tbuckley/cabot-search huggingface dataset:
Influence of Pre- and Post-Transplantation Responses on Outcome of Patients With Multiple Myeloma: Sequential Improvement of Response and Achievement of Complete Response Are Associated With Longer Survival
Authors: Juan José Lahuerta, Maria Victoria Mateos, Joaquin Martínez-López, Laura Rosiñol, Anna Sureda, Javier de la Rubia, José García-Laraña, Rafael Martínez-Martínez, Miguel T. Hernández-García, Dolores Carrera, Joan Besalduch, Felipe de Arriba, José María Ribera, Lourdes Escoda, Belén Hernández-Ruiz, Javier García-Frade, Concepción Rivas-González, Adrían Alegre, Joan Bladé, Jesús F. San Miguel
Journal: Journal of Clinical Oncology (2008)

Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM.We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation.Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10(-5)) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival.Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.
SOME FEATURES OF AORTIC REGURGITATION IN YOUNG SUBJECTS
Authors: J. M. Clarke
Journal: BMJ (1911)

AORTIC valve disease, causing regurgitation, in young sub.jects, presents some features of especial interest and importance, runs a course which in many respects is differene from the same disease in adults, and gives a clinical picture which has certain distinctive features.Certain 'of the vascalar phenomena which are consequent upon free regurgitation through the valve are seen in m,ost marked and characteristic form in the young, partly, no doubt, from the more yielding nature of t4eir vessels.Comi pensatory changes in the heart and circulation are rarely satisfaotorily esablished, and the disease is an even more serious one, and runs a shorter course than in adults.In all the cases mentioned in this paper the patients were so ill as to -require admission to hospital, and I have limited myself to in-patient cases, because of the greater opportunity for systematic observation.It follows also from this selection that I deal only with the more serious eases of the disease.Many of them were under my care at intervals for several years, so that the piogress of the affection could be followed.In all of them, though in the large& majority other valvular lesions co-existed, aortio regurgitation and its results were the predominant feature in the case.The general incidence of aortic valve disease in hospital in-patient practice is not withoat interest. 0! 3,300 cases admitted to my beds daring the time the cases under contideration occurred, there were 96, or nearly 3 per cent., of cases of aortic valve disease; of these 33,or 1 per pent., were under 28 years of age.The age oi 28 mayseem i' ¢somewhat arbibrary upper limit, but-it was taken as su h; in order to include 4 cases in whom the disease began in childhobd, and who had beeii tinder my' observation for many years., Cases in which there Was an'y possibility of' congenital heart disease were, of course, exmluded.iTetables which follow show the sexi and age" incidence.colleague, Dr. Carey Coombs,-has also kindly given me a
Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States
Authors: George Ostapowicz, Robert J Fontana, Frank V Schiødt, Anne Larson, Timothy J Davern, Steven H B Han, Timothy M McCashland, A Obaid Shakil, J Eileen Hay, Linda Hynan, Jeffrey S Crippin, Andres T Blei, Grace Samuel, Joan Reisch, William M Lee
Journal: Annals of Internal Medicine (2002)

Background: Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition. Objective: To describe the clinical features, presumed causes, and short-term outcomes of acute liver failure. Design: Prospective cohort study. Setting: 17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group. Patients: 308 consecutive patients with acute liver failure, admitted over a 41-month period. Measurements: Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission. Results: 73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not. Conclusions: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients. * For members of the U.S. Acute Liver Failure Study Group, see Appendix.
Deguelin-Induced Inhibition of Cyclooxygenase-2 Expression in Human Bronchial Epithelial Cells
Authors: Ho-Young Lee, Young-Ah Suh, Jerome W. Kosmeder, John M. Pezzuto, Waun Ki Hong, Jonathan M. Kurie
Journal: Clinical Cancer Research (2004)

