tbuckley/cabot-search huggingface dataset:
Adjuvant Chemotherapy for Early-Stage Ovarian Cancer: Review of the Literature
Authors: Claes Tropé, Janne Kaern
Journal: Journal of Clinical Oncology (2007)

This overview summarizes studies with acceptable quality and validity and presents a synthesis of the effectiveness on adjuvant therapy after surgery for early ovarian cancer (EOC) patients.The literature published between 1970 and 2006 was identified systematically by computer-based searches in MEDLINE and Cochrane library.Twenty-two prospective randomized studies were analyzed, which included 4,626 patients. No difference between adjuvant chemotherapy (AC) and radiotherapy was found. There is agreement on that patients with stage IA, grade 1 tumors have excellent survival and do not need postsurgical therapy. The International Collaborative Ovarian Neoplasm 1/Adjuvant Chemotherapy in Ovarian Neoplasm trials were the first to show an effect on survival of AC, but in patients with adequate surgical staging, there was no additional effect of AC. For patients who are staged incompletely at the time of initial surgery, completion of the staging procedure with either laparoscopy or laparotomy is a reasonable approach before a final decision is made regarding the need for AC. If full staging cannot be performed due to medical contraindication or patient refusal, consideration of AC is reasonable in selected patients. Using prognostic variables such as grade, International Federation of Gynecology and Obstetrics substage, pretreatment of CA-125 < or = 30 U/mL, and DNA ploidy, it is possible to divide patients into risk groups to avoid overtreatment. Gynecologic Oncology Group study 157 suggests that it may be possible to minimize chemotherapy-induced toxicity by using three instead of six cycles of AC, although it is not known fully whether this will compromise effectiveness.Future randomized studies in EOC will include the investigation of new targeted therapies and new prognostic factors in adequately staged patients.
Thyroidal dysfunction and environmental chemicals--potential impact on brain development.
Authors: S P Porterfield
Journal: Environmental Health Perspectives (2000)

Certain polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins (dioxins, 2,3,7, 8-tetrachlorodibenzo-p-dioxin) have been shown to have neurotoxic effects and to alter thyroid function during critical periods of thyroid hormone-dependent brain development. This has led to the suggestion that some of the neurotoxic effects of these compounds could be mediated through the thyroid system. Thyroid hormones are essential for normal brain development during a critical period beginning in utero and extending through the first 2 years postpartum. They regulate neuronal proliferation, migration, and differentiation in discrete regions of the brain during definitive time periods. Even transient disruption of this normal pattern can impair brain development. Thyroid hormones are necessary for normal cytoskeletal assembly and stability and the cytoskeletal system is essential for migration and neuronal outgrowth. In addition, they regulate development of cholinergic and dopaminergic systems serving the cerebral cortex and hippocampus. Animals perinatally exposed to certain environmental organohalogens such as many of the PCBs and dioxins have abnormal thyroid function and neurologic impairment. Although there are both species and congener variabilities, most reports show exposure results in thyroid enlargement and reduced serum T(4) levels with normal T(3) levels. Initial research concentrated on studying the direct actions of xenobiotics on the thyroid; however, some of these compounds bear a structural resemblance to the natural thyroid hormones and have high affinity with thyroid hormone-binding proteins such as transthyretin. These compounds could act as agonists or antagonists for receptors of the thyroid/steroid/retinoic acid superfamily. These structurally similar organohalogens could act at multiple points to alter thyroid hormone action. The similarity of the neurologic impairment seen in thyroid disorders to that seen following PCB or dioxin exposure suggests that one mechanism of neurotoxicity of these compounds could involve interaction with the thyroid system.
Mapping the Code: The Human Genome Project and the Choices of Modern Science
Authors: Michael A. Schmidt
Journal: JAMA (1992)

