tbuckley/cabot-search huggingface dataset:
The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses
Authors: John F. Deeken, Wolfgang Löscher
Journal: Clinical Cancer Research (2007)

Abstract Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors. The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor. The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.
Psychotherapy and the Single Synapse
Authors: Eric R. Kandel
Journal: New England Journal of Medicine (1979)

THE title of this lecture is at best premature and more likely absurd, but I have adopted it for two reasons. In the first place, I want to emphasize the continuing tension within psychiatry between biologic and psychologic explanations of behavior. Secondly, I want to consider the simplistic but perhaps useful idea that the ultimate level of resolution for understanding how psychotherapeutic intervention works is identical with the level at which we are currently seeking to understand how psychopharmacologic intervention works — the level of individual nerve cells and their synaptic connections.I will discuss the second issue later. First, . . .
Drug makers' adverse event reports are often incomplete, US report finds
Authors: M. McCarthy
Journal: BMJ (2015)

Drug manufacturers’ reports of adverse drug events are often incomplete, lacking such basic information as the patient’s age or gender or the date of the event, a US investigation by an independent drug safety group has found.

Researchers from the Institute for Safe Medication Practices looked at the quality of reports made to the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) over one year to the first quarter of 2014.1 During that period 847 039 reports were made to the system, including reports of 45 688 patient deaths from US sources and 41 884 deaths from foreign sources.

FAERS reports come from two main sources: from consumers or healthcare providers, who voluntarily submit reports either directly to the Food and Drug Administration (FDA) or to the drug makers; or from the drug makers, who are required by law to submit …
Cyril Jacob Kaplan
Authors: J. Kaplan
Journal: BMJ (2012)

Born in Durban, In 1940, during the final year of his medical studies at the University of Cape Town, Cyril Kaplan served as a volunteer gunner in the University Company of the Cape Garrison Artillery. He followed his house officer training by enlistment in 1942 in the South African Medical Corps. At Oribi Military Hospital he developed an interest in orthopaedics under Arthur Eyre-Brooks, treating wounded allied soldiers and Italian prisoners of war, before being posted to North Africa. Visiting Palestine on leave, he found himself attracted to the communal nature of kibbutz life, managing to divert to local doctors some medical equipment from captured German stores. 

He was …
Selective Uptake of Radiolabeled Annexin V on Acute Porcine Left Atrial Thrombi
Authors: John R. Stratton, Timothy A. Dewhurst, Sudhakar Kasina, John M. Reno, Manuel D. Cerqueira, Dennis G. Baskin, Jonathan F. Tait
Journal: Circulation (1995)

Background Annexin V is a human phospholipid binding protein that binds to activated platelets in vitro. We sought to determine the potential of this agent for imaging intracardiac thrombi in swine. Methods and Results Left atrial thrombi were formed by crush injury. In initial nonimaging experiments using intravenous 125 I-labeled human annexin V, the mean thrombus/whole blood ratio was 13.4±4.8 for the entire thrombus using well counting of resected specimens (n=8). Using intravenously injected 99m Tc-labeled human annexin V, the left atrial thrombus/blood ratio by well counting was similar (14.2±10.6 for the entire thrombus and 26.2±14.9 for the peak section) (n=12). The ratio for a control protein, 125 I-ovalbumin, was only 1.0±0.2. 99m Tc tomographic imaging was positive (n=10) or equivocal (n=2) in all experiments with but negative in 10 controls without left atrial thrombi. By region-of-interest analysis of the tomographic images, the mean left atrial appendage/blood ratio at 2 hours in animals with a thrombus was 3.90±1.12 compared with 0.84±0.10 in closed chest controls and 1.01±0.23 in open chest controls ( P &lt;.001). Conclusions We conclude that 99m Tc-labeled human annexin V detects acute left atrial thrombi in vivo in swine. The combination of a new thrombus detection agent, annexin V, with a 99m Tc label may allow in vivo imaging of thrombi in humans.
The Role of Growth Factor Receptor Pathways in Human Breast Cancer Cells Adapted to Long-term Estrogen Deprivation
Authors: Gauri J. Sabnis, Danijela Jelovac, Brian Long, Angela Brodie
Journal: Cancer Research (2005)

