tbuckley/cabot-search huggingface dataset:
Transient epidermal necrosis associated with disseminated intravascular coagulation in a patient with urticaria
Authors: J. P. CAMILLERI, A. Y. FINIAY, A.G. DOUGLAS-JONES, P. A. KITCHING, B. D. WILLIAMS
Journal: British Journal of Dermatology (1991)

Summary A patient with intermittent erythema developed urticaria and a systemic illness associated with the development of disseminated intravascular coagulation and a widespread bullous eruption. A skin biopsy showed intravascular fibrin and epidermal necrosis with no evidence of vasculitis. The patient made a complete recovery following therapy with fresh frozen plasma and platelets and pulsed intravenous methylprednisolone.
Multiple colonic aphthoid ulcers caused by<i>Diphyllobothrium latum</i>infection
Authors: T. Byun, D. Han, S. Ahn, H. Cho, C. Eun, J. Ryu, Y. Oh
Journal: Endoscopy (2009)

A 15-year-old boy attended our outpatient clinic for recurrent lower abdominal pain. He did not have any remarkable medical and family history. The cramping abdominal pain was localized around the right lower quadrant region, and he had no other gastrointestinal symptoms. He often ate raw fish, and sometimes his feces contained noodle-like material. Serum chemistries were all within the normal ranges, and the hematologic examination revealed mild microcytic hypochromic anemia (hemoglobin 12.4 g/dL, hematocrit 36.3 %, MCV 77.9 fL, MCH 26.7 pg). No eggs were seen in the stool examination.
Metabolic clearance rate of radioiodinated human growth hormone in man
Authors: Donald P. Cameron, Henry G. Burger, Kevin J. Catt, Alison Doig
Journal: Journal of Clinical Investigation (1969)

The nature of the disappearance of radioiodinated human growth hormone (HGH) from plasma has been reexamined. The metabolic clearance rate (MCR) was determined both from single injection and constant infusion studies. After single injection of highly purified radioiodinated HGH, the disappearance curve remained multiexponential during the period of study (4 hr). The shape of the curve was independent of the growth hormone preparation used. Similar disappearance curves were obtained with unlabeled HGH.MCR values calculated from constant infusion studies were 203 +/-7.8 liters/day per m(2) and values derived from single injection studies agreed closely with this. The multiexponential nature of the disappearance curve does not permit meaningful calculation of volume of distribution or half-time of disappearance.
Analysis and Interpretation of Treatment Effects in Subgroups of Patients in Randomized Clinical Trials
Authors: Salim Yusuf
Journal: JAMA (1991)

A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct<i>P</i>values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis. (<i>JAMA</i>. 1991;266:93-98)
Pulmonary Thromboembolism Presenting as Asthma
Authors: W. J. Windebank, G. Boyd, F. Moran
Journal: BMJ (1973)

When a patient presents with wheezing, pulmonary embolism is not usually considered as a possible cause. However, undoubtedly bronchoconstriction can be caused by pulmonary emboli and occasionally wheezing may be so obvious as to suggest a diagnosis of bronchial asthma. Eleven cases are reported in which wheezing was attributable to recurrent pulmonary emboli and one in which it was a clamant feature after a single embolic incident.
The effect of drugs which are known inducers and inhibitors of human cytochrome P450 3A on the platelet inhibitory activity of clopidogrel
Authors: Wei C. Lau, Lucy Waskell, Paul B. Watkins, Charlene Neer, David Carville, Kirk E. Guyer, Kevin Horowitz, Eric R. Bates
Journal: Journal of the American College of Cardiology (2002)
Abstract 2262: Contribution of autophagy in anticancer immune response induced by chemotherapy
Authors: Abdul Qader Sukkurwala, Mickaël Michaud, Isabelle Martins, Guido Kroemer
Journal: Cancer Research (2012)

