tbuckley/cabot-search huggingface dataset:
Phase I and Pharmacokinetic Study of XRP6258 (RPR 116258A), a Novel Taxane, Administered as a 1-Hour Infusion Every 3 Weeks in Patients with Advanced Solid Tumors
Authors: Alain C. Mita, Louis J. Denis, Eric K. Rowinsky, Johann S. DeBono, Andrew D. Goetz, Leonel Ochoa, Bahram Forouzesh, Muralidhar Beeram, Amita Patnaik, Kathleen Molpus, Dorothée Semiond, Michèle Besenval, Anthony W. Tolcher
Journal: Clinical Cancer Research (2009)

To assess the feasibility of administering XRP6258, a new taxane with a low affinity for the multidrug resistance 1 protein, as a 1-hour i.v. infusion every 3 weeks. The study also sought to determine the maximum tolerated dose and the recommended dose, to describe the pharmacokinetic (PK) behavior of the compound, and to seek preliminary evidence of anticancer activity.Twenty-five patients with advanced solid malignancies were treated with 102 courses of XRP6258 at four dose levels ranging from 10 to 25 mg/m(2). Dose escalation was based on the occurrence of dose-limiting toxicity (DLT) at each dose level, provided that PK variables were favorable. The maximum tolerated dose was defined as the dose at which at least two patients developed a DLT at the first course.Neutropenia was the principal DLT, with one patient experiencing febrile neutropenia and two others showing prolonged grade 4 neutropenia at the 25 mg/m(2) dose level. Nonhematologic toxicities, including nausea, vomiting, diarrhea, neurotoxicity, and fatigue, were generally mild to moderate in severity. XRP6258 exhibited dose-proportional PK, a triphasic elimination profile, a long terminal half-life (77.3 hours), a high clearance (mean CL, 53.5 L/h), and a large volume of distribution (mean V(ss), 2,034 L/m(2)). Objective antitumor activity included partial responses in two patients with metastatic prostate carcinoma, one unconfirmed partial response, and two minor responses.The recommended phase II dose of XRP6258 on this schedule is 20 mg/m(2). The general tolerability and encouraging antitumor activity in taxane-refractory patients warrant further evaluations of XRP6258.
Marriage costs women doctors in the US an 11% salary drop
Authors: Roger Dobson
Journal: BMJ (2005)

Married women doctors in the United States earn 11% less than men and unmarried women without children, according to research reported in the Journal of Human Resources (2005;40:477-504). They earn another 14% less if they have one child and 22% less if they have more than one child.

The research, which was carried out by a team from Mount Holyoke College, Massachusetts, and based on the American Medical Association's young physicians survey, a nationally representative sample of US doctors aged under 40, looked at how much of the earnings gap between men and women doctors is due to women's greater family responsibilities.

Changes over time in men's and women's incomes were compared with marital status and numbers of children. The study also included data on specialties, type of job chosen, and hours worked.

The results …
Endpiece: Basis of Zen practice
Authors: R. Pirsig
Journal: BMJ (1998)

Philosophical mysticism, the idea that truth is indefinable and can be apprehended only by non-rational means, has been with us since the beginning of history. It’s the basis of Zen practice. But it’s not an academic subject. The academy, the Church of Reason, is concerned exclusively with those things that can be defined, and if one wants to be a mystic, his place is in a monastery, not a University. Universities are places where things should be spelled out.
Autoimmunity in primary antibody deficiency is associated with protein tyrosine phosphatase nonreceptor type 22 (PTPN22)
Authors: Gary Y.J. Chew, Umang Sinha, Paul A. Gatenby, Theo DeMalmanche, Stephen Adelstein, Roger Garsia, Pravin Hissaria, Martyn A. French, Anastasia Wilson, Belinda Whittle, Philippa Kirkpatrick, D. Sean Riminton, David A. Fulcher, Matthew C. Cook
Journal: Journal of Allergy and Clinical Immunology (2012)
Birth characteristics of women who develop gestational diabetes: population based study
Authors: G. M Egeland, R. Skjarven, L. M Irgens
Journal: BMJ (2000)