Abstract To study the long-term effects of estrogen deprivation on breast cancer, MCF-7Ca human estrogen receptor–positive breast cancer cells stably transfected with human aromatase gene were cultured in the steroid-depleted medium for 6 to 8 months until they had acquired the ability to grow. Proliferation of these cells (UMB-1Ca) was accompanied by increased expression of human epidermal growth factor receptor 2, increased activation of AKT through phosphorylation at Ser473 and Thr308, and increased invasion compared with parental MCF-7Ca cells. Estrogen receptor expression was also increased 5-fold. Although growth was inhibited by the antiestrogen fulvestrant, the IC50 was 100-fold higher than for parental MCF-7Ca cells. Aromatase inhibitor letrozole also inhibited growth at 10,000-fold higher concentration than required for MCF-7Ca cells, whereas anastrozole, exemestane, formestane, and tamoxifen were ineffective at 100 nmol/L. Growth of UMB-1Ca cells was inhibited by phosphatidylinositol 3-kinase inhibitor wortmannin (IC50 ∼25 nmol/L) and epidermal growth factor receptor kinase inhibitor gefitinib (ZD 1839; IC50 ∼10 μmol/L) whereas parental MCF-7Ca cells were insensitive to these agents. Concomitant treatment of UMB-1Ca cells with the signal transduction inhibitors and anastrozole and tamoxifen restored their growth inhibitory effects. These studies show that estrogen deprivation results in up-regulation of growth factor signaling pathways, which leads to a more aggressive and hormone refractory phenotype. Cross-talk between ER and growth factor signaling was evident as inhibition of these pathways could restore estrogen responsiveness to these cells.
Access controls on bmj.com: Restore true open access to bmj.com
Authors: Iain Chalmers
Journal: BMJ (2005)

<h3>Objective</h3> Shift work is an essential element of modern labour, ensuring ideal conditions of service for today’s economy and society. Despite the beneficial properties, its impact on the neurobehavioural performance of exposed subjects remains controversial. This meta-analysis aimed to provide the first summarising effects regarding the association between shift work exposure and different cognitive functions. <h3>Methods</h3> A literature search was performed using the databases PubMed, PsyINFO, PsyARTICLES, MedLine, PsycNET and Scopus including eligible studies up to April 2021 that compared shift workers with non-shift workers regarding neurobehavioural performance tests. We carried out a random-effects model using Hedges’ g as a meta-analytical effect size with a restricted likelihood estimator to summarise the mean differences between the exposure group and controls. Positive effect sizes indicate higher performance for non-shift workers. The heterogeneity of effect sizes was addressed by sensitivity analysis using funnel plots, Egger’s tests, p-curve analysis, meta-regressions and subgroup analysis. <h3>Results</h3> We included 18 studies resulting in a total sample of 18 802 participants and 37 effect sizes concerning six different neurobehavioural outcomes. Our results showed significantly worse performance in shift workers compared with non-shift workers in the following cognitive functions with g (95% CI): processing speed 0.16 (0.02 to 0.30), working memory 0.28 (0.51 to 0.50), psychomotor vigilance 0.21 (0.05 to 0.37), cognitive control 0.86 (0.45 to 1.27) and visual attention 0.19 (0.11 to 0.26). <h3>Conclusions</h3> We provide the first meta-analytical findings that associate shift work with decreased cognitive performance in processing speed, working memory, psychomotor vigilance, cognitive control and visual attention.
621 THE ROLE OF SUBSTITUTIONS IN THE CORE AND NS5A REGION OF HEPATITIS C VIRUS GENOTYPE 1B ON RESPONSIVENESS TO PEGYLATED INTERFERON AND RIBAVIRIN COMBINATION THERAPY
Authors: Y. Katano, M. Ishigami, I. Nakano, K. Hayashi, T. Honda, H. Goto
Journal: Journal of Hepatology (2009)
Thyroid-Stimulating Hormone–Initiated Proliferative Signals Converge <i>In vivo</i> on the mTOR Kinase without Activating AKT
Authors: Charlene Brewer, Nicole Yeager, Antonio Di Cristofano
Journal: Cancer Research (2007)