Abstract The increased expression of cyclooxygenase (COX)-2 significantly enhances carcinogenesis and inflammatory reactions, and its regulation may be a reasonable target for cancer chemoprevention. We demonstrated previously that deguelin inhibits proliferation of premalignant human bronchial epithelial (HBE) cells, such as 1799 cells and squamous HBE cells, by regulating phosphatidylinositol-3-kinase Akt activity, which is involved in COX-2 expression. We sought to determine the effect of deguelin on COX-2 expression in squamous HBE cells. Deguelin strongly inhibited COX-2 expression in squamous HBE cells, without affecting the COX-1 protein level. Deguelin inhibited proliferation of a variety of non-small cell lung carcinoma (NSCLC) cell lines through apoptosis and induced Bax expression in the H322 NSCLC and squamous HBE cells. Deguelin treatment did not affect Bcl-2 protein levels but increased expression levels of the proapoptotic protein p53 and the cyclin-dependent kinase inhibitors p21 and p27 in the squamous HBE cells. The sensitivity of the squamous HBE and NSCLC cells to deguelin and the inhibitory effects of deguelin on COX-2 expression in the squamous HBE cells indicate that regulation of COX-2 expression is involved in the chemopreventive action of deguelin in lung cancer.
Dual Targeting of the Cyclin/Rb/E2F and Mitochondrial Pathways in Mantle Cell Lymphoma with the Translation Inhibitor Silvestrol
Authors: Lapo Alinari, Courtney J. Prince, Ryan B. Edwards, William H. Towns, Rajeswaran Mani, Amy Lehman, Xiaoli Zhang, David Jarjoura, Li Pan, A. Douglas Kinghorn, Michael R. Grever, Robert A. Baiocchi, David M. Lucas
Journal: Clinical Cancer Research (2012)

During cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. This critical pathway is typically deregulated in cancer, and novel inhibitory strategies would be effective in a variety of tumors. The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression.Mantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. Silvestrol was also evaluated in vivo using an aggressive model of MCL.Silvestrol showed low nanomolar potency both in MCL cell lines and primary MCL tumor cells. D-cyclins were depleted with just 10 nmol/L silvestrol at 16 hours, with subsequent reductions of phosphorylated Rb, E2F1 protein, and E2F1 target transcription. As showed in other leukemias, silvestrol caused Mcl-1 depletion followed by mitochondrial depolarization and caspase-dependent apoptosis, effects not related to inhibition of CDK4/6. Silvestrol significantly (P < 0.0001) prolonged survival in a MCL xenograft model without detectable toxicity.These data indicate that silvestrol effectively targets the cyclin/CDK/Rb pathway, and additionally induces cytotoxicity via intrinsic apoptosis. This dual activity may be an effective therapeutic strategy in MCL and other malignancies.
Helicobacter pylori may induce bile reflux: link between H pylori and bile induced injury to gastric epithelium.
Authors: S D Ladas, J Katsogridakis, H Malamou, H Giannopoulou, M Kesse-Elia, S A Raptis
Journal: Gut (1996)

Helicobacter pylori and duodenogastric reflux are both recognised as playing aetiological roles in chronic gastritis. This study investigated whether H pylori colonisation of the antral mucosa and duodenogastric reflux are independent phenomena or have a causal relationship. Thirty eight patients (15 men, 23 women) aged (mean (SD)) 48 (17) years participated. Each patient underwent gastroscopy. Antral biopsy specimens were taken to investigate H pylori colonisation. In addition BrIDA-99mTc/111In-DTPA scintigraphy was used to quantify duodenogastric reflux. H pylori positive patients who were found to have duodenogastric reflux were treated with amoxycillin (1 g/d) and metronidazole (1.5 g/d) for seven days and four tablets of bismuth subcitrate daily for four weeks. Follow up antral biopsies and scintigraphy were repeated at six months. Duodenogastric reflux could not be found in 18 patients, including eight (44%) who were H pylori positive. Ten of the 11 patients who had duodenogastric reflux (reflux % 11.6 (9.2)), however, were H pylori positive (chi 2 = 6.26, p = 0.01). These 10 patients were given eradication treatment. At six months, in six patients who became H pylori negative, duodenogastric reflux was significantly reduced from a pretreatment value of 14.3% to 3.3% (two tail, paired t = 2.57, p = 0.016). These data suggest that H pylori may induced duodenogastric reflux which may be important in the pathogenesis of H pylori gastritis or carcinogenesis, or both.
Bayesian Estimation of Divergence Times from Large Sequence Alignments
Authors: S. Guindon
Journal: Molecular Biology and Evolution (2010)

