tbuckley/cabot-search huggingface dataset:
Impact of a Clinical Guidelines Program for Breast and Colon Cancer in a French Cancer Center
Authors: Isabelle Ray-Coquard
Journal: JAMA (1997)

<h3>Context.</h3> —Between 1993 and 1994, the 80 physicians in the French comprehensive cancer center, Léon Bérard, developed and implemented a Clinical Practice Guidelines (CPGs) project based on an analysis of the literature and a consensus of intrainstitutional experts. <h3>Objective.</h3> —The aims of this project are to assist community-based oncologists in their decision making and to minimize inappropriate variation in practices. A study was designed to assess the impact of CPGs on management of breast and colon cancer. <h3>Design.</h3> —A "before-after" study, using institutional computerized records of patients with breast or colon cancer. <h3>Setting.</h3> —Records for 100 women with localized breast cancer were randomly selected from those available in 1993 and 1995, and those for all patients newly referred with colon cancer in 1993 and 1995 (77 and 81 patients, respectively). Medical decisions on these records were analyzed to assess their compliance with the CPGs. (A systematic search of the literature was performed to determine the scientific evidence for noncompliant decisions.) <h3>Results.</h3> —Of 375 available medical decisions, 350 were assessable. The compliance rate with CPGs for breast cancer was significantly higher in 1995 compared with 1993, 54% (54/99; 95% confidence interval [CI], 44%-64%) vs 19% (18/95; 95% CI, 11%-27%) (<i>P</i>&lt;.001). The compliance rate for colon cancer was also significantly higher in 1995 than in 1993, 70% (62/88; 95% CI, 60%-80%) vs 50% (34/68; 95% CI, 38%-62%) (<i>P</i>=.009). In 1993, 42% (40/95; 95% CI, 32%-52%) of medical decisions for breast cancer and in 1995, 68% (67/99; 95% CI, 59%-77%) conformed with the CPGs or were judged to be based on "scientific evidence." In 1993, 71% (48/68; 95% CI, 60%-81%) of medical decisions for colon cancer, and in 1995 81% (71/88; 95% CI, 73%-89%) conformed with the CPGs or were judged to be based on scientific evidence. <h3>Conclusions.</h3> —Compliance rates were significantly higher in 1995 for both cancers. The development and implementation of CPGs for cancer management seem to result in significant changes in medical practice, although a causal relationship between changes and CPGs is not demonstrated in this study.
Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial
Authors: A.D. Ormerod, S.A.A. Shah, P. Copeland, G. Omar, A. Winfield
Journal: British Journal of Dermatology (2005)

Background Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. Objectives To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. Methods In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double‐blind, left–right comparative, dose‐ranging study consisting of treatment with 2·2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. Results A significant reduction in the clinical score (P = 0·03) (mean score 9·1 following sirolimus vs. 11·2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0·0054) and proliferating cells (stained by Ki‐67) in the epidermis (P = 0·0153) with sirolimus treatment compared with control. Conclusions Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.
Introduction to working group on tropospheric ozone, Health Effects Institute environmental epidemiology planning project.
Authors: I B Tager
Journal: Environmental Health Perspectives (1993)

