tbuckley/cabot-search huggingface dataset:
Factors Associated With Failure to Publish Large Randomized Trials Presented at an Oncology Meeting
Authors: Monika K. Krzyzanowska
Journal: JAMA (2003)

Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.Publication rate at 5 years; time from presentation to full publication.Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.
Glucocorticoids Suppress Tumor Lymphangiogenesis of Prostate Cancer Cells
Authors: Akihiro Yano, Yasuhisa Fujii, Aki Iwai, Satoru Kawakami, Yukio Kageyama, Kazunori Kihara
Journal: Clinical Cancer Research (2006)

Glucocorticoids such as prednisone, hydrocortisone, and dexamethasone are known to provide some clinical benefit for patients with hormone-refractory prostate cancer. However, the underlying mechanisms by which glucocorticoids affect hormone-refractory prostate cancer progression are not well established as yet. Our previous study has shown that glucocorticoids inhibit tumor angiogenesis possibly by down-regulation of vascular endothelial growth factor (VEGF) and interleukin 8. Here, we hypothesized that the therapeutic effect of dexamethasone on hormone-refractory prostate cancer can be partly attributed to a direct inhibition of lymphangiogenesis through the glucocorticoid receptor by down-regulating a major lymphangiogenic factor, VEGF-C.The effects of dexamethasone on the expression of VEGF-C and its receptor, VEGF receptor-3 (VEGFR-3), were examined using an androgen-independent human prostate cancer cell line, DU145, which expresses glucocorticoid receptor. The effects of dexamethasone on tumor-associated lymphangiogenesis in DU145 xenografts were determined by analyzing VEGF-C gene expression, lymphatic vessel density, and relative lymphatic vessel area.Dexamethasone significantly down-regulated VEGF-C gene expression and protein production by 48% (P = 0.003) and 44% (P = 0.002), respectively, under normoxic condition. Similarly, hydrocortisone down-regulated VEGF-C gene expression. The effects of dexamethasone were completely reversed by the glucocorticoid receptor antagonist RU486. Even under hypoxia-like conditions, dexamethasone inhibited VEGF-C gene expression. In DU145 xenografts, dexamethasone significantly down-regulated VEGF-C gene expression and decreased lymphangiogenesis. Dexamethasone did not affect VEGFR-3 gene expression in vitro and in vivo.Glucocorticoids suppressed tumor-associated lymphangiogenesis by down-regulating VEGF-C through glucocorticoid receptor in androgen-independent prostate cancer cells in vivo.
Points: GMC and the recognition of overseas postgraduate diplomas
Authors: J. Crofton
Journal: BMJ (1984)

known inhibitors of the enzyme-for example, isoniazide.Isoniazide interferes with the ALA- synthase coenzyme, pyridoxal phosphate, and, chronically administered, has a potent inhibitory effect on the hepatic enzyme in guinea pigS.2 3 I know of no trial concerning the effect of the drug in acute porphyria, either clinical or experimental.
Care in the early newborn period
Authors: William McGuire, Peter McEwan, Peter Fowlie
Journal: BMJ (2004)

The first week after birth is a time of major metabolic and physiological adaptation for newborn infants. Preterm infants have to cope with additional stresses because most of their organ systems are immature or because of associated illnesses, such as congenital infection. Very preterm infants (< 32 weeks' gestation) or ill infants often need intensive monitoring and support during this critical period of postnatal adaptation.

Preterm infants are susceptible to heat and fluid loss, especially immediately after delivery and in the first few days after birth. Hypothermia is associated with increased morbidity and mortality. Trials in the 1950s showed that reducing heat loss improves survival for preterm and low birthweight infants. Measures to prevent cold stress should start immediately after delivery—for example, resuscitating newborns under radiant heaters, drying them, and wrapping them in warmed towels straight away. A randomised controlled trial showed that wrapping the infant in polyethylene immediately (without drying) is at least as effective in reducing evaporative heat loss in extremely preterm infants (< 28 weeks' gestation).

