tbuckley/cabot-search huggingface dataset:
National leadership: driving forward the updated Global Strategy for Women’s, Children’s and Adolescents’ Health
Authors: C K Mishra, Joe Thomas, Rakesh Kumar, Trupthi Basavaraj, A J James, Anshu Mohan, Shyama Kuruvilla, S Basavaraj
Journal: BMJ (2015)

Implementing the updated global strategy means effective leadership, nationally and sub-nationally—requiring country led health plans, partnerships, accountability, advocacy, and collective action at all levels, say <b>C K Mishra and colleagues</b>
Onset and severity of atopic dermatitis, atopy and hand eczema in adolescents
Authors: C. Apfelbacher
Journal: British Journal of Dermatology (2015)

Journal Article Onset and severity of atopic dermatitis, atopy and hand eczema in adolescents Get access C. Apfelbacher C. Apfelbacher Institute of Epidemiology and Preventive Medicine University of Regensburg Dr.‐Gessler‐Str. 17 93051 Regensburg Germany https://orcid.org/0000-0003-3805-8219 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1121–1122, https://doi.org/10.1111/bjd.14192 Published: 01 November 2015
The long wait for a breakthrough in chronic fatigue syndrome
Authors: A. R. Lloyd, J. W. M. v. d. Meer
Journal: BMJ (2015)

Not over yet

There hasn’t been much good news for patients with the prevalent but enigmatic disorder chronic fatigue syndrome (also referred to as myalgic encephalomyelitis). Over decades, research into the pathophysiology has failed to find convincing evidence of either persistent infection or immunological, endocrine, or metabolic change, and has rejected simplistic notions of depression (typical or atypical) or primary sleep disorder. Several notable “breakthroughs” have failed independent replication. The most noteworthy is the recent rise and fall of xenotropic murine leukaemia virus related virus (XMRV) as the cause, which was ultimately established as a murine DNA laboratory contaminant.1 Similarly, an exhaustive array of randomised controlled trials seeking curative outcomes from antiviral, immunological, hormonal, antidepressant, and many other therapies have failed to show any benefit over placebo, or failed the replication test.

Where then is the progress? Firstly, there is reproducible evidence implicating certain infections as a trigger—notably, infectious mononucleosis caused by Epstein-Barr virus, but also infection with other pathogens.2 Secondly, there is clear evidence that a substantial proportion of patients have a coexisting mood disorder, and sometimes a sleep-wake disorder, and that these conditions may exacerbate or perpetuate the …
Assuring the optimal use of serotonin antagonist antiemetics: the process for development and implementation of institutional antiemetic guidelines at Memorial Sloan-Kettering Cancer Center.
Authors: M J Nolte, R Berkery, B Pizzo, L Baltzer, D Grossano, C D Lucarelli, M G Kris
Journal: Journal of Clinical Oncology (1998)

The need to foster the appropriate and cost-effective use of serotonin-antagonist antiemetic drugs spurred the creation of guidelines. The process by which institution-wide guidelines at Sloan-Kettering were developed, implemented, assessed, and modified is described.A multidisciplinary group working with disease-specific management teams assigned the emetic potential of chemotherapy programs to one of five categories. Antiemetic regimens, including a specified dose and schedule of a serotonin-antagonist and dexamethasone, were assigned to each emetic category. The information was collated by disease site and chemotherapy program into hospital-wide antiemetic regimen recommendations. Quality assessment was conducted initially and repeated each time the guidelines were modified.Patient surveys demonstrated a high level of satisfaction with emetic control, which was similar to reported results. Data from the latest survey showed zero emetic episodes in 93% and 87% of participants given moderate and highly emetogenic chemotherapy, respectively. Compliance with the guidelines, initially in 73%, has been improved using a standardized chemotherapy order "check box" labeled, "Antiemetics as per Guidelines." Antiemetic drug expenditures decreased from a projected $2.8 million to $1.3 million annually.The guidelines became an educational tool that ensured the delivery of optimal antiemetic therapy chosen by professionals with the greatest knowledge of both the particular chemotherapy regimen and cancer site. Implementation of the guidelines resulted in substantial savings while treating more patients. The guidelines were easily modified as new chemotherapeutic agents and antiemetic drugs became available.
OC-007 Double blind randomised controlled trial of percutaneous tibial nerve stimulation for the treatment of faecal incontinence in adults
Authors: E Horrocks, SA Bremner, N Stevens, C Norton, PR O’Connell, S Eldridge, CH Knowles
Journal: Gut (2015)