The working group on tropospheric ozone of the Health Effects Institute has evaluated the need for epidemiologic studies on the health effects of ozone (O3) exposure. This paper summarizes current data and identifies possible research questions. The extent to which ozone exposure results in chronic health effects is largely undefined and is the central issue for epidemiologic studies. Most current data focus on transient endpoints; the link between acute changes in symptoms and/or lung function and possible chronic effects has not been established. Concepts of ozone-induced health effects have been extended to include processes of chronic disease (e.g., markers of ongoing inflammation and repair, markers of accelerated lung aging). Traditional epidemiologic studies performed have focused only on accelerated lung aging and are limited by a number of methodologic problems. Recent, very preliminary, studies suggest new opportunities for the use of human lung tissue and a variety biological response markers as part of epidemiologic studies. The identification of sensitive subpopulations with regard to ozone-induced health effects has been studied incompletely and is important both in terms of study efficiency and mechanistic insight. Methodologic advances in the reconstruction of past ozone exposure are seen as essential, as is the incorporation of emerging markers of biologic response to ozone into traditional epidemiologic study designs. Finally, more data on the joint and independent contribution of other ambient air pollutants to putative ozone-induced health effects is warranted.
THE OBESITY PARADOX IN TYPE II DIABETES MELLITUS: IMPACT OF BODY MASS INDEX ON PROGNOSIS
Authors: Pierluigi Costanzo, Pierpaolo Pellicori, John Cleland, Andrew Clark, Eric Kilpatrick, David Hepburn, Pasquale Perrone-Filardi, Jufen Zhang, Stephen Atkin
Journal: Journal of the American College of Cardiology (2014)
Keratin mutations in patients with epidermolysis bullosa simplex: correlations between phenotype severity and disturbance of intermediate filament molecular structure
Authors: B. Jeřábková, J. Marek, H. Bučková, L. Kopečková, K. Veselý, J. Valíčková, J. Fajkus, L. Fajkusová
Journal: British Journal of Dermatology (2009)

Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in the keratin 5 (KRT5) and keratin 14 (KRT14) genes, with fragility of basal keratinocytes leading to epidermal cytolysis and blistering.In this study, we characterized mutations in KRT5 and KRT14 genes in patients with EBS and investigated their possible structure-function correlations.Mutations were characterized using polymerase chain reaction (PCR) and DNA sequencing. Further, to explore possible correlations with function, the structural effects of the mutations in segment 2B of KRT5 and KRT14 and associated with EBS in our patients, as well as those reported previously, were modelled by molecular dynamics with the aid of the known crystal structure of the analogous segment of human vimentin.We have identified mutations in the KRT5 and KRT14 genes in 16 of 23 families affected by EBS in the Czech Republic. Eleven different sequence variants were found, of which four have not been reported previously. Novel mutations were found in two patients with the EBS-Dowling-Meara variant (EBS-DM) [KRT14-p.Ser128Pro and KRT14-p.Gln374_Leu387dup(14)] and in three patients with localized EBS (KRT14-p.Leu136Pro and KRT5-p.Val143Ala). Molecular dynamics studies show that the mutations p.Glu411del and p.Ile467Thr perturb the secondary alpha-helical structure of the mutated polypeptide chain, the deletion p.Glu411del in KRT14 has a strong but only local influence on the secondary structure of KRT14, and the structural impact of the mutation p.Ile467Thr in KRT5 is spread along the helix to the C-terminus. In all the other point mutations studied, the direct structural impact was significantly weaker and did not destroy the alpha-helical pattern of the secondary protein structure. The changes of 3-D structure of the KRT5/KRT14 dimer induced by the steric structural impact of the single point mutations, and the resulting altered inter- and intramolecular contacts, are spread along the protein helices to the protein C-terminus, but the overall alpha-helical character of the secondary structure is not destroyed and the atomic displacements induced by mutations cause only limited-scale changes of the quaternary structure of the dimer.The results of molecular modelling show relationships between patients' phenotypes and the structural effects of individual mutations.
Gallium Scan: Clue to Diagnosis of Starch Peritonitis
Authors: ALBERT D. NEWCOMER, HEINZ W. WAHNER
Journal: Clinical Nuclear Medicine (1979)

A patient with starch peritonitis was given a gallium scan which showed diffuse uptake in the abdomen and intense uptake in a noninfected incision six weeks after surgery. The accumulation of gallium in a noninfected surgical incision later than one week after surgery, accompanied by diffuse abdominal uptake, may indicate the presence of starch peritonitis.
Perinatal mortality in Netherlands third worst in Europe
Authors: T. Sheldon
Journal: BMJ (2008)

Researchers in the Netherlands fear that Dutch babies “may not be getting the start they should” after data have shown that perinatal mortality continues to compare badly with the country’s European neighbours. The comparative study of mothers’ and babies’ health outcomes in 26 European countries, Peristat II, showed that the Netherlands had the third worst figures, after France and Latvia (www.europeristat.com).

