tbuckley/cabot-search huggingface dataset:
Managing the clinical performance of doctors
Authors: R. Smith
Journal: BMJ (1999)

News p 1319 

The last few years have seen a progression of “rogue doctors” and health care scandals through the media.1 Now, unsurprisingly, we have a series of proposals that attempt to guarantee to patients that the doctors treating them are up to standard. Public confidence must be restored, or trust in the National Health Service will be destroyed. Three weeks ago the prime minister launched the Commission on Health Improvement (CHI), which will inspect health services in England and Wales and respond to services in trouble.2 Two weeks ago the General Medical Council discussed its proposals for revalidation for every doctor in the United Kingdom.3 Now the chief medical officer of England has issued his proposals on how poor clinical performance among doctors will be prevented, recognised, and dealt with.4 The old system—based on an expectation that professionals would keep up to date and do something about poorly performing colleagues combined with some half hearted systems of self regulation—is dead.

Nobody can deny that there is a problem. “Bristol”—the case of poor performance in paediatric cardiothoracic services—heads the list and, I have argued, changed everything.5 But there have been several other episodes, and chillingly the chief medical officer seems to accept there are more to come: “We expect that over the …
Hepatitis B virus infection enhances susceptibility toward adeno-associated viral vector transduction<i>in vitro</i>and<i>in vivo</i>
Authors: Marianna Hösel, Julie Lucifora, Thomas Michler, Gisela Holz, Marion Gruffaz, Stephanie Stahnke, Fabien Zoulim, David Durantel, Mathias Heikenwalder, Dirk Nierhoff, Rachel Millet, Anna Salvetti, Ulrike Protzer, Hildegard Büning
Journal: Hepatology (2014)

Gene therapy has become an accepted concept for the treatment of a variety of different diseases. In contrast to preclinical models, subjects enrolled in clinical trials, including gene therapy, possess a history of infection with microbes that may influence its safety and efficacy. Especially, viruses that establish chronic infections in the liver, one of the main targets for in vivo gene therapy, raise important concerns. Among them is the hepatitis B virus (HBV), which has chronically infected more than 350 million people worldwide. Here, we investigated the effect of HBV on adeno-associated viral (AAV) vectors, the most frequently applied gene transfer vehicles for in vivo gene therapy. Unexpectedly, we found that HBV greatly improved AAV transduction in cells replicating HBV and identified HBV protein x (HBx) as a key factor. Whereas HBV-positive and -negative cells were indistinguishable with respect to cell-entry efficiency, significantly higher numbers of AAV vector genomes were successfully delivered to the nucleus in the presence of HBV. The HBV-promoting effect was abolished by inhibitors of phosphatidylinositol 3-kinase (PI3K). PI3K was required for efficient trafficking of AAV to the nucleus and was enhanced in HBV-replicating cells and upon HBx expression. Enhancement of AAV transduction was confirmed in vivo using HBV transgenic mice and could successfully be applied to inhibit HBV progeny release. Conclusion : Our results demonstrate that acute, as well as chronic, infections with unrelated viruses change the intracellular milieu, thereby likely influencing gene therapy outcomes. In the case of HBV, HBx-mediated enhancement of AAV transduction is an advantage that could be exploited for development of novel treatments of HBV infection. (Hepatology 2014;59:2110-2120)
Penicillin Treatment of Infected Hands
Authors: F. D'Abreu, C. M. Flood, H. B. Hewitt
Journal: BMJ (1947)

us the victory, but which to the young obstetrician will appear but meaningless ritual.Then there will be a tendency, which it will be hard to resist, to relax some of the precautions, but so long as Str.pyogenes continues to exist in the throats of the people such relaxation will inevitably be followed by the reappearance of puerperal sepsis, the history of which is reflected in the history of the Rotunda Hospital.
Serum cytokeratin-18 fragments as quantitative markers of epithelial apoptosis in liver and intestinal graft-versus-host disease
Authors: Thomas Luft, Michael Conzelmann, Axel Benner, Michael Rieger, Michael Hess, Ulrich Strohhaecker, Martin Görner, Ute Hegenbart, Anthony D. Ho, Peter Dreger
Journal: Blood (2007)
Direct in vitro effect of a sulfonylurea to increase human fibroblast insulin receptors.
Authors: M J Prince, J M Olefsky
Journal: Journal of Clinical Investigation (1980)

