tbuckley/cabot-search huggingface dataset:
A biochemical mechanism for the role of allopurinol in TMPT inhibition
Authors: P. A. Blaker, M. Arenas, L. Fairbanks, P. Irving, A. M. Marinaki, J. Sanderson
Journal: Gut (2011)

<h3>Introduction</h3> Hypermethylation of thiopurines has been associated with drug toxicity and non-response to treatment. In such patients the use of low dose thiopurines with concomitant allopurinol is advocated12. Allopurinol is observed to cause a reduction in methylated metabolites of thiopurines; however the biochemical mechanisms remain incompletely understood. Using an intact erythrocyte model we propose a novel pathway of allopurinol mediated thiopurine-<i>S-</i>methyltransferase (TPMT) inhibition, through the production of 2-hydroxy-6-thiopurine (2OH6MP). <h3>Methods</h3> EDTA whole blood was obtained from healthy volunteers; the plasma and top 5<sup>th</sup> were removed and the red cells washed with 0.9% saline. 150 μL of Earl9s balanced salt solution was added to 100 μL of packed red cells. Cells were incubated with 250 μM of 6-mercaptopurine (6-MP) for 0, 2, 4 and 6 h at 37°C. In the second experiment cells were pre-incubated for 2 h with 280 μM of 2OH6MP prior to the addition of 250 μM 6-MP for either 2 or 4 h. At the end of the incubation period, the media was removed and the red cells lysed with 15% perchloric acid after the addition of dithiotreitol. Methylated thiopurine-metabolites were reduced to the base by boiling at 100°C for 1 h. 75 μL of the red cell lysates and supernatant media were separated by reverse phase HPLC to detect the methylated metabolites of 6-MP. <h3>Results</h3> In packed red cells there was an increase in the concentration of 6-methylmercaptopurine (6-MeMP) detected at each time point. However, the rate of 6-MeMP production remained constant (mean 0.825 pmol L<sup>−1</sup> h<sup>−1</sup>, SEM ± 0.038). The concentration of 6-MeMP observed in the media was up to 7-fold lower than the concentration in red cells (mean 0.133 pmol L<sup>−1</sup> h<sup>−1</sup>, SEM ± 0.009). In red cells pre-incubated with 2OH6MP prior to the addition of 6-MP there was a significant reduction in the rate of 6-MeMP production at both 2 (0.878 pmol L<sup>−1</sup> h<sup>−1</sup> vs 0.135 pmol L<sup>−1</sup> h<sup>−1</sup>, p &lt;0.0001, two-sided T-test) and 4 h (0.732 pmol L<sup>−1</sup> h<sup>−1</sup> vs 0.096 pmol L<sup>−1</sup> h<sup>−1</sup>, p&lt;0.0001, two-sided T-test). <h3>Conclusion</h3> The data suggests that 6-MP enters red blood cells, where it undergoes methylation to 6-MeMP. The presence of 2OH6MP leads to a reduction in the rate of 6-MeMP production, most likely through direct inhibition of TPMT. We propose that 6-MP undergoes preferential oxidation via aldehyde oxidase, producing 2OH6MP, which leads to feed-back inhibition of TMPT and thereby a reduction in methylated thiopurine-metabolites. This mechanism may explain why patients treated with a combination of thiopurine and allopurinol have dramatically decreased methylated metabolites.
Balance between medical education and medical servce in medical school
Authors: R. O. Egeberg
Journal: JAMA (1968)

Historically, medical education and medical service have been teammates since before Hippocrates. Recently, however, things seem to have fallen out of balance; service has regrettably become subordinate. I would like to suggest, that if we are to deal squarely with the increased and increasing responsibilities which confront the medical community, two issues are vital: First, we must restore the balance by assuring the exposure of the medical student to service during his own medical education within the framework of the medical schools. Second, and of equal importance, we must involve the medical school more actively in service beyond its walls. Before proceeding any further, let me define what I mean by service. The simplest definition is that service is every activity of a medical school, exclusive of research, not essential to the education of an undergraduate medical student, intern, resident, or fellow. More broadly defined, it is a continuum that
Conflicts of Interest in Medical Center/Industry Research Relationships
Journal: JAMA (1990)

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
Methane Negative Chemical Ionization Analysis of 1,3-Dihydro-5-Phenyl-1,4-Benzodiazepin-2-Ones
Authors: W. A. Garland, B. J. Miwa
Journal: Environmental Health Perspectives (1980)