<h3>Introduction</h3> Percutaneous Tibial Nerve Stimulation (PTNS) is a relatively new ambulatory therapy for faecal incontinence. Case series data suggest beneficial outcomes in 50–80% patients however the effectiveness of PTNS vs. sham has not been trialled. We aimed to assess the short-term efficacy of PTNS compared to sham electrical stimulation in adults with faecal incontinence. <h3>Method</h3> In this multicentre, parallel-group, double-blind, randomised controlled trial involving 17 UK specialist centres, patients aged 18 years or over with significant faecal incontinence, who had failed conservative treatments were randomly assigned (1:1) to receive either PTNS or sham electrical stimulation. Randomisation was stratified by sex and then by centre in females. Patients and outcome assessors were masked to allocation for the 14-week duration of the trial when the effect of the intervention on severity of FI and quality of life was assessed using bowel diaries and validated questionnaires. A clinical response to treatment (primary outcome) was defined as a ≥50% reduction in weekly FI episodes. Secondary outcomes included reduction in mean weekly FI episodes, summative symptom scores, disease-specific and generic quality of life measures. ISRCTN registration number: 88559475. <h3>Results</h3> 227 patients were randomised (from 373 screened) to receive PTNS (n = 115) or sham stimulation (n = 112). 12 patients withdrew; 7 from the PTNS group and 5 from the sham group. Missing data were multiply imputed. 39 patients in the PTNS group (38%) had a 50% or greater reduction in weekly FI episodes compared to 32 in the sham group (31%) (OR 1.28, 95% CI 0.72–2.28, p = 0.396). There was a significantly greater decrease in mean total weekly FI episodes in the PTNS compared to sham group (difference in means –2.3, 95% CI (–4.2 to –0.3), p = 0.02). This reflected a significant reduction in mean weekly urge (–1.5, 95% CI (–2.7 to –0.2), p = 0.02) but not passive episodes (–0.64, 95% CI (–1.67 to 0.40), p = 0.23). No significant difference in St Mark’s Continence Score was observed between groups (difference in means –0.047, 95% CI (–1.033 to 0.939), p = 0.93). No differences in the disease-specific Faecal Incontinence Quality of Life and Gastrointestinal Quality of life tools or the generic SF-36 quality of life tool were observed between the groups. No serious adverse events related to treatment were reported. <h3>Conclusion</h3> PTNS did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. <h3>Funding</h3> This project was funded by the NIHR Health Technology Assessment programme. <h3>Disclosure of interest</h3> None Declared.
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells
Authors: Mathew C. Casimiro, Gabriele Di Sante, Xiaoming Ju, Zhiping Li, Ke Chen, Marco Crosariol, Ismail Yaman, Michael Gormley, Hui Meng, Michael P. Lisanti, Richard G. Pestell
Journal: Cancer Research (2015)

Abstract Therapy resistance and poor outcome in prostate cancer is associated with increased expression of cyclin D1. Androgens promote DNA double-strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclin D1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of γH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1 dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance. Cancer Res; 76(2); 329–38. ©2015 AACR.
Prospectively randomized North Central Cancer Treatment Group trial of intensive-course fluorouracil combined with the l-isomer of intravenous leucovorin, oral leucovorin, or intravenous leucovorin for the treatment of advanced colorectal cancer.
Authors: R M Goldberg, A K Hatfield, M Kahn, D J Sargent, J A Knost, M J O'Connell, J E Krook, J A Maillard, M Wiesenfeld, P L Schaefer, M T Tirona, C G Moertel
Journal: Journal of Clinical Oncology (1997)

