tbuckley/cabot-search huggingface dataset:
Depressant effects of fast sodium channel blockade on the electrical activity of ischaemic canine ventricle: mediation by the sympathetic nervous system
Authors: R. F GILMOUR, D. G MORRICAL, P. J ERTEL, J. F MAESAKA, D. P ZIPES
Journal: Cardiovascular Research (1984)

In this study we examined the possibility that local anaesthetic agents such as tetrodotoxin may exacerbate electrical changes during acute myocardial ischaemia by inhibiting fast sodium channels, both in cardiac cells and in sympathetic nerve terminals. Bipolar electrograms were recorded during serial 2 to 5 min occlusions of the left anterior descending coronary artery in open-chest, anaesthetised dogs. Tetrodotoxin (1 or 2 μg·kg−1 iv) given prior to occlusion did not affect activation times or electrograms in normal myocardium but exacerbated activation delay and loss of electrogram amplitude during ischaemia. Bilateral stellectomy reversed the effects of tetrodotoxin during ischaemia. Tetrodotoxin (1 μg·kg−1 iv) reduced changes in heart rate and mean arterial blood pressure produced by stellate ganglia stimulation. Intracoronary infusion of tetrodotoxin (10−5 mol·litre−1) during normal perfusion lengthened mean effective ventricular refractory periods and propranolol (0.5 mg·kg−1 iv) or bilateral stellectomy prevented this effect. Thus, tetrodotoxin appeared to increase ventricular refractoriness and exacerbate ischaemia-induced activation delay by inhibiting sympathetic nerve activity. Other agents with local anaesthetic properties may have similar effects.
Editor earned more than $20m in royalties from device manufacturer
Authors: J. Lenzer
Journal: BMJ (2010)

A medical journal editor who received millions of dollars from a medical device manufacturer wrote and edited articles favourable to the manufacturer without stating his conflicts of interest to readers.

Thomas Zdeblick, a University of Wisconsin orthopaedic surgeon who took over as editor in chief of the Journal of Spinal Disorders & Techniques in 2002, received more than $20m (€12.4m; £14m) in patent royalties and $2m in consulting fees from Medtronic for spinal implants sold by the company during his tenure as editor. The amount of money Dr Zdeblick received became public in January 2009 as a result of an investigation into spinal device products launched by the US senator Charles Grassley (http://policymed.typepad.com/files/grassley-letter-to-university-of-wisconsin-january-12\---|2009.pdf).

Now a Milwaukee, Wisconsin, newspaper, the Journal Sentinel , has conducted a …
Students like new curriculum.
Authors: J A Dent
Journal: BMJ (1993)

this screening interval but did not strictly fulfil all the criteria.By analysing the smear histories of all women over the age of 50 living in the Dundee and Angus areas who were diagnosed as having cervical neoplastic disease in 1991 and 1992 we extended out initial study to cover four consecutive years.In 1991 and 1992 a total of 47 461 smears were taken and 710 cases of cervical intraepithelial neoplasia were diagnosed.Altogether 15-5% of smear tests
Obama warns of climate change threat to public health
Authors: M. McCarthy
Journal: BMJ (2015)

Climate change poses a threat to the health of all Americans, President Barack Obama said on 7 April, citing the dangers posed by deteriorating air quality associated with higher temperatures, more extreme weather, and the spread of insect-borne diseases that previously have been confined to nations further south. “All of our families are going to be vulnerable. You can’t cordon yourself off from air or from the climate,” the president said.

Obama made …
Cross-species amplification of soybean (Glycine max) simple sequence repeats (SSRs) within the genus and other legume genera: implications for the transferability of SSRs in plants
Authors: R. Peakall, S. Gilmore, W. Keys, M. Morgante, A. Rafalski
Journal: Molecular Biology and Evolution (1998)