Abstract Antineoplastic chemotherapies are particularly efficient when they elicit immunogenic cell death, thus provoking an anticancer immune response. We demonstrate that autophagy, which is often disabled in cancer, is dispensable for chemotherapy-induced cell death but required for its immunogenicity. In response to chemotherapy, autophagy-competent, but not autophagy-deficient, cancers attracted dendritic cells and T lymphocytes into the tumor bed. Suppression of autophagy inhibited the release of adenosine triphosphate (ATP) from dying tumor cells. Conversely, inhibition of extracellular ATP-degrading enzymes increased pericellular ATP in autophagy-deficient tumors, re-established the recruitment of immune cells, and restored chemotherapeutic responses, but only in immunocompetent hosts. Thus, autophagy is essential for the release of immunogenic ATP from dying cells, and increased extracellular ATP concentrations improve the efficacy of antineoplastic chemotherapies when autophagy is disabled. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2262. doi:1538-7445.AM2012-2262
Climbing Fiber Input Shapes Reciprocity of Purkinje Cell Firing
Authors: Aleksandra Badura, Martijn Schonewille, Kai Voges, Elisa Galliano, Nicolas Renier, Zhenyu Gao, Laurens Witter, Freek E. Hoebeek, Alain Chédotal, Chris I. De Zeeuw
Journal: Neuron (2013)
Abstract 5367: Long-term survival in a phase II atudy of belagenpumatucel-L (TGF-β antisense modified tumor cell vaccine) in non-small cell lung cancer (NSCLC).
Authors: Lyudmila Bazhenova, Ewa Carrier, Daniel Shawler, Habib Fakhrai
Journal: Cancer Research (2012)

Abstract Background: Cancer therapeutics vaccines continue to be investigated in a variety of solid malignancies. Belagenpumatucel-L (Lucanix®), a therapeutic vaccine comprised of 4 TGF-β2 antisense gene-modified allogeneic NSCLC cell lines. Phase II trial finished its enrollment in March of 2004 and was published in 2006. We now report an updated survival analysis with over 5 years of follow up. Methods: Three arms, open label clinical trial enrolled seventy-five subjects. 2 stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients were randomized into three dose cohorts of 1.25, 2.5, or 5 107 cells/injection. Several cellular (ELISPOT and cytoplasmic cytokine expression) and humoral (antibody ELISA) immunity assays were also performed and correlated with survival. Results: Median follow up for all patients was 14.5 months and for patients with stable disease 44 months. Median survival for all subjects was 14.5 months and one-year, two-years and five-year survival were respectively 55%, 35% and 20%. Stages IIIB/IV subjects enrolled into cohorts 2 and 3 (N=40) had a median survival of 15.9 months and one-year, two-year and five-year survivals were respectively 61%, 41% and 18%. For stage IIIB/IV patients with non progressive disease following frontline chemotherapy, median survival was 44.4 months and five-year survival was 50%. For subjects who progressed following frontline chemotherapy, median survival was 14.1 months and five-year survival was 9.1%. Subjects who demonstrated an increase in both cellular and humoral immune reactivity following treatment had a significant survival advantage over subjects who showed an increase in only one measure of immunity with a median survival of 32.5 months vs. 11.6 months (p = 0.015). Conclusion: Long term follow up of a phase II clinical trial confirmed encouraging survival for patients with stage IIIB/IV disease. Based on these data, we have instituted an international, randomized, pivotal Phase III trial to evaluate the efficacy of belagenpumatucel-L in a maintenance setting in stage III/IV NSCLC patients who have stable disease or better following frontline chemotherapy. The trial is designed to enroll 506 patients and is powered to measure a 3.5 month survival difference. There are two planned interim analyses. To date, 285 patients have been enrolled in 8 countries. Confirmation of the phase II data in a randomized, phase III setting would provide an important improvement for the treatment of non-small cell lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5367. doi:1538-7445.AM2012-5367
Chronic regulation of arterial blood pressure in ANP transgenic and knockout mice: Role of cardiovascular sympathetic tone
Authors: L Melo
Journal: Cardiovascular Research (1999)

