tbuckley/cabot-search huggingface dataset:
The BMJ's website scales up
Authors: T. Delamothe, R. Smith
Journal: BMJ (1998)

Three years ago, it was hard to find a medical journal on the internet. Now most have websites, providing selections from their paper journals in electronic form. This week the BMJ joins the Lancet and a host of specialist journals in taking the obvious next step: providing the full text of the paper journal online. Soon most other medical journals interested in their long term survival will follow suit.

If “surfing the net” has become the defining catchphrase of the age then the wave we caught three years ago has turned out to be a tsunami. Since the world wide web was first used commercially the number of websites has grown exponentially. When the BMJ launched its original website in May 1995 there were fewer than 20 000 other websites. Last month the total was 2.1m.1 The number of people online has also been growing exponentially—to an estimated 107m.2 The widespread adoption of webTV should increase this figure by at least an order of magnitude.

The BMJ embraced the world wide web so avidly because it looked like fun and offered an almost miraculous escape from the limitations of paper publication. Costly and cumbersome, the printing presses and binding lines take 30 hours to churn out the 117 000 copies of the paper BMJ each week. The Royal Mail takes another day or two to deliver copies to most addresses in the United Kingdom. Further afield, the delays rapidly escalate—four days to get journals to continental Europe, two to three weeks to Australia. The resources we devote to increasing topicality are wasted for most of our non-UK readers.

By comparison, the electronic journal is available to all countries with world wide web access at 00.01 (GMT or BST) on the Friday preceding the cover date. The geographical reach …
Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: extrapolation of effects in rodents to man.
Authors: C Rhodes, T C Orton, I S Pratt, P L Batten, H Bratt, S J Jackson, C R Elcombe
Journal: Environmental Health Perspectives (1986)

Certain phthalate esters and hypolipidemic agents are known to induce morphological and biochemical changes in the liver of rodents, which have been associated with an increased incidence of hepatocellular tumors in these species. There is evidence that hypolipidemic agents do not induce these effects in either subhuman primates or man. The oral and intraperitoneal administration of di(2-ethylhexyl) phthalate (DEHP) to the marmoset monkey at doses up to 5 mmole DEHP/kg body weight/day for 14 days did not induce morphological or biochemical changes in the liver or testis comparable with those obtained in rats given the same amount of DEHP. In the marmoset, the excretion profile of [14C]-DEHP following oral, IP, and IV administration and the lower tissue levels of radioactivity demonstrated a considerably reduced absorption in this species compared to the rat. The urinary metabolite pattern in the marmoset was in many respects qualitatively similar to but quantitatively different from that in the rat; the marmoset excreted principally conjugated metabolites derived from omega- 1 oxidation. The pharmacokinetic differences between these two species indicate that the tissues of the marmoset are exposed to a level of DEHP metabolites equivalent to the complete absorption of a dose of Ca. 0.1 to 0.25 mmole DEHP/kg body weight/day without significant toxicological effects. These exposure levels are at least 100-fold greater than the worst estimates of incidental human exposure (ca. 0.0015 mmole/kg/day). They are comparable with the human therapeutic dose of many hypolipidemic drugs (ca. 0.15 mmole/kg/day), a dose at which it is claimed that there is an absence of morphological or biochemical changes to human or subhuman primate liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Sites of prostaglandin synthesis in the bovine heart and isolated bovine coronary microvessels.
Authors: M E Gerritsen, M P Printz
Journal: Circulation Research (1981)

