cell, 23, 533-42; Isermann et al., Curr. Protoc. Cell Biol., 2012). Patient-derived human glioma stem cells (GSCs) were isolated and maintained as described (Cheng et al., Cell, 153, 139-52). RESULTS: Myosin II: Myosin II isoforms are upregulated in all four subtypes of GBM, and expression correlates inversely with survival. We find that PDGF abolishes the anti-invasive effect of the EGFR inhibitior erlotinib on EGF-stimulated tumor dispersion, and, likewise, EGF abolishes the corresponding effect of the PDGFRα inhibitor imatinib on PDGF-stimulated tumor migration. However, blebbistatin, an allosteric inhibitor of myosin II, effectively blocks glioma dispersion even with simultaneous activation of both pathways. Furthermore, the rho kinase inhibitor fasudil, which inhibits myosin II and is used clinically for the treatment of pulmonary hypertension, also blocks PDGF-stimulated tumor invasion. Eg5: We find that Eg5 is consistently overexpressed in GSCs, compared to non-GSCs and that GSCs exhibit a greater sensitivity to ispinesib, a clinically available Eg5 inhibitor, compared to non-GSCs. Eg5 inhibition compromises the tumor initiation capability of GSCs as well as tumor progression in an orthotopic xenograft model. CONCLUSIONS: Prior efforts to block glioma invasion and proliferation have been hampered both by therapy-resistant GSCs and the redundancy present in pro-migratory signaling cascades. Our results indicate that molecular motors represent a set of targets whose inhibition blocks glioma dispersion and proliferation regardless of the activity of upstream growth and dispersion-promoting pathways and they imply that further pre-clinical and clinical development of molecular motor inhibitors in malignant glioma is warranted. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
Coexistent pulmonary and portal hypertension: Yin and yang
Authors: I. R. Wanless
Journal: Hepatology (1989)

Nodular regenerative hyperplasia (NRH), a rare hyperplastic condition of the liver, is reported in two patients with primary pulmonary hypertension (PPH). The first patient was a 26-year-old man who died of PPH and showed multiple NRH without cirrhosis of the liver. The second patient was a 25-year-old man who had a PPH with pulmonary arterial thrombi and NRH of the liver. NRH has been described in association with immune disease, hematopoietic disorder, and diabetes mellitus, so that NRH with PPH is considered to be very rare. Histologic findings of the lungs show typically plexogenic pulmonary arteriopathy in both cases, and the livers of these patients are composed of multiple nodules that are histologically represented by slightly larger hepatocytes arranged in a cobblestone-like fashion, and are ultramicroscopically characterized by massive proliferation of mitochondria. The pathogenetic association of nodular regenerative hyperplasia with primary pulmonary hypertension will be discussed.
Promoting physical activity at the workplace: a global view
Authors: Wolf Kirsten
Journal: British Journal of Sports Medicine (2010)

Chronic disease has become a global phenomenon affecting developing and developed countries alike. According to the WHO (2008), non-communicable diseases cause 38 million deaths annually (70% of all global deaths when adding injuries), which is estimated to increase. In India, chronic diseases account for 53% of all deaths (2005) which will further increase by 18% by 2015. Deaths from diabetes will increase by 35%. The economic impact is massive: India is projected to lose $237 billion in national income due to chronic disease. The WHO has identified four related risk factors to address: tobacco use, unhealthy diets, physical inactivity and the harmful use of alcohol. This paper will highlight the current global efforts to promote physical activity with a focus on the workplace. The workplace has been identified as a key setting to tackle the chronic disease challenge and accordingly workplace health promotion is experiencing significant growth. While approaches differ from country to country business drivers and targeted health issues are quite similar across the globe according to the most recent Global Survey on Health Promotion and Workplace Wellness Strategies. For example, employers worldwide use physical activity as a means to improve productivity and reduce healthcare costs. Several global initiatives in workplace health promotion have been launched, for example, the World Economic Forum Working Towards Wellness Initiative and the International Association for Worksite Health Promotion. Physical activity plays a key role in these initiatives due to the enormous potential to make lifestyle challenges and reduce chronic disease. The chronic disease challenge remains daunting and will intensify in emerging countries, like China and India. Therefore, additional resources need to be invested and initiatives strengthened on a local, regional and global scale.
Monitoring of renal transplants with ultrasound.
Authors: M. L. Nicholson, A. Bell, S. D. Parvin, A. M. Madden, P. K. Donnelly, P. S. Veitch, P. R. Bell
Journal: BMJ (1989)

