tbuckley/cabot-search huggingface dataset:
A theme issue by, for, and about Africa
Authors: Douglas M Bowley, Euan J Dickson, Nigel Tai, Jacques Goosen, Kenneth D Boffard
Journal: BMJ (2005)

A theme issue by, for, and about Africa Results from Ugandan programme preventing maternal transmission of HIVEditor-Since the efficacy of antiretroviral drugs in preventing HIV transmission from mother to child was first shown, much effort has been devoted in many countries in Africa to implement sustainable regimens. [1]2][3][4] To identify potential reasons affecting uptake we evaluated the five year performance of a programme at St Francis Hospital Nsambya in Kampala, Uganda.The programme included voluntary counselling and confidential HIV testing for pregnant women and administration of antiretroviral prophylaxis in the peripartum period (zidovudine or nevirapine) for HIV positive women.Overall 24 133 women received counselling, 76% (18 384) agreed to be tested, and 2011 (10.9%) were HIV positive; 1341 (66.7% of the HIV positive women) were enrolled in the programme and received antiretroviral drugs.Acceptance of the test increased from 72.7% (9103/12 524) in 2000-2 to 79.9% (9281/11 609) in 2003-4, when a drug access programme became available in the hospital.Acceptance of the test and enrolment in the programme were lower in married or cohabitating women (test acceptance rate 72.9% (7735/10 605)) than single women (78% (860/1106)), indicating that the fear of being identified as HIV positive in the family is still a strong limiting factor and that men could have an important role.Acceptance of the test was lower in women belonging to the local tribe in Kampala (Baganda), probably because of fear of being recognised by hospital health workers.Higher education was associated with a lower prevalence of HIV and a higher enrolment in the programme, confirming that education can have a key role not only in protecting against HIV but also in allowing HIV positive people to benefit from existing measures against the spread of HIV.
Genotype-Driven Phase I Study of Irinotecan Administered in Combination With Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer
Authors: Giuseppe Toffoli, Erika Cecchin, Giampiero Gasparini, Mario D'Andrea, Giuseppe Azzarello, Umberto Basso, Enrico Mini, Sergio Pessa, Elena De Mattia, Giovanni Lo Re, Angela Buonadonna, Stefania Nobili, Paolo De Paoli, Federico Innocenti
Journal: Journal of Clinical Oncology (2009)

PURPOSE We aimed to identify the maximum-tolerated dose (MTD) of irinotecan in patients with cancer with UGT1A1*1/*1 and *1/*28 genotypes. We hypothesize that the patients without the *28/*28 genotype tolerate higher doses of irinotecan. PATIENTS AND METHODS Patients undergoing first-line treatment for metastatic colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype and excluded from the study. Fifty-nine white patients with either the *1/*1 or the *1/*28 genotype were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 215 mg/m(2) for both genotype groups, whereas the dose of infusional fluorouracil was fixed. Pharmacokinetic data of irinotecan and metabolites were also obtained. Results The dose of irinotecan was escalated to 370 mg/m(2) in patients with the *1/*28 genotype and to 420 mg/m(2) in those with the *1/*1 genotype. Dose-limiting toxicities (DLTs) were observed in two of four of *1/*28 patients at 370 mg/m(2) and in two of three of *1/*1 patients at 420 mg/m(2). No DLTs were observed in 10 *1/*28 patients at 310 mg/m(2) and in 10 *1/*1 patients at 370 mg/m(2); hence these dose levels were the MTD for each genotype group. The most common grade 3 to 4 toxicities were neutropenia and diarrhea. The pharmacokinetics of irinotecan and SN-38 exhibit linear kinetics. CONCLUSION The recommended dose of 180 mg/m(2) for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated when patients with the UGT1A1*28/*28 genotype are excluded. Prospective genotype-driven studies should test the efficacy of higher irinotecan doses in the FOLFIRI schedule.
Talent: Don't confuse necessity with sufficiency, or science with policy
Authors: Ellen Winner
Journal: Behavioral and Brain Sciences (1998)