Metabolically active coronary microvessels (generally less than 100 micrometers in diameter) were isolated from bovine hearts. These preparations were virtually free of contaminating myocytes and consisted of a mixture of arterioles, venules, capillaries, and collagen fibers. The prostaglandin biosynthetic capacity of isolated coronary microvessels was assessed by quantitating conversion of 14C-arachidonic acid and 14C-prostaglandin endoperoxide (PGH2) to prostaglandins. Coronary microvessels were found to exhibit low cyclooxygenase activity, i.e., minimal conversion (less than 1%) of arachidonic acid (AA) to prostaglandins when compared with either the coronary artery (3.6% conversion of AA) or coronary vein (3.3%). Isolated myofibril fractions demonstrated virtually no cyclooxygenase activity (less than 0.1%). Two enzymatic endoperoxide metabolizing activities were evident in the microvessels, prostacyclin synthetase and PGE isomerase. When compared on a microsomal protein basis, the coronary artery exhibited higher prostacyclin synthetase activity than the microvessels but was devoid of PGE isomerase activity. In contrast, whereas PGE isomerase activity was detectable in the coronary vein, the activity was lower than that of the microvessels; further, it could not be demonstrated in the other myocardial fractions. A glutathione-enhanced PGD-forming activity was present in high speed supernatants derived from the coronary artery and vein preparations, but was not present in the coronary microvessel or isolated myofibril fractions. From these studies we conclude that (1) the major source of prostaglandins released into the coronary circulation is the coronary vasculature, and (2) the resistance elements of the coronary circulation differ from the larger elements (i.e., arteries and veins) in the enzymes of the prostaglandin biosynthetic pathway present and thus in the nature and perhaps quantity of prostaglandins biosynthesized.
Free radicals and intracellular events associated with cerebrovascular spasm
Authors: D. A. Cook, B. Vollrath
Journal: Cardiovascular Research (1995)

Journal Article Free radicals and intracellular events associated with cerebrovascular spasm Get access David A. Cook, David A. Cook * Department of Pharmacology, University of Alberta, Edmonton, Alta., Canada T6G 2H7 *Tel. (+1-403) 492-6848; Fax (+1-403) 492-5487. Search for other works by this author on: Oxford Academic PubMed Google Scholar Bozena Vollrath Bozena Vollrath Department of Pharmacology, University of Alberta, Edmonton, Alta., Canada T6G 2H7 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 4, October 1995, Pages 493–500, https://doi.org/10.1016/S0008-6363(95)00087-9 Published: 01 October 1995 Article history Received: 19 January 1995 Accepted: 24 May 1995 Published: 01 October 1995
Long Noncoding RNAs in Patients With Acute Myocardial Infarction
Authors: Mélanie Vausort, Daniel R. Wagner, Yvan Devaux
Journal: Circulation Research (2014)

Rationale: Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. Objective: To measure lncRNAs in patients with myocardial infarction (MI). Methods and Results: We enrolled 414 patients with acute MI treated by primary percutaneous coronary intervention. Blood samples were harvested at the time of reperfusion. Expression levels of 5 lncRNAs were measured in peripheral blood cells by quantitative polymerase chain reaction: hypoxia inducible factor 1A antisense RNA 2, cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL), potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), myocardial infarction–associated transcript, and metastasis-associated lung adenocarcinoma transcript 1. Levels of hypoxia inducible factor 1A antisense RNA 2, KCNQ1OT1, and metastasis-associated lung adenocarcinoma transcript 1 were higher in patients with MI than in healthy volunteers ( P &lt;0.01), and levels of ANRIL were lower in patients with MI ( P =0.003). Patients with ST-segment–elevation MI had lower levels of ANRIL ( P &lt;0.001), KCNQ1OT1 ( P &lt;0.001), myocardial infarction–associated transcript ( P &lt;0.001), and metastasis-associated lung adenocarcinoma transcript 1 ( P =0.005) when compared with patients with non–ST-segment–elevation MI. Levels of ANRIL were associated with age, diabetes mellitus, and hypertension. Patients presenting within 3 hours of chest pain onset had elevated levels of hypoxia inducible factor 1A antisense RNA 2 when compared with patients presenting later on. ANRIL, KCNQ1OT1, myocardial infarction–associated transcript, and metastasis-associated lung adenocarcinoma transcript 1 were significant univariable predictors of left ventricular dysfunction as assessed by an ejection fraction ≤40% at 4-month follow-up. In multivariable and reclassification analyses, ANRIL and KCNQ1OT1 improved the prediction of left ventricular dysfunction by a model, including demographic features, clinical parameters, and cardiac biomarkers. Conclusions: Levels of lncRNAs in blood cells are regulated after MI and may help in prediction of outcome. This motivates further investigation of the role of lncRNAs after MI.
Neonatal Osteomyelitis Due to Proteus mirabilis
Authors: Harvey L. Levy
Journal: JAMA (1967)