Women with gestational diabetes are at increased risk of non-insulin dependent diabetes and their babies are at increased risk of adverse perinatal outcomes. 1These risks can be reduced by better detection and control of diabetes. 2Identifying risk factors for gestational diabetes may improve screening programmes.As low birth weight has been related to non-insulin dependent diabetes in elderly populations, 3 we decided to investigate whether women's characteristics at birth could predict their subsequent risk of gestational diabetes. Subjects, methods, and resultsWe used linked generation data from the medical birth registry of Norway to study all women born in 1967-84 who had given birth between 1988 and 1998.The registry is a compulsory reporting system and files used for analysis are anonymised.Although there were 141 107 women in the cohort, we excluded 2393 who were not singletons.We compared the birth characteristics of women with and without self reported gestational diabetes in one or more pregnancies.Data were analysed in relation to categories of birth weight; the ponderal index at birth (m/g 3 ×100); gestational age (excluding women who were considered misclassified) 4 ; weight for gestational age; and whether the woman had a mother whose pregnancy had been complicated by diabetes (any type), pre-eclampsia, eclampsia, placental abruption, or hypertension.We also considered diabetes in relation to the women's age and parity and their mothers' age and parity when they were born.We calculated odds ratios obtained from logistic regression analyses in which we adjusted for the women's age and parity and their mothers' diabetes.Altogether 498 of these women aged less than 32 reported gestational diabetes.Prevalence increased with age, from 1.5 per 1000 deliveries for women aged <20 to 4.2 for women aged >30 (odds ratio 2.8; 95% confidence interval 1.9 to 4.3).Parity increased the risk of gestational diabetes; age adjusted odds ratios (95% confidence intervals) for women with two, three, and four or more deliveries compared with one delivery were 1.5 (1.2 to 1.9), 1.9 (1.4 to 2.5), and 3.3 (2.1 to 5.1) respectively.Women whose mothers had had diabetes during pregnancy were at increased risk of gestational diabetes (table).The table also shows that there were significant inverse trends in diabetes in relation to birth weight and weight for gestational age (P < 0.001).The increased risks of gestational diabetes were 80%, 60%, and 40% in women whose birth weights were <2500 g, 2500-2999 g, and 3000-3499 g respectively compared with women in the 4000-4500 g group.We observed similar findings in relation to categories of weight for gestational age.Birth weight and weight for gestational age are strongly related; the three highest birthweight
Comparison of glial fibrillary acidic protein and desmin staining in normal and CCl4-induced fibrotic rat livers
Authors: T Niki, P J De Bleser, G Xu, K Van der Berg, E Wisse, A Geerts
Journal: Hepatology (1996)

Fat-storing cells are the major producers of extracellular matrix in the liver. A good immunocytochemical marker is, however, still lacking for this cell type. Desmin, frequently used by most investigators, fails to stain many pericentral fat-storing cells in normal rat liver. The aim of the present study is to evaluate glial fibrillary acidic protein (GFAP) as an alternative marker of fat-storing cells. In normal rat liver, immunostaining of GFAP revealed numerous fat-storing cells with characteristic cytoplasmic extensions. Unlike desmin, which was preferentially expressed in periportal fat-storing cells, GFAP-positive fat-storing cells were distributed more evenly in the lobules. In a narrow periportal zone, however, GFAP-positive cells were occasionally absent. Dual GFAP/desmin staining revealed colocalization of these markers, but fat-storing cells positive only for GFAP or desmin were also present. Chronic carbon tetrachloride exposure induced a spatial change in the expression of GFAP and desmin. At 3 weeks, accumulation of GFAP/desmin double-positive cells was observed in developing fibrotic septa. At 8 weeks, the GFAP positivity in the septa persisted but became weak, while desmin expression became stronger. In contrast, the expression of GFAP within the lobule was gradually decreased as fibrosis progressed. We conclude that GFAP is expressed by a subpopulation of fat-storing cells, which differs partially from the population that expresses desmin. Because in normal rat liver desmin-negative fat-storing cells can be identified by GFAP staining and vice versa, dual GFAP/desmin staining allows more complete identification of fat-storing cells. In chronically injured liver, GFAP may not be as useful as in normal rat liver. The coexpression of GFAP/desmin in developing septa and the subsequent downregulation of GFAP in an advanced stage of fibrosis may reflect different stages of fat-storing cell activation. Further investigation is required to determine the functional significance of alteration of GFAP expression in fat-storing cells.
Jobs for the boys
Authors: Wendy Moore
Journal: BMJ (2007)

Climbing the greasy medical career ladder used to be so much simpler. Before the advent of tedious form-filling, maddening technical hitches, and the unseemly scramble for too few posts, obtaining a plum job for life was governed by an application system that everyone could understand: nepotism.