The methane negative chemical ionization (NCI) mass spectra of the medically important 1,3-dihydro-5-phenyl-1,4-benzodiazepin-2-ones generally consisted solely of M- and (M-H)- ions. Attempts to find the location of the H lost in the generation of the (M-H)- ion were unsuccessful, although many possibilities were eliminated. A Hammett correlation analysis of the relative sensitivities of a series of 7-substituted benzodiazepines suggested that the initial ionization takes place at the 4,5-imine bond. For certain benzodiazepines, the (M-H)- ion generated by methane NCI was 20 times more intense than the MH+ ion generated by methane positive chemical ionization (PCI). By using NCI, a sensitive and simple GC-MS assay for nordiazepam was developed that can quantitate this important metabolite of many of the clinically used benzodiazepines in the blood and brain of rats.
Case 26-2009 — A 34-Year-Old Man with Cystic Fibrosis with Abdominal Pain and Distention
Journal: New England Journal of Medicine (2011)

361:807-16).In the Pathological Discussion (page 815), the penultimate paragraph, which currently begins with "Damage to the liver . . .," should be corrected as follows: The final sentence, which begins, "The pancreas was atrophic," should instead appear at the beginning of the paragraph and should cite Figure 4C, not 4D.In the sentence that begins, "In this case," the two parenthetical figure citations should be "(Fig.4D)" and "(Fig.4D, inset)," rather than "(Fig.4C)" and "(Fig.4C, inset)."The article is correct at NEJM.org.(June 11, 2009;360:2564-8).In the Commentary (page 2567), the parenthetical in the final sentence of the third paragraph, "(e.g., intravenous immune globulin for hepatitis A infection)," should be deleted, so that the sentence reads, "The treatment of other viral infections is generally not initiated until a specific diagnosis has been made."The article is correct at NEJM.org. Kiss of Death
SOLANIN.
Authors: WILLIAM F. WAUGH
Journal: JAMA (1906)

Solanin is an alkaloid found in several species of<i>Solanaceæ</i>, such as<i>Dulcamara ferox, lycopersicum, nigrum</i>and<i>carolinense;</i>and especially in the young shoots of the potato and tubers that have grown while exposed to direct sunlight, and those that have sprouted. Traces have also been detected in<i>Scopola</i>. At some period in the growth of the potato the deep layers of the skin contain enough solanin to cause toxic symptoms. It is extracted by boiling water, and that in which potatoes are boiled may prove toxic. Rotting potatoes contain large quantities of solanin, and the young buds, enormous amounts. Most instances of poisoning follow the use of the small, green, unripe tubers that have been exposed to the sun at the surface of the ground. In an epidemic described by Schmiedeburg the symptoms were headache, colic, vomiting, diarrhea, depression, mental confusion and in severe cases pallor or cyanosis, dilated
EMULSIFIED VACCINE LYMPH.
Journal: JAMA (1892)

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
Carotid bruit or carotid stenosis: what is the significance?
Authors: C. K. Zarins
Journal: JAMA (1981)

The carotid bruit has long been recognized as an indicator of possible atherosclerotic disease at the carotid bifurcation and possible stroke. While there is no disagreement that patients with cerebrovascular symptoms need prompt examination and treatment, the clinical implication of an asymptomatic carotid bruit is unclear. Does the bruit indicate a significant carotid artery stenosis? Are such patients at increased risk for stroke? More precisely, what is the risk of stroke or death without antecedent transient neurological symptoms that might prompt diagnosis and treatment? Reports in the literature dealing with the clinical course of patients with asymptomatic carotid disease have provided conflicting information. The risk of stroke has been reported to be as high as 19% in patients with asymptomatic carotid bruits<sup>1</sup>and as low as 2% in patients with angiographically proved stenosis followed up to 12 years.<sup>2</sup>The debate continues in the articles by Busuttil et al (p
NCCN NewsNew, Reliable Source of Free Information for People with Liver, Gallbladder, or Bile Duct Cancer, Offered by NCCNNCCN Convenes Summit on Providing High-Quality Cancer Care in an Evolving Policy and Tech Landscape
Authors: Benson Iii, Robert Lurie
Journal: Journal of the National Comprehensive Cancer Network (2018)

