tbuckley/cabot-search huggingface dataset:
Randomized Comparison of Cooked and Noncooked Diets in Patients Undergoing Remission Induction Therapy for Acute Myeloid Leukemia
Authors: Alison Gardner, Gloria Mattiuzzi, Stefan Faderl, Gautam Borthakur, Guillermo Garcia-Manero, Sherry Pierce, Mark Brandt, Elihu Estey
Journal: Journal of Clinical Oncology (2008)

A neutropenic diet is often used to prevent infection in patients with acute myeloid leukemia (AML). Although such a diet potentially entails inconvenience, its value is uncertain.One hundred fifty-three patients admitted to a high-efficiency particulate air-filtered room (protected environment [PE]) to receive induction therapy for newly diagnosed AML were randomly assigned to a diet containing no raw fruits or vegetables (cooked diet) or to a diet containing fresh fruit and fresh vegetables (raw diet). Stratification was based on the patients' early risk of mortality (ERM) score. All patients received antibacterial and antifungal prophylaxis and remained on study until they were discharged from the PE. The outcomes of principal interest were major infection (pneumonia, bacteremia, or fungemia) and death; if the true probability of either event was 20% on the cooked arm and 40% on the raw arm, then the probability that the cooked arm would be selected as superior was 83%.Seventy-eight patients were randomly assigned to the cooked arm, and 75 were assigned to the raw arm. The two groups were similar with respect to age, ERM, chemotherapy received, and days at risk. Twenty-nine percent of patients in the cooked group and 35% of patients in the raw group developed a major infection (P = .60). Time to major infection and survival time were similar in the two groups. Fever of unknown origin occurred in 51% of the cooked group and 36% of the raw group.In patients treated in a PE, a neutropenic diet did not prevent major infection or death.
Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial
Authors: V. Zamvar
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess neurocognitive impairment after the off-pump and on-pump techniques for coronary artery bypass graft surgery in patients with triple vessel disease. <b>Design:</b>Randomised controlled trial. <b>Setting:</b> University Hospital of Wales, Cardiff. <b>Participants:</b> 60 patients undergoing coronary artery bypass graft surgery for triple vessel disease prospectively randomised to the off-pump or on-pump technique. <b>Main outcome measures:</b> Change in scores in nine standard neuropsychometric tests administered preoperatively and at 1 and 10 weeks postoperatively. <b>Results:</b> The on-pump group showed a significantly greater deterioration in scores for two and three tests at 1 week and 10 weeks postoperatively, respectively, than the off-pump group. The on-pump group also showed a significantly higher incidence of major deterioration in one of the tests both 1 week and 10 weeks postoperatively. The incidence of neurocognitive impairment at 1 week postoperatively was 27% (8 out of 30) in the off-pump group and 63% (19 out of 30) in the on-pump group (P=0.004); and at 10 weeks postoperatively was 10% (3 out of 30) in the off-pump group and 40% (12 out of 30) in the on-pump group (P=0.017). <b>Conclusion:</b> Off-pump coronary artery bypass graft surgery results in less neurocognitive impairment than the on-pump technique.
Regulation of diacylglycerol metabolism by vasoconstrictor hormones in intact small arteries.
Authors: J Ohanian, A Izzard, M Littlewood, A Heagerty
Journal: Circulation Research (1993)