Howe et al. fail to provide evidence that practice is sufficient and ignore evidence of high ability before instruction. They unsuccessfully discount savants; provide weak evidence against heritability of music, criticize retrospective evidence selectively, using it when it supports their position; and ultimately both accept and deny talent. Finally, they conflate a scientific question with one of policy.
Futility Rules for Telaprevir Combination Treatment for Patients With Hepatitis C Virus Infection
Authors: Nathalie Adda, Doug J. Bartels, Linda Gritz, Tara L. Kieffer, Frank Tomaka, Leif Bengtsson, Don Luo, Ira M. Jacobson, Robert S. Kauffman, Gaston Picchio
Journal: Clinical Gastroenterology and Hepatology (2012)
A piece of my mind. Another 'taste of lemonade'
Authors: R. C. Bone
Journal: JAMA (1995)

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
Quantitative echocardiography of the mitral complex in dilated cardiomyopathy: the mechanism of functional mitral regurgitation.
Authors: C M Boltwood, C Tei, M Wong, P M Shah
Journal: Circulation (1983)

We sought to elucidate the mechanism of mitral regurgitation (MR) in dilated cardio- myopathy (DCM).Quantitative two-dimensional echocardiographic examinations were performed in 27 patients, 18 with DCM (nine with MR on physical examination, nine without MR) and nine without underlying heart disease.The MR and "no MR" patients were clinically comparable.Spatial recon- structions from multiple apical cross sections were used to estimate the mitral leaflet area needed to occlude the orifice for a given midsystolic coaptation configuration (LEAF), as well as mitral annular area index, left ventricular volume, and left atrial volume.Similarly, reconstructions from parasternal short-axis views were used to estimate central chordae tendinae length and angulation.From selective parasternal views papillary muscle (PM) length and contraction and the tethering length from the PM base to the annular plane were measured.The MR group was characterized by markedly enlarged occlusional leaflet area (LEAF 19.8 + 3.1 in MR vs 13.8 + 2.8 in no MR group vs 6.3 + 0.9 cm2 in normal group; p < .01),striking mitral annular dilatation (midsystolic annular area index 7.5 + 0.8 in MR vs 4.6 + 0.9 in no MR group vs 2.9 + 0.4 cm2/m2 in normal group; p < .01),and left atrial enlargement (end-systolic left atrial volume 129 + 39 in MR vs 73 14 in no MR group vs 29 + 5 ml in normal group; p < .01).Chordal length and angulation, PM length, contraction, and tethering length, and left ventricular volume were not significantly different in the MR vs the no MR group.Noncoaptation of the mitral leaflets at their free margins was not observed in any MR patient.With the use of stepwise linear regression LEAF was determined chiefly by annular size (R2 .868)with left ventricular size having little additional influence (R2 increment .071).Thus, DCM is associated with enlargement of the mitral anulus, which is more pronounced in those patients with MR.Based on the quantitative estimates of occlusional leaflet area, we postulate that mitral leaflet tissue can stretch somewhat to accommodate dilatation of the mitral complex, but as the requirement for occlusional leaflet area increases less tissue is available for coaptation.Thus, although coaptation continues to occur, the valvular seal becomes ineffective once a critical LEAF is reached.The chief determinant of LEAF is the mitral annular size, while left ventricular size is a less important factor.Circulation 68, No. 3, 498-508, 1983.THE PROPER FUNCTION of the mitral valve re- quires coordinated motion of its six components: the posterior left atrial wall, the mitral anulus and leaflets, the chordae tendinae, papillary muscles, and free left
Cytochrome P450 2C expression and EDHF-mediated relaxation in porcine coronary arteries is increased by cortisol
Authors: J. Bauersachs, M. Christ, G. Ertl, U.R. Michaelis, B. Fisslthaler, R. Busse, I. Fleming
Journal: Cardiovascular Research (2002)