We have studied the effects of the oral sulfonylurea agent glyburide to modulate insulin receptors on nontransformed human fibroblasts in tissue culture. When glyburide was added to monolayers of human fibroblasts, a dose-dependent increase in the number of cell surface receptors was observed with a maximum effect (19% increase) seen at 1 microgram/ml glyburide. Insulin can induce a loss of insulin receptors in these cells, and when fibroblasts are exposed to 100 ng/ml insulin for 6 h, approximately 60% of the initial complement of cell surface receptors are lost. When the process of insulin-induced receptor loss (or down regulation) was studied in the presence of glyburide, the drug exerted a marked inhibitory effect on this regulatory process. Thus, glyburide inhibited insulin-induced receptor loss in a dose-dependent fashion, and the maximally effective drug concentration (1 microgram/ml) inhibited 34% of the receptor loss. These studies demonstrate a direct in vitro effect of this oral hypoglycemic agent to increase the number of cell surface insulin receptors or prevent their loss, presumably by slowing the rate of receptor internalization. These findings may explain the well known extrapancreatic effect of sulfonylurea agents to improve insulin-mediated tissue glucose metabolism.
Caught red-handed: uric acid is an agent of inflammation
Authors: Yan Shi
Journal: Journal of Clinical Investigation (2010)

Inflammation occurs in response to both pathogenic insult and tissue damage under sterile conditions, with the latter contributing to the pathogenesis of many diseases. Although several endogenous substances, including uric acid, have been suggested to alert the body to danger and to stimulate inflammation, little is known about their contribution to such responses in vivo. In this issue of the JCI, Kono et al. use newly generated mice with reduced levels of uric acid to investigate its role as an endogenous signal of tissue damage in inflammatory responses to hepatic injury. They find that uric acid is released from dying tissues and induces inflammation to cell death but is not involved in the response to microbial molecules or sterile irritant particles. I believe this to be the first report of an endogenous danger signal acting as a physiological regulator of inflammation.
Nonhematopoietic antigen blocks memory programming of alloreactive CD8+ T cells and drives their eventual exhaustion in mouse models of bone marrow transplantation
Authors: Barry Flutter, Noha Edwards, Farnaz Fallah-Arani, Stephen Henderson, Jian-Guo Chai, Shivajanani Sivakumaran, Sara Ghorashian, Clare L. Bennett, Gordon J. Freeman, Megan Sykes, Ronjon Chakraverty
Journal: Journal of Clinical Investigation (2010)

Allogeneic blood or BM transplantation (BMT) is the most commonly applied form of adoptive cellular therapy for cancer. In this context, the ability of donor T cells to respond to recipient antigens is coopted to generate graft-versus-tumor (GVT) responses. The major reason for treatment failure is tumor recurrence, which is linked to the eventual loss of functional, host-specific CTLs. In this study, we have explored the role of recipient antigen expression by nonhematopoietic cells in the failure to sustain effective CTL immunity. Using clinically relevant models, we found that nonhematopoietic antigen severely disrupts the formation of donor CD8+ T cell memory at 2 distinct levels that operate in the early and late phases of the response. First, initial and direct encounters between donor CD8+ T cells and nonhematopoietic cells blocked the programming of memory precursors essential for establishing recall immunity. Second, surviving CD8+ T cells became functionally exhausted with heightened expression of the coinhibitory receptor programmed death-1 (PD-1). These 2 factors acted together to induce even more profound failure in long-term immunosurveillance. Crucially, the functions of exhausted CD8+ T cells could be partially restored by late in vivo blockade of the interaction between PD-1 and its ligand, PD-L1, without induction of graft-versus-host disease, suggestive of a potential clinical strategy to prevent or treat relapse following allogeneic BMT.
STUDIES ON THE PATHOGENESIS OF THE ETHANOL-INDUCED FATTY LIVER. I. SYNTHESIS AND OXIDATION OF FATTY ACIDS BY THE LIVER*
Authors: Gilberto Rebouças, Kurt J. Isselbacher
Journal: Journal of Clinical Investigation (1961)