For centuries, all that was needed for an aspiring trainee physician or surgeon to secure a lucrative countryside practice or a top post at an eminent teaching hospital were the right family connections. In a spirit of continuity only equalled by The Forsyte …
Remarks on the Treatment of Wounds
Authors: G. Humphry
Journal: BMJ (1895)

SOME years ago, before the days of antiseptics, at a com- bined meeting of these Branches of the British Medical Association in this place (Bedford), I gave a short history of the treatment of wounds in past times, and added that apposition of surfaces was the thing to be aimed at, and that, speaking generally, nothing further was really required.I said that incised wounds would, with few exceptions, heal well if only the cut surfaces were maintained in good apposition and allowed to be at rest; but that the great difficulty in effecting this was the escape into the wound of serum or blood which separated the surfaces, and, further, caused trouble and suppuration by itself undergoing decomposition.I based this statement much upon the observation of wounds of the lips and cheek, which seareely ever fail to heal at once when the skin edges are united by sutures, the reason
447 Evaluation of percutaneous ablation treatments of hepatocellular carcinoma (HCC) as a risk factor for neoplastic recurrence in patients who underwent liver transplant (LT)
Authors: V MIRANTE, M POMPILI, G RONDINARA, D FORTI, G ROSSI, L FASSATI, S AGNES, M CASTAGNETO, G PELECCA, G GASBARRINI
Journal: Hepatology (2003)
IT Bill Criticized
Authors: Mike Mitka
Journal: JAMA (2008)

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
A Comparative Study of Prothrombinopenic Anticoagulant Drugs
Authors: Robert Smith
Journal: JAMA (1960)

Previous studies in this laboratory had shown little difference among 4 commonly used anticoagulants, bishydroxycoumarin, coumadin sodium, phenindione, and diphenadione. Two newer agents, anisindione and acenocoumarol, for which distinct superiority has been claimed, were compared under controlled conditions with two of the earlier drugs, bishydroxycoumarin and diphenadione, in 230 patients. No clinically significant differences that would recommend one agent over the other were observed. Using a large initial loading dose the majority of the patients could be brought into the therapeutic range at 40 hours and maintained at therapeutic levels approximately 85 per cent of the time with any of the drugs. The authors feel that any of the available prothrombinopenic agents, properly handled, is satisfactory for routine use in anticoagulant therapy, and that physicians should be slow to abandon one with which they are experienced.
Plasma Lipids and Proteins and their Relationship to Coronary Disease among Navajo Indians
Authors: IRVINE H. PAGE, LENA A. LEWIS, JARVEY GILBERT
Journal: Circulation (1956)

Coronary disease is rare among the Navajo Indians. Their plasma proteins and lipids differ from those of the population of Cleveland in that albumin is low normal and α- and γ-globulin elevated; total cholesterol was much lower. Since the diet and living habits are not strikingly different from those of the control group, it is suggested that heredity, in this case, is the most likely explanation for the low incidence of coronary disease and low level of cholesterol. Neither in the control nor Navajo group did mean serum total cholesterol rise with age.
International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy
Authors: Boyd E. Metzger, Steven G. Gabbe, Bengt Persson, Lynn P. Lowe, Alan R. Dyer, Jeremy J.N. Oats, Thomas A. Buchanan
Journal: Diabetes Care (2010)

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort.

The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …
ARMS Depletion Facilitates UV Irradiation–Induced Apoptotic Cell Death in Melanoma
Authors: Yi-Hua Liao, Su-Ming Hsu, Pei-Hsin Huang
Journal: Cancer Research (2007)

Abstract Tumor cells often aberrantly reexpress molecules that mediate proper embryonic development for advantageous growth or survival. Here, we report that ankyrin repeat-rich membrane spanning (ARMS), a transmembrane protein abundant in the developing and adult neural tissues, is overexpressed in melanoma, a tumor ontogenetically originating from neural crest. Immunohistochemical study of 79 melanocytic lesions showed significantly increased expression of ARMS in primary malignant melanomas (92.9%) and metastatic melanoma (60.0%) in comparison with benign nevocellular nevi (26.7%). To investigate the role of ARMS in melanoma formation, murine B16F0 melanoma cells with stable knockdown of ARMS were established by RNA interference. Down-regulation of ARMS resulted in significant inhibition of anchorage-independent growth in soft agar and restrictive growth of melanoma in severe combined immunodeficient mice. Importantly, depletion of ARMS facilitated UVB-induced apoptosis in melanoma cells through inactivation of mitogen-activated protein kinase/extracellular signal–regulated kinase (ERK) kinase (MEK)/ERK. Addition of MEK inhibitor PD98059 further sensitized ARMS-depleted melanoma cells to UVB-induced apoptosis, whereas constitutively active MEK rescued ARMS-depleted cells from apoptosis. We further showed that BRAF, a downstream signaling molecule of ARMS in ERK pathway, is not mutated as a constitutively active form in acral lentiginous melanoma; in contrast, BRAFT1799A mutation, which leads to constitutive activation of ERK signaling, was detected in 57.1% of superficial spreading melanoma. Our study suggests that overexpression of ARMS per se serves as one mechanism to promote melanoma formation by preventing stress-induced apoptotic death mediated by the MEK/ERK signaling pathway, especially in acral lentiginous melanoma, most of which does not harbor BRAF mutation. [Cancer Res 2007;67(24):11547–56]
Health Education by Television and Radio
Authors: Alan B. Cantor
Journal: JAMA (1982)