The initiation of receptor-mediated small artery contraction is dependent on inositol 1,4,5-trisphosphate-stimulated release of stored calcium. The role of the other product of inositol lipid hydrolysis, 1,2-diacylglycerol, in maintaining contraction remains controversial. Therefore, we have determined the contractile response of rat subcutaneous small arteries (&lt; 300 microns i.d.), when mounted as ring preparations in a myograph, to noradrenaline, angiotensin II, KCl-induced membrane depolarization, and a cell-permeable diglyceride, dioctanoylglycerol. In parallel experiments, the conversion of this diglyceride to dioctanoylphosphatidate was studied in 32P-labeled vessels. Dioctanoylglycerol produced a slow-onset sustained contraction that was dependent on extracellular calcium. This was accompanied by the generation of the lipid dioctanoylphosphatidate. Noradrenaline and KCl induced rapid-onset sustained contractions and increased the production of dioctanoylphosphatidate (75% and 91%, respectively). In addition, dioctanoylglycerol levels were reduced (41%) after noradrenaline stimulation, suggesting activation of diacylglycerol kinase. In contrast, the contractile response to angiotensin II was transient, and this agonist did not significantly affect the conversion of dioctanoylglycerol to phosphatidate. Noradrenaline markedly increased (fourfold) the formation of endogenous phosphatidate, whereas endogenous 1,2-diacylglycerol was increased (47%) with angiotensin II. These results demonstrate that phosphatidate formation is regulated by vasoconstrictor hormones during receptor-mediated contraction, independent of diglyceride mass. Modulation of the levels of lipid second messengers downstream from phospholipid hydrolysis may represent a mechanism by which agonists that act through the same signaling system produce different contractile responses.
Role of microtubuli in secretion of very-low-density lipoprotein in isolated rat hepatocytes: Early effects of thiol reagents
Authors: J. Fred Nagelkerke, Bob van de Water, Irene M. Twiss, J. Paul Zoetewey, Hans J. G. M. de Bont, Peter Dogterom, Gerard J. Mulder
Journal: Hepatology (1991)

The secretion of very-low-density lipoprotein from hepatocytes proceeds through the microtubules. In this study, the role of glutathione in the maintenance of intact microtubules and the secretion of very-low-density lipoprotein has been investigated. When rat hepatocytes were incubated with reagents that deplete glutathione (e.g., diethylmaleate, alpha-bromoisovalerylurea or allyl alcohol) or reacted directly with protein thiols (disulfiram), the secretion of very-low-density lipoprotein by the cells was inhibited and the microtubules were severely damaged as visualized by immunofluorescence staining. Both events occurred within 30 min; long before, an effect on the energy status of the cells became evident. The observed inhibition of the secretion therefore seems due to an effect of the toxicants on the microtubules. For alpha-bromoisovalerylurea, diethylmaleic acid and allyl alcohol, it may be related to glutathione depletion; preincubation of the hepatocytes with N-acetyl-L-cysteine reduced the decrease of glutathione by alpha-bromoisovalerylurea and allyl alcohol (but not of diethylmaleic acid) and almost completely prevented the inhibition of very-low-density lipoprotein secretion and microtubule damage. Depletion of glutathione may result in modification of a small group of essential free protein thiols. Disulfiram did not deplete glutathione, and N-acetyl-L-cysteine could not prevent the effects of disulfiram on microtubules. The binding to protein thiols of radiolabeled disulfiram, which binds to microtubules in vitro, was determined. At 0.2 mmol/L disulfiram, only 3% of total cellular protein thiols were conjugated, but secretion of very-low-density lipoprotein was already inhibited by 25%, and microtubules were severely affected. We propose that modification of a small fraction of cellular protein thiols results in the loss of microtubular ultrastructure and thereby leads to inhibition of very-low-density lipoprotein secretion.
Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
Authors: Shigeki Chiba, Muhammad Baghdadi, Hisaya Akiba, Hironori Yoshiyama, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoichiro Fujioka, Yusuke Ohba, Jacob V Gorman, John D Colgan, Mitsuomi Hirashima, Toshimitsu Uede, Akinori Takaoka, Hideo Yagita, Masahisa Jinushi
Journal: Nature Immunology (2012)
Global Air Quality and Health Co-benefits of Mitigating Near-Term Climate Change through Methane and Black Carbon Emission Controls
Authors: Susan C. Anenberg, Joel Schwartz, Drew Shindell, Markus Amann, Greg Faluvegi, Zbigniew Klimont, Greet Janssens-Maenhout, Luca Pozzoli, Rita Van Dingenen, Elisabetta Vignati, Lisa Emberson, Nicholas Z. Muller, J. Jason West, Martin Williams, Volodymyr Demkine, W. Kevin Hicks, Johan Kuylenstierna, Frank Raes, Veerabhadran Ramanathan
Journal: Environmental Health Perspectives (2012)