Objective: Atrial natriuretic peptide (ANP) lowers arterial blood pressure (ABP) chronically, in association with vasodilation of the resistance vasculature. The mechanism mediating the chronic relaxant effect of ANP is likely indirectly mediated by interactions with tonic vasoeffector mechanisms, inasmuch as the resistance vasculature is relatively insensitive to direct cGMP-mediated relaxation by ANP. On the basis of evidence that ANP has widespread sympatholytic activity, the current study investigated whether the chronic hypotensive effect of ANP is mediated by attenuation of tonic cardiovascular sympathetic tone. Methods: Total plasma catecholamine concentration and changes in basal ABP and heart rate (HR) following autonomic ganglionic blockade were measured as indices of underlying sympathetic nerve activity in hypotensive ANP-overexpressing transgenic mice (TTR–ANP), hypertensive ANP knockout mice (−/−) and the genetically-matched wild type (NT and +/+, respectively) control mice. Pressor and chronotropic responses to norepinephrine infusion were measured in ganglion-blocked mice of all genotypes, and norepinephrine receptor binding was assessed in representative tissues of −/− and +/+ mice, in order to determine whether peripheral adrenergic receptor responsiveness is altered by ANP-genotype. Results: Basal ABP was significantly lower in TTR–ANP and higher in −/− compared to their wild-type controls. Basal HR did not differ significantly between mutant and control mice. Autonomic ganglionic blockade reduced ABP and HR in all genotypes, however, the relative decrease in ABP was significantly smaller in TTR–ANP and greater in −/− mice than in their respective controls. Total plasma catecholamine was significantly higher in −/− than in +/+ mice but did not differ significantly between TTR–ANP and NT mice. Norepinephrine infusion during ganglionic blockade elicited quantitatively similar pressor and chronotropic responses in mutant and control mice. Tissue norepinephrine binding did not differ significantly between −/− and +/+ mice. Conclusions: The present study shows that differences in endogenous ANP activity in mice, resulting in chronic alterations in ABP are accompanied by directional changes in underlying cardiovascular sympathetic tone, and suggests that the chronic vasodilator effect of ANP is, at least partially, dependent on attenuation of vascular sympathetic tone, possibly at a prejunctional site(s).
Importance of past occupational exposures in the rising incidence of idiopathic pulmonary fibrosis in the UK
Authors: C M Barber, D Fishwick
Journal: Thorax (2011)

to patients and colleagues responsible for acutely ill patients with COPD.In keeping with the NICE guidelines, COPD severity should be described in terms of functional status using at least the modified MRC score, as well as previous severity of lung function impairment.It should be made clear that the severity of lung function impairment in COPD does not necessarily correlate with clinical severity or outcome of inpatient care, which may include ITU and IMV management.
The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study
Authors: M. Caproni, D. Torchia, E. Antiga, M. Terranova, W. Volpi, E. Del Bianco, A. D'Agata, P. Fabbri
Journal: British Journal of Dermatology (2006)

Background While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. Objectives To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. Methods Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon‐γ, interleukin (IL)‐4, IL‐5, IL‐12, IL‐13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. Results CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post‐treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. Conclusions Tacrolimus not only inhibits T‐lymphocyte proliferation and cytokine production, but also plays an important role in the IL‐12‐induced shift from a T‐helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.
Exploring the Geometry of Treatment Networks
Authors: Georgia Salanti, Fotini K. Kavvoura, John P.A. Ioannidis
Journal: Annals of Internal Medicine (2008)

Background: Several treatment options exist for many conditions. Randomized trial evidence on the relative merits of various options may be missing or biased. Purpose: To examine the patterns of trial evidence (network geometry) and explain their implications for the interpretation of the existing evidence on a treatment's relative effectiveness. Data Sources: PubMed and Thompson ISI Web of Knowledge (last search April 2007). Study Selection: Published networks of randomized trials that included at least 4 treatments were identified. Data Extraction: For each network, data on the number of studies per treatment comparison were extracted by one investigator and verified by a second investigator. Data Synthesis: Indices were adopted from the ecological literature that measure diversity (number of treatments and how often they were tested) and co-occurrence (whether some treatment comparisons were preferred and others avoided). Eighteen eligible treatment networks were identified for different diseases, involving 4 to 16 alternative treatments and 10 to 84 trials. Networks in which 1 option (placebo or no treatment) was the typical comparator were star-shaped, even though several treatments might have had proven effectiveness. Other networks had different shapes. Some showed important co-occurrence that avoided specific head-to-head comparisons. Comparison choices sometimes seemed justified, such as when newer treatments were not compared with older ones already shown to be inferior, whereas other choices seemed to reflect preference bias. Limitations: Networks evolve over time as new trials accumulate, and their geometry may change. Statistical testing for co-occurrence is underpowered when few trials exist. Conclusion: Evaluation of the geometry of a treatment network can offer valuable insights for the interpretation of total evidence when many treatment options are available.
New Weapons Needed to Fight HIV
Authors: Gianna Zuccotti, Jeanette M. Smith
Journal: JAMA (2007)

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3-Hydroxy-3-methylglutaryl coenzyme A reductase in anencephalic and normal human fetal liver.
Authors: B R Carr, W E Rainey, J I Mason
Journal: Journal of Clinical Investigation (1985)