Abstract Thyroid-stimulating hormone (TSH) has long been recognized as the major proliferative and functional stimulus for thyroid follicular cells. TSH receptor (TSHR) engagement stimulates the production of cyclic AMP and the subsequent activation of downstream effector molecules, including protein kinase A, S6K1, and Rap1, whereas the role of the RAS and phosphatidylinositol-3-kinase signaling cascades downstream of TSHR is still controversial. Despite the abundance of candidates, it is still unclear which of these pathways represent(s) the key mitogenic output of TSH-initiated signaling. We have used an in vivo model of goitrogenesis to dissect the contribution of these pathways to TSH-induced thyrocyte proliferation and thyroid hyperplasia. We show that the in vivo proliferative response to chronic TSHR stimulation relies heavily on the activation of the mTOR/S6K1 axis, and that mTOR inhibition during goitrogenic stimulation abrogates the hyperplastic but not the hypertrophic thyrocyte responses to TSH, thus functionally uncoupling these two processes. Strikingly, goitrogenesis was not associated with an increase in AKT phosphorylation levels, underlining the existence of an AKT-independent pathway leading to mTOR activation upon TSH stimulation. [Cancer Res 2007;67(17):8002–6]
Successful treatment for acute lymphoblastic leukemia without blood transfusion in a Jehovah's Witness
Authors: Shogo Takeuchi, Atae Utsunomiya, Torahiko Makino, Shigemi Shimotakahara, Yoshifusa Takatsuka, Hisashi Kawabata, Akira Nakashima
Journal: American Journal of Hematology (1999)

Fulminant Brain Lymphoid Infiltration in a Patient With Chronic Lymphocytic LeukemiaTo the Editor: Symptomatic involvement of the central nervous system (CNS) in chronic lymphocytic leukemia (CLL) is very rare.We present a TABLE I. Drugs Associated With Lymphadenopathy* Phenytoin Carbamazepine Para-amino salicylic
The effects of desloratadine (DL) on the allergic inflammatory response of the nasal mucosa associated with seasonal allergic rhinitis (SAR): A nasal mucosal biopsy study (NMBX)
Authors: D.P. Skoner, D.A. Gentile, A. Gungor, S.N. Belenky, B.L. Angelini, H.M. Richards, S. Hart, W.J. Doyle
Journal: Journal of Allergy and Clinical Immunology (2003)
Feasibility of a large prospective study in general practice: an Italian experience. Gruppo di Studio sulla Pressione Arteriosa nell'Anziano.
Authors: F Avanzini, C Alli, G Bettelli, F Colombo, L Conforti, F Pirone, A Spagnoli, E Taioli, G Tognoni, M Villella
Journal: BMJ (1987)

A study of blood pressure control in elderly outpatients was carried out with the participation of 444 Italian general practitioners. Of 4096 patients aged 65 years or over who were considered for recruitment, 3959 (96.7%) fulfilled all the criteria of admission and were followed up for 12 months. The findings regarding one of the aims of the study--that is, to assess the feasibility of a large scale trial in general practice--are reported. Most (87%) of the doctors completed the study. Their adherence to the protocol was highly satisfactory, leading to an acceptable quality of work. Patients9 compliance was also good; 98.6% (3898) of the patients who had fulfilled the admission criteria agreed to participate in the study, and only 4% (158) dropped out. Both of these observations support the feasibility of carrying out prospective studies in general practice. The creation of networks of general practitioners who are prepared to carry out research in their practices would allow treatment and preventive measures to be studied simply and at low cost in the appropriate setting.
Diagnosing and Treating Infections in Young Infants in Developing Countries
Authors: M. J. Friedrich
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The impact of response on bone-directed therapy in patients with multiple myeloma
Authors: Alessandra Larocca, J. Anthony Child, Gordon Cook, Graham H. Jackson, Nigel Russell, Alexander Szubert, Walter M. Gregory, Annamaria Brioli, Roger G. Owen, Mark T. Drayson, Ping Wu, Antonio Palumbo, Mario Boccadoro, Faith E. Davies, Gareth J. Morgan
Journal: Blood (2013)
Helping refugee doctors
Authors: K. Adams
Journal: BMJ (2000)

The 20th century has seen populations displaced on an unprecedented scale. One country's displaced person is another's asylum seeker, and the United Kingdom, like other countries, is struggling to cope with increased numbers of refugees. About 6500 people seek asylum in the UK each month.1 If this is granted they are classified as refugees.2 Some 98 000 cases are awaiting decisions, with an average wait of 27 months.3 Among the refugees are a few doctors. Should we be doing more to help them use their skills in their adopted country?