On September 8, 1991, Dr James Watson was interviewed on the progress of the Human Genome Project. One statement alluded to the fact that there are probably 250000 human genes, rather than the 100 000 of pre-Human Genome Project dogma. This is just one of the new findings from the Human Genome Project, a vast undertaking by molecular biologists. The biological sciences have never really had a "Big Science" event like other areas, for example, astrophysics and space exploration. This is probably because the biological sciences are so diverse and, therefore, not amenable to an overarching project. However, one of those eclectic areas, molecular biology, has emerged and given biological scientists the foundation for an important contribution—defining all the genes of the human species. "a 'Big Science' event" The early price tag of the project was about a dollar per base pair, ie, $3 billion. One might think this is
Genetic Flaw Linked to Early Heart Disease
Authors: Tracy Hampton
Journal: JAMA (2007)

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
Abstract 5135: Breast cancer antiestrogen resistance-3 influences breast cancer cell migration by regulating Rac and Rho GTPase signaling
Authors: Randy S. Schrecengost, Ashley L. Wilson, Michael S. Guerrero, Amy H. Bouton
Journal: Cancer Research (2010)

Abstract Breast Cancer Antiestrogen Resistance-3 (BCAR3) was initially identified as a gene whose expression confers resistance to endocrine therapy, such as the antiestrogen tamoxifen. However, work from our group as well as others implicate BCAR3 as a prominent regulator of cell migration and invasion. This is of interest because expression of BCAR3 is elevated in more aggressive breast cancer cell lines. In this study, we have taken both a gain-of-function and loss-of-function approach to determine the mechanism by which BCAR3 regulates cell migration and invasion. We found that overexpression of BCAR3 in less aggressive breast cancer cells resulted in enhanced cell migration and increased protrusive activity. Additionally, BCAR3 was co-localized at the cell membrane with an established scaffold protein, p130Cas (also known as BCAR1 or Cas). Conversely, siRNA-mediated depletion of BCAR3 in more aggressive breast cancer cells inhibited cell migration and decreased membrane protrusiveness, coincident with a significant reduction in Rac GTPase activity. This was accompanied by mislocalization of Cas and a decrease in Cas tyrosine phosphorylation. Loss of BCAR3 was also associated with stabilization of stress fibers, reduced adhesion turnover, and increased ROCK-dependent phosphorylation of myosin light chain, a major downstream target of Rho GTPase. Inhibition of ROCK in BCAR3-depleted cells disrupted stress fibers and restored membrane protrusions, confirming and indicating that the effect of BCAR3 depletion on stress fiber dynamics was dependent on ROCK. Furthermore, Cas localization to the cell periphery was restored and partial rescue of Cas tyrosine phosphorylation was observed. Taken together, these results suggest a model whereby BCAR3 expression influences cell migration and invasion by promoting Cas phosphorylation and Cas-mediated Rac activation, while negatively regulating Rho-mediated contractility. While the major mechanisms of BCAR3 as a critical regulator of breast cancer cell migration are addressed here, future studies will determine whether elevated BCAR3 expression promotes metastasis in animal models and is associated with clinical outcome in patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5135.
Human Hypertension Is Characterized by a Lack of Activation of the Antihypertensive Cardiac Hormones ANP and BNP
Authors: Fima Macheret, Denise Heublein, Lisa C. Costello-Boerrigter, Guido Boerrigter, Paul McKie, Diego Bellavia, Sarah Mangiafico, Yasuhiro Ikeda, Kent Bailey, Christopher G. Scott, Sharon Sandberg, Horng H. Chen, Lorenzo Malatino, Margaret M. Redfield, Richard Rodeheffer, John Burnett, Alessandro Cataliotti
Journal: Journal of the American College of Cardiology (2012)
THE DEMONSTRATION OF LESIONS AND VIRUS IN THE LUNGS OF MICE RECEIVING LARGE INTRA-PERITONEAL INOCULATIONS OF EPIDEMIC INFLUENZA VIRUS
Authors: E. R. Rickard, Thomas Francis
Journal: The Journal of Experimental Medicine (1938)