During acute rejection a transplanted kidney swells, and so a subjective evaluation of the the size of the graft by palpation is generally used to diagnose rejection.Ultrasound scanning, however, provides a more accu- rate assessment of renal size.'
ABC of transfusion. Red cell substitutes.
Authors: W Odling-Smee
Journal: BMJ (1990)

Need for a red cell substituteThe ability to transfuse blood successfully has made possible some of the important medical advances this century.It has played a considerable part in lowering maternal mortality during childbirth and in the development of cardiac surgery.It has made most operations so much safer that it is difficult for those of us who qualified after 1945 to envisage surgery without blood transfusion.There are, however, disadvantages, which become apparent at The disadvantages of blood transfusion the extremes of use.* Storage * Transport Blood has to be stored at 4°C, which means that it must be kept in a * Short shelf life refrigerator.It cannot be stored on a shelf in a pharmacy; transport can Short shelf life therefore be an additional problem.Blood has a short shelf (36 days), even Difficult to obtainwhen the more advanced storage solutions are used, and this results in much * Needs crossmatching of the blood that has been collected being disposed of unused, although many of the products of whole blood may have been extracted and stored.This is a pity because blood is usually given in this country in the expectation that it will "save a life."In many parts of the world, however, it is not so freely available.Religious taboos forbid its donation, and in many cultures it is believed that life resides in the blood and if it is given away then some of that person's "life force" is lost, thereby weakening that person. An ideal red cell substituteThe other problem of blood transfusion is the need to crossmatch blood.The antigenicity of the blood is carried in the red cell envelope, and there is * Easily picks up oxygen in the lungs no evidence that the haemoglobin that is removed from the red cell is * Easily delivers oxygen to the tissues antigenic.Despite accurate crossmatching transfusion reactions still occur, * Does not need crossmatching probably because of an unidentified antigen.* Long shelf life * Stable at room temperature
Blurred Vision after Cardiac Catheterization
Authors: Carsten H Meyer, Frank G Holz
Journal: New England Journal of Medicine (2009)

A 56-year-old woman with hypertension presented with a sudden onset of painless impaired vision in the right eye. On the previous day, she had undergone cardiac catheterization for evaluation of hypertensive emergency (chest pain and blood pressure of 235/110 mm Hg) with mild troponin elevation. On physical examination, the visual acuity in the right eye was 20/100 with significant visual-field defects in the inferior temporal quadrant. Biomicroscopy revealed cholesterol emboli (Panel A, arrows) with surrounding white lucency representing retinal edema. Fluorescein angiography confirmed occlusion of the cilioretinal artery with nonperfusion of the tissue bed in the hypofluorescent areas (Panel B). . . .
Clinical Outcomes of Pulmonary Arterial Hypertension in Patients Carrying an <i>ACVRL1</i> (<i>ALK1</i>) Mutation
Authors: Barbara Girerd, David Montani, Florence Coulet, Benjamin Sztrymf, Azzeddine Yaici, Xavier Jaïs, David Tregouet, Abilio Reis, Valérie Drouin-Garraud, Alain Fraisse, Olivier Sitbon, Dermot S. O'Callaghan, Gérald Simonneau, Florent Soubrier, Marc Humbert
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) mutation is a cause of hereditary hemorrhagic telangiectasia (HHT) and/or heritable pulmonary arterial hypertension (PAH).Objectives: To describe the characteristics of patients with PAH carrying an ACVRL1 mutation.Methods: We reviewed clinical, functional, and hemodynamic characteristics of 32 patients with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French PAH Network and 23 from literature analysis. These cases were compared with 370 patients from the French PAH Network (93 with a bone morphogenetic protein receptor type 2 [BMPR2] mutation and 277 considered as idiopathic cases without identified mutation). Distribution of mutations in the ACVRL1 gene in patients with PAH was compared with the HHT Mutation Database.Measurements and Main Results: At diagnosis, ACVRL1 mutation carriers were significantly younger (21.8 ± 16.7 yr) than BMPR2 mutation carriers and noncarriers (35.7 ± 14.9 and 47.6 ± 16.3 yr, respectively; P < 0.0001). In seven of the nine patients from the French PAH Network, PAH diagnosis preceded manifestations of HHT. ACVRL1 mutation carriers had better hemodynamic status at diagnosis, but none responded to acute vasodilator challenge and they had shorter survival when compared with other patients with PAH despite similar use of specific therapies. ACVRL1 mutations in exon 10 were more frequently observed in patients with PAH, as compared with what was observed in the HHT Mutation Database (33.3 vs. 5%; P < 0.0001).Conclusions: ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis. Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression.
Hepatocellular carcinoma and gene profiling: Back from perspective to reality
Authors: Alain Braillon
Journal: Hepatology (2011)

