tbuckley/cabot-search huggingface dataset:
Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells
Authors: Sébastien Anthérieu, Pamela Bachour-El Azzi, Julie Dumont, Ziad Abdel-Razzak, Christiane Guguen-Guillouzo, Bernard Fromenty, Marie-Anne Robin, André Guillouzo
Journal: Hepatology (2012)

Drugs induce cholestasis by diverse and still poorly understood mechanisms in humans. Early hepatic effects of chlorpromazine (CPZ), a neuroleptic drug known for years to induce intrahepatic cholestasis, were investigated using the differentiated human hepatoma HepaRG cells. Generation of reactive oxygen species (ROS) was detected as early as 15 minutes after CPZ treatment and was associated with an altered mitochondrial membrane potential and disruption of the pericanalicular distribution of F-actin. Inhibition of [3H]-taurocholic acid efflux was observed after 30 minutes and was mostly prevented by N-acetyl cysteine (NAC) cotreatment, indicating a major role of oxidative stress in CPZ-induced bile acid (BA) accumulation. Moreover, 24-hour treatment with CPZ decreased messenger RNA (mRNA) expression of the two main canalicular bile transporters, bile salt export pump (BSEP) and multidrug resistance protein 3 (MDR3). Additional CPZ effects included inhibition of Na+ -dependent taurocholic cotransporting polypeptide (NTCP) expression and activity, multidrug resistance-associated protein 4 (MRP4) overexpression and CYP8B1 inhibition that are involved in BA uptake, basolateral transport, and BA synthesis, respectively. These latter events likely represent hepatoprotective responses which aim to reduce intrahepatic accumulation of toxic BA. Compared to CPZ effects, overloading of HepaRG cells with high concentrations of cholic and chenodeoxycholic acids induced a delayed oxidative stress and, similarly, after 24 hours it down-regulated BSEP and MDR3 in parallel to a decrease of NTCP and CYP8B1 and an increase of MRP4. By contrast, low BA concentrations up-regulated BSEP and MDR3 in the absence of oxidative stress.These data provide evidence that, among other mechanisms, oxidative stress plays a major role as both a primary causal and an aggravating factor in the early CPZ-induced intrahepatic cholestasis in human hepatocytes.
Colles's Fracture and its Treatment
Authors: J. Griffiths
Journal: BMJ (1901)

three days.There was also a great deal of oozing of blood and serum from the tube but no pus.n the fifth day the drainage tube was removed and on the twenty-eighth day the wound was soundly healed.On January 3rd, I9oo, it was noted that the limb was not so straight as desirable, there being a considerable amount of genu valgum and the
Analyses of Cancer Data from Three Ezetimibe Trials
Authors: Richard Peto, Jonathan Emberson, Martin Landray, Colin Baigent, Rory Collins, Robert Clare, Robert Califf
Journal: New England Journal of Medicine (2008)

Five years of statin therapy lowers low-density lipoprotein (LDL) cholesterol substantially and, over a 5-year period, results in reductions in the incidence of cardiovascular events. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (ClinicalTrials.gov number, NCT00092677) has raised the hypothesis that adding ezetimibe to statin therapy for larger LDL cholesterol reductions might increase the incidence of cancer.We compared the results of a hypothesis-generating analysis of the incidence of cancer in the SEAS trial of ezetimibe plus simvastatin in 1873 patients (mean follow-up after ezetimibe or matching placebo was begun, 4.1 years) with a hypothesis-testing analysis of cancer data from the two large ongoing trials of this regimen: the Study of Heart and Renal Protection (SHARP) (NCT00125593) with 9264 patients (mean follow-up, 2.7 years) and the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) (NCT00202878), currently with 11,353 patients (mean follow-up, 1.0 year).In the SEAS trial, assignment to ezetimibe was associated with an increase in any new onset of cancer (101 patients in the active-treatment group vs. 65 in the control group) from several cancer sites. In SHARP and IMPROVE-IT combined, there was no overall excess of cancer (313 active-treatment vs. 326 control; risk ratio, 0.96; 95% confidence interval, 0.82 to 1.12; P=0.61) and no significant excess at any particular site. Among patients assigned to ezetimibe, there were more, albeit not significantly more, deaths from cancer (97, vs. 72 in the control group; P=0.07), but there were also fewer, although not significantly fewer, other cases of cancer (216, vs. 254 in the control group; P=0.08). There was no evidence of a trend in the risk ratio for incidence of or death from cancer with increasing duration of follow-up.The available results from these three trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer. Follow-up of longer duration will permit the balance of risks and benefits to be determined more reliably.
A mathematical model of parasystole and its application to clinical arrhythmias.
Authors: G K Moe, J Jalife, W J Mueller, B Moe
Journal: Circulation (1977)