The findings reinforce the findings of the Peristat I study, in which the Netherlands had some of the worst rates among 15 European Union countries. Perinatal mortality …
Oxidants and asthma
Authors: G Caramori
Journal: Thorax (2004)

Many decades of research have produced a significant amount of data showing increased oxidative stress in asthma and indicating a potential role for oxidants in the pathogenesis of the disease, particularly during exacerbations. Putatively relevant pro-oxidative mechanisms have also been identified. Currently available asthma drugs are generally effective for the treatment of the disease, but their effects on oxidative stress have still not been completely elucidated. From the data available in the literature one can conclude that antioxidant compounds may have a potential role in the treatment of asthma, especially of asthma exacerbations. More convincing evidence from controlled clinical trials is required.
Recognizing and Treating Depression in the Elderly
Authors: M. J. Friedrich
Journal: JAMA (1999)

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
Submission to multiple journals: a method of reducing time to publication?
Authors: David J Torgerson, Joy Adamson, Sarah Cockayne, Jo Dumville, Emily Petherick
Journal: BMJ (2005)

Getting a manuscript accepted by a journal can be a long, drawn out process and delays dissemination of clinical research. Allowing authors to submit to several journals simultaneously could speed up publication

Most medical journals do not allow simultaneous submission of articles to more than one journal. The need for sequential submission is an important factor in delaying the publication of research. We propose that journals should allow authors to submit to two or more journals at the same time. This would lead to greater competition among journals and shorten publication delay, which would benefit both patients and authors.

Timely publication of research findings is crucial because delays will have a harmful effect on patients' health. In a review of AIDS trials, Ioannidis found a delay of between 1.7 and 3 years between study completion and publication, with negative trials taking significantly longer to be published.1 Furthermore, a study looking at economic evaluations found that on average the economic results were published two years after the clinical results.2

Morally, as well as ethically, all those involved in the research process have a duty to report their findings as quickly as possible. An important barrier to early publication and dissemination is often the researcher. Many researchers take too long to write up their findings. However, another big factor is sequential submission, whereby authors are allowed to submit to only one journal at a time.

Authors intending to submit a manuscript that they consider to be of high quality and general appeal may consider a general medical journal ( BMJ, JAMA, Lancet, New England Journal of Medicine, etc). These journals have a fairly rapid turnaround. Even so, unless the journal considers the paper for its “rapid” publication section, a decision usually takes six to eight weeks. If the decision is positive …
Imipramine for Nightmares
Authors: Leon Tec
Journal: JAMA (1974)

To the Editor.—  In connection with the question by Dr. Leo Sell and the answer by Dr. Anthony Kales (227:1066, 1974), I would like to draw your attention to clinical observations we have made in a study of 12 sleepwalking and pavor nocturnus children. We used 25 to 50 mg of imipramine before bedtime with great success. From the psychotherapeutic point of view, although imipramine does not modify the personality structure, it does alleviate the symptoms and brings a certain degree of relaxation and well-being that is therapeutic in itself. It is of interest to note that even enuretic children who did not respond to imipramine therapy as far as their bed-wetting was concerned, were helped in alleviating pavor nocturnus or nightmares. There was no substitution of symptoms, regardless of whether the child was in psychotherapy or only seen in follow-up.  At present, our procedure is as follows: We start
Interference of antihypertrophic molecules and signaling pathways with the Ca2+?calcineurin?NFAT cascade in cardiac myocytes
Authors: B FIEDLER
Journal: Cardiovascular Research (2004)