No one knows how many doctors are among the refugees, since profession is not recorded on arrival. About 1000 are estimated to be in the London area (personal communication, Refugee Council), most of whom are motivated professionals who want to contribute to their adopted society …
CLINICAL EFFECTS OF "NATURAL" AND "SYNTHETIC" SODIUM SALICYLATE"NATURAL"
Authors: A. W. HEWLETT
Journal: JAMA (1913)

<h3>A COOPERATIVE INVESTIGATION</h3> It has been claimed that the sodium salicylate prepared from natural oils is superior as a therapeutic agent to the sodium salicylate prepared by synthetic methods. If this claim be justified, then the natural form of the drug should be prescribed by physicians; but if the claim be unsubstantiated, then the additional expense of the natural product is unnecessary and the synthetic drug is to be preferred. The Council on Pharmacy and Chemistry of the American Medical Association has undertaken to investigate various aspects of this question, and papers dealing with the literature,<sup>1</sup>the effect of the drug on animals<sup>2</sup>and the chemical purity of commercial sodium salicylate<sup>3</sup>have already appeared. In determining the relative therapeutic value of the two forms of sodium salicylate, however, clinical evidence of the proper sort is of paramount importance. The efficacy of the drug in relieving pain, and
Stenting of Unprotected Left Main Coronary Artery Stenoses: Immediate and Late Outcomes
Authors: Seung-Jung Park, Seong-Wook Park, Myeong-Ki Hong, Sang-Sig Cheong, Cheol Whan Lee, Jae-Joong Kim, Mun K Hong, Gary S Mintz, Martin B Leon
Journal: Journal of the American College of Cardiology (1998)
Kenneth Gordon Lowe
Authors: G. Lowe, G. Lowe, H. MacDougall
Journal: BMJ (2011)

Professor Kenneth Lowe (“Ken”), a pioneer in nephrology and cardiology, was consultant physician in Dundee from 1952 to 1982, where he taught thousands of medical students and trainee doctors.

Born in Arbroath and educated at its High School, he achieved first place in open bursary competitions for St Andrews University and University College Dundee and was awarded a Harkness residential scholarship. He graduated MB ChB with commendation in 1941 and shared the Low gold medal with Nancy Young, and then married.

In 1942 he assisted Professor Dan Cappell in the Pathology Department to set up Dundee’s first blood transfusion service. Joining the Royal Army Medical Corps, he specialised in tropical diseases and served in the Caribbean, India, Egypt, and Panama.

Rejoining his family in London after the second world war, he resumed postgraduate training and was medical registrar at the Postgraduate Medical School, …
An analysis of consultations with the crowd doctors at Glasgow Celtic football club, season 1999–2000
Authors: M Crawford, J Donnelly, J Gordon, R MacCallum, I MacDonald, M McNeill, N Mulhearn, S Tilston, G West
Journal: British Journal of Sports Medicine (2001)

To analyse all clinical presentations to the crowd doctors at Scotland's largest football stadium over the course of one complete season.A standard clinical record form was used to document all consultations with the crowd doctors including treatment and subsequent referrals. The relevance of alcohol consumption was assessed.A total of 127 casualties were seen at 26 matches, a mean of 4.88 per match. Twenty casualties were transferred to hospital, including one successfully defibrillated after a cardiac arrest. Alcohol excess was a major contributing factor in 26 cases.The workload of the crowd doctors was very variable and diverse. The social problem of excessive alcohol consumption contributed considerably to the workload. The provision of medical facilities at football grounds means that attendance there is now one of the least adverse circumstances in which to have a cardiac arrest. The study confirmed previous impressions that more casualties are seen at high profile matches.
Preparation of Cell Cultures from Human Amnion
Authors: J. Ferguson, J. OH. Tobin
Journal: BMJ (1958)