Tropospheric ozone and black carbon (BC), a component of fine particulate matter (PM ≤ 2.5 µm in aerodynamic diameter; PM(2.5)), are associated with premature mortality and they disrupt global and regional climate.We examined the air quality and health benefits of 14 specific emission control measures targeting BC and methane, an ozone precursor, that were selected because of their potential to reduce the rate of climate change over the next 20-40 years.We simulated the impacts of mitigation measures on outdoor concentrations of PM(2.5) and ozone using two composition-climate models, and calculated associated changes in premature PM(2.5)- and ozone-related deaths using epidemiologically derived concentration-response functions.We estimated that, for PM(2.5) and ozone, respectively, fully implementing these measures could reduce global population-weighted average surface concentrations by 23-34% and 7-17% and avoid 0.6-4.4 and 0.04-0.52 million annual premature deaths globally in 2030. More than 80% of the health benefits are estimated to occur in Asia. We estimated that BC mitigation measures would achieve approximately 98% of the deaths that would be avoided if all BC and methane mitigation measures were implemented, due to reduced BC and associated reductions of nonmethane ozone precursor and organic carbon emissions as well as stronger mortality relationships for PM(2.5) relative to ozone. Although subject to large uncertainty, these estimates and conclusions are not strongly dependent on assumptions for the concentration-response function.In addition to climate benefits, our findings indicate that the methane and BC emission control measures would have substantial co-benefits for air quality and public health worldwide, potentially reversing trends of increasing air pollution concentrations and mortality in Africa and South, West, and Central Asia. These projected benefits are independent of carbon dioxide mitigation measures. Benefits of BC measures are underestimated because we did not account for benefits from reduced indoor exposures and because outdoor exposure estimates were limited by model spatial resolution.
Effect of Cycle-Length Alteration upon the Configuration of the Canine Ventricular Action Potential
Authors: ROBERT E. EDMONDS, KALMAN GREENSPAN, CHARLES FISCH
Journal: Circulation Research (1966)

Action potentials recorded from canine ventricular fibers displayed characteristic alterations in configuration upon abrupt change in the cycle length. After a relative prolongation of the diastolic interval, abbreviation of phase 2 and slowing of phase 3 were consistently observed, while a relative shortening of diastole was terminated by an action potential displaying prolongation of phase 2 and a steeper phase 3. Neither circumstance was attended by a consistent alteration in action potential duration. The more conventional view, directly relating duration of phase 2 to the length of the preceding diastole, clearly does not obtain immediately following an abrupt alteration of cycle length. This cycle-length-dependent phenomenon may account, in part, for the post-extrasystolic T-wave alterations observed in the human electrocardiogram. It is also consistent with the clinical observation that such T-wave changes may occur without premature contractions, requiring only a relative prolongation of the R-R interval. Evidence is also presented which relates electrical alter-nans of the T wave to this interval-dependent phenomenon. This characteristic change in action potential configuration occurs under the same temporal circumstances that others have associated with potentiation of contractility. It is therefore suggested that these inotropic phenomena and changes in action potential configuration may relate to alterations in membrane permeability.
Pharmacologically Active Drug Metabolites: Impact on Drug Discovery and Pharmacotherapy
Authors: R. Scott Obach
Journal: Pharmacological Reviews (2013)

Metabolism represents the most prevalent mechanism for drug clearance. Many drugs are converted to metabolites that can retain the intrinsic affinity of the parent drug for the pharmacological target. Drug metabolism redox reactions such as heteroatom dealkylations, hydroxylations, heteroatom oxygenations, reductions, and dehydrogenations can yield active metabolites, and in rare cases even conjugation reactions can yield an active metabolite. To understand the contribution of an active metabolite to efficacy relative to the contribution of the parent drug, the target affinity, functional activity, plasma protein binding, membrane permeability, and pharmacokinetics of the active metabolite and parent drug must be known. Underlying pharmacokinetic principles and clearance concepts are used to describe the dispositional behavior of metabolites in vivo. A method to rapidly identify active metabolites in drug research is described. Finally, over 100 examples of drugs with active metabolites are discussed with regard to the importance of the metabolite(s) in efficacy and safety.
A CASE OF CUTANEOUS AND CONJUNCTIVAL DIPHTHERIA.
Authors: R. M. BATES
Journal: British Journal of Dermatology (1939)

Journal Article A CASE OF CUTANEOUS AND CONJUNCTIVAL DIPHTHERIA. Get access R. M. BATES, F.R.C.S., D.P.M. R. M. BATES, F.R.C.S., D.P.M. Medical Officer, Stoke Park Colony Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 51, Issue 2, 1 February 1939, Pages 76–79, https://doi.org/10.1111/j.1365-2133.1939.tb10652.x Published: 01 February 1939
Cardiac effects of statins—advancements and open questions
Authors: U LAUFS, M BOHM
Journal: Cardiovascular Research (2005)

See also article by Di Napoli et al.  [8]  (pages 462-471) in this issue. 