Cardiac hypertrophy occurs in a number of disease states associated with chronic increases in cardiac work load. Although cardiac hypertrophy may initially represent an adaptive response of the myocardium, ultimately, it often progresses to ventricular dilatation and heart failure. Much investigation has focused on the signaling pathways controlling cardiac hypertrophy at the level of the single cardiac myocyte. One prohypertrophic pathway that has received much attention involves the ubiquitously expressed Ca2+/calmodulin-activated phosphatase calcineurin. Upon activation by Ca2+, calcineurin dephosphorylates nuclear factor of activated T cell (NFAT) transcription factors, leading to their nuclear translocation. As common in complex biological systems, cardiac hypertrophy is controlled simultaneously by stimulatory (prohypertrophic) and counter-regulatory (antihypertrophic) pathways. Given the potent prohypertrophic effects of the Ca2+–calcineurin–NFAT pathway in cardiac myocytes, it is not surprising that the activity of this pathway is tightly controlled at multiple levels. Inhibitory mechanisms upstream (nitric oxide (NO), cGMP, cGMP-dependent protein kinase type I (PKG I), heme oxygenase-1 (HO-1), biliverdin, carbon monoxide (CO)) and downstream from calcineurin (glycogen synthase kinase-3 (GSK3), c-Jun N-terminal kinases (JNKs), p38 mitogen-activated protein kinase (MAPKs)) have been described. Moreover, several inhibitors directly target calcineurin enzymatic activity (cyclosporine A (CsA), tacrolimus (FK506), calcineurin-binding protein-1 (Cabin-1)/calcineurin-inhibitory protein (Cain), A-kinase-anchoring protein-79 (AKAP79), calcineurin B homology protein (CHP), MCIPs, VIVIT). Considering the dominant role of the calcineurin pathway in cardiac hypertrophy and failure, calcineurin-inhibitory strategies may lead to the identification of novel therapeutic approaches for patients with cardiac disease.
P16. Differential susceptibility of human and mouse NK cells to malignant cell-induced abnormalities in autologous combinations: a potential mechanism for the NK cell-based immunotherapy efficacy
Authors: G Sconocchia, R Arriga, S Caratelli, A Coppola, GC Spagnoli, G Lanzilli, B Capuani, F Ferrelli, D Lauro, S Ferrone
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Natural killer (NK) cells are highly effective in controlling tumour growth, in mice, but have no significant effect in humans. The reason(s) of this phenomenon is(are) unclear. The effects of cancer cells on NK cells during target-effector cell conjugation was investigated
HIV-1 integrase inhibitors: 2007-2008 update
Authors: Kavya Ramkumar, Erik Serrao, Srinivas Odde, Nouri Neamati
Journal: Medicinal Research Reviews (2010)

In recent years, HIV-1 integrase (IN) has become an attractive target for designing antiretroviral agents. The first IN inhibitor approved for clinical use, raltegravir, has validated the pharmacological viability of IN inhibitors and signals the advent of a new generation of antiretroviral drugs. The development of raltegravir and other successful lead IN inhibitors has also influenced the IN inhibitor design strategy. This has led to the identification of several potent inhibitors in these last two years. Further, an increased understanding of IN structural biology has opened up novel approaches to inhibiting IN, such as targeting its multimerization or interaction with cellular cofactors. This review covers recent developments in the field of IN inhibitor design from 2007 to 2008. © 2010 Wiley Periodicals, Inc. Med Res Rev, 30, No. 6, 890–954, 2010
To determine the age and gender of patients with coeliac disease 1958-2008 in a single centre
Authors: G. K. T. Holmes, F. Moor
Journal: Gut (2011)