We investigated the transferability of 31 soybean (Glycine max) simple sequence repeat (SSR) loci to wild congeners and to other legume genera. Up to 65% of the soybean primer pairs amplified SSRs within Glycine, but frequently, the SSRs were short and interrupted compared with those of soybeans. Nevertheless, 85% of the loci were polymorphic within G. clandestina. Cross-species amplification outside of the genus was much lower (3%-13%), with polymorphism restricted to one primer pair, AG81. AG81 amplified loci in Glycine, Kennedia, and Vigna (Phaseoleae), Vicia (Vicieae), Trifolium (Trifolieae), and Lupinus (Genisteae) within the Papilionoideae, and in Albizia within the Mimosoideae. The primer conservation at AG81 may be explained by its apparent proximity to the seryl-tRNA synthetase gene. Interspecific differences in allele size at AG81 loci reflected repeat length variation within the SSR region and indels in the flanking region. Alleles of identical size with different underlying sequences (size homoplasy) were observed. Our findings and the emerging patterns in other plant studies suggest that in contrast to animals, successful cross-species amplification of SSRs in plants is largely restricted to congeners or closely related genera. Because mutations in both the SSR region and the flanking region contribute to variation in allele size among species, knowledge of DNA sequence is essential before SSR loci can be meaningfully used to address applied and evolutionary questions.
Development of adult bone marrow stem cells in H-2-compatible and -incompatible mouse fetuses.
Authors: R A Fleischman, B Mintz
Journal: The Journal of Experimental Medicine (1984)

Bone marrow of normal adult mice was found, after transplacental inoculation, to contain cells still able to seed the livers of early fetuses. The recipients' own hematopoietic stem cells, with a W-mutant defect, were at a selective disadvantage. Progression of donor strain cells to the bone marrow, long-term self-renewal, and differentiation into myeloid and lymphoid derivatives was consistent with the engraftment of totipotent hematopoietic stem cells (THSC) comparable to precursors previously identified (4) in normal fetal liver. More limited stem cells, specific for the myeloid or lymphoid cell lineages, were not detected in adult bone marrow. The bone marrow THSC, however, had a generally lower capacity for self-renewal than did fetal liver THSC. They had also embarked upon irreversible changes in gene expression, including partial histocompatibility restriction. While completely allogeneic fetal liver THSC were readily accepted by fetuses, H-2 incompatibility only occasionally resulted in engraftment of adult bone marrow cells and, in these cases, was often associated with sudden death at 3-5 mo. On the other hand, H-2 compatibility, even with histocompatibility differences at other loci, was sufficient to ensure long-term success as often as with fetal liver THSC.
Folic acid, ageing, depression, and dementia
Authors: E H Reynolds
Journal: BMJ (2002)

It is becoming clear that folic acid affects mood and cognitive function, especially in older people. Edward Reynolds draws together the evidence

Folic acid is important for functioning of the nervous system at all ages.1–4 In the fetus the relation between maternal folate status and the risk of neural tube defects is well established: clinical trials have shown that periconceptual preventive treatment with 400 μg or higher of folic acid significantly reduces the risks of such defects.4

In neonates, infants, children, and adolescents, inborn errors of folate transport and metabolism are associated with a variety of overlapping syndromes which are influenced by age of clinical presentation. These include developmental delay, cognitive deterioration, motor and gait abnormalities, behavioural or psychiatric symptoms, seizures, signs of demyelination or failure of myelination, and vascular changes seen on magnetic resonance imaging or postmortem examination.4 Less commonly, subacute combined degeneration and peripheral neuropathy may also occur.

In adult patients presenting with megaloblastic anaemia due to folate deficiency, approximately two thirds have neuropsychiatric disorders which overlap considerably with those associated with anaemia due to vitamin B-12 deficiency. 2 5 However, depression is commoner in patients with folate deficiency, and subacute combined degeneration with peripheral neuropathy is more frequent in those with vitamin B-12 deficiency. The degree of anaemia is poorly correlated with the presence of neuropsychiatric disorders, but if these anaemias were left untreated nearly all patients would eventually develop neuropsychiatric complications.2 Over the past 35 years numerous studies have shown a high incidence of folate deficiency correlated with mental symptoms, especially depression and cognitive decline in epileptic, neurological, psychiatric, geriatric, and psychogeriatric populations. 3 4 Furthermore, recent studies in elderly people suggest a link between folic acid, homocysteine, ageing, depression, and dementia, including Alzheimer's disease and vascular disease. 4 6 …
Oxford Textbook of Surgery, vols 1 and 2
Authors: Ben Eiseman
Journal: JAMA (1995)