Proteus mirabilis osteomyelitis occurred in two neonates. The clinical symptoms and roentgenographic findings did not differ significantly from those seen in other forms of bacterial osteomyelitis in the newborn. Nursery contamination with the offending organism was not found, although the circumstances of multiple P mirabilis infections in a single nursery suggested this possibility. Antibiotic therapy consisted of potassium penicillin (G) and kanamycin sulfate in one case, and kanamycin and chloramphenicol sodium succinate in the other case. Both patients made uneventful recoveries.
Dissociation between early recovery of regional function and purine nucleotide content in postischaemic myocardium in the conscious dog
Authors: D. D GLOWER, J. A SPRATT, J. R NEWTON, J A. WOLFE, J S. RANKIN, J. L SWAIN
Journal: Cardiovascular Research (1987)

Since abnormalities in regional myocardial function and nucleotide metabolism persist for a prolonged period after a brief coronary occlusion the temporal relation between the resolution of myocardial dysfunction and repletion of nucleotide pools in postischaemic myocardium was studied in conscious mildly sedated animals. In a second experiment 5-amino-4-imidazolecarboxamide riboside (AICAriboside) was infused in an attempt to influence myocardial function by altering the rate of adenine nucleotide synthesis. Conscious dogs mildly sedated with morphine underwent coronary occlusion for 15 min followed by reperfusion for 30 min or 12 h, at which time a myocardial sample was obtained for nucleotide analysis. Segment shortening averaged 62% of control values at 15 min of reperfusion and increased to 81% of control by 12 h of reperfusion (p<0.05). Adenine nucleotide content was 75(5)% of control after 30 min of reperfusion and did not change significantly over the next 12 h of reperfusion. Thus the early return of systolic function was not accompanied by a detectable increase in total adenine nucleotide content. In the second experiment a pronounced stimulation of the proximal purine nucleotide synthetic pathway occurred as evidenced by a 13-fold to 25-fold increase in inosine monophosphate content. One branch of the distal purine pathway was also stimulated as evidenced by complete repletion of guanine nucleotide pools, but the product of the other branch (adenine nucleotides) did not increase significantly. These results indicate a selective limitation of the distal adenine nucleotide synthetic pathway in postischaemic myocardium. The findings suggest that to achieve rapid repletion of adenine nucleotide pools agents that stimulate the purine synthetic pathway distal to inosine monophosphate may be most successful.
THE ASSOCIATION OF OPTIC NEURITIS AND FACIAL PARALYSIS.
Authors: EDWARD A. SHUMWAY
Journal: JAMA (1905)

The relative infrequency with which optic neuritis occurs in association with facial paralysis makes the following case worthy of record: <h3>The Patient.</h3> —Miss G. W., age 19, came to the eye dispensary of the University Hospital, Philadelphia, Dec. 8, 1903, in the service of Dr. George E. de Schweinitz, to whose courtesy I am indebted for permission to publish the case. She complained of blurring of print and aching in the eyes in reading or other close work. She was unaware that her eyesight had failed, but examination showed that vision of the right eye was 6/15 and of the left eye only 6/30. She was able to read Jaeger 0.50 D. with each eye at 13 cm. slowly. <h3>Ophtltalmoscopic Examination.</h3> —There was atrophy of each optic nerve, more advanced on the left side. The nerve heads were covered with a delicate, white tissue, which blurred their
Varicose veins and their management
Authors: Bruce Campbell
Journal: BMJ (2006)

Varicose veins are tortuous, widened veins in the subcutaneous tissues of the legs and are often easily visible. Their valves are usually incompetent so that reflux of blood occurs, and the resulting venous hypertension can cause symptoms. Varicose veins are widely seen as medically unimportant and deserving low priority for treatment. They are common, affecting nearly a third of adults in Western societies, and few people with varicose veins are ever harmed by them. However, they cause concern and distress on a large scale, most of which can be dealt with by good explanation and reassurance, or by a variety of treatments which are evolving rapidly at present. Patients can now be referred for more precise assessment and a greater range of therapeutic options than ever before.