PURPOSE A three-arm randomized phase III trial in advanced colorectal cancer patients was designed to test whether substitution of an equivalent dose of (1) l-leucovorin or (2) oral leucovorin would more effectively potentiate fluorouracil (5-FU) than standard intravenous (I.V.) (d,l)-leucovorin. PATIENTS AND METHODS A total of 926 chemotherapy-naive patients participated. Patients received one of three treatments: (A) intensive-course 5-FU plus l-leucovorin with I.V. leucovorin (Immunex Corp, Seattle, WA) at 100 mg/m2 and I.V. 5-FU at 370 mg/m2; (B) intensive-course 5-FU plus oral (d,l)-leucovorin with oral leucovarin at 125 mg/m2 on hours 0, 1, 2, and 3 (total dose, 500 mg/m2) followed by 5-FU 370 mg/m2 on hour 4; or (C) intensive-course 5-FU plus I.V. (d,l)-leucovorin with I.V. leucovorin 200 mg/m2 and 5-FU 370 mg/m2. Drugs were administered daily for 5 consecutive days. Courses were repeated at 4 and 8 weeks, and every 5 weeks thereafter. Dosage was reduced for neutropenia, thrombocytopenia, diarrhea, stomatitis, and dermatitis. RESULTS Of 926 eligible patients, 756 have died. The overall response rate for patients with measurable disease was 32% (165 of 514). There were no differences between regimens in response rates (arm A, 28% [47 of 140]; arm B, 34% [60 of 174]; and arm C, 34% [58 of 170]) or in survival. There have been nine possible chemotherapy-related fatalities. Grade III to IV toxic effects did not differ appreciably by arm and included stomatitis (12% to 14%), diarrhea (15% to 19%), nausea (7% to 9%), and vomiting (6% to 8%). CONCLUSION There was no difference in response, survival, or toxicity between these three different leucovorin formulations combined with 5-FU.
Recent Advances in the Development of Antineoplastic Agents Derived from Natural Products
Authors: Matthew Trendowski
Journal: Drugs (2015)

Through years of evolutionary selection pressures, organisms have developed potent toxins that coincidentally have marked antineoplastic activity. These natural products have been vital for the development of multiagent treatment regimens currently employed in cancer chemotherapy, and are used in the treatment of a variety of malignancies. Therefore, this review catalogs recent advances in natural product-based drug discovery via the examination of mechanisms of action and available clinical data to highlight the utility of these novel compounds in the burgeoning age of precision medicine. The review also highlights the recent development of antibody-drug conjugates and other immunotoxins, which are capable of delivering highly cytotoxic agents previously deemed too toxic to elicit therapeutic benefit preferentially to neoplastic cells. Finally, the review examines natural products not currently used in the clinic that have novel mechanisms of action, and may serve to supplement current chemotherapeutic protocols.
Physical and psychologic distress associated with adjuvant chemotherapy in women with breast cancer.
Authors: M T Knobf
Journal: Journal of Clinical Oncology (1986)