Considering critical mass-to-surface ratio, this textbook is an encyclopedia. By all criteria, this massive publication by Morris and Malt qualifies as an encyclopedia of general surgery. Its multiple authors completely encircle the subject. With more than 3000 pages—the index alone runs to 122 pages—307 authors, and more than 3000 color illustrations and weighing in at 19 1b,<i>Oxford Textbook of Surgery</i>is a physical and intellectual heavyweight. Encyclopedia editors have three responsibilities: to define their objectives, to select authoritative contributors who share their professional philosophy and style, and to wisely allocate page space. Peter Morris and Ronald Malt are ideally situated to meet each of these challenges. They are senior professors of surgery whose institutions, Oxford and the Massachusetts General Hospital, have for more than a century shared a common professional philosophy: to train respected, solid general clinical surgeons. Wisely, this is the focus of their book. Another advantage is
Diabetes Mellitus Following Rodenticide Ingestion in Man
Authors: Peterman R. Prosser
Journal: JAMA (1978)

Ketotic, insulin-requiring diabetes mellitus and a severe peripheral neuropathy developed in a previously healthy 25-year-old man several days after he attempted suicide with rat poison containing N-3-pyridylmethyl N'-p-nitrophenyl urea. Study of islet-cell function ten months after ingestion showed a reduced disappearance rate of intravenous glucose and depressed C-peptide response to intravenous glucose when compared with a normal control but no impairment of glucagon release after intravenous arginine stimulation. Nerve conduction studies demonstrated severe sensory and mild motor neuropathy. Quadriceps capillary basement membrane thickness was in the diabetic range. Because at least 15 similar occurrences have been reported to the manufacturer, this agent appears to be diabetogenic in man, probably causing β-cell destruction. Niacinamide, which can prevent glucose intolerance in both streptozocin- and alloxantreated animals and prevents death in rats given this rodenticide, may be a useful antidote. (<i>JAMA</i>239:1148-1150, 1978)
Extreme Binge Drinking Among 12th-Grade Students in the United States
Authors: Megan E. Patrick, John E. Schulenberg, Meghan E. Martz, Jennifer L. Maggs, Patrick M. O’Malley, Lloyd D. Johnston
Journal: JAMA Pediatrics (2013)

<h3>Importance</h3> The prevalence of underage alcohol use has been studied extensively, but binge drinking among youth in the United States is not yet well understood. In particular, adolescents may drink much larger amounts than the threshold (5 drinks) often used in definitions of binge drinking. Delineating various levels of binge drinking, including extreme levels, and understanding predictors of such extreme binge drinking among youth will benefit public health efforts. <h3>Objective</h3> To examine the prevalence and predictors of 5+ (≥5 drinks) binge drinking and of 10+ (≥10 drinks) and 15+ (≥15 drinks) extreme binge drinking among 12th graders in the United States. <h3>Design, Setting, and Participants</h3> A nonclinical nationally representative sample of high school seniors in the annual Monitoring the Future study between 2005 and 2011. The sample included 16 332 high school seniors (modal age, 18 years) in the United States. Response rates were 79.1% to 84.7%. <h3>Main Outcomes and Measures</h3> Prevalence of consuming 5 or more, 10 or more, and 15 or more drinks in a row in the last 2 weeks. <h3>Results</h3> Between 2005 and 2011, a total of 20.2% of high school seniors reported 5+ binge drinking, 10.5% reported 10+ extreme binge drinking, and 5.6% reported 15+ extreme binge drinking in the last 2 weeks. Rates of 5+ binge drinking and 10+ extreme binge drinking have declined since 2005, but rates of 15+ extreme binge drinking have not significantly declined. Students with college-educated parents were more likely to consume 5 or more drinks but were less likely to consume 15 or more drinks than students whose parents were not college educated. Students from more rural areas were more likely than students from large metropolitan areas to consume 15 or more drinks. Substance-related attitudes, socializing with substance-using peers, the number of evenings out with friends, and other substance use (cigarettes and marijuana) predicted all 3 levels of binge and extreme binge drinking. <h3>Conclusions and Relevance</h3> Binge drinking at the traditionally defined 5+ drinking level was common among high school seniors representative of all 12th graders in the contiguous United States. A significant segment of students also reported extreme binge drinking at levels 2 and 3 times higher. These data suggest the importance of assessing multiple levels of binge drinking behavior and their predictors among youth to target effective screening and intervention efforts.
Suppression of Delayed Hypersensitivity in Schistosome-Infected Patients by Niridazole
Authors: Leslie T. Webster, Anthony E. Butterworth, Adel A.F. Mahmoud, Eric N. Mngola, Kenneth S. Warren
Journal: New England Journal of Medicine (1975)

