tbuckley/cabot-search huggingface dataset:
Comparative effects of volume loading, dobutamine, and nitroprusside in patients with predominant right ventricular infarction.
Authors: L J Dell'Italia, M R Starling, R Blumhardt, J C Lasher, R A O'Rourke
Journal: Circulation (1985)

To assess the value of volume loading and to determine the relative efficacy of dobutamine compared with nitroprusside therapy in acute right ventricular infarction (RVMI), 13 patients with clinical, hemodynamic, and radionuclide angiographic evidence of RVMI were evaluated. In 10 patients who had an initial pulmonary arterial wedge pressure less than 18 mm Hg, volume loading did not improve cardiac index (1.9 +/- 0.5 [SD] to 2.1 +/- 0.4 liters/min/m2), despite significant increases in mean right atrial pressure (11 +/- 2 to 15 +/- 2 mm Hg, p less than .001) and pulmonary arterial wedge pressure (10 +/- 4 to 15 +/- 2 mm Hg, p less than .001). Nine patients received dobutamine or nitroprusside in random order, while hemodynamic measurements and radionuclide angiograms were obtained simultaneously. Compared with nitroprusside, dobutamine produced a statistically significant increase in cardiac index (2.0 +/- 0.4 to 2.7 +/- 0.5 vs 2.1 +/- 0.4 to 2.3 +/- 0.5 liters/min/m2, p less than .001), stroke volume index (29 +/- 6 to 36 +/- 8 vs 29 +/- 6 to 30 +/- 6 ml/m2, p = .02), and right ventricular ejection fraction (30 +/- 8% to 42 +/- 7% vs 34 +/- 8% to 37 +/- 4%, p less than .01) by two-way analysis of variance. We conclude that volume loading does not improve cardiac index in patients with acute RVMI despite a rise in cardiac filling pressures and that infusion of dobutamine, after appropriate volume loading, produces a significant improvement in cardiac index and right ventricular ejection fraction over those after infusion of nitroprusside.
Loss of imprinting of <i>IGF2</i> characterises high IGF2 mRNA-expressing type of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Alejandro Martin-Trujillo, Johanna G I van Rietschoten, Trieneke C G Timmer, Francisco Milena Rodríguez, Tom W J Huizinga, Paul P Tak, Sara Marsal, Saleh M Ibrahim, Ben A C Dijkmans, Tineke C T M van der Pouw Kraan, Cornelis L Verweij
Journal: Annals of the Rheumatic Diseases (2009)

Objective Increased expression of insulin-like growth factor 2 (IGF2) by fibroblast-like synoviocytes (FLS) was associated with low inflammatory synovium of patients with rheumatoid arthritis (RA). The aim of this study was to analyse whether the differential expression of IGF2, whose expression is normally restricted to one allele, is due to activation of the normally suppressed allele. Methods IGF2 gene expression of RA FLS was quantified by quantitative real-time PCR. FLS heterozygous for a 3′-untranslated region IGF2 polymorphism were selected to measure the relative contribution of the allelic transcripts by allele-specific transcript quantification assay. Proliferation was determined by [ 3 H]thymidine incorporation. Results IGF2 was shown to contribute to RA FLS proliferation. FLS could be classified in IGF2 high and IGF2 low-expressing cell lines. Allelic IGF2 transcript quantification analysis revealed that in part of the RA FLS the normally suppressed allele was activated, resulting in biallelic expression of the IGF2 gene. Biallelic expression was associated with increased levels of IGF2 mRNA production. Conclusion The findings indicate that the imprinting status of IGF2 might underlie the increased expression of IGF2, which may contribute to autonomous growth of RA FLS of low inflammatory synovial tissues.
Risk factors for coronary heart disease and infection with Helicobacter pylori: meta-analysis of 18 studies
Authors: J. Danesh, R. Peto
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To find out if chronic infection with <i>Helicobacter pylori</i> is correlated with risk factors for coronary heart disease. <b>Design:</b> Meta-analysis of 18 epidemiological studies, involving a total of 10 000 patients, that measured serum antibody titres to <i>H pylori</i> and risk factors for coronary heart disease. Any study published in any language before 1998 was eligible for inclusion. <b>Results:</b> Only small absolute differences in body mass index, blood pressure, or haematological risk factors were found between subjects who were seropositive and those who were seronegative. In those who were seropositive body mass index was slightly higher (0.37, SE 0.09) and concentrations of high density lipoprotein cholesterol were slightly lower (0.032 mmol/l, 0.008). None of the other differences were highly significant. <b>Conclusion:</b> Previous claims of substantial correlations between <i>H pylori</i> seropositivity and certain vascular risk factors were largely or wholly due to chance or the preferential publication of positive results, or both.
A monoclonal antibody that defines an idiotope with two subsites in galactan-binding myeloma proteins.
Authors: M Pawlita, E Mushinski, R J Feldmann, M Potter
Journal: The Journal of Experimental Medicine (1981)