The incidence of physical toxicity and psychosocial effects associated with adjuvant chemotherapy for stage II breast cancer have been reported in previous studies. The purpose of this exploratory study was to quantify the degree of physical and psychologic distress experienced by patients and identify life-style changes. A semistructured interview was conducted with 78 subjects to elicit demographic data, distress, and life-style changes using the Symptoms Distress Scale (SDS), the Psychiatric Status Schedule (PSS), and questions and scales developed by the investigator. All subjects received adjuvant chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil with or without vincristine and prednisone) following primary treatment for breast carcinoma. Fifty subjects were currently on therapy and 28 had completed treatment. Fatigue was the most distressful physical symptom. Although physical distress was rated higher by subjects receiving treatment, generally all rating scores indicated only mild symptom distress. Subjects perceived more distress for the psychologic and emotional response to disease and treatment, and this persisted for women who completed therapy. Changes in role performance and daily activity were minimal.
Lymphocyte-Predominant Hodgkin's Disease: How Little Therapy Is Enough?
Authors: Jon C. Aster
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.3.744 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10071261 Lymphocyte-Predominant Hodgkin's Disease: How Little Therapy Is Enough? Jon C. AsterxJon C. AsterSearch for articles by this author Show More Brigham and Women's Hospital, Boston, MA https://doi.org/10.1200/JCO.1999.17.3.744 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
The Molecular Mechanism of Insulin Action
Authors: C R Kahn
Journal: Annual Review of Medicine (1985)

Insulin initiates its action by binding to a glycoprotein receptor on the surface of the cell. This receptor consists of an alpha-subunit, which binds the hormone, and a beta-subunit, which is an insulin-stimulated, tyrosine-specific protein kinase. Activation of this kinase is believed to generate a signal that eventually results in insulin's action on glucose, lipid, and protein metabolism. The growth-promoting effects of insulin appear to occur through activation of receptors for the family of related insulin-like growth factors. Both genetic and acquired abnormalities in the number of insulin receptors, the activity of the receptor kinase, and the various post-receptor steps in insulin action occur in disease states leading to tissue resistance to insulin action.
Update: A food-borne outbreak of hepatitis A in the Netherlands related to semi-dried tomatoes in oil, January-February 2010
Authors: M Petrignani, M Harms, L Verhoef, R van Hunen, C Swaan, J van Steenbergen, I Boxman, R Peran i Sala, H J Ober, H Vennema, M Koopmans, W van Pelt
Journal: Eurosurveillance (2010)

Between 31 December 2009 and 10 February 2010, 13 patients were infected by an identical hepatitis A virus strain not previously detected in the Netherlands. They had not been abroad and were widely distributed over the Netherlands. A case-control study including 12 cases and 44 controls identified semi-dried tomatoes in oil as the source of the outbreak (odds ratio: 20.0; 95% confidence interval: 1.5-274). The virus was not detected in any of 81 tested food samples. International trace-back is still ongoing.
A randomized controlled trial of daily sedation interruption in critically ill children
Authors: Nienke J. Vet, Saskia N. de Wildt, Carin W. M. Verlaat, Catherijne A. J. Knibbe, Miriam G. Mooij, Job B. M. van Woensel, Joost van Rosmalen, Dick Tibboel, Matthijs de Hoog
Journal: Intensive Care Medicine (2015)

To compare daily sedation interruption plus protocolized sedation (DSI + PS) to protocolized sedation only (PS) in critically ill children.In this multicenter randomized controlled trial in three pediatric intensive care units in the Netherlands, mechanically ventilated critically ill children with need for sedative drugs were included. They were randomly assigned to either DSI + PS or PS only. Children in both study arms received sedation adjusted on the basis of validated sedation scores. Provided a safety screen was passed, children in the DSI + PS group received daily blinded infusions of saline; children in the PS group received blinded infusions of the previous sedatives/analgesics. If a patient's sedation score indicated distress, the blinded infusions were discontinued, a bolus dose of midazolam was given and the 'open' infusions were resumed: DSI + PS at half of infusion rate, PS at previous infusion rate. The primary endpoint was the number of ventilator-free days at day 28. Data were analyzed by intention to treat.From October 2009 to August 2014, 129 children were randomly assigned to DSI + PS (n = 66) or PS (n = 63). The study was terminated prematurely due to slow recruitment rates. Median number of ventilator-free days did not differ: DSI + PS 24.0 days (IQR 21.6-25.8) versus PS 24.0 days (IQR 20.6-26.0); median difference 0.02 days (95 % CI -0.91 to 1.09), p = 0.90. Median ICU and hospital length of stay were similar in both groups: DSI + PS 6.9 days (IQR 5.2-11.0) versus PS 7.4 days (IQR 5.3-12.8), p = 0.47, and DSI + PS 13.3 days (IQR 8.6-26.7) versus PS 15.7 days (IQR 9.3-33.2), p = 0.19, respectively. Mortality at 30 days was higher in the DSI + PS group than in the PS group (6/66 versus 0/63, p = 0.03), though no causal relationship to the intervention could be established. Median cumulative midazolam dose did not differ: DSI + PS 14.1 mg/kg (IQR 7.6-22.6) versus PS 17.0 mg/kg (IQR 8.2-39.8), p = 0.11.In critically ill children, daily sedation interruption in addition to protocolized sedation did not improve clinical outcome and was associated with increased mortality compared with protocolized sedation only.
Optimizing Delivery of Preexposure Prophylaxis—The Next Frontier
Authors: Raphael J. Landovitz
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies.
Authors: G A Masters, D J Haraf, P C Hoffman, L C Drinkard, S A Krauss, M K Ferguson, J Olak, B L Samuels, H M Golomb, E E Vokes
Journal: Journal of Clinical Oncology (1998)