The beneficial vascular effects of statins are important for the primary and secondary prevention of coronary heart disease and stroke; however, their cardiac effects are less clear. In addition to their lipid-lowering properties, statins have been shown to exert extrahepatic, cholesterol-independent effects in animal studies that have been called “pleiotropic” effects. There is indirect evidence from human studies suggesting that pleiotropic action may contribute to the reduction of clinical endpoints by statin treatment (for review see [1]). These data are important because in addition to the advancement of our understanding of cardiovascular pathophysiology, they imply that patients at risk for adverse cardiovascular events may benefit from statins irrespective of their cholesterol levels [2].

In experimental models of ischemia and reperfusion, statins have been shown to limit the size of myocardial infarction, an effect that seems to be shared by all members of the statin family (for review see [3]). Mechanistically, upregulation of endothelial nitric oxide synthase (eNOS) by statin treatment is important for protection during ischemia–reperfusion [1,4]. Wolfrum et al. showed that activated simvastatin given intravenously only 3 min before reperfusion after temporary coronary artery occlusion increased myocardial PI 3-kinase activity, AktSer473 and eNOSSer1177 phosphorylation, and reduced infarct size by 42% in rats [5]. Lefer et al. demonstrated that reduction of neutrophil adherence to the vascular endothelium and subsequent infiltration into the post-ischemic myocardium represents an important consequence of statin-induced eNOS regulation [4,6], and Birnbaum et al. recently showed that prostaglandins are essential for mediating the myocardial protective effects of statins and that their production is downstream of eNOS phosphorylation [7].

In an elegant paper published …
Lymphangioleiomyomatosis: a case-control study of perinatal and early life events
Authors: C I Whale
Journal: Thorax (2003)

Lymphangioleiomyomatosis (LAM), a rare disease affecting women, is caused by somatic mutations in the tuberous sclerosis complex genes.A case-control questionnaire study was carried out examining parental and family history, prenatal events, and early life events to try to shed light on the aetiology of the condition. Forty five patients identified from a national LAM register completed a questionnaire and 31 were compared with 117 age and sex matched control subjects using conditional logistic regression.No differences were found in perinatal events, childhood infections, and parental or family history, except that patients were more likely to be an only child (odds ratio (OR) 4.3 (95% confidence interval (CI), 1.5 to 11.8)) and have a relative with uterine fibroids (OR 4.2 (1.4 to 13)). Patients with LAM had had fewer pregnancies and fewer children but no differences in miscarriage rates. A non-matched analysis using all 45 cases and 117 controls gave similar results.No features in the family history, perinatal events, or early life events were detected that were associated with having LAM. Being more likely to be an only child and having an increased family history of uterine fibroids may, if confirmed, indicate some differences in reproductive function within the families of affected individuals.
Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study
Authors: Anoop Shankar, Liping Sun, Barbara E.K. Klein, Kristine E. Lee, Paul Muntner, F. Nieto Javier, Michael Y. Tsai, Karen J. Cruickshanks, Carla R. Schubert, Peter C. Brazy, Josef Coresh, Ronald Klein
Journal: Kidney International (2011)
A UK training programme for nurse practitioner flexible sigmoidoscopy and a prospective evaluation of the practice of the first UK trained nurse flexible sigmoidoscopist
Authors: G S Duthie, P J Drew, M A P Hughes, R Farouk, R Hodson, K R Wedgwood, J R T Monson
Journal: Gut (1998)