In previous investigations, we have found that the liver appears to be the major source of cholesterol in the human fetus, and, in particular, a principal source of circulating low density lipo-protein-cholesterol (LDL-C). LDL-C plasma levels are low in the normal fetus, most likely due to the rapid uptake and metabolism by the fetal adrenal as precursor for steroid hormone biosynthesis. In contrast, in the anencephalic fetus the adrenals are atrophic, the rate of estrogen and glucocorticoid production is low, and the levels of LDL-C in fetal plasma are high. The purpose of the present investigation was to determine the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the primary rate-limiting enzyme of cholesterol biosynthesis, in anencephalic liver and normal fetal liver. We found that the specific activity of HMG-CoA reductase in normal fetal liver microsomes was 0.428 +/- 0.054 nmol mevalonate formed times mg-1 protein X min-1 (mean +/- SE, n = 9). The rate of HMG-CoA reductase in anencephalic liver microsome preparations was 10-fold less (0.040 +/- 0.003) (mean +/- SE, n = 7) P less than 0.001. Furthermore, we detected HMG-CoA reductase (97,000-mol wt protein) in normal human fetal liver after SDS PAGE and immunoblotting by using a monoclonal antibody directed against HMG-CoA reductase. We were unable to detect any significant quantity of HMG-CoA reductase protein in anencephalic fetal liver, which indicates that low reductase activity was due to low amounts of enzyme protein rather than inactive enzyme. In summary, we conclude that the low levels of cholesterol synthesis observed in anencephalic fetal liver are probably due to both the high levels of LDL-C in fetal plasma as well as the presence of low circulating levels of estrogens and glucocorticoids and that these factors regulate cholesterol synthesis both in vivo and in vitro in fetal liver. This occurs most probably by the modulation of the amount of HMG-CoA reductase, a primary rate-limiting and regulatory enzyme of the cholesterol biosynthetic sequence.
Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion
Authors: Mónica Guevara, Pere Ginès, Glòria Fernández-Esparrach, Pau Sort, Joan Manuel Salmerón, Wladimiro Jiménez, Vicente Arroyo, Juan Rodés
Journal: Hepatology (1998)

Hepatorenal syndrome is caused by a marked vasoconstriction of the renal circulation. It is suggested that the renal vasoconstriction is related to an overactivity of vasoconstrictor systems secondary to a vasodilation of the arterial circulation that causes a reduction in effective arterial blood volume. To test this hypothesis, 16 cirrhotic patients with hepatorenal syndrome were treated with a combination of ornipressin, a potent vasoconstrictor agent, and plasma volume expansion with albumin to improve effective arterial blood volume. The combined treatment was administered either for 3 or 15 days (8 patients each), and the effects on renal function, vasoactive systems, and systemic hemodynamics were assessed. The 3-day treatment with ornipressin and albumin was associated with a normalization of the overactivity of renin-angiotensin and sympathetic nervous systems, a marked increase in atrial-natriuretic peptide levels, and only a slight improvement in renal function. However, when ornipressin and albumin were administered for 15 days, a remarkable improvement in renal function was observed, with normalization of serum-creatinine concentration, a marked increase in renal plasma flow and glomerular filtration rate, and a persistent suppression in the activity of vasoconstrictor systems. However, 3 of 8 patients on 15-day therapy treatment had to be discontinued because of ischemic complications. In conclusion, the decrease in effective arterial blood volume and the activation of vasoconstrictor systems play a crucial role in the pathogenesis of hepatorenal syndrome. Although the prolonged administration of ornipressin combined with plasma volume expansion reverses hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications.
Trace metal mobilization in soil by bacterial polymers.
Authors: J H Chen, D R Czajka, L W Lion, M L Shuler, W C Ghiorse
Journal: Environmental Health Perspectives (1995)

Enhanced transport of trace metal in porous media can occur in the presence of a ligand or "carrier" that has a high affinity for binding the pollutant, is dispersed and mobile in the soil environment, is recalcitrant with respect to microbial degradation, and is acceptable to the public. These aspects of the facilitated transport to trace metals are discussed with respect to a naturally occurring carrier: extracellular polymers of bacterial origin. The literature is reviewed regarding the production and composition of bacterial extracellular polymers, the processes relevant to the facilitated transport of trace metals in soil by bacterial polymers, and potential for transformation of polymers in soils by microbial degradation. Model calculations of contaminant retardation are presented for the case of polymer-mediated transport of cadmium in a sandy aquifer material. The available information suggests that extracellular polymers can bind metal ions and are mobile in the soil environment. Extracellular polymers also appear to be relatively slowly degraded by soil microorganisms. These properties and the supporting model calculations indicate that extracellular polymers of bacterial origin merit consideration as agents that may be applied to contaminated soils to enhance trace metal mobility.