tbuckley/cabot-search huggingface dataset:
S58 Surfactant Phospholipid Kinetics in Patients with Acute Respiratory Distress Syndrome (