Following the intraperitoneal inoculation of mice with large doses of epidemic influenza virus (50,000 to 1 million intranasal M.L.D.) it can be recovered from the lungs in high concentration, and pulmonary lesions of moderate extent may be observed. The virus reaches its highest titer in the lungs 48 to 72 hours after intraperitoneal injection and may persist for 10 days. Virus may be recovered from the blood in the first 24 hours, but is readily detected in the omentum and peritoneum for 5 to 6 days. Mice which as a result of the intraperitoneal injection of virus show a high concentration of virus in the lungs do not die but become solidly immune to intranasal infection. Moreover, as early as 24 to 48 hours after intraperitoneal inoculation of large amounts of virus the animals may exhibit resistance to infection with fatal doses of virus given intranasally. Influenza virus given intravenously to mice is rapidly removed from the blood but persists in the lungs and induces pulmonary lesions. Virus can also be recovered from the liver for several days. With subcutaneous inoculation of influenza virus, however, the virus does not reach the blood or lungs in detectable amounts although the regional lymph nodes may yield considerable quantities of the agent. A brief consideration is presented of the mechanisms of infection and resistance which may be involved.
NHS organisations, let's all sign up to the 10:10 campaign
Authors: D. Evans, I. Carruthers, J. King, M. Edwards, N. Deans, P. Geoghegan, P. Homa, R. Naylor, T. Ballard, T. Riley, S. Dutton
Journal: BMJ (2009)

We have joined the 10:10 campaign to cut our carbon dioxide emissions by at least 10% during 2010.1

The business reasons for joining are compelling:
Universal health checks should be abandoned
Authors: L. T. Krogsboll, K. J. Jorgensen, P. C. Gotzsche
Journal: BMJ (2013)

Last autumn, a Cochrane review (also in the BMJ ) on general health checks in adults found no benefit for morbidity and mortality from disease.1 2 NHS Diabetes and Kidney Care and the Department of Health published an eBulletin, “Response to the Cochrane review,” on the NHS Health Check programme’s website.3 It looks like serious criticism of our work, but it is …
Cardiac services have improved in UK but more capacity needed
Authors: Z. Kmietowicz
Journal: BMJ (2009)

Twenty four patients with malignant bile duct obstruction were treated with intraluminal radiotherapy using iridium-192 wire inserted through an endoscopically placed nasobiliary catheter. Biliary drainage after treatment was maintained by an endoprosthesis. The median dose of intraluminal radiotherapy was 6000 cGy; two patients with cholangiocarcinoma were given a second course because of disease extension; four patients with pancreatic carcinoma received additional external irradiation (3000 cGy). There was one early death from a cerebrovascular accident (30 day mortality, 4.2%). Cholangitis (30%) was the major early complication and stent blockage (40%) the major late complication; there were no complications directly attributable to radiotherapy. The median survival for patients with pancreatic carcinoma was 250 days and for cholangiocarcinoma, 300 days. This method is technically feasible and may prove safer than the transhepatic technique. The ability of intraluminal irradiation to improve palliation or lengthen survival in patients with malignant bile duct obstruction remains uncertain. Assessment by a prospective, controlled trial is essential.
Atorvastatin advertising misled over benefits for women, study claims
Authors: R. Dobson
Journal: BMJ (2008)

Advertising of the world’s best selling drug failed to disclose the absence of benefits for women, who should be entitled to compensation to recoup the costs of treatment, claim experts in epidemiology and law in a new analysis.

They argue that unqualified claims of protection against heart attacks made in advertisements for the lipid lowering drug atorvastatin (which is made by Pfizer and sold as Lipitor) may be misleading and that the advertising raises concerns about the way the US Food and Drug Administration regulates drugs ( Journal of Empirical Legal Studies 2008;5:507-50, doi:10.1111/j.1740-1461.2008.00132.x)

The authors, Theodore Eisenberg, a professor of law at Cornell Law School, and Martin Wells, professor of clinical epidemiology at Cornell University Weill Medical College, claim that a substantial portion of the multibillion dollar market in statins may be made up of users for whom the drugs offer no benefit.