Bayesian estimation of divergence times from molecular sequences relies on sophisticated Markov chain Monte Carlo techniques, and Metropolis–Hastings (MH) samplers have been successfully used in that context. This approach involves heavy computational burdens that can hinder the analysis of large phylogenomic data sets. Reliable estimation of divergence times can also be extremely time consuming, if not impossible, for sequence alignments that convey weak or conflicting phylogenetic signals, emphasizing the need for more efficient sampling methods. This article describes a new approach that estimates the posterior density of substitution rates and node times. The prior distribution of rates accounts for their potential autocorrelation along lineages, whereas priors on node ages are modeled with uniform densities. Also, the likelihood function is approximated by a multivariate normal density. The combination of these components leads to convenient mathematical simplifications, allowing the posterior distribution of rates and times to be estimated using a Gibbs sampling algorithm. The analysis of four real-world data sets shows that this sampler outperforms the standard MH approach and demonstrates the suitability of this new method for analyzing large and/or difficult data sets.
Early Respiratory Microbiota Composition Determines Bacterial Succession Patterns and Respiratory Health in Children
Authors: Giske Biesbroek, Evgeni Tsivtsivadze, Elisabeth A. M. Sanders, Roy Montijn, Reinier H. Veenhoven, Bart J. F. Keijser, Debby Bogaert
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Many bacterial pathogens causing respiratory infections in children are common residents of the respiratory tract. Insight into bacterial colonization patterns and microbiota stability at a young age might elucidate healthy or susceptible conditions for development of respiratory disease.To study bacterial succession of the respiratory microbiota in the first 2 years of life and its relation to respiratory health characteristics.Upper respiratory microbiota profiles of 60 healthy children at the ages of 1.5, 6, 12, and 24 months were characterized by 16S-based pyrosequencing. We determined consecutive microbiota profiles by machine-learning algorithms and validated the findings cross-sectionally in an additional cohort of 140 children per age group.Overall, we identified eight distinct microbiota profiles in the upper respiratory tract of healthy infants. Profiles could already be identified at 1.5 months of age and were associated with microbiota stability and change over the first 2 years of life. More stable patterns were marked by early presence and high abundance of Moraxella and Corynebacterium/Dolosigranulum and were positively associated with breastfeeding in the first period of life and with lower rates of parental-reported respiratory infections in the consecutive periods. Less stable profiles were marked by high abundance of Haemophilus or Streptococcus.These findings provide novel insights into microbial succession in the respiratory tract in infancy and link early-life profiles to microbiota stability and respiratory health characteristics. New prospective studies should elucidate potential implications of our findings for early diagnosis and prevention of respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00189020).
Unilateral Vitelline Vein Ligation Alters Intracardiac Blood Flow Patterns and Morphogenesis in the Chick Embryo
Authors: B. Hogers, M.C. DeRuiter, A.C. Gittenberger-de Groot, R.E. Poelmann
Journal: Circulation Research (1997)

Abstract To study the role of blood flow in normal and abnormal heart development, an embryonic chicken model was developed. The effect of altered venous inflow on normal intracardiac blood flow patterns was studied by visualization of blood flow with India ink. At stage 17, India ink was injected into a capillary or small venule within a specific yolk sac region. After determination of the normal intracardiac flow pattern, the right lateral vitelline vein was ligated, and the new intracardiac flow pattern was studied. Ligation resulted in disturbance of normal intracardiac flow patterns, which was most obvious in the conotruncus. The long-term effect of these abnormal intracardiac flow patterns on the development of the heart and pharyngeal arch arteries was investigated by permanent ligation in ovo with a microclip at stage 17 and subsequent evaluation at stages 34, 37, and 45. These experiments revealed anomalies of the vascular system in 58 of the 91 ligated embryos studied. We observed intracardiac malformations consisting of subaortic ventricular septal defects (n=52), semilunar valve anomalies (n=19), atrioventricular anomalies (n=7), and pharyngeal arch artery malformations (n=32). It is concluded that abnormal intracardiac blood flow, resulting from hampered venous inflow, may result in serious intracardiac and pharyngeal arch artery malformations comparable to defects observed in embryonic chicken models subjected to neural crest ablation, cervical flexure experiments, and excessive retinoic acid treatment.
READY MODE OF APPLYING THE DOUCHE, AND OF ADMINISTERING INJECTIONS OF WATER
Authors: J. I. Ikin
Journal: BMJ (1853)