In addition to nitric oxide (NO) and prostacyclin, endothelium-dependent dilation is mediated by the endothelium-derived hyperpolarizing factor (EDHF) which, in the coronary circulation, has been characterised as a metabolite of arachidonic acid synthesised by an cytochrome P450 (CYP) epoxygenase homologous to CYP 2C8/9. As the promotor regions of CYP 2C8 and 2C9 contain consensus sequences for glucocorticoid response elements, we determined the effect of cortisol on EDHF-mediated relaxations as well as on the expression of CYP 2C in isolated segments of porcine coronary artery.Bradykinin-induced NO-mediated relaxation of KCl-constricted arterial rings was slightly attenuated following exposure to cortisol. However, EDHF-mediated relaxations of U46619-constricted arterial rings assessed in the presence of the cyclo-oxygenase inhibitor diclofenac and the NO synthase inhibitor N(omega)nitro-L-arginine (0.3 mM), were significantly enhanced (maximum relaxation: 66+/-7%, P<0.05 vs. control rings: 36+/-8%). Cortisol treatment (0.1 microM, 24 h) did not affect the endothelium-independent relaxation elicited by sodium nitroprusside and acute incubation with cortisol (0.1 microM, 30 min) did not alter either NO- or EDHF-mediated responses. The expression of CYP 2C (quantified by RT-PCR, Western blot analysis and confocal microscopy) was enhanced in porcine coronary endothelial cells following incubation with cortisol for 18-24 h.These results demonstrate the concomitant upregulation of EDHF-mediated relaxations and CYP 2C expression by long-term treatment with cortisol. These observations support the concept that an epoxygenase homologous to CYP 2C8/9 plays a crucial role in the generation of EDHF-mediated responses in the coronary endothelium.
Dr. Zimmermann and Frederick the Great
Authors: Heinrich G. Brugsch
Journal: New England Journal of Medicine (1966)

THE recent protest against Lord Moran's publication of his experiences as Sir Winston Churchill's personal physician is a reminder that the Swiss physician, Johann Georg Zimmermann, had also been severely criticized for making public his conversations with Frederick II of Prussia, whom he had attended during his last illness.Zimmermann,1 one of the most successful physicians of his time, was also a prolific and popular writer. His books were reprinted many times and translated from the original German into English, French, Dutch, Spanish and Italian. His classic "On Dysentery among the People in the Year 1765," is today recognized as . . .
The Importance of Empathy as an Interviewing Skill in Medicine
Authors: Paul S. Bellet
Journal: JAMA (1991)

IN HIS RESEARCH on the physician-patient relationship, Cousins<sup>1</sup>found that 85% of people had changed physicians or were thinking of changing in the past 5 years. Many of those who changed did so because of their physician's poor communication skills. One of the qualities of effective communication is the use of empathy. Because some physicians have not learned to use empathy in their training as medical students and residents, they may be ineffective in the care of patients.<sup>2</sup>In this article, we discuss the importance of empathy in medical practice and illustrate its use with two examples. <h3>What Is Empathy?</h3> Empathy is the capacity to understand what another person is experiencing from within the other person's frame of reference, ie, the capacity to place oneself in another's shoes.<sup>3</sup>The essence of empathic interaction is accurate understanding of another person's feelings. According to Aring,<sup>4</sup>it is hardly
Primary Tumors of the Brain and Spinal Cord S. Clifford Schold, Jr., Peter C. Burger, Dianne B. Mendelsohn, Eli J. Glatstein, Bruce E. Mickey, John D. Minna, eds. Newton, MA: Butterworth-Heinemann, 1997. 184 pp. $80. ISBN 0-7506-9060-7
Authors: G. J. Lesser
Journal: JNCI Journal of the National Cancer Institute (1997)
Positive selection is not required for thymic maturation of transgenic gamma delta T cells.
Authors: E Schweighoffer, B J Fowlkes
Journal: The Journal of Experimental Medicine (1996)