A large UK population study has shown age adjusted prevalences of 40% in men and 32% in women, although women more often present for treatment.1 The age of onset varies; some people develop varicose veins in their teens, but prevalence rises with age. Varicose veins often appear first in pregnancy, and further pregnancies can make them worse. A family history is common,1 but people should be reassured that having close relatives with severe symptoms from varicose veins or ulcers does not confer any great likelihood that they will have similar problems.

#### Data sources and selection criteria

This review is based on three main sources:

#### Summary points

Most people with varicose veins are never harmed by them—good explanation and reassurance are fundamental

Ultrasound techniques (hand held …
Neostigmme-resistant Curarization
Authors: G. B. Burchell
Journal: BMJ (1956)

<h3>ABSTRACT</h3> <h3>Background</h3> Selective serotonin reuptake inhibitors (SSRIs), used to treat prenatal maternal depression, have been associated with neurobehavioral disturbances in exposed neonates, though the underlying molecular mechanisms remain poorly understood. <i>In utero</i> exposure to SSRIs may have an effect on DNA methylation (DNAme) in the human placenta, which is an epigenetic mark that is established during development and is associated with gene expression. <h3>Methods</h3> Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip and clinical assessments of maternal mood were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression using a mean maternal Hamilton Depression score &gt;8 to indicate symptomatic depressed mood (“maternally-depressed”) further classified cases into SSRI-exposed, maternally-depressed (n=14); SSRI-exposed, not maternally-depressed (n=6); SSRI non-exposed, maternally-depressed (n=20); and SSRI non-exposed, not maternally-depressed (n=24). To provide a replication cohort, Illumina 450K DNAme profiles were obtained from 34 additional cases from an independent cohort (n=17 SSRI-exposed, n=17 SSRI non-exposed). <h3>Results</h3> No CpGs were differentially methylated at FDR &lt; 0.05 comparing SSRI-exposed to non-exposed placentas, while adjusting for mean maternal Hamilton Depression score, nor comparing SSRI-exposed maternally-depressed to SSRI-non-exposed maternally-depressed cases. At a relaxed threshold of FDR &lt; 0.25, five CpGs were differentially methylated (|Δβ| &gt; 0.03) by SSRI exposure status. Four of these CpGs were covered by the 450K array and were examined in the replication cohort, but none replicated. Amongst SSRI non-exposed cases, no CpGs were differentially methylated (FDR &lt; 0.25) comparing maternally depressed to not depressed cases. In sex-stratified analyses for SSRI-exposed versus non-exposed cases (females n=31; males n=33), three additional CpGs in females, but none in males, were differentially methylated at the relaxed FDR &lt; 0.25 cut-off. <h3>Conclusions</h3> We did not observe large-scale alterations of DNAme in placentas exposed to maternal SSRI treatment compared to placentas with no SSRI exposure. We also found no evidence for altered DNAme in maternal depression-exposed versus depression non-exposed placentas. This novel work in a prospectively recruited cohort with clinician-ascertained SSRI exposure and mood assessments would benefit from future replication.
West Berkshire perineal management trial: three year follow up.
Authors: J Sleep, A Grant
Journal: BMJ (1987)