I can hardly share the passionate enthusiasm of Breuhahn et al. for the "dramatic" improvements in understanding of molecular pathogenesis of hepatocellular carcinoma (HCC) and the claim for "further rationally designed clinical trials based on molecular evidence".1 Among the causes of HCC, they cite aflatoxins and hemochromatosis but failed, as too many do, to cite tobacco, which represents the cause of one-third of the cases.2 Despite the success of the hepatitis B vaccine and the cure for hepatitis C, HCC remains a growing epidemic due to alcohol, tobacco, and processed foods (obesity and diabetes).3 Here are the three agents of the modern epidemics. Considering "molecular evidence", a PubMed search for "gene-expression profiling" and "cancer" provides more than 17,000 references since 1999. However, out of hundreds of biomarkers, KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is the only one integrated into clinical practice. It is limited to metastatic colorectal cancer, which constitutes half of all patients with colorectal cancer. Evidence was obtained in 2008 from a post hoc analysis of the CRYSTAL trial (study EMR 62202-013) with cetuximab, and the first trial designed with an intention-to-treat analysis, PRIME (study 20050203), has just been published.4 The effect, although statistically significant, has very limited relevance: in wild-type KRAS, panitumumab–FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) increases progression-free survival by 1.6 months compared with FOLFOX4 alone. Medicine must avoid "sciensationalism" (sensationalism in science).5 If more research is needed, it must be concerned with how to improve the implementation of evidence-based care and public policies against the leading avoidable causes of cancer worldwide: tobacco, alcohol, and obesity. A focus on molecular biology that ignores medical practice, interventional epidemiology, and social and political sciences will improve neither patient care nor prevention. Alain Braillon M.D., Ph.D.*, * Gres. 27 rue Voiture, Amiens, France.
Management of Acute Kidney Problems
Authors: Eric P. Cohen
Journal: JAMA (2010)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Draft EU research programme doesn't deal with disease risk factors, say public health doctors
Authors: R. Watson
Journal: BMJ (2013)

Leading European epidemiology and public health scientific associations are pressing for major changes to the European Commission’s health research programme over the next two years.

They have argued that, in its current form, the programme focuses too much on personalised medicine and biotechnology and too little on identifying research priorities that would tackle major personal, social, environmental, and occupational risk factors of disease.

They added that the 50 page document did not cover research that would mitigate the effects on health of the international economic crisis and that it severely underestimated the importance of health systems and policy research.

Although acknowledging …
Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts.
Authors: F P Guengerich, L A Peterson, J L Cmarik, N Koga, P B Inskeep
Journal: Environmental Health Perspectives (1987)

Ethylene dibromide (1,2-dibromoethane, EDB) can be activated to electrophilic species by either oxidative metabolism or conjugation with glutathione. Although conjugation is generally a route of detoxication, in this case it leads to genetic damage. The major DNA adduct has been identified as S-[2-(N7-guanyl)ethyl]glutathione, which is believed to arise via half-mustard and episulfonium ion intermediates. The adduct has a half-life of about 70 to 100 hr and does not appear to migrate to other DNA sites. Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed.
Rosiglitazone increases fatty acid Δ9-desaturation and decreases elongase activity index in human skeletal muscle in vivo
Authors: Knut Mai, Janin Andres, Thomas Bobbert, Anke Assmann, Katrin Biedasek, Sven Diederich, Ian Graham, Tony R. Larson, Andreas F.H. Pfeiffer, Joachim Spranger
Journal: Metabolism (2011)
Binding interactions between peptides and proteins of the class II Major Histocompatibility Complex
Authors: Benjamin J. McFarland, Craig Beeson
Journal: Medicinal Research Reviews (2002)