Previously published reports describing thymic differentiation in two TCR gamma delta transgenic mouse models have suggested that gamma delta T cells require MHC-mediated positive selection to reach full maturity. Recent studies indicate that recognition of antigen by mature gamma delta T cells is not MHC restricted, raising the issue of why developing gamma delta T cells would even require MHC-driven positive selection. Therefore, we have reinvestigated the requirements for development and selection in G8 gamma delta T cell receptor (TCR) transgenic mice. Analyses of absolute cell numbers, phenotypic subsets, and functional competence of thymic and peripheral G8 gamma delta T cells indicate that these cells can fully mature in class I MHC-deficient mice. Moreover, mixed bone marrow chimeras demonstrate that gamma delta T cells of mutant B2-microglobulin (beta 2m zero) origin are partially deleted in the presence of H-2d-bearing thymocytes (previously believed to be the haplotype mediating positive selection). We conclude that there is no requirement for class I-like molecules for the maturation/development of these transgenic gamma delta T cells and that the differences in thymocyte phenotype and number observed are, instead, attributable to effects of clonal deletion.
Malaria in a Heroin User
Authors: Arthur S. Dover
Journal: JAMA (1971)

To the Editor.—  A recently reported case 1 of malaria in a heroin user reminds us that malaria is a bloodborne disease which may be seen with increasing frequency as a complication of illicit parenteral drug use.  A 20-year-old serviceman stationed at Ft. Bragg, North Carolina, was found to have a Plasmodium falciparum infection on Aug 20, 1970. He had never traveled to Vietnam or any other malarious region. The acquisition of his infection by mosquito transmission within the United States was considered unlikely because all outbreaks reported since the end of World War II have been with P vivax . The serviceman admitted having used heroin intravenously during the six months preceding his illness, and he stated that he had shared needles and syringes with other enlisted men, some of whom had returned recently from Vietnam.  In 1969, nearly 4,000 servicemen had attacks of malaria which were confirmed by the
Nitric Oxide–Dependent Bone Marrow Progenitor Mobilization by Carbon Monoxide Enhances Endothelial Repair After Vascular Injury
Authors: Barbara Wegiel, David J. Gallo, Kathleen G. Raman, Jenny M. Karlsson, Brett Ozanich, Beek Y. Chin, Edith Tzeng, Shakil Ahmad, Asif Ahmed, Catherine J. Baty, Leo E. Otterbein
Journal: Circulation (2010)

Carbon monoxide (CO) has emerged as a vascular homeostatic molecule that prevents balloon angioplasty-induced stenosis via antiproliferative effects on vascular smooth muscle cells. The effects of CO on reendothelialization have not been evaluated.Exposure to CO has diametrically opposite effects on endothelial cell (EC) and vascular smooth muscle cell proliferation in rodent models of carotid injury. In contrast to its effect of blocking vascular smooth muscle cell growth, CO administered as a gas or as a CO-releasing molecule enhances proliferation and motility of ECs in vitro by >50% versus air controls, and in vivo, it accelerates reendothelialization of the denuded artery by day 4 after injury versus day 6 in air-treated animals. CO enhanced EC proliferation via rapid activation of RhoA (Ras homolog gene family, member A), followed by downstream phosphorylation of Akt, endothelial nitric oxide (NO) synthase phosphorylation, and a 60% increase in NO generation by ECs. CO drives cell cycle progression through phosphorylation of retinoblastoma, which is dependent in part on endothelial NO synthase-generated NO. Similarly, endothelial repair in vivo requires NO-dependent mobilization of bone marrow-derived EC progenitors, and CO yielded a 4-fold increase in the number of mobilized green fluorescent protein-Tie2-positive endothelial progenitor cells versus controls, with a corresponding accelerated deposition of differentiated green fluorescent protein-Tie2-positive ECs at the site of injury. CO was ineffective in augmenting EC repair and the ensuing development of intimal hyperplasia in eNOS(-/-) mice.Collectively, the present data demonstrate that CO accelerates EC proliferation and vessel repair in a manner dependent on NO generation and enhanced recruitment of bone marrow-derived endothelial progenitor cells.
Intracellular Interleukin-1 Receptor 2 Binding Prevents Cleavage and Activity of Interleukin-1α, Controlling Necrosis-Induced Sterile Inflammation
Authors: Yue Zheng, Melanie Humphry, Janet J. Maguire, Martin R. Bennett, Murray C.H. Clarke
Journal: Immunity (2013)