View this table:

Heat and fluid loss



### Maintaining the neutral thermal environment

After admission to the neonatal unit unnecessary oxygen and energy consumption must be minimised. Several options are available for nursing preterm infants in a neutral thermal environment. Bigger and more mature infants (weighing > 1800 g) can usually maintain their body temperatures in open cots with clothing (including a hat), covers, and possibly a heated mattress. Smaller and less mature infants, particularly very preterm infants, are usually cared for in air heated perspex incubators or in open cots, where they are placed under clear polyethylene blankets and there are overhead radiant heaters. The air temperature of the incubator or the power of the overhead heater can be set …
Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis
Authors: Rigopoulou Ei, Davies Et, Pares A, Zachou K, Liaskos C, Bogdanos Dp, Rodes J, Dalekos Gn, Vergani D
Journal: Gut (2005)

<b>Background:</b> Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MND) pattern are highly specific for primary biliary cirrhosis (PBC). <b>Aim and subjects:</b> To assess the prevalence of PBC specific ANAs, their Ig isotype, and their clinical significance in 90 PBC patients from Greece and Spain. Twenty eight patients with chronic hepatitis C, 23 patients with systemic lupus erythematosus, and 17 healthy subjects were studied as controls. <b>Methods:</b> PBC specific ANA reactivity was tested by indirect immunofluorescence using HEp2 cells as substrate and individual Ig class (IgG, IgA, IgM) and IgG subclass (IgG1, IgG2, IgG3, IgG4) specific antisera as revealing reagents. <b>Results:</b> Fourteen of 90 (15.6%) PBC patients had PBC specific ANA reactivity when an anti-IgG (total) antiserum was used as the revealing reagent while 58 (64.4%) were positive when specific antisera to each of the four IgG isotypes were used. The prevailing isotype was IgG3 for MND and IgG1 for RL/M. PBC patients with specific ANA, in particular of the IgG3 isotype, had significantly more severe biochemical and histological disease compared with those who were seronegative. None of the controls was positive. <b>Conclusions:</b> Disease specific ANA are present in the majority of patients with PBC when investigated at the level of immunoglobulin isotype. PBC specific ANA, in particular of the IgG3 isotype, are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.
The Epidemic of Squamous Cell Carcinoma
Authors: Martin A. Weinstock
Journal: JAMA (1989)

Human skin takes a lot of abuse. It is our largest organ and the major barrier between our other organs and the natural and man-made hazards that surround us. These hazards may lead to cancer. Among cancers of the keratinocyte (the predominant cell of skin) in whites, basal cell carcinoma is the more common, yet squamous cell carcinoma (SCC) metastasizes more frequently and causes more deaths.<sup>1-3</sup> Although UV radiation is the most important etiologic factor, other factors are known to cause some cases of cutaneous SCC. The first documentation of chemical carcinogenesis was Percivall Pott's description, in 1775, of SCC of the scrotum induced by chimney soot.<sup>4</sup>Certain other hydrocarbons derived from coal and oils cause SCC.<sup>5</sup>Arsenic in well water was shown to cause SCC in the classic studies from Taiwan,<sup>6</sup>and exposure to arsenic in medicinals (such as Fowler's solution, Donovan's solution, and "Asiatic
Transient Retinopathy in Acute Aortic Dissection
Authors: Kenshiro Arao, Asuka Kuribara, Hiroyuki Jinnouchi, Mitsunari Matsumoto, Takayuki Fujiwara, Nozomi Kinoshita, Akihiro Kakehashi, Junya Ako, Shin-ichi Momomura
Journal: Ophthalmology (2014)
Professional Behaviors of Physicians and Pursuing Social Justice
Authors: Mark Earnest
Journal: JAMA (2009)

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
Coronary blood flow measurements with left atrial injection of microspheres in conscious rats
Authors: P. WICKER, R. C TARAZI
Journal: Cardiovascular Research (1982)