A ventricular parasystolic focus capable of generating manifest ectopic beats should not be totally insulated from the electrical events that accompany depolarization in the surrounding tissue; the intrinsic cycle length of the ectopic discharge may be modulated by electrotonic influences transmitted across the zone of "protection." To study the nature of the interaction, response patterns were examined in a mathematical model programmed to simulate an ectopic pacemaker protected, but not divorced from ventricular responses to the normal pacemaker. Computer runs covered a wide range of heart rates, and a wide range of magnitudes of the simulated electrotonic influence. Application of the results obtained in the model to published examples of complex arrhythmias revealed a remarkably close fit to many clinical examples. This findings suggests that many patterns attributed to a re-entrant "extrasystolic" rhythm may, in fact, represent the modulated activity of a parasystolic focus.
Measles infection of human mononuclear cells. I. Acute infection of peripheral blood lymphocytes and monocytes.
Authors: J L Sullivan, D W Barry, S J Lucas, P Albrecht
Journal: The Journal of Experimental Medicine (1975)

A study of the susceptibility of human peripheral blood mononuclear cells to measles virus infection and replication is reported. Resting lymphocytes obtained from adults showed very low levels of infection and virus replication while lymphocytes activated by plant mitogens or allogenic lymphocytes supported mononuclear cells obtained from the umbilical cord of healthy neonates were more susceptible to measles virus infection than those of adults; however, activated cord lymphocytes supported viral replication in the range observed with adult activated lymphocytes. Monocytes obtained from adults were relatively resistant to measles virus infection and replication while neonatal cord blood monocytes supported viral replication to the degree observed with activated lymphocytes. It is hypothesized that infection of acitivated lymphocytes may explain the depression of cell-mediated immunity seen during acute measles virus infection. The significance of the finding that neonatal monocytes are more susceptible to viral infection and replication than adult monocytes is discussed.
Specialty training in the United States
Authors: G. Matfin
Journal: BMJ (1998)

For five centuries, travellers have been bringing their hopes and dreams to America. Every visitor to the United States has some idea of what to expect through the medium of films and television but junior doctors considering spending substantial time in the United States should first visit the country - and preferably the city or region where they would work. Junior doctors will not receive reimbursement for interviews in the United States.

Americans have the best healthcare system in the world - true or false? From a patient's perspective, it depends on where you live, what your income is, and, more importantly, whether you have health insurance. Most people have private healthcare insurance: a third party agency will pay their medical bill for consultations and other expenses. However, patients may have to meet some of the expenses incurred themselfves.

The boom in health maintenance organisations (HMOs) over the past few years has revolutionised health delivery. The old days of “fee-for-service,” are virtually extinct. Consequently, many physicians' salaries, independence, self esteem, and job satisfaction have declined.

Other healthcare delivery systems include the Veterans Administration (delivers care to former servicemen and women), public clinics and hospitals that care for those with no healthcare insurance, and university affiliated institutions. Most teaching programmes will include exposure to most of these diverse settings.