PURPOSE The cisplatin-vinorelbine regimen has superior activity in advanced non-small-cell lung cancer (NSCLC). We conducted a phase I trial to identify the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this regimen with concomitant thoracic radiation (RT) in patients with advanced chest malignancies. PATIENTS AND METHODS Patients with advanced chest malignancies that required RT were enrolled onto this phase I study of standard chest radiation (30 daily 2-Gy fractions for a total of 60 Gy) and concurrent chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine starting at 20 mg/m2/wk. RESULTS Thirty-seven patients were treated on this study. Two of three patients treated at the maximum-administered dose of cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT (neutropenia), which required deescalation. The dose level of cisplatin 100 mg/m2 and vinorelbine 20 mg/m2/wk, although tolerated acutely, produced delayed esophagitis, which proved dose-limiting. The recommended phase II dose was cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3 weeks with concomitant chest RT. CONCLUSION Concomitant chemoradiotherapy with cisplatin and vinorelbine is feasible. The recommended phase II dose is cisplatin 80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a day 1/day 8 schedule. Esophagitis is the DLT, with neutropenia occurring at higher dose levels. A Cancer and Leukemia Group B (CALGB) phase II trial is currently underway to evaluate further the efficacy and toxicities of this regimen in unresectable stage III NSCLC.
Day case procedure is safe
Authors: A. C Douds, J D. Maxwell
Journal: BMJ (1995)

Radiologists, who every year scan hundreds of livers of all shapes, positions, and sizes, are better placed than anyone else to comment on the inappropriateness of performing blind right intercostal punctures with large calibre needles.They are also, by training and experience, the most expert in placing biopsy needles of all kinds under imaging guidance and are probably just waiting to be asked.
Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine.
Authors: D C Hohn, R J Stagg, D C Price, B J Lewis
Journal: Journal of Clinical Oncology (1985)

Gastroduodenal inflammation and ulceration have been frequently observed in patients receiving continuous hepatic arterial infusions of 5-fluoro-2'-deoxyuridine (FUDR) for liver malignancy. Thirty-five patients with metastatic colon cancer received hepatic arterial FUDR administered with implanted infusion pumps. At surgery, particular care was taken to identify and divide those vessels arising from the hepatic arteries distal to the point of cannulation that supplied the superior border of the distal stomach and proximal duodenum. None of the patients developed signs or symptoms of gastritis or ulcer attributable to chemotherapy. We contend that gastritis and ulcer in patients receiving hepatic arterial FUDR are due to misperfusion of drug into the upper gastrointestinal tract and that these complications can be largely avoided by use of appropriate surgical techniques.
Continuous Oxygen Therapy for the Chronically Hypoxemic Patient
Authors: D Georgopoulos, N R Anthonisen
Journal: Annual Review of Medicine (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More