Since left atrial (LA) injection of microspheres has been shown to give more precise coronary blood flow (CBF) determinations, and also since studies in a conscious state have obvious advantages, we have developed a technique of chronic LA catheterisation for these purposes in rats. Through a thoracotomy in the third left intercostal space, the LA appendage was cannulated and a catheter (PE-10 tubing) advanced into the left atrium. The catheter itself was passed through the chest and exteriorised at the back of the neck. Following recovery over 24 to 48 h, flow studies with microspheres could be performed for 3 to 8 days. One-hundred and twenty procedures performed over a 4 month period were analysed. Left atrial catheterisation could be performed in approximately 45 min with no bleeding in 79% of cases and only minimal or moderate bleeding in the rest (13% and 4%, respectively); respiratory complications were rare (<1%). The rats recovered rapidly, and all catheters remained patent for the duration of the preparation. Infections developed in 5% and the total mortality rate was 7%; a complete haemodynamic study could be obtained in 103/120 rats (86%). Small renal infarcts were found in 25% of the rats, but neither the infarcts nor the intraoperative blood loss had any significant effect on haemodynamic indices and flow measurements performed 3 to 8 days after atrial catheterisation. Coronary blood flow values in 33 normal rats were within the range of values reported in the literature. These results demonstrate that chronic LA catheterisation is possible in rats with no major difficulties and will allow the precise determination of coronary blood flow with microspheres in conscious animals.
Authors' reply to Huffman and colleagues
Authors: J. D. Abramson, H. G. Rosenberg, N. Jewell, J. M. Wright
Journal: BMJ (2014)

We thank the Cochrane review authors for their thoughtful comments (highlighted in quotes below), which give us the opportunity to clarify unresolved issues about the benefits and harms of statins in low risk people.1

> “This article predated by three weeks the publication of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines (12 November 2013), but statements were made about ‘proposed standards’ without full knowledge of these guidelines.”

The “proposed standards” that we referred to in our article were not the yet to be published 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on cholesterol treatment.2 3 Rather, they were the 2013 update of the Cochrane review on statins for the primary prevention of cardiovascular disease,4 which had incorporated the findings and recommendations of the 2012 Cholesterol Treatment Trialists’ (CTT) meta-analysis.5

The 2012 CTT meta-analysis reported that statins significantly reduce major vascular events in people “with 5-year risk of major vascular events lower than 10%.” It concluded that the current major guidelines—ATP-III in the US, the European Society of Cardiology task force, and the National Institute for Health and Care Excellence guidelines in the UK—“might need to be reconsidered.”

The 2013 Cochrane review stated: “in light of new evidence derived from the CTT Collaboration on primary prevention, there is a need to update existing cost-effective analysis.”

We based our comments about “proposed standards” on these calls to update existing recommendations. Although we had no advanced knowledge of the contents of the forthcoming ACC/AHA cholesterol treatment guidelines, we anticipated that these findings and recommendations would be influential.

> “Abramson and colleagues state: ‘Under the proposed 2013 standards, however, no level of risk would preclude statin therapy’”

The 2012 CTT meta-analysis concluded: “The present report shows that statins are indeed both effective and safe for …
Mutations in the K-ras oncogene induced by 1,2-dimethylhydrazine in preneoplastic and neoplastic rat colonic mucosa.
Authors: R F Jacoby, X Llor, B B Teng, N O Davidson, T A Brasitus
Journal: Journal of Clinical Investigation (1991)

These experiments were conducted to determine whether point mutations activating K-ras or H-ras oncogenes, induced by the procarcinogen 1,2-dimethylhydrazine (DMH), were detectable in preneoplastic or neoplastic rat colonic mucosa. Rats were injected weekly with diluent or DMH at 20 mg/kg body wt for 5, 10, 15, or 25 wk, killed, and their colons dissected. DNA was extracted from diluent-injected control animals, histologically normal colonic mucosa from carcinogen-treated animals, and from carcinomas. Ras mutations were characterized by differential hybridization using allele-specific oligonucleotide probes to polymerase chain reaction--amplified DNA, and confirmed by DNA sequencing. While no H-ras mutations were detectable in any group, K-ras (G to A) mutations were found in 66% of DMH-induced colon carcinomas. These mutations were at the second nucleotide of codons 12 or 13 or the first nucleotide of codon 59 of the K-ras gene. The same type of K-ras mutations were observed in premalignant colonic mucosa from 2 out of 11 rats as early as 15 wk after beginning carcinogen injections when no dysplasia, adenomas, or carcinomas were histologically evident, suggesting that ras mutation may be an early event in colon carcinogenesis.
Studies of the Equivalent Cardiac Generator Behavior of Isolated Turtle Hearts
Authors: Daniel A. Brody, Otis S. Warr, James R. Wennemark, John W. Cox, Francis W. Keller, Fred H. Terry
Journal: Circulation Research (1971)