The present report is a study of changes in hepatic fatty acid synthesis and oxidation following ethanol administration in vivo and in vitro.Observations on the role of reduced and oxidized diphosphopyridine nucleotides are also presented.A subsequent report will deal with studies on lipid transport. MATERIALS AND METHODSPalmitate-1-C1' (specific activity 5 X 10' cpm per j.mole) was obtained from Volk Radiochemical Co., Chicago, Ill., and purified as described previously (8).Acetate- 1-C"' was purchased from New England Nuclear Corporation, Boston, Mass.Diphosphopyridine nucleotide (DPN) was obtained from Sigma Chemical Co., St. Louis, Mo.Hyamine-1OX was prepared according to the method of Passman, as modified by Eisenberg (9).Female albino rats (Charles River Laboratories, Boston, Mass.), weighing between 180 and 250 g and maintained on Purina Chow were used throughout this investigation.
Proinflammatory gene expression and macrophage recruitment in the rat remnant kidney
Authors: Maarten W. Taal, Kambiz Zandi-Nejad, Berber Weening, Aliakbar Shahsafaei, Shinichiro Kato, Kang-Wook Lee, Farzad Ziai, Tang Jiang, Barry M. Brenner, Harald S. Mackenzie
Journal: Kidney International (2000)
Subnutrition in the elderly.
Authors: W J MacLennan
Journal: BMJ (1986)

relative efficacy of two screening procedures, and the curve provides a rational estimate of the threshold to be used in a given setting since one can see the best trade off between sensitivity and specificity.This threshold is then used to calculate the predicted prevalence of disorder and positive and negative predictive values.It is necessary to use a stratified sampling strategy only if the prevalence of disorder is below 40%, to avoid spending too much time interviewing non-cases.If this is done, however, it is essential to weight the data back to the original sample of consecutive subjects; otherwise the estimate of specificity will be too low and the estimate of sensitivity will be too high.It is advisable to calculate an ROC curve to check that the threshold chosen is appropriate: in medical and neurological inpatients, for example, the threshold may have to be raised as high as 9/10 on the general health questionnaire-28 to take account of-symptoms and social dysfunction produced by medical illness.
Relationship Between Regional Spending on Vascular Care and Amputation Rate
Authors: Philip P. Goodney, Lori L. Travis, Benjamin S. Brooke, Randall R. DeMartino, David C. Goodman, Elliott S. Fisher, John D. Birkmeyer
Journal: JAMA Surgery (2013)

IMPORTANCEAlthough lower extremity revascularization is effective in preventing amputation, the relationship between spending on vascular care and regional amputation rates remains unclear.OBJECTIVE To test the hypothesis that higher regional spending on vascular care is associated with lower amputation rates for patients with severe peripheral arterial disease. DESIGN, SETTING, AND PARTICIPANTSRetrospective cohort study of 18 463 US Medicare patients who underwent a major peripheral arterial disease-related amputation during the period between 2003 and 2010.EXPOSURE Price-adjusted Medicare spending on revascularization procedures and related vascular care in the year before lower extremity amputation, across hospital referral regions. MAIN OUTCOMES AND MEASURESCorrelation coefficient between regional spending on vascular care and regional rates of peripheral arterial disease-related amputation.RESULTS Among patients who ultimately underwent an amputation, 64% were admitted to the hospital in the year prior to the amputation for revascularization, wound-related care, or both; 36% were admitted only for their amputation.The mean cost of inpatient care in the year before amputation, including costs related to the amputation procedure itself, was $22 405, but it varied from $11 077 (Bismarck, North Dakota) to $42 613 (Salinas, California) (P < .001).Patients in high-spending regions were more likely to undergo vascular procedures as determined by crude analyses (12.0 procedures per 10 000 patients in the lowest quintile of spending and 20.4 procedures per 10 000 patients in the highest quintile of spending; P < .001)and by risk-adjusted analyses (adjusted odds ratio for receiving a vascular procedure in highest quintile of spending, 3.5 [95% CI, 3.2-3.8];P < .001).Although revascularization was associated with higher spending (R = 0.38, P < .001),higher spending was not associated with lower regional amputation rates (R = 0.10, P = .06).The regions that were most aggressive in the use of endovascular interventions were the regions that were most likely to have high spending (R = 0.42, P = .002)and high amputation rates (R = 0.40, P = .004). CONCLUSIONS AND RELEVANCERegions that spend the most on vascular care perform the most procedures, especially endovascular interventions, in the year before amputation.However, there is little evidence that higher regional spending is associated with lower amputation rates.This suggests an opportunity to limit costs in vascular care without compromising quality.
PROGRESS IN ANATOMY.
Authors: Frank Baker
Journal: JAMA (1899)