An IgG1 monoclonal antibody HyX24-14 was derived from A/J mice that were immunized with the IgA XRPC24 (X24) galactan binding myeloma protein (GalBMP) of BALB/c origin by the Kohler-Milstein hybridoma technology. HyX24-14 specifically binds some but all GalBMP. Different patterns of binding using a panel of nine Gal BMP were found, depending upon the concentration of antibody and the antigenic target. From molecular models and amino acid sequence data, ti was proposed that the idiotope defined by HyX24-14 had two subsites, each of which appeared to be able to bind independently to the antibody.
STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade
Authors: Juan Fu, David B. Kanne, Meredith Leong, Laura Hix Glickman, Sarah M. McWhirter, Edward Lemmens, Ken Mechette, Justin J. Leong, Peter Lauer, Weiqun Liu, Kelsey E. Sivick, Qi Zeng, Kevin C. Soares, Lei Zheng, Daniel A. Portnoy, Joshua J. Woodward, Drew M. Pardoll, Thomas W. Dubensky, Young Kim
Journal: Science Translational Medicine (2015)

Cyclic dinucleotide formulated cancer vaccine combined with PD-1 blockade can induce regression of tumors that do not express PD-L1 constitutively.
Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes.
Authors: M C Poon, D H Chui, M Patterson, D M Starozik, L S Dimnik, D I Hoar
Journal: Journal of Clinical Investigation (1987)

We have used two strategies to study 14 hemophilia B families from 11 kindreds for possible carrier detection and prenatal diagnosis. First, we sequentially used the Factor IX probes (sequentially with restriction enzymes Taq I, Xmn I, and Dde I), and the linked probes p45h (Taq I), p45d (Pst I), and 52a (Taq I) for restriction fragment length polymorphism (RFLP) analysis. Second, we searched for useful variant Taq I digestion fragments using the Factor IX complementary DNA. Two separate new Taq I variants in exon VIII were identified. Using both strategies, 11 of 14 families (from 9 of 11 kindreds) were informative for further studies. In five kindreds studied in detail, the carrier status of all 11 at risk females was determined and prenatal diagnosis could be offered to the offsprings of each of the six carriers identified. Thus, in this study, we have identified a higher proportion of informative families than has previously been reported.
<i>Call the Midwife</i>, it’s a social issue
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

A reader recently complained that social issues are too prominent in JRSM. It is a difficult argument to refute if you accept, as I do, the findings of Michael Marmot’s report on the socioeconomic determinants of health, one of the most important analyses published in the last decade.1 Social issues should have a place in medical journals, just as patients should. The criticism may be directed at the decline in case reports and some clinical studies published in JRSM. Again, any such criticism is fair as certain papers have been phased out of JRSM and now find a home in our open access companion journal, JRSM Open.2

Our ambition with JRSM is to publish articles that interest a broad readership. Any research we publish should be as widely generalisable as possible, like this month’s study answering the question of whether female doctors provide longer patient consultations.3 Case reports and narrower clinical studies tend not to meet these criteria, although each and every such paper will find adoring readers. Our editorial policies have helped to increase both citations and impact factor in recent years, at a faster rate than comparable journals.

The nature of JRSM papers also reflects the fashions of the day, as this month’s article from our archive shows. For soldiers returning to many countries from the Great War, medical baths were an important intervention for treatment and recuperation.4 Our faith in the effectiveness of medical baths a hundred years ago seems surprising now, but R Fortescue Fox sensibly noted in 1915 that treatment of military cases should first be in hospital, second in town and only finally in the health resort. The full back archive of JRSM issues is available on the journal’s website and provides ample evidence that social issues are familiar themes in these pages.