_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~EIA JORA hypertension or the borderline of pulmonary oedema from mitral stenosis.Unfortunately, however, this still occurs, and, in spite of the added difficulties of the diagnosis in pregnancy due to the changes in blood volume and anaemia, we feel surgery is indicated without delay if the possibility of pulmonary oedema is suggested by paroxysmal dyspnoea, repeated haemoptyses, basal rales, and radiological evidence of pulmonary congestion or hypertension.
Regular Spiking and Intrinsic Bursting Pyramidal Cells Show Orthogonal Forms of Experience-Dependent Plasticity in Layer V of Barrel Cortex
Authors: Vincent Jacob, Leopoldo Petreanu, Nick Wright, Karel Svoboda, Kevin Fox
Journal: Neuron (2012)

Most functional plasticity studies in the cortex have focused on layers (L) II/III and IV, whereas relatively little is known of LV. Structural measurements of dendritic spines in vivo suggest some specialization among LV cell subtypes. We therefore studied experience-dependent plasticity in the barrel cortex using intracellular recordings to distinguish regular spiking (RS) and intrinsic bursting (IB) subtypes. Postsynaptic potentials and suprathreshold responses in vivo revealed a remarkable dichotomy in RS and IB cell plasticity; spared whisker potentiation occurred in IB but not RS cells while deprived whisker depression occurred in RS but not IB cells. Similar RS/IB differences were found in the LII/III to V connections in brain slices. Modeling studies showed that subthreshold changes predicted the suprathreshold changes. These studies demonstrate the major functional partition of plasticity within a single cortical layer and reveal the LII/III to LV connection as a major excitatory locus of cortical plasticity.
Postnatal Transmission of Rubella Virus to Nurses
Authors: Janet Hardy
Journal: JAMA (1965)

To the Editor:—  Since babies with the congenital rubella syndrome have been found to excrete virus, 1 we should consider the possibility that such babies are contagious. This possibility appears to have become a reality in the face of a small outbreak of rubella among nurses caring for such infants at the Children's Medical and Surgical Center of the Johns Hopkins Hospital, and in view of a similar outbreak reported by Cooper et al 2 as this letter was being written.  The original source of infection for the Johns Hopkins nurses appears to have been a group of 18 babies with congenital rubella. All but one were born to mothers who had rubella (by history) during pregnancy. Their disease was manifested by one or more of the following: low birth weight, icterus, hepatosplenomegaly, thrombocytopenic purpura, nuclear cataracts, glaucoma, patent ductus arteriosus, peripheral pulmonic stenosis, and failure to thrive. All
Sonographic Identification of Second-Trimester Fetuses with Down's Syndrome
Authors: B R Benacerraf, R Gelman, F D Frigoletto
Journal: New England Journal of Medicine (1987)

Fetuses with Down's syndrome are more likely than normal fetuses to have a thickened nuchal skin fold and relatively short femurs on ultrasound examination in the second trimester. We evaluated these measures in more than 5500 fetuses, including 28 who were later found to have Down's syndrome by means of amniocentesis with cytogenetic analysis. Normal femur length was established as a function of biparietal diameter in 192 of the normal fetuses. We found that with use of a nuchal skin-fold thickness of 6 mm or more and a ratio of actual to expected femur length of 0.91 or less, fetuses with Down's syndrome could be identified with a sensitivity of 75 percent and a specificity of 98 percent. When other anomalies, such as an atrioventricular canal and meconium peritonitis, were added to these two criteria, the sensitivity of sonographic detection of Down's syndrome in the second-trimester fetus rose to 82 percent. The potential predictive value of these sonographic signs far exceeds that of advanced maternal age and low alpha-fetoprotein levels, which currently identify only 10 to 30 percent of affected fetuses. We recommend that fetuses with a thickened nuchal skin fold or shortened femurs on ultrasound examination be evaluated for Down's syndrome by amniocentesis and cytogenetic analysis.