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
Health outcomes following treatment for 6 months with once daily tiotropium compared with twice daily salmeterol in patients with COPD
Authors: V Brusasco
Journal: Thorax (2005)

Background: A study was undertaken to record exacerbations and health resource use in patients with COPD during 6 months of treatment with tiotropium, salmeterol, or matching placebos.Methods: Patients with COPD were enrolled in two 6-month randomised, placebo controlled, double blind, double dummy studies of tiotropium 18 µg once daily via HandiHaler or salmeterol 50 µg twice daily via a metered dose inhaler.The two trials were combined for analysis of heath outcomes consisting of exacerbations, health resource use, dyspnoea (assessed by the transitional dyspnoea index, TDI), health related quality of life (assessed by St George's Respiratory Questionnaire, SGRQ), and spirometry.Results: 1207 patients participated in the study (tiotropium 402, salmeterol 405, placebo 400).Compared with placebo, tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation.Fewer COPD exacerbations/patient year occurred in the tiotropium group (1.07) than in the placebo group (1.49, p<0.05); the salmeterol group (1.23 events/year) did not differ from placebo.The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo (not statistically different).For all causes (respiratory and non-respiratory) tiotropium, but not salmeterol, was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group.The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group (tiotropium 8.3 (0.8), salmeterol 11.1 (0.8), placebo 10.9 (0.8), p<0.05).SGRQ total score improved by 4.2 (0.7), 2.8 (0.7) and 1.5 (0.7) units during the 6 month trial for the tiotropium, salmeterol and placebo groups, respectively (p<0.01 tiotropium v placebo).Compared with placebo, TDI focal score improved in both the tiotropium group (1.1 (0.3) units, p<0.001) and the salmeterol group (0.7 (0.3) units, p<0.05).Evaluation of morning pre-dose FEV 1 , peak FEV 1 and mean FEV 1 (0-3 hours) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo.Conclusions: Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium.With the exception of the number of hospital days associated with all causes, salmeterol twice daily resulted in no significant changes compared with placebo.Tiotropium also improved health related quality of life, dyspnoea, and lung function in patients with COPD. . . . . . . . . . . .
Use of Aspirin to Reduce Risks of Cardiovascular Disease in Patients With Diabetes
Authors: Charles H. Hennekens, Genell L. Knatterud, Marc A. Pfeffer
Journal: Diabetes Care (2004)

In their third version of U.S. federal guidelines, the National Cholesterol Education Program Adult Treatment Panel III elevated diabetes from a major risk factor to a coronary heart disease (CHD) risk equivalent (1, 2). The rationale for this change derives, in part, from earlier observations that patients with diabetes have several-fold increased risks of CHD (3), which are even greater in women than men (4). In fact, it has been suggested that at any given age, diabetes eliminates the lower absolute risk of CHD in women compared with men. Specifically, a middle-aged woman with diabetes has an absolute risk of CHD approximately equal to her male counterpart without diabetes. Furthermore, in a prospective cohort study, nondiabetic subjects with prior CHD had a 7-year event rate of ∼18.8%, whereas diabetic subjects without prior CHD had an event rate of ∼20% (5). Whether such high absolute risks apply to patients with newly diagnosed diabetes is less clear. Nonetheless, current U.S. federal guidelines recommend that patients with diabetes be treated just as aggressively as secondary prevention patients without diabetes (i.e., those who have already experienced a CHD event).