Abstract The activation of helper T cells by peptides bound to proteins of the class II Major Histocompatibility Complex (MHC II) is pivotal to the initiation of an immune response. The primary functional requirement imposed on MHC II proteins is the ability to efficiently bind thousands of different peptides. Structurally, this is reflected in a unique architecture of binding interactions. The peptide is bound in an extended conformation within a groove on the membrane distal surface of the protein that is lined with several pockets that can accommodate peptide side‐chains. Conserved MHC II protein residues also form hydrogen bonds along the length of the peptide main‐chain. Here we review recent advances in the study of peptide‐MHC II protein reactions that have led to an enhanced understanding of binding energetics. These results demonstrate that peptide‐MHC II protein complexes achieve high affinity binding from the array of hydrogen bonds that are energetically segregated from the pocket interactions, which can then add to an intrinsic hydrogen bond‐mediated affinity. Thus, MHC II proteins are unlike antibodies, which utilize cooperativity among binding interactions to achieve high affinity and specificity. The significance of these observations is discussed within the context of possible mechanisms for the HLA‐DM protein that regulates peptide presentation in vivo and the design of non‐peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators. © 2002 John Wiley &amp; Sons, Inc. Med Res Rev, 22, No. 2, 168–203, 2002; DOI 10.1002/med.10006
Impact of Obesity and Knee Osteoarthritis on Morbidity and Mortality in Older Americans
Authors: Elena Losina, Rochelle P. Walensky, William M. Reichmann, Holly L. Holt, Hanna Gerlovin, Daniel H. Solomon, Joanne M. Jordan, David J. Hunter, Lisa G. Suter, Alexander M. Weinstein, A. David Paltiel, Jeffrey N. Katz
Journal: Annals of Internal Medicine (2011)

Background: Obesity and knee osteoarthritis are among the most frequent chronic conditions affecting Americans aged 50 to 84 years. Objective: To estimate quality-adjusted life-years lost due to obesity and knee osteoarthritis and health benefits of reducing obesity prevalence to levels observed a decade ago. Design: The U.S. Census and obesity data from national data sources were combined with estimated prevalence of symptomatic knee osteoarthritis to assign persons aged 50 to 84 years to 4 subpopulations: nonobese without knee osteoarthritis (reference group), nonobese with knee osteoarthritis, obese without knee osteoarthritis, and obese with knee osteoarthritis. The Osteoarthritis Policy Model, a computer simulation model of knee osteoarthritis and obesity, was used to estimate quality-adjusted life-year losses due to knee osteoarthritis and obesity in comparison with the reference group. Setting: United States. Participants: U.S. population aged 50 to 84 years. Measurements: Quality-adjusted life-years lost owing to knee osteoarthritis and obesity. Results: Estimated total losses of per-person quality-adjusted life-years ranged from 1.857 in nonobese persons with knee osteoarthritis to 3.501 for persons affected by both conditions, resulting in a total of 86.0 million quality-adjusted life-years lost due to obesity, knee osteoarthritis, or both. Quality-adjusted life-years lost due to knee osteoarthritis and/or obesity represent 10% to 25% of the remaining quality-adjusted survival of persons aged 50 to 84 years. Hispanic and black women had disproportionately high losses. Model findings suggested that reversing obesity prevalence to levels seen 10 years ago would avert 178 071 cases of coronary heart disease, 889 872 cases of diabetes, and 111 206 total knee replacements. Such a reduction in obesity would increase the quantity of life by 6 318 030 years and improve life expectancy by 7 812 120 quality-adjusted years in U.S. adults aged 50 to 84 years. Limitations: Comorbidity incidences were derived from prevalence estimates on the basis of life expectancy of the general population, potentially resulting in conservative underestimates. Calibration analyses were conducted to ensure comparability of model-based projections and data from external sources. Conclusion: The number of quality-adjusted life-years lost owing to knee osteoarthritis and obesity seems to be substantial, with black and Hispanic women experiencing disproportionate losses. Reducing mean body mass index to the levels observed a decade ago in this population would yield substantial health benefits. Primary Funding Source: The National Institutes of Health and the Arthritis Foundation.