Background —Flexible sigmoidoscopy is a technical skill that has been successfully performed by suitably trained colorectal nurse practitioners in the USA. However, no recognised training course exists for nurse practitioners in the UK. Aims —To design and evaluate a training programme for nurse endoscopists. Methods —A multidisciplinary committee of nurses and clinicians developed a structured programme of study and practice. This involved a staged process of observations, withdrawals, and ultimately, full procedures. Once training had been completed the nurse practitioner was permitted to practice independently. Patients with colorectal symptoms referred for flexible sigmoidoscopy were examined for the final stages of training and independent practice. A prospective evaluation of the training and practice of the first trained nurse flexible sigmoidoscopist was performed. Barium enema, video, clinical follow up, and histology were used to validate the results of the flexible sigmoidoscopies. Results —The training programme required that 35 observations, 35 withdrawals, and 35 supervised full procedures were performed prior to the development of independent practice. Subsequent to the completion of this programme 215 patients have been examined independently by the nurse practitioner. Ninety three per cent of the examinations were judged successful and pathology was identified in 51%. The nurse endoscopist successfully identified all “significant” pathology whereas barium enema failed to identify pathology in 12.5%. There were no complications. Conclusion —With suitable training nurse endosocopists are able to perform flexible sigmoidoscopy safely and effectively.
High-Altitude–Induced Right-Heart Failure
Authors: Sandrine Huez, Vitalie Faoro, Jean-Luc Vachiéry, Philippe Unger, Jean-Benoit Martinot, Robert Naeije
Journal: Circulation (2007)

Echocardiographic recordings at sea level (top) and within the first hours of arrival at 3700 m (bottom).From left to the right: the inferior vena cava
Consolidative Dendritic Cell-based Immunotherapy Elicits Cytotoxicity against Malignant Mesothelioma
Authors: Joost P. Hegmans, Joris D. Veltman, Margaretha E. Lambers, I. Jolanda M. de Vries, Carl G. Figdor, Rudi W. Hendriks, Henk C. Hoogsteden, Bart N. Lambrecht, Joachim G. Aerts
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

We previously demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with a prolonged survival rate in mice. However, the clinical relevance is still in question. To examine this, we designed a clinical trial using chemotherapy followed by antigen-pulsed dendritic cell vaccination in mesothelioma patients.The aim of this study was to assess the safety and immunological response induced by the administration of tumor lysate-pulsed dendritic cells in patients with mesothelioma.Ten patients with malignant pleural mesothelioma received three vaccinations of clinical-grade autologous dendritic cells intradermally and intravenously at 2-week intervals after chemotherapy. Each vaccine was composed of 50 x 10(6) mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) as surrogate marker. Delayed-type hypersensitivity activity to tumor antigens and KLH was assessed, both in vivo and in vitro. Peripheral blood mononuclear cells during the treatment were analyzed for immunological responses.Administration of dendritic cells pulsed with autologous tumor lysate in patients with mesothelioma was safe with moderate fever as the only side effect. There were no grade 3 or 4 toxicities associated with the vaccines or any evidence of autoimmunity. Local accumulations of infiltrating T cells were found at the site of vaccination. The vaccinations induced distinct immunological responses to KLH, both in vitro and in vivo. Importantly, after three vaccinations, cytotoxic activity against autologous tumor cells was detected in a subgroup of patients.This study demonstrated that autologous tumor lysate-pulsed dendritic cell-based therapy is feasible, well-tolerated, and capable of inducing immunological response to tumor cells in mesothelioma patients. Clinical trial registered with www.clinicaltrials.gov (NCT00280982).
SOCIAL FACTORS IN THE PLACEMENT OF THE CHRONIC SCHIZOPHRENIC PATIENT
Authors: DANIEL ADELSON
Journal: American Journal of Psychiatry (1964)

Our findings are that the ataraxic drugs do improve the condition of chronic patients sufficiently to effect leave for 25% as compared with 1%-4% in the past, and that various social factors appear related to leave potential. We are left, nonetheless, with 60% to 75%7 of the chronic patient population on our hands in the 20 to 50 years of age and 2 to 10 years hospitalized group, even after intensive drug treatment. The best planning now stresses the need to strengthen community ties—to build mental health centers and various day, night and other bridging facilities,8 to decentralize hospitals and/or see them as only one posibility in a whole gamut of services and the drugs have made this more than ever possible for the majority of new and acute patients. But when we look at the chronic patient, we are led to ask, "What community ties?" and to suggest that for the chronic patient we have not only to strengthen ties but possibly to build and preserve a whole community—a community so shaped that in it he, too, can make a functional contribution.
Complications of Lyme Borreliosis
Authors: W D Cooke, R J Dattwyler
Journal: Annual Review of Medicine (1992)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More