This book contains most of the papers presented at International Week 1980 on Health Education by Television and Radio, a conference that took place from Nov 17 through 21, 1980, in Munich. The papers deal with the broad issues of health education, strategies that promote effectiveness, and descriptions and analyses of particular programs. They are generally well written and informative. In some cases the papers seem disjointed, and the editor explains that slides that accompanied the presentations were not included in the book (probably for reasons of economy). In fairness to authors and readers alike, the contents of the slides should have been included or the papers omitted. Part 1 consists of general considerations about relationships between journalists and physicians and the role of mass media in health education. Problems faced by broadcasters and opportunities for enhancement of public health are also discussed. Part 2 presents conflicting evidence of the
350 Amphiregulin a novel determinant in the resistance of HCC cells to apoptosis induced by TGF-β and cytostatic drugs
Authors: J. Castillo, E. Erroba, M.J. Perugorria, M. Santamaria, D.C. Lee, J. Prieto, C. Berasain, M.A. Avila
Journal: Journal of Hepatology (2006)
Anticoagulant Options — Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran
Authors: B. Nhi Beasley, Ellis F. Unger, Robert Temple
Journal: New England Journal of Medicine (2011)

Last fall, the FDA approved dabigatran, in a 150-mg dose only, for reducing risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A 110-mg regimen was also effective, but the agency believes that patients should receive the higher dose.
Commercial partnerships in chronic disease management: proceeding with caution
Authors: T. Greenhalgh
Journal: BMJ (2000)

The spirit of “new Labour” strongly supports efforts to align commercial and NHS interests. The use of private funding for capital projects, such as building hospitals, is now well established, although this practice is not without controversy.1 We discuss a different form of private finance initiative—the development of packages for disease management in collaboration with commercial companies. We describe our preliminary experiences from a health authority perspective. The Clinical Effectiveness Review Group was established in 1995 at Barnet Health Authority to address the implementation of evidence based practice at health authority level. The Director of Public Health (SF) noted that he occasionally received offers from independent organisations of “free” packages of services, directed ultimately at general practices, hospital departments, or community pharmacies. These organisations were pharmaceutical companies, producers of medical equipment, or their agents, which, despite a clear conflict of interests were perceived as offering a potentially important contribution to the health of the population (box 1). Somewhat confusingly, these offers were often presented as “managed care” packages, a term that generally implies a different approach aimed at centralised control and cost containment.2 #### Summary points Commercial companies, especially the manufacturers of drugs and medicines, increasingly seek to work in collaboration with NHS service providers to manage particular diseases or problems With such relations there are risks, but also potential benefits, and it may be more realistic to require all parties to be explicit about their potential conflicts of interest than to impose a blanket ban on negotiations One London health authority developed and used a set of standards for collaborating with the commercial sector in “managed care” initiatives The draft proposals could be used with a view to developing definitive guidance for health authorities, primary care groups, and trusts when considering such collaborative relations ### Box 1 : Examples of “disease management packages” offered by commercial companies to a London health authority 1997-9
Fenestrated Sagittal Sinus Mimicking Posterior Cerebral Infarction
Authors: REX B. SHAFER, JOHN M. WOLFF
Journal: Clinical Nuclear Medicine (1978)

Two patients who presented with abnormal neurological findings and focal abnormalities on static brain imaging, were felt to have infarction in the distribution of the posterior cerebral artery. However, the posterior flow study delineated the cause of the abnormality as being a fenestrated anomaly of the sagittal sinus. The incidence of occlusive disease of the posterior cerebral artery, its clinical and scintigraphic presentation and the potential pitfalls for misinterpretation are reviewed.
Involving patients in drug licensing decisions
Authors: N. Britten, S. Denford, K. Stein
Journal: BMJ (2013)

Gale’s editorial about the adverse consequences of incretins concludes that: “The problem lies in a system that subordinates the public interest to commercial secrecy.”1 Another problem is that the system does not regard patients, or the public, as legitimate stakeholders whose judgments could or should contribute to licensing decisions.

The National Institute for Health Research Collaboration for Leadership in Applied Health Care …