Equivalent cardiac generator components were determined for a series of excised turtle hearts immersed in Ringer's solution. Relatively large preparations were contained within a specially designed spherical chamber, and electric field potentials were derived from 20 evenly spaced electrodes on the chamber wall. A laboratory computer was used to acquire and store the 20 leads of signal data in digitized form in real time. An eccentric dipole was optimally fitted to the surface potentials for each 2 msec sample; the remaining voltages were used to determine a centric multipolar series through octapolar content. In addition to the purely quantitative parameters which were thus determined, sequential mapping of isopotential distribution over the spherical boundary gave valuable qualitative insights into the behavior of the equivalent generator throughout ventricular depolarization. This activity varied in complexity from predominantly dipolar to strongly nondipolar among different preparations. Peak quadripolar activity ranged from a low of 10 to a high of 60%; the corresponding figures for octapole content were 5-61%. The overall technique permits experimental exploration of several theoretical principles which have been advanced since 1954. Pilot studies on rabbit hearts indicate that the method will also be applicable to mammalian hearts.
Interleukin 5 (IL-5) provides a signal that is required in addition to IL-4 for isotype switching to immunoglobulin (Ig) G1 and IgE.
Authors: J M Purkerson, P C Isakson
Journal: The Journal of Experimental Medicine (1992)

We have examined the contributions of Interleukin 4 (IL-4), IL-5, and other stimuli to the expression of Immunoglobulin G1 (IgG1) and IgE in murine B lymphoblasts activated with anti-Ig. The combination of IL-4 and -5 induced B lymphoblasts to proliferate and to secrete IgM and IgG1. However, an additional stimulus was required along with IL-4 and -5 for induction of IgE secretion. This stimulus was provided by lipopolysaccharides (LPS) or cytokines produced by TC-1 or EL4 cells. In the absence of IL-5, exceptionally high concentrations of IL-4 (greater than 1,000 U/ml) were required to elicit IgG1 and IgE secretion from B lymphoblasts cultured with either LPS or TC-1-conditioned media (CM). To investigate regulation of expression of gamma 1 and epsilon genes by IL-4, -5, and LPS, the requirements for induction of gamma 1 and epsilon germline and productive transcripts were examined. Germline gamma 1, but not epsilon, transcripts were detected in RNA from B lymphoblasts treated with IL-4 and -5 for 48 h. In contrast, both germline gamma 1 and epsilon transcripts could be detected in B lymphoblasts cultured with IL-4 and LPS, and steady state levels of germline gamma 1 transcripts were four- to sevenfold higher in blasts cultured with LPS and IL-4, compared with blasts cultured with IL-4 and -5. LPS enhanced steady state levels of germline transcripts induced by IL-4, but LPS did not promote substantial accumulation of productive gamma 1 and epsilon transcripts. In contrast, IL-5 did not affect steady state levels of germline transcripts stimulated by IL-4, but did markedly increase levels of productive gamma 1 and epsilon transcripts. Thus, lymphokines regulate two distinct events in isotype switching: induction of germline transcripts (IL-4), and production of VDJ-C gamma 1 and VDJ-C epsilon mRNA (IL-5), which leads to secretion of IgG1 and IgE.
Avascular necrosis of the femoral head presenting as trochanteric bursitis.
Authors: B F Mandell
Journal: Annals of the Rheumatic Diseases (1990)

Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement.
Meta-Analysis of First-Line Therapies in Advanced Non–Small-Cell Lung Cancer Harboring EGFR-Activating Mutations
Authors: Benjamin Haaland, Pui San Tan, Gilberto de Castro, Gilberto Lopes
Journal: Journal of Thoracic Oncology (2014)

Introduction:Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non–small-cell lung cancer harboring epidermal growth factor receptor–activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy.Methods:Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I2 statistics and predictive intervals (PIs).Results:Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non–small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31–0.63; 95% PI, 0.22–0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15–0.42; 95% PI, 0.11–0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26–0.75; 95% PI, 0.20–0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30–1.08; 95% PI, 0.24–1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53–1.92; 95% PI, 0.41–2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27–1.18; 95% PI, 0.22–1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy.Conclusion:Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.