Women who had participated in a randomised controlled trial of policies of restricted (10%) versus liberal (51%) episiotomy during spontaneous vaginal delivery were recontacted by postal questionnaire three years after delivery. Altogether 674 out of 1000 responded, and there was no evidence of a differential response rate between the two trial groups. Similar numbers of women in the two groups reported further deliveries, almost all of which had been vaginal and spontaneous. Fewer women allocated to restrictive use of episiotomy required perineal suturing after subsequent delivery, but this difference was not significant. Pain during sexual intercourse and incontinence of urine were equally reported in the two groups. The similarity in incontinence rates persisted when severity, type of incontinence, and subsequent deliveries were taken into account. Liberal use of episiotomy does not seem to prevent urinary incontinence or increase long term dyspareunia.
The government's drug pricing policy is falling apart messily
Authors: Nigel Hawkes
Journal: BMJ (2013)

What is the future for England’s Cancer Drugs Fund and value based pricing?



Promises made in the heat of an election campaign have a way of coming back and biting politicians. In the run up to polling day in 2010, the Tories Andrew Lansley and David Cameron promised a new pot of money to provide anticancer drugs that would otherwise not be available because they had failed to meet criteria on cost effectiveness.1 How could this be squared with their support for the National Institute for Clinical (now Care) Excellence (NICE), which makes those decisions? By explaining—as one of Lansley’s more cogent spin doctors obligingly did for me at the time—that the Cancer Drugs Fund was a temporary device to act as a “bridge” between the present and a future in which drugs would be priced by the value they provided.

Thus were two incompatible policies—one unashamedly populist, the other obscure enough to sound impressive while eluding precise definition—harnessed together. They are now rather messily coming apart. Nobody knows what will become of the Cancer Drugs Fund when the three years’ funding promised by the coalition government comes to an end; and value based pricing, promised for the start of …
Crohn's disease complicated by strictures: a systematic review
Authors: Florian Rieder, Ellen M Zimmermann, Feza H Remzi, William J Sandborn
Journal: Gut (2013)

The occurrence of strictures as a complication of Crohn9s disease is a significant clinical problem. No specific antifibrotic therapies are available. This systematic review comprehensively addresses the pathogenesis, epidemiology, prediction, diagnosis and therapy of this disease complication. We also provide specific recommendations for clinical practice and summarise areas that require future investigation.
793 Edaravone, a novel free radical scavenger, prevents liver injury and mortality in rats administered endotoxin
Authors: H KONO, M ASAKAWA, H FUJII, A MAKI, H AMEMIYA, Y HIRAI, M YAMAMOTO
Journal: Hepatology (2003)

We postulated that a novel free radical scavenger, 3-methyl-1phenyl-2-pyrazolin-5-one (edaravone; EDA), would attenuate inflammatory cytokine and chemokine expression in the liver after lipopolysaccharide (LPS) challenge through its antioxidant effect. Rats were administered EDA (0.3, 1.5, 3.0, 6.0, and 12.0 mg/kg) or the same volume of saline intravenously just after LPS (10 mg/kg) injection and then was continued intermittently every 2 h (five administrations in total). Survival was assessed for the next 24 h. In separate experiments, rats were sacrificed at 60 min, 90 min, 6 h, and 9 h after LPS injection. Serum and liver sections were collected for further analysis. Survival was improved by EDA in a dose-dependent manner up to 3 mg/kg, and maximum effects were observed at a dose of 3 mg/kg. After LPS injection, alanine aminotransferase levels increased significantly to about 1,250 IU/l in the vehicle-treated group, whereas values were blunted by about 80% by EDA. Furthermore, increases in 4-hydroxynonenal-modified proteins were also blunted in the liver by EDA. Moreover, mRNA expressions of macrophage infiltrating protein-2, monocyte chemoattractant protein (MCP)-1 and MCP-5 were attenuated by EDA. As a result, increases in the number of infiltrating inflammatory cells and mRNA expression of inflammatory cytokines such as tumor necrosis factor- and interleukin-6 were significantly blunted in the liver by EDA. This reduction was accompanied by a significant reduction of their serum levels. In conclusion, EDA prevented liver injury by both inhibition of recruitments of inflammatory cells and expression of inflammatory cytokine levels in the liver.