To underline the point, Stephen McGann, actor and star of the BBC’s hit period medical drama, Call the Midwife, explains how he ‘loves to explore the relationship between medical science and the wider society it serves’. Considering I asked him to write about the challenges he faces in authenticating his role as Patrick Turner, an overworked doctor ‘on the front line of post-war urban health’, it was a pleasant surprise to learn of the research and attention to detail that goes into each episode. There is acute awareness among actors and programme makers of the health and social implications of the show.5

Indeed, as William Osler said, ‘The good physician treats the disease; the great physician treats the patient who has the disease’. Perhaps the best physician treats the disease, the patient and the society the patient lives in?
Clinical and immunologic variables in skin of patients with atopic eczema and either positive or negative atopy patch test reactions
Authors: Elisabeth G. Langeveld-Wildschut, Piet L.B. Bruijnzeel, Geert C. Mudde, Coraline Versluisa, Adrie G. Van Ieperen-Van Dijka, Ilse C. Biharia, Edward F. Knol, Theo Thepen, Carla A.F.M. Bruijnzeel-Koomen, Frank C. van Reijsen
Journal: Journal of Allergy and Clinical Immunology (2000)
An unusual paracetamol overdose
Authors: M W J Adams, P. Chrispin, M. Spice
Journal: Journal of the Royal Society of Medicine (2004)

A patient with complications from surgery was admitted to intensive care with sepsis, adult respiratory distress syndrome, and signs of impending renal failure. After 18 days of ventilation, further surgical intervention, and every trick in the microbiologist's book, he had recovered sufficiently for his sedation to be lightened. In addition, his persistent pyrexia gradually came under the control of paracetamol 1 g four times daily. Nutrition was supplied via a jejunostomy tube, and as his condition improved the paracetamol was administered in a soluble preparation by the same route.

By day ten he was much improved, with his sepsis resolving. Yet his sodium concentration was 159 mmol/L—13 mmol/L above our laboratory's upper limit. Changing jejunostomy feed to a low-sodium preparation, and swapping normal saline infusions to dextrose saline had no effect, and we assumed that a polyuric renal crisis was evolving.

Then one of the authors (MS), a senior staff nurse, remembered that soluble paracetamol contains sodium. Further investigation revealed that the preparation we were using contained 388 mg of sodium in each 500 mg tablet. In other words, the patient was receiving 3 g sodium a day, and had been doing so for 6 days. Back-of-envelope calculations then showed:



3 g Na=0.130 mmol Na


In a patient weighing 85 kg,


this gives a body water volume of 59.5 L.


Thus each day he received 0.130/59.5=218 mmol/L






Over 6 days the excess sodium equals 13 mmol/L, which happens to be the exact amount over the upper limit of normal.
THE STUDY AND TREATMENT OF ALCOHOLISM IN THE 5TH S. C. REHABILITATION CENTER
Authors: HAROLD J. LAWN
Journal: American Journal of Psychiatry (1946)

1. A new alcoholic terminology was developed to bridge the 'gap' between the social drinker and the chronic alcoholic. 2. About a third of our population shows essentially normal personalities, and psychoses and psychoneuroses are quite rare. 3. Although many people express the view that alcoholism originates in the Army; a careful survey showed that this was an exceedingly rare occurrence. 4. Those who were diagnosed chronic alcoholics (in the Army) generally showed a previous history of drinking for 5 to 15 years. 5. Survey of case records indicates that an overwhelming majority of alcoholics have an underlying defect of schizoid or neurotic personality. 6. The thorough program promulgated at this Center has been effective in treating and reeducating alcoholics, and is particularly successful in those labeled 'alcoholism.' 7. A most recent review of more than 550 men restored to duty from the 5th Service Command Rehabilitation Center in the last 2 years (alcoholics and others) revealed that less than 5% had to be returned to a disciplinary barracks. 8. Education of the public, and reeducation of chronic alcoholics on a scale of world wide publicity is advocated as an important method of prophylaxis.
Antitumor Effect of 2-Methoxyestradiol in a Rat Orthotopic Brain Tumor Model
Authors: Seung-Hee Kang, Heidi T. Cho, Sarojini Devi, Zhaobin Zhang, Daniel Escuin, Zhongxing Liang, Hui Mao, Daniel J. Brat, Jeffrey J. Olson, Jonathan W. Simons, Theresa M. LaVallee, Paraskevi Giannakakou, Erwin G. Van Meir, Hyunsuk Shim
Journal: Cancer Research (2006)