Niridazole, an anti-parasitic drug, suppresses manifestations of delayed hypersensitivity and retards allograft rejection in laboratory animals. We investigated the immunosuppressive effects of the standard antihelminthic regimen of niridazole (25 mg/kg/day for seven days) in five patients with schistosomiasis. Although 15-minute skin reactions to schistosomal antigens remained unchanged, niridazole reduced or ablated positive 48-hour skin reactions to tuberculin (PPD), mumps and schistosome antigens in all patients tested six and 15 days after therapy began. Complete recovery of delayed dermal hypersensitivity was observed by 114 days. PPD-induced lymphocyte transformation was severely depressed in three and partially depressed in two of the five patients. Suppression was observed at either six or 15 days (or both) after beginning of treatment, and complete recovery at 114 days. It is concluded that therapeutic doses of niridazole suppress delayed hypersensitivity and antigen-induced lymphocyte transformation in man.
Association Between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis
Authors: Adriaan J. van der Meer, Bart J. Veldt, Jordan J. Feld, Heiner Wedemeyer, Jean-François Dufour, Frank Lammert, Andres Duarte-Rojo, E. Jenny Heathcote, Michael P. Manns, Lorenz Kuske, Stefan Zeuzem, W. Peter Hofmann, Robert J. de Knegt, Bettina E. Hansen, Harry L. A. Janssen
Journal: JAMA (2012)

<h3>Context</h3>Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.<h3>Objective</h3>To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.<h3>Design, Setting, and Patients</h3>An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011.<h3>Main Outcome Measures</h3>All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation.<h3>Results</h3>The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P &lt; .001). In time-dependent multivariate Cox regression analysis, SVR was associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P &lt; .001) and reduced risk of liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02-0.19; P &lt; .001), the latter occurring in 3 patients with SVR and 103 without SVR. The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9% (95% CI, 0.0%-4.1%) with SVR and 27.4% (95% CI, 22.0%-32.8%) without SVR (P &lt; .001). There were 7 patients with SVR and 76 without SVR who developed HCC (10-year cumulative incidence rate, 5.1%; 95% CI, 1.3%-8.9%; vs 21.8%; 95% CI, 16.6%-27.0%; P &lt; .001), and 4 patients with SVR and 111 without SVR experienced liver failure (10-year cumulative incidence rate, 2.1%; 95% CI, 0.0%-4.5%; vs 29.9%; 95% CI, 24.3%-35.5%; P &lt; .001).<h3>Conclusion</h3>Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.
Guidelines on neuraminidase inhibitors in children are not supported by evidence
Authors: M. Symmonds
Journal: BMJ (2004)

EDITOR—Guidelines from the National Institute for Clinical Excellence (NICE) on the use of neuraminidase inhibitors recommend oseltamivir for the treatment of at risk children with influenza-like illness of fewer than 48 hours' duration—for example, those with underlying chronic respiratory disease.1 The drug is not recommended for otherwise healthy children.

In our systematic review on the use of neuraminidase …
Diurnal Patterns of Triglycerides, Free Fatty Acids, Blood Sugar, and Insulin during Carbohydrate-Induction in Man and Their Modification by Nocturnal Suppression of Lipolysis
Authors: G. Schlierf, E. Dorow
Journal: Journal of Clinical Investigation (1973)

Previous studies have shown that carbohydrate induction of hypertriglyceridemia in normal subjects occurs at night and appears to be related to a rise of free fatty acids after diurnal feeding of high-carbohydrate formula diet. The present investigation was undertaken to observe the effect on 24-h triglyceride, free fatty acid, blood sugar, and plasma insulin profiles of inhibition of nocturnal lipolysis by glucose or nicotinic acid in normal subjects and in patients with type IV hyperlipoproteinemia.
II. HEMOGLOBIN AND BILE PIGMENT OVERPRODUCTION IN THE SPLENECTOMIZED BILE FISTULA DOG
Authors: R. E. Knutti, W. B. Hawkins, G. H. Whipple
Journal: The Journal of Experimental Medicine (1935)