New, Reliable Source of Free Information for People with Liver, Gallbladder, or Bile Duct Cancer, Offered by NCCNNCCN has released a brand-new resource to help people with liver, gallbladder, and bile duct cancers better understand the critical decisions they make about their care.This new edition of the NCCN Guidelines for Patients takes the evidence-based, expert consensus treatment recommendations from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and creates a patient-friendly version with easy-to-follow wording.Funding was provided by the NCCN Foundation, with sponsorship from the Global Liver Institute, with content endorsed by the Cholangiocarcinoma Foundation."An essential element of patient empowerment is accessible, actionable, high-quality information," said Donna R. Cryer, JD, President & CEO, Global Liver Institute."The Global Liver Institute is proud to work with NCCN to provide this information to support liver and bile duct patients with cancer and their families in the hope that together we can make the cancer journey easier and more successful."More than 50,000 people in the United States are diagnosed every year with a cancer involving the liver, gallbladder, or bile ducts-collectively known as hepatobiliary cancers. 1 Globally, both the number of incidents and the number of deaths from liver cancer are on the rise, despite declining numbers for both in cancer overall. 2 This correlates with rising rates of hepatitis B and, more frequently, hepatitis C infections, which is often a precursor to liver cancer. 3Metabolic disorders (including obesity, diabetes, and nonalcoholic fatty liver disease) are also associated with increased risk of liver cancer, 4,5 and there is growing evidence for an association with nonalcoholic steatohepatitis. 6,7Additionally, people with liver cancer often also suffer from underlying cirrhosis, which can create limitations for their cancer treatment options.Common treatments include liver transplantation, surgery, radiation, ablation/embolization, or drug therapy."When people are diagnosed with liver cancer, patients hope their doctor will be able to present them with a definitive best course of action, but there are often multiple treatments from which to choose.The best choice for any given individual has been to take into account their disease status, symptoms, laboratory results, and, of course, personal preferences," explained Al B.
Rushing the net and retinal detachment
Authors: M. H. Seelenfreund
Journal: JAMA (1976)

With the growth in popularity of tennis has come an increase in ocular injuries due to tennis balls. This report describes ten patients who sustained ocular contusion from high-speed tennis balls. Seven of the patients required either retinal surgery, laser photocoagulation, or both. Early detection of retinal damage is essential, but of greater importance is prevention. For that reason, we advise use of some sort of ocular protection device for high-risk individuals. (<i>JAMA</i>235:2723-2726, 1976)
FRACTURES OF THE SPINE
Authors: R. W. Jones
Journal: BMJ (1932)

The role of D<sub>1</sub> dopamine (DA) receptors in mediating the ability of DA to modulate responses attributable to activation of NMDA receptors was examined in mice lacking D<sub>1A</sub> dopamine receptors. Specifically, experiments were designed to test the hypothesis that the ability of DA to potentiate responses mediated by activation of NMDA receptors was attributable to activation of D<sub>1</sub> receptors. Based on this hypothesis, we would predict that in the D<sub>1A</sub> mutant mouse, either DA would not induce enhancement of NMDA-mediated responses, or the enhancement would be severely attenuated. The results provided evidence to support the hypothesis. In mutant mice, DA and D<sub>1</sub> receptor agonists did not potentiate responses mediated by activation of NMDA receptors. In contrast, in control mice, both DA and D<sub>1</sub> receptor agonists markedly potentiated responses mediated by activation of NMDA receptors. The effects of DA in attenuating responses mediated by activation of non-NMDA receptors also were altered in the mutant, suggesting that this action of DA may require coupling or interactions between D<sub>1</sub> and D<sub>2</sub> receptors. The present studies also provided an opportunity to assess some of the basic electrophysiological and morphological properties of neostriatal neurons in mice lacking D<sub>1A</sub> DA receptors. Resting membrane potential, action potential parameters, input resistance, excitability, somatic size, dendritic extent, and estimates of spine density in mutants and controls were similar, suggesting that these basic neurophysiological and structural properties have not been changed by the loss of the D<sub>1A</sub> DA receptor.
Urinary retention following cannabis ingestion
Authors: T. A. Burton
Journal: JAMA (1979)

WITH growing public acceptance of cannabis, use of this drug has spread to the older segment of the population. Although age brings certain rewards, it also brings a generalized decline in the functional reserve of most organ systems. It therefore seems reasonable to expect that this population will show more adverse reactions to cannabis. <h3>Report of a Case</h3> A 55-year-old man was referred for psychiatric evaluation because of depression and persistent low-back pain without physical or roentgenographic findings. He had been a moderately severe alcoholic for approximately 33 years. He stopped drinking altogether after he began smoking cannabis daily at age 50 years. Psychotherapy began in the spring of 1975, and his depression gradually lifted. The major psychiatric problem then appeared to be his passive-aggressive personality. Between November 1976 and August 1977, he ate leftover cannabis butts in the evening on four occasions. Each time, he awoke in the morning
Patologia tropicale: Clinica delle malattie tropicali, protozoologia, elmintologia, entomologia nozioni di tecnica generale.
Journal: JAMA (1930)