Abstract Grade 4 malignant glioma (GBM) is a fatal disease despite aggressive surgical and adjuvant therapies. The hallmark of GBM tumors is the presence of pseudopalisading necrosis and microvascular proliferation. These tumor cells are hypoxic and express hypoxia-inducible factor-1 (HIF-1), a prosurvival transcription factor that promotes formation of neovasculature through activation of target genes, such as vascular endothelial growth factor. Here, we evaluated whether 2-methoxyestradiol, a microtubule and HIF-1 inhibitor, would have therapeutic potential for this disease in a 9L rat orthotopic gliosarcoma model using a combination of noninvasive imaging methods: magnetic resonance imaging to measure the tumor volume and bioluminescence imaging for HIF-1 activity. After imaging, histologic data were subsequently evaluated to elucidate the drug action mechanism in vivo. Treatment with 2-methoxyestradiol (60–600 mg/kg/d) resulted in a dose-dependent inhibition of tumor growth. This effect was also associated with improved tumor oxygenation as assessed by pimonidazole staining, decreased HIF-1α protein levels, and microtubule destabilization as assessed by deacetylation. Our results indicate that 2-methoxyestradiol may be a promising chemotherapeutic agent for the treatment of malignant gliomas, with significant growth inhibition. Further studies are needed to assess the effect of low or intermediate doses of 2-methoxyestradiol in combination with chemotherapeutic agents in clinical studies focused on malignant gliomas. In addition to showing tumor growth inhibition, we identified three potential surrogate biomarkers to determine the efficacy of 2-methoxyestradiol therapy: decreased HIF-1α levels, α-tubulin acetylation, and degree of hypoxia as determined by pimonidazole staining. (Cancer Res 2006; 66(24): 11991-7)
Quantitative Guidance for Stove Usage and Performance to Achieve Health and Environmental Targets
Authors: Michael A. Johnson, Ranyee A. Chiang
Journal: Environmental Health Perspectives (2015)

BackgroundDisplacing the use of polluting and inefficient cookstoves in developing countries is necessary to achieve the potential health and environmental benefits sought through clean cooking solutions. Yet little quantitative context has been provided on how much displacement of traditional technologies is needed to achieve targets for household air pollutant concentrations or fuel savings.ObjectivesThis paper provides instructive guidance on the usage of cooking technologies required to achieve health and environmental improvements.MethodsWe evaluated different scenarios of displacement of traditional stoves with use of higher performing technologies. The air quality and fuel consumption impacts were estimated for these scenarios using a single-zone box model of indoor air quality and ratios of thermal efficiency.ResultsStove performance and usage should be considered together, as lower performing stoves can result in similar or greater benefits than a higher performing stove if the lower performing stove has considerably higher displacement of the baseline stove. Based on the indoor air quality model, there are multiple performance–usage scenarios for achieving modest indoor air quality improvements. To meet World Health Organization guidance levels, however, three-stone fire and basic charcoal stove usage must be nearly eliminated to achieve the particulate matter target (< 1–3 hr/week), and substantially limited to meet the carbon monoxide guideline (< 7–9 hr/week).ConclusionsModerate health gains may be achieved with various performance–usage scenarios. The greatest benefits are estimated to be achieved by near-complete displacement of traditional stoves with clean technologies, emphasizing the need to shift in the long term to near exclusive use of clean fuels and stoves. The performance–usage scenarios are also provided as a tool to guide technology selection and prioritize behavior change opportunities to maximize impact.CitationJohnson MA, Chiang RA. 2015. Quantitative guidance for stove usage and performance to achieve health and environmental targets. Environ Health Perspect 123:820–826; http://dx.doi.org/10.1289/ehp.1408681
Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima
Authors: Shomron Ben-Horin, Miri Yavzori, Itai Benhar, Ella Fudim, Orit Picard, Bella Ungar, SooYoung Lee, SungHwan Kim, Rami Eliakim, Yehuda Chowers
Journal: Gut (2015)