Family (general) practice is not as advanced in the USA as in Britain, and it may be advisable to set your sights …
Using the Placebo Effect to Treat Cold Symptoms in Children
Authors: James A. Taylor, Douglas J. Opel
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
The future application of induced pluripotent stem cells in vascular regenerative medicine
Authors: P. Religa
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Functional vascular smooth muscle cells derived from human induced pluripotent stem cells via mesenchymal stem cell intermediates’ by V.K. Bajpai et al. , pp. 391–400, this issue. 

The transplantation of autologous stem cells is the gold standard for regenerative therapy, which includes both local transplantation of the cells to injured organs and the engineering of organs. The use of smooth muscle cells (SMCs) has been shown to improve cardiac, vascular, and respiratory function. SMCs in the vasculature mimic natural healing mechanisms.1 The important cells for vascular regenerative medicine are mesenchymal stromal cells.2 The sources of mesenchymal stem cells (MSCs) are well defined and include bone marrow, fat, amniotic fluid, umbilical cord, muscle-derived stem cells, and hair follicle-derived MSCs.3,4

The major problem with regenerative therapy remains the source of the cells. MSCs have limited proliferative potential that decreases with increasing donor age. Thus, finding new types of cells remains an important problem. Human induced pluripotent stem cells (iPSCs) are an interesting alternative to MSCs and embryonic stem cells. The iPSCs described in 2006 were of interest because they were collected from adult somatic cells and transformed into stem cells by the ectopic expression of factors, including Oct3/4, Sox2, and c-Myc. The cells have great differentiation potential, similar to embryonic stem cells, as shown by a number of rigorous tests. …
The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract
Authors: A. Straumann, H.‐U. Simon
Journal: Allergy (2003)

Eosinophils and the gastrointestinal tract interact in an intimate and enigmatic relationship. Under healthy conditions, the presence of eosinophils is limited almost exclusively to the digestive tract mucosa where they exert several effector and immunoregulatory functions. While their precise function in the gastrointestinal tract is not completely understood, it is likely that, together with different T cell subsets, eosinophils are involved in maintaining the immunologic homeostastis across the mucosal barrier under resting conditions. Eosinophils also play a role in several inflammatory conditions, such as intestinal infections, hypersensitivity reactions, primary eosinophilic inflammations and several other chronic intestinal disorders. Depending on the responsible trigger, their effects may be beneficial or detrimental. Here, we discuss the available information regarding the physiological and pathological functions of eosinophils within the gastrointestinal tract.
THE STUDY OF MOTOR DEVELOPMENT IN INFANCY AND ITS RELATIONSHIP TO PSYCHOLOGICAL FUNCTIONING
Authors: BARBARA FISH
Journal: American Journal of Psychiatry (1961)

The analysis of early postural development and locomotion can be used as one measure of the integration of central nervous system maturation in the first 2 years of life. Using this index, involvement of the central nervous system was found in the histories of half the children with organic brain disorder and half the children who had severe schizophrenia with defective intellectual functioning. However, there was no absolute division of children with schizophrenia or primary behavior disorders into those with and without evidence of early neurological disorder. It is suggested that there may be a spectrum of developmental disturbances and that the severity of these may be related to the difficulties some individuals experience in maintaining psychological integrity in the face of stress.
Urinary incontinence in women.
Authors: P. Oakeshott, G. M. Hunt
Journal: BMJ (1992)

from the area.Moreover, data from Soviet studies met, even when services are available.The reasons The Berlin nosology attempted to establish strict based on much larger samples' or the total popula-for this are not clear, and the issue merits further criteria for diagnosing Marfan's syndrome.'As tion' seem to have been arbitrarily dismissed.One attention.Young comments, skeletal characteristics may be of the most perturbing aspects of the published MARTIN BRIGYGS striking.We have studied families with no such summary is the elimination of the estimates of E S WILLIAMS skeletal features but with aortic dilatation and increased incidences of cancer and leukaemia Department of Public Health Medicine,
Reliability of Editors' Subjective Quality Ratings of Peer Reviews of Manuscripts
Authors: Michael L. Callaham
Journal: JAMA (1998)