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
The Contributions of Emissions and Spatial Microenvironments to Exposure to Indoor Air Pollution from Biomass Combustion in Kenya
Authors: Majid Ezzati, Homayoun Saleh, Daniel M. Kammen
Journal: Environmental Health Perspectives (2000)

Acute and chronic respiratory diseases, which are causally linked to exposure to indoor air pollution in developing countries, are the leading cause of global morbidity and mortality. Efforts to develop effective intervention strategies and detailed quantification of the exposure-response relationship for indoor particulate matter require accurate estimates of exposure. We used continuous monitoring of indoor air pollution and individual time-activity budget data to construct detailed profiles of exposure for 345 individuals in 55 households in rural Kenya. Data for analysis were from two hundred ten 14-hour days of continuous real-time monitoring of concentrations of particulate matter [less than/equal to] 10 microm in aerodynamic diameter and the location and activities of household members. These data were supplemented by data on the spatial dispersion of pollution and from interviews. Young and adult women had not only the highest absolute exposure to particulate matter (2, 795 and 4,898 microg/m(3) average daily exposure concentrations, respectively) but also the largest exposure relative to that of males in the same age group (2.5 and 4.8 times, respectively). Exposure during brief high-intensity emission episodes accounts for 31-61% of the total exposure of household members who take part in cooking and 0-11% for those who do not. Simple models that neglect the spatial distribution of pollution within the home, intense emission episodes, and activity patterns underestimate exposure by 3-71% for different demographic subgroups, resulting in inaccurate and biased estimations. Health and intervention impact studies should therefore consider in detail the critical role of exposure patterns, including the short periods of intense emission, to avoid spurious assessments of risks and benefits.
Editorial Board
Journal: Allergy (2017)

US$2518 (Rest of World), €1907 (Europe), £1500 (UK).Prices are exclusive of tax.Asia-Pacifi c GST, Canadian GST/HST and European VAT will be applied at the appropriate rates.For more information on current tax rates, please go to www.wileyonlinelibrary.com/tax-vat.The price includes online access to the current and all online back fi les to January 1st 2013, where
'Pertussis vaccine encephalopathy': it is time to recognize it as the myth that it is
Authors: J. D. Cherry
Journal: JAMA (1990)

The article by Griffin et al<sup>1</sup>in this issue ofThe Journalis the third recent controlled study that has examined the risk of seizures and other acute neurological illnesses after immunization with pertussis-containing vaccines.<sup>1-3</sup>In these three studies, which involved about 230 000 children and 713 000 immunizations, no evidence of a causal relationship between pertussis vaccine and permanent neurological illness was found. In the two previously published studies, an association between immunization and first febrile seizures was noted; Walker and associates<sup>2</sup>found that the incidence of febrile seizures in the immediate postimmunization period was 3.7 times that in the period 30 days or more after immunization. Shields and colleagues<sup>3</sup>estimated about one febrile seizure for every 1000 children 10 months of age or older who were immunized. In addition to the three recent studies mentioned above, which fail to show a causal relationship between
BBS volume 15 issue 2 Back matter
Authors: Stephen Hanson, Lee Giles, Davi Chair, Chuck Anderson, Aedy Barto, U Mass, Jim Burr, David Haussler, Alan Lapedes, Brace Mcnaughton, U Arizona, Barlett Mel, Mike Mozer, U Colorado, John Pearson, Terry Sejnowski, David Touretzky, Alex Waibel, Halbert White, Alan Yuille, Geny Tesauro, Terrence Fine, Mitsuo Kawato, Marwan Jabri, Andreas Meier, Simon Bolivar
Journal: Behavioral and Brain Sciences (1992)

An abstract is not available for this content so a preview has been provided. As you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Peripheral to medicine
Journal: JAMA (1970)

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
Multivessel stenting: Is it time to reconsider recommendations for coronary artery bypass surgery? Vasant B. Patel, Steven P. Marso, Philip G. Jones, Steven B. Laster, Kenneth C. Huber, Lee V. Giorgi, Warren L. Johnson, Barry D. Rutherford. Mid America Heart Institute, Kansas City, MO
Journal: Journal of the American College of Cardiology (2001)