Necrosis can induce profound inflammation or be clinically silent. However, the mechanisms underlying such tissue specificity are unknown. Interleukin-1α (IL-1α) is a key danger signal released upon necrosis that exerts effects on both innate and adaptive immunity and is considered to be constitutively active. In contrast, we have shown that necrosis-induced IL-1α activity is tightly controlled in a cell type-specific manner. Most cell types examined expressed a cytosolic IL-1 receptor 2 (IL-1R2) whose binding to pro-IL-1α inhibited its cytokine activity. In cell types exhibiting a silent necrotic phenotype, IL-1R2 remained associated with pro-IL-1α. Cell types possessing inflammatory necrotic phenotypes either lacked IL-1R2 or had activated caspase-1 before necrosis, which degraded and dissociated IL-1R2 from pro-IL-1α. Full IL-1α activity required cleavage by calpain after necrosis, which increased its affinity for IL-1 receptor 1. Thus, we report a cell type-dependent process that fundamentally governs IL-1α activity postnecrosis and the mechanism allowing conditional release of this blockade.
Targeting drugs to the brain by redox chemical delivery systems
Authors: Laszlo Prokai, Katalin Prokai-Tatrai, Nicholas Bodor
Journal: Medicinal Research Reviews (2000)

Chemical delivery systems (CDSs) based on the redox conversion of a lipophilic dihydropyridine to an ionic, lipid-insoluble pyridinium salt have been developed to improve the access of therapeutic agents to the central nervous system. A dihydropyridinium-type CDS or a redox analog of the drug is sufficiently lipophilic to enter the brain by passive transport, then undergoes an enzymatic oxidation to an ionic pyridinium compound, which promotes retention in the CNS. At the same time, peripheral elimination of the entity is accelerated due to facile conversion of the CDS in the body. This review discusses chemical, physicochemical, biochemical, and biological aspects in relation to the principles and practical implementation of the redox brain-targeting approach to various classes of drugs. Representative examples to the brain-enhanced delivery of neurotransmitters, steroids, anticonvulsants, antibiotics, antiviral, anticancer and antidementia agents, and neuropeptides and their analogs are presented in detail. In vivo and in vitro studies and preliminary clinical data of several novel derivatives have been promising, which could lead to a practical use of the redox CDSs after proper pharmaceutical development. The investigations accentuate the need for considering physicochemical, metabolic, and pharmacokinetic properties in designing of carrier systems that are able to target drugs into the central nervous system. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 5, 367–415, 2000
Changes in transcripts of basement components during rat liver development: Increase in laminin messenger RNAs in the neonatal period
Authors: Shimon Reif, Donald Sykes, Thomas Rossi, Milton M. Weiser
Journal: Hepatology (1992)

The expression of laminin and type IV collagen messenger RNA in rat liver was investigated in relation to liver development. Levels of messenger RNA for laminin chains A, B1 and B2, and α1 and α2 chains of type IV collagen were studied by Northern-blot and dot-blot analysis. Although the expression of messenger RNAs for laminin B1 and B2 chains was higher in 19-day gestational fetal liver when compared with the adult, the highest level was detected in 15-day newborns. This finding coincides with the final establishment of the mature liver. Laminin A messenger RNA was not detected in the 19-day gestational fetus or in the neonatal period. In contrast, α1-(IV) and α2-(IV) collagen messenger RNAs maintained high levels in the early neonate and then decreased gradually after 15 days. Our findings suggest that during late stages of liver ontogeny the main components of liver basement membrane proteins undergo a significant alteration in their synthesis. The data further suggest that laminin may play a role in the final stages of hepatic differentiation.