Quality of reviewers is crucial to journal quality, but there are usually too many for editors to know them all personally. A reliable method of rating them (for education and monitoring) is needed.Whether editors' quality ratings of peer reviewers are reliable and how they compare with other performance measures.A 3.5-year prospective observational study.Peer-reviewed journal.All editors and peer reviewers who reviewed at least 3 manuscripts.Reviewer quality ratings, individual reviewer rate of recommendation for acceptance, congruence between reviewer recommendation and editorial decision (decision congruence), and accuracy in reporting flaws in a masked test manuscript.Editors rated the quality of each review on a subjective 1 to 5 scale.A total of 4161 reviews of 973 manuscripts by 395 reviewers were studied. The within-reviewer intraclass correlation was 0.44 (P<.001), indicating that 20% of the variance seen in the review ratings was attributable to the reviewer. Intraclass correlations for editor and manuscript were only 0.24 and 0.12, respectively. Reviewer average quality ratings correlated poorly with the rate of recommendation for acceptance (R=-0.34) and congruence with editorial decision (R=0.26). Among 124 reviewers of the fictitious manuscript, the mean quality rating for each reviewer was modestly correlated with the number of flaws they reported (R=0.53). Highly rated reviewers reported twice as many flaws as poorly rated reviewers.Subjective editor ratings of individual reviewers were moderately reliable and correlated with reviewer ability to report manuscript flaws. Individual reviewer rate of recommendation for acceptance and decision congruence might be thought to be markers of a discriminating (ie, high-quality) reviewer, but these variables were poorly correlated with editors' ratings of review quality or the reviewer's ability to detect flaws in a fictitious manuscript. Therefore, they cannot be substituted for actual quality ratings by editors.
ARTIFICIAL ACIDOSIS IN TRYPANOSOMA LEWISI INFECTIONS, AND ITS BEARING ON THE PATHOGENIC ACTION OF TRYPANOSOMA EQUIPERDUM
Authors: Richard W. Linton, H. A. Poindexter
Journal: The Journal of Experimental Medicine (1931)

When the alkali reserve is artificially lowered in rats infected with Trypanosoma lewisi, the number of parasites in the blood is increased. The increase is large in the early stages of the disease, and becomes less marked as the number crisis is approached. Near the crisis, and after it, a lowered alkali reserve does not affect the number of trypanosomes. It has been shown that the observed increase does not result from a contraction of the capillaries of the inner organs, which would throw a large number of trypanosomes into the peripheral circulation; nor is the increase due to a greater reproductive activity on the part of the trypanosomes. The increase must, therefore, be due to an inhibition of the destructive forces of the host. It is suggested that the known production of organic acids by the pathogenic trypanosomes plays a similar rôle in inhibiting the destructive mechanism of the host, and is therefore of significance in the pathogenic activity of these organisms.
Cholelithiasis and Choledocholithiasis
Authors: Kim Eagle, Alexandra L. Gibas, Craig Philpot
Journal: New England Journal of Medicine (1993)

Figure 1. Cholelithiasis and Choledocholithiasis. An endoscopic retrograde cholangiogram from a 20-year-old woman with pain in the right upper quadrant and jaundice reveals stones in the left and right hepatic ducts (open arrows) and the common bile duct (small arrows) and multiple stones in the gallbladder (large arrow). The common bile duct is dilated, but the intrahepatic ducts are normal. A sphincterotomy was performed, the stones were extracted, and the patient had an uneventful laparoscopic cholecystectomy the following day.
Indian academy recommends whole cell pertussis vaccine for primary vaccination
Authors: C. Travasso
Journal: BMJ (2013)

The Indian Academy of Pediatrics has recommended the whole cell pertussis vaccine over the acellular version for primary vaccination, contrary to the situation in many developed countries, which have shifted to acellular vaccine.1