They add that remedies to recover costs should …
Formalin therapy for radiation proctitis
Authors: G. A. Isenberg
Journal: JAMA (1994)

To the Editor.  —In the June 15, 1994, JAMA Questions and Answers 1 regarding radiation proctitis with prostate cancer, no mention was made of a new application of an old technique: formalin therapy has been used for hemorrhagic cystitis for years. Rubinstein et al 2 and Seow-Choen et al 3 adapted this for radiation proctitis using 4% formalin. The patient is sedated, a local block is administered, and sponges moistened with 4% formalin are applied for 4 minutes to each bleeding area of the rectum. Care is taken to protect the perianal skin from any caustic effects of the formalin. We used this method for two patients and have had excellent short-term (3-month) results. Long-term follow-up is still needed; however, our two patients have not required additional transfusions after formalin application. We believe this treatment may offer relief to patients in whom conventional measures have failed and who would otherwise
Challenges in Using Nonrandomized Studies in Systematic Reviews of Treatment Interventions
Authors: Susan L. Norris, David Atkins
Journal: Annals of Internal Medicine (2005)

Randomized, controlled trials (RCTs) are firmly established as the standard for determining which medical treatments are effective. In some areas of health care, however, among them surgery, public health, and the organization of health care delivery, most evidence addressing the effectiveness of clinical or policy interventions rests on nonrandomized studies. We examine the use of study designs other than RCTs in Evidence-based Practice Center reports addressing questions of the effectiveness of treatment interventions. These reports offer the opportunity to examine the approaches used and the challenges faced by reviewers when nonrandomized studies are included and their quality assessed. We then offer recommendations for using these studies in systematic reviews of treatment interventions.
Arthritis With Nodules Following Ankylosing Spondylitis
Authors: Stuart H. Rosenthal
Journal: JAMA (1968)

Seropositive peripheral arthritis and subcutaneous rheumatoid nodules developed in a 50-year-old patient with preexisting ankylosing spondylitis. Subcutaneous nodules occurred in only 2 of 1,306 patients with ankylosing spondylitis previously reported.
Complications of Carbenoxolone Therapy
Authors: G. J. Davies, J. Rhodes, B. J. Calcraft
Journal: BMJ (1974)

Side effects from carbenoxolone are common and are due to electrolyte disturbance, such as sodium retention and hypokalaemia. They occur particularly in the elderly, who may already be being treated for other illnesses. Eight patients are described with serious side effects from carbenoxolone therapy, some of which were unrecognized for some time because of inadequate follow-up or because clinicians were unfamiliar with them.
The Death of Wolfgang Amadeus Mozart: An Epidemiologic Perspective
Authors: Richard H.C. Zegers
Journal: Annals of Internal Medicine (2009)

The early death of the composer Wolfgang Amadeus Mozart on 5 December 1791 has fascinated the world for more than 2 centuries. It has been suggested that his final illness was caused by poisoning, renal failure, Henoch–Schönlein purpura, trichinosis, and many other conditions. The official daily register of deaths in Mozart's Vienna was evaluated to provide an epidemiologic framework into which the observations of contemporary witnesses of his death can be integrated. All recorded deaths in Vienna during November and December 1791 and January 1792 were analyzed, together with the corresponding periods in 1790 to 1791 and 1792 to 1793. The deaths of 5011 adults (3442 men, 1569 women) were recorded over these periods. The mean ages of death were 45.5 years (SD, 18.5) for men and 54.5 years (SD, 19.9) for women. Tuberculosis and related conditions accounted for the highest number of deaths; cachexia and malnutrition ranked second, and edema was the third most common cause. According to eyewitness accounts, the hallmark of Mozart's final disease was severe edema. Deaths from edema were markedly increased among younger men in the weeks surrounding Mozart's death compared with the previous and following years. This minor epidemic may have originated in the military hospital. Our analysis is consistent with Mozart's last illness and death being due to a streptococcal infection leading to an acute nephritic syndrome caused by poststreptococcal glomerulonephritis. Scarlet fever, which represents the same underlying disease from an etiologic perspective, is a less likely possibility.
Preserved Relative Dispersion but Blunted Stimulation of Mean Flow, Absolute Dispersion, and Blood Volume by Insulin in Skeletal Muscle of Patients With Essential Hypertension
Authors: Hanna Laine, M. Juhani Knuuti, Ulla Ruotsalainen, Tapio Utriainen, Vesa Oikonen, Maria Raitakari, Matti Luotolahti, Olli Kirvelä, Paolo Vicini, Claudio Cobelli, Pirjo Nuutila, Hannele Yki-Järvinen
Journal: Circulation (1998)