With respect to secondary prevention, aspirin conclusively reduces risks of subsequent myocardial infarction (MI) by about one-third, stroke by about one-fourth, and vascular death by about one-sixth (6, 7). In primary prevention, aspirin conclusively reduces the risk of a first MI by about one-third, but the numbers of strokes and vascular deaths in the five published primary prevention trials preclude firm conclusions. Nonetheless, based on meta-analyses of risks (8) and benefits (9), recent U.S. Preventive Services Task Force Guidelines recommend that aspirin also be considered for all apparently …
Toll-like receptor 2 expression level on monocytes in patients with viral infections: Monitoring infection severity
Authors: Takashi Kajiya, Koji Orihara, Shuichi Hamasaki, Ryutaro Oba, Hiroyuki Hirai, Kinya Nagata, Tomoaki Kumagai, Sanemasa Ishida, Naoya Oketani, Hitoshi Ichiki, So Kuwahata, Shoji Fujita, Nobuhiro Uemura, Chuwa Tei
Journal: Journal of Infection (2008)
Spirochaeta Pallida in the Lesions of Syphilis.
Authors: F. F. Russell
Journal: JAMA (1905)

San Francisco, Oct. 2, 1905. <h3>To the Editor:</h3> —Since Schaudinn and Hoffmann described a fine corkscrew-like organism in the lesions of syphilis in May of this year various confirmatory reports have been published on the continent of Europe and in England, but as yet I have seen no reports of the demonstration of the organism in this country. It, therefore, seems proper to report the finding of the<i>Spirochœta pallida</i>in two case of untreated secondary syphilis which have lately been under observation in this hospital. The<i>S. pallida</i>was demonstrated in a smear made from a papule located on the patient's back, that is, as far away from the mouth, anus and genitals as it was possible to get, in order to avoid the spirobacteria which normally occur in those regions. In the second case the smear was made from a mucous patch in the mouth. Both preparations showed
Abstract 3183: Dysregulated expression and function of Plexin-B1 in ovarian cancers
Authors: Wong GW Oscar, Michelle KY Siu, Hextan YS Ngan, Annie NY Cheung
Journal: Cancer Research (2010)

Abstract Background: Ovarian cancer has a tendency to spread within the peritoneal cavity early in the disease course. Understanding the metastatic pathways of ovarian cancer is thus of high importance for devising ovarian cancer treatment. Plexin-B1 is a cognate receptor of Semaphorin 4D (Sema4D). This study aims at investigating the role of Plexin-B1 in ovarian cancer. Materials and Methods: Expression of Plexin-B1 and its ligand in ovarian epithelial cell lines was examined by western blot and qPCR. Their expression in benign, borderline, and malignant tumors was revealed by immunohistochemistrty of paraffin embedded tissues. High-resolution melting (HRM) curve analysis was used to screen for mutation in Rac binding region of PLXNB1. Recombinant Sema4D was purified and used to treat OVCA420 cells which express high level of Plexin-B1. siRNA was used to knock-down Plexin-B1 in OVCA420. Cell migration and invasion ability was assayed by transwell migration and invasion assay. Results: Plexin-B1 was most highly overexpressed in serous ovarian cancer cell lines OVCA420, OVCA429, and SW626, whereas Sema4D was ovexpressed in OVCAR3, TOV21G, and PAI. In contrast, Plexin-B1 and Sema4D were not expressed in immortalized normal ovarian epithelial cell lines. Immunohistochemical studies also revealed high Plexin B1 expression in ovarian borderline tumors and invasive cancers while no Plexin B1 expression was detectable in benign tumor. On the other hand, downregulation of Plexin-B1 was observed in the metastatic foci compared with their corresponding primary tumors. There is also a tendency of higher Plexin-B1 expression in serous histotype than in other histotypes. A preliminary HRM screening of Plexin-B1 cDNA from 28 ovarian cancers detected no mutation in the Rac binding region. Knock-down of Plexin-B1 by siRNA caused increased migration and invasion of ovarian cancer cells. In contrast to Sema4D, treatment of ovarian cancer cells OVCA420 by follicle-stimulating hormone which enhances ovarian cancer growth, led to Plexin-B1 downregulation. Conclusion: Our study suggested that Plexin-B1 may contribute to early ovarian carcinogenesis. Its dyregulation in ovarian cancers is paradoxically associated with altered cancer cell invasion and migration. The role of Plexin B1 in ovarian cancer progression is complex. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3183.