Blood destruction associated with Bartonella or with a drug (hydrazine) in bile fistula dogs yields a large pigment excess. These dogs form large amounts of new hemoglobin and bile pigment on a diet which permits of but little new hemoglobin production in standard anemic dogs. When hemoglobin formation and hemoglobin destruction are occurring rapidly and simultaneously, estimations of the percentage of circulating hemoglobin alone, though showing the eventual total increase or decrease of this substance, do not permit one to determine the actual amounts formed or destroyed. It is suggested that the body can produce readily a large amount of the pyrrol aggregate (four pyrrol rings) which may go to form new hemoglobin. At the same time the globin is probably saved from destroyed red cells and turned over into new hemoglobin for new red cells. It is certain that globin may be a determining factor under certain circumstances in the construction of new hemoglobin for new red cells. Our knowledge about the construction and internal metabolism of globin is extraordinarily limited.
Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling
Authors: D. A. Dixon, N. D. Tolley, K. Bemis-Standoli, M. L. Martinez, A. S. Weyrich, J. D. Morrow, S. M. Prescott, G. A. Zimmerman
Journal: Journal of Clinical Investigation (2006)

Tight regulation of COX-2 expression is a key feature controlling eicosanoid production in atherosclerosis and other inflammatory syndromes. Adhesive interactions between platelets and monocytes occur in these conditions and deliver specific signals that trigger inflammatory gene expression. Using a cellular model of monocyte signaling induced by activated human platelets, we identified the central posttranscriptional mechanisms that regulate timing and magnitude of COX-2 expression. Tethering of monocytes to platelets and to purified P-selectin, a key adhesion molecule displayed by activated platelets, induces NF-kappaB activation and COX-2 promoter activity. Nevertheless, COX-2 mRNA is rapidly degraded, leading to aborted protein synthesis. Time-dependent signaling of monocytes induces a second phase of transcript accumulation accompanied by COX-2 enzyme synthesis and eicosanoid production. Here, generation of IL-1beta, a proinflammatory cytokine, promoted stabilization of COX-2 mRNA by silencing of the AU-rich mRNA decay element (ARE) in the 3'-untranslated region (3'UTR) of the mRNA. Consistent with observed mRNA stabilization, activated platelets or IL-1beta treatment induced cytoplasmic accumulation and enhanced ARE binding of the mRNA stability factor HuR in monocytes. These findings demonstrate that activated platelets induce COX-2 synthesis in monocytes by combinatorial signaling to transcriptional and posttranscriptional checkpoints. These checkpoints may be altered in disease and therefore useful as targets for antiinflammatory intervention.
Atopic dermatitis: therapeutic challenge in an infant with dystrophic epidermolysis bullosa
Authors: V. Sibaud, S. Roul, C. Leaute-Labreze, G. Meneguzzi, A. Taieb
Journal: British Journal of Dermatology (2002)

Journal Article Atopic dermatitis: therapeutic challenge in an infant with dystrophic epidermolysis bullosa Get access V. Sibaud, V. Sibaud Paediatric Dermatology Unit, Hôpital Pellegrin, Place Amelie Raba‐Léon, 33076 Bordeaux cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar S. Roul, S. Roul Paediatric Dermatology Unit, Hôpital Pellegrin, Place Amelie Raba‐Léon, 33076 Bordeaux cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar C. Leaute‐Labreze, C. Leaute‐Labreze Paediatric Dermatology Unit, Hôpital Pellegrin, Place Amelie Raba‐Léon, 33076 Bordeaux cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar G. Meneguzzi, G. Meneguzzi INSERM U. 385, Faculté de Médecine, Avenue de Valombrose, 06107 Nice cedex 02, France Search for other works by this author on: Oxford Academic Google Scholar A. Taïeb A. Taïeb Paediatric Dermatology Unit, Hôpital Pellegrin, Place Amelie Raba‐Léon, 33076 Bordeaux cedex 9, France Alain Ta. E‐mail: alain.taieb@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 2, 1 August 2002, Pages 350–352, https://doi.org/10.1046/j.1365-2133.2002.04774.x Published: 01 August 2002 Article history Accepted: 19 December 2001 Published: 01 August 2002