and replace the wrom-out tissues; and the non-azotised, or combustive, which furnish food for the lungs, supporinug respiration and animal heat.Now, it is a curious fact, which he also eablished that, though the fibrin, albu- men, and casein, which constitute the chief of the first or aszotised class of alimentary substances, exist in vegetable as well as animal food, animals have not the pwer of fo- ing in their own bodies any of those otised alimentary pnnciples.They are primarily derived from the vegetable kingdom; and the digestive org-ans of animals have no
Is ATP (Adenosine 5'-Triphosphate), like STP(R), a Performance-Enhancing Additive for the Tanks of Cancer Patients?
Authors: A. Jatoi
Journal: JNCI Journal of the National Cancer Institute (2000)

Among 1000 patients with advanced cancer, Donnelly and Walsh (1) found that anorexia, weakness, and weight loss (o10% of premorbid weight) were among the 10 most bothersome signs and symptoms. Despite the impact of the cancer anorexia/cachexia syndrome, relatively few clinical trials target its palliation as their primary end point. Observations that the drugs megestrol acetate, dexamethasone, and cyproheptadine caused unwanted weight gain when they were used to treat other illnesses led to clinical trials in cancer patients with anorexia/ cachexia. In this setting, these agents may stimulate appetite and permit some patients to regain weight but do not appear to increase lean tissue mass (2‐4). Treatment with megestrol acetate causes a 5% or greater weight gain in only 20% of cancer patients with the anorexia/cachexia syndrome (2). This limited success underscores the need to identify therapeutic alternatives. In this issue of the Journal, Agteresch et al. (5) describe a randomized, controlled trial studying adenosine 5’-triphosphate (ATP) infusions as therapy for cancer anorexia/cachexia in patients with non-small-cell lung cancer. This trial sought to determine the effect of ATP infusions on body weight change, muscle strength, serum albumin concentration, and quality-oflife scores. Why might ATP infusion be useful in this setting? Weight maintenance is a balance of energy demand and supply. Illness often increases energy demands. A comparison between a group of healthy individuals and patients with non-small-cell lung cancer found that patients with lung cancer had an increase in basal metabolic rate, as high as 130 kcal/day after adjustment for lean body mass (6). Anorexia or treatment-related toxic effects may also cause a deficit on the supply side of the equation. The administration of ATP, a direct hydrolyzable source of energy,
Fighting Renal Diseases in Poor Countries
Authors: Arrigo Schieppati, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2004)

The incidence of sudden infant death syndrome (SIDS) between birth and 2 years of age in South Australia was found to be 2.1/1000 live births. The incidence in previous siblings was 10 times that expected, in second degree relatives five times, and in third degree relatives four times that expected for the community. The minimum incidence in the next subsequent sibling was five times that expected. Except for one family in which both twins died during the same night, the surviving twin has never died (23 infants). The incidence of SIDS in adopted infants was similar to the incidence in natural born infants. Families in which two or more siblings died from SIDS differed from families in which only one infant died from SIDS in several ways. More infants were over 12 months old, and the mothers had an increased incidence of previous miscarriage and threatened miscarriage during the pregnancy with the infant who died. In one family both infants had bronchomalacia, and two families were severely socially deprived. For most families (92%) in which an infant died from SIDS the risk of recurrence is small (less that twice the expected risk). We have identified a small subgroup (8%) with a significantly increased risk of recurrence.
Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity
Authors: Robert G. Weiss, Marco A. Mejia, David A. Kass, Anthony F. DiPaula, Lewis C. Becker, Gary Gerstenblith, V.P. Chacko
Journal: Journal of Clinical Investigation (1999)

Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin–oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin–oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment–length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin–oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.