Despite high vaccination coverage, pertussis remains an important cause of infant mortality in India. The introduction of whole cell vaccines in the 1960s and 1970s led to a dramatic reduction in incidence and mortality across the world. However, some minor adverse reactions, such as redness, swelling, and fever, prompted a shift in some industrialised countries to the acellular vaccine. …
Medical hypothesis: xenoestrogens as preventable causes of breast cancer.
Authors: D L Davis, H L Bradlow, M Wolff, T Woodruff, D G Hoel, H Anton-Culver
Journal: Environmental Health Perspectives (1993)

Changes in documented risk factors for breast cancer and rates of screening cannot completely explain recent increases in incidence or mortality. Established risk factors for breast cancer, including genetics, account for at best 30% of cases. Most of these risk factors can be linked to total lifetime exposure to bioavailable estrogens. Experimental evidence reveals that compounds such as some chlorinated organics, polycyclic aromatic hydrocarbons (PAHs), triazine herbicides, and pharmaceuticals affect estrogen production and metabolism and thus function as xenoestrogens. Many of these xenoestrogenic compounds also experimentally induce mammary carcinogenesis. Recent epidemiologic studies have found that breast fat and serum lipids of women with breast cancer contain significantly elevated levels of some chlorinated organics compared with noncancer controls. As the proportion of inherited breast cancer in the population is small, most breast cancers are due to acquired mutations. Thus, the induction of breast cancer in the majority of cases stems from interactions between host factors, including genetics and environmental carcinogens. We hypothesize that substances such as xenoestrogens increase the risk of breast cancer by mechanisms which include interaction with breast-cancer susceptibility genes. A series of major epidemiologic studies need to be developed to evaluate this hypothesis, including studies of estrogen metabolism, the role of specific xenoestrogenic substances in breast cancer, and relevant genetic-environmental interactions. In addition, experimental studies are needed to evaluate biologic markers of suspect xenoestrogens and biologic markers of host susceptibility and identify pathways of estrogenicity that affect the development of breast cancer. If xenoestrogens do play a role in breast cancer, reductions in exposure will provide an opportunity for primary prevention of this growing disease.(ABSTRACT TRUNCATED AT 250 WORDS)
THE DISAPPEARANCE OF DEXTROSE FROM THE BLOOD AFTER INTRAVENOUS INJECTION
Authors: Israel S. Kleiner
Journal: The Journal of Experimental Medicine (1916)

1. As has been found by other investigators, when a large amount of dextrose is injected intravenously into a normal dog it disappears from the circulating blood in about 90 minutes after the end of the injection. Varying amounts (an average of 60 per cent) are excreted in the urine. 2. Even in nephrectomized animals the same quantity will leave the circulation in the same length of time as in normal animals. 3. This phenomenon seems to be, at least to a great extent, independent of vital processes, since dextrose, after intravenous injection into dead animals, is found to leave the blood rapidly. 4. The phenomenon is independent of the important abdominal organs, for it also occurs in animals (living or dead) in which the aorta and inferior vena cava have been ligated near the diaphragm, thus abolishing most of the circulation posterior to the diaphragm. 5. The fact that a considerable amount of the sugar passes from the circulation into the surrounding tissues was established by finding an increase in the carbohydrates of the muscle tissue. This was done in the case of the living anterior animals and in the whole and anterior dead animals. In most of these experiments there was also evidence of the formation of polysaccharides in the muscle tissue.
Nef Proteins from Simian Immunodeficiency Viruses Are Tetherin Antagonists
Authors: Fengwen Zhang, Sam J. Wilson, Wilmina C. Landford, Beatriz Virgen, Devon Gregory, Marc C. Johnson, Jan Munch, Frank Kirchhoff, Paul D. Bieniasz, Theodora Hatziioannou
Journal: Cell Host & Microbe (2009)
Intramural Left Atrial Hematoma Complicating Catheter Ablation for Atrial Fibrillation
Authors: Jen-Li Looi, Alex Pui-Wai Lee, Chin-Pang Chan, Joseph Yat-Sun Chan, Anna Kin-Yin Chan, Mable Tong, Ka-Tak Wong, Cheuk-Man Yu
Journal: Journal of the American College of Cardiology (2013)