Background —We examined the integrity of the effects of insulin on mean muscle blood flow, flow heterogeneity, and blood volume in essential hypertension. Methods and Results —Positron emission tomography, combined with [ 15 O]H 2 O and [ 15 O]CO as tracers for direct measurement of blood flow and volume in skeletal muscle, and a new bayesian iterative reconstruction algorithm allowing pixel-by-pixel quantitation of blood flow and flow dispersion, were used. Measurements were performed basally after an overnight fast and under normoglycemic hyperinsulinemic conditions in 11 newly diagnosed, untreated mildly hypertensive men (age, 35±1 years; body mass index, 25.2±0.4 kg/m 2 , blood pressure 141±4/96±2 mm Hg, mean±SE) and 11 matched normotensive men. Insulin-stimulated whole body glucose uptake was significantly decreased in the hypertensive men (41±4 μmol/kg per minute) compared with the normotensive (59±4 μmol/kg per minute, P &lt;0.005) men. Mean blood flow in skeletal muscle was significantly lower in the hypertensive than the normal subjects basally (1.7±0.2 versus 2.7±0.4 mL/0.1 kg per minute, P &lt;0.05) and during hyperinsulinemia (2.3±0.2 versus 4.2±0.8, P &lt;0.05). The flow response to insulin (0.6±0.2 versus 1.9±0.5 mL/0.1 kg per minute, hypertensive versus normal subjects, P &lt;0.05) was also significantly blunted. Muscle blood volume was significantly lower in the hypertensive than in the normal subjects, both basally (3.0±0.2 versus 3.5±0.2 mL/0.1 kg, P &lt;0.05) and during hyperinsulinemia (3.1±0.2 versus 4.0±0.2 mL/0.1 kg muscle, P &lt;0.02). The increase in muscle blood volume by insulin was significant in the normal ( P &lt;0.05) but not the hypertensive subjects. Regional pixel-by-pixel analysis within femoral muscles revealed significant spatial heterogeneity of blood flow. Insulin increased absolute dispersion of blood flow significantly more in the normal subjects than in the hypertensive subjects ( P &lt;0.05). Conclusions —True flow heterogeneity, as judged from the coefficients of variation (relative dispersion), was comparable between the groups basally and during hyperinsulinemia. We conclude that mean flow, its absolute dispersion, and blood volume exhibit insulin resistance in patients with essential hypertension.
Antithrombotic Therapy in Cerebrovascular Disease
Authors: John F. Rothrock, Robert G. Hart
Journal: Annals of Internal Medicine (1991)

For more than two decades, anticoagulant and antiplatelet agents have been used routinely to prevent and treat ischemic stroke. Although recent clinical trials have shown that such treatment can be helpful in certain cases, antithrombotic therapy currently remains of unproven benefit in many clinical settings of cerebrovascular disease. Although the absence of data confirming clinical efficacy has generated uncertainty and hesitancy in some clinicians, the lingering conviction that antithrombotic therapy is efficacious has led others to continue a policy of routine and active therapeutic intervention. A critical analysis of the literature on antithrombotic therapy and cerebrovascular disease suggests that many acceptable management options lie between the extremes of therapeutic nihilism and "routine" intervention.
Vitamin A supplements in newborns and child survival
Authors: James M Tielsch
Journal: BMJ (2008)

Benefit depends on the setting, baseline infant mortality, and vitamin A deficiency

Vitamin A supplementation at 6-72 months of age has become a mainline intervention for improving survival in populations with endemic vitamin A deficiency.1 However, in the same setting, supplementation at 1-6 months of age has little or no effect on mortality, whether given with immunisation or not.2 3

Giving vitamin A supplements to newborns within the first few days of life significantly reduced early infant mortality in Asian populations with endemic maternal vitamin A deficiency andhigh infant mortality.4 5 6 In Africa, however, this strategy had no beneficial effect on early infant survival in an urban setting7 or—as reported in the accompanying paper by Benn and colleagues—in a peri-urban setting.8 

How can these findings be reconciled? Some might suggest that a meta-analysis of all the newborn dosing studies would provide a more accurate estimate of the true effect on early infant mortality. But combining these studies would be a fundamental mistake, because the variation in effect on early infant …