<h3>Objective</h3> The cross-immunogenicity of the recently approved infliximab-biosimilar Remsima (CT-P13) with the originator drug Remicade is still unknown. <h3>Design</h3> Sera of patients with IBD with or without measurable anti-Remicade antibodies to infliximab (ATI) were tested for their cross-reactivity to two batches of Remsima. Experiments were repeated after deglycosylation of Remicade/Remsima, IgG purification, excipients' dialysis and monomer purification by size exclusion chromatography. Anti-Remicade antibodies were tested for their functional inhibition of TNF-α binding by Remsima/Remicade by competition assay. Cross-reactivity of anti-adalimumab antibodies with Remicade/Remsima was also investigated. <h3>Results</h3> 125 patients' and controls' sera were tested (median age 31 years, IQR 24.5–39.5). All 56 anti-Remicade ATI-negative controls (14 healthy individuals, 42 patients with IBD) were also negative for anti-Remsima ATI. All 69 positive anti-Remicade IBD sera were cross-reactive with Remsima. ATI titres against Remicade or Remsima were strongly correlated (r values between 0.92 and 0.99, p&lt;0.001 for all experiments, Spearman9s correlation test). The background ELISA signal for Remsima was slightly higher compared with Remicade in negative controls (1.25±0.6 µg/mL vs 0.76±0.5 µg/mL, respectively, p&lt;0.001), and persisted after deglycosylation, dialysis or protein size filtration, but abolished by IgG purification and significantly diminished by monomer purification. Anti-Remicade ATIs of patients with IBD (n=10) exerted similar functional inhibition on Remsima or Remicade TNF-α binding capacity (p=NS for all inhibition curve points). Antibodies-to-adalimumab in adalimumab-treated patients with IBD (n=7) did not cross-react with either Remicade or Remsima. <h3>Conclusions</h3> Anti-Remicade antibodies in patients with IBD recognise and functionally inhibit Remsima to a similar degree, suggesting similar immunogenicity and shared immunodominant epitopes on these two infliximab agents. In contrast, anti-adalimumab antibodies do not cross-react with Remsima or Remicade.
Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin.
Authors: G S Kansas, K Ley, J M Munro, T F Tedder
Journal: The Journal of Experimental Medicine (1993)

L-selectin (leukocyte adhesion molecule 1/MEL-14), a member of the selectin family of cell adhesion molecules, mediates leukocyte rolling and leukocyte adhesion to endothelium at sites of inflammation. In addition, L-selectin mediates the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes. The strong amino acid sequence conservation of the cytoplasmic domain of L-selectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the approximately 17 amino acid cytoplasmic domain of L-selectin eliminated binding of lymphocytes to HEV in the in vitro frozen section assay, and also abolished leukocyte rolling in vivo in exteriorized rat mesenteric venules, but did not alter the lectin activity of L-selectin. Pretreatment of cells with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of L-selectin regulates leukocyte adhesion to endothelium independent of ligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.
Myosin IIA is required for cytolytic granule exocytosis in human NK cells
Authors: Milena M. Andzelm, Xi Chen, Konrad Krzewski, Jordan S. Orange, Jack L. Strominger
Journal: The Journal of Experimental Medicine (2007)

Natural killer (NK) cell cytotoxicity involves the formation of an activating immunological synapse (IS) between the effector and target cell through which granzymes and perforin contained in lytic granules are delivered to the target cell via exocytosis. Inhibition of nonmuscle myosin II in human NK cells with blebbistatin or ML-9 impaired neither effector–target cell conjugation nor formation of a mature activating NK cell IS (NKIS; formation of an actin ring and polarization of the microtubule-organizing center and cytolytic granules to the center of the ring). However, membrane fusion of lytic granules, granzyme secretion, and NK cell cytotoxicity were all effectively blocked. Specific knockdown of the myosin IIA heavy chain by RNA interference impaired cytotoxicity, membrane fusion of lytic granules, and granzyme secretion. Thus, myosin IIA is required for a critical step between NKIS formation and granule exocytosis.