<h3>Introduction</h3> A dedicated coeliac clinic has been running regularly in Derby since 1978. Accurate records have allowed the number of patients with coeliac disease (CD) and the gender split through the years to be determined in an area in Southern Derbyshire served by the Derby hospitals. It is accepted that more females that males are diagnosed with coeliac disease although at what ages this occurs is less clear. The aim of the study was to determine the number of women and men diagnosed with CD in successive 5 year age bands in a large series of biopsy proven patients. <h3>Methods</h3> The diagnosis of CD was based on characteristic appearances of the small intestinal mucosa. Extensive efforts were made to identify all adult patients (≤ 15 years of age) in the area served by the Derby hospitals. Sources of information included the hospital diagnostic index, histopathology records, dermatitis herpetiformis clinic, immunology laboratory, dietetics, and membership records of the Coeliac Society (Coeliac UK). Patients were followed prospectively since 1978. The numbers of diagnoses made in successive quinquennia for men and women were determined. Information was stored on an Access data base. <h3>Results</h3> For women a steady increase in the number of diagnoses with increasing age up to the age of 40 was observed with the greatest number in the age band 35–45 years. A plateau effect was seen between 45 and 65 years and then a steady decline. For men a steady increase was found to the age band 35–40 years when a plateau was reached which lasted until the age of 70. Thereafter a steady decline was seen. For the age band 20–25 the female to male ratio was 5.6:1. The ratio declined throughout life being 2.53:1 for ages 35–40 and 1.25:1 for the band 85–90. <h3>Conclusion</h3> CD in men below the age of 25 years is uncommon compared with women with a female to male ratio of 5.6:1. The greatest number of diagnoses in women is made during the years 35–45. This may be because women consult their doctors more that men so that CD is more likely to be diagnosed. Also the influences of hormones and pregnancy in provoking CD are other factors to be considered. From the age of 40 in men and 45 in women a plateau effect was observed with a decline in old age. In every age band up to 90 years more females than males were diagnosed but the female to male ratio gradually declined throughout life being 1.25:1 in the age band 85–90. It may well be that CD is being missed, particularly in men under 40, and that the diagnosis should be more actively pursued in this group.
Abstract LB-395: Hepatocyte growth factor: a potential therapeutic target in pancreatic cancer
Authors: Arun SJ, Xu Z, E Fiala-Beer, P Phillips, D Goldstein, A Biankin, R Pirola, JS Wilson, MV Apte
Journal: Cancer Research (2011)

Abstract Pancreatic stellate cells (PSCs, which produce the desmoplastic reaction of pancreatic cancer) interact with pancreatic cancer (PC) cells to potentiate PC progression. A candidate factor that may mediate this interaction is the hepatocyte growth factor (HGF). High serum HGF levels in PC patients correlate with poor outcome. However, there is limited knowledge about the role of HGF in PC. Aims: To i) determine whether human PSCs and PC cell lines express HGF; and ii) assess the effects of HGF inhibition on PC progression in an orthotopic mouse model. Methods: i) HGF expression in PSCs and PC cells assessed by RT-PCR, immunoblotting/immunocytochemistry. ii) Orthotopic model: AsPC-1 (a human PC cell line) ± human PSCs implanted into the pancreas mice. One week later, mice divided into groups (n=8 mice/group) and treated with: HGF antibody AMG102 [(Amgen Inc.), 300 or 600μg IP biweekly] or isotype IgG (600 μg IP biweekly). Seven weeks later, tumour size and metastasis assessed. Results: i) PSCs express HGF at both mRNA and protein levels. In contrast, PC cells (MiaPaCa2, Panc-1, AsPC-1) express negligible HGF mRNA. ii) Orthotopic model: a) IgG treated AsPC-1+PSC mice showed larger tumours than mice injected with AsPC-1 alone (Table); b) 300 and 600μg AMG102 inhibited tumour growth in AsPC-1+PSC mice compared to the IgG treated group. However, AMG102 did not reduce tumour size in mice injected with AsPC-1 alone (Table). c) 600μg AMG102 inhibited metastasis (liver, diaphragm, mediastinum) in AsPC-1+PSC mice (p&amp;lt;0.05) compared to IgG treated mice. Conclusions: We have shown for the first time that i)human PSCs synthesise HGF; ii)HGF inhibition reduces tumour growth and metastasis of tumours representative of human PC i.e., exhibiting both tumour elements and a stromal reaction, but not in the clinically non-representative cancers formed by PC cells alone. Implication: Targeting the stromal reaction with relevant specific inhibitors may represent a novel therapeutic approach in PC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-395. doi:10.1158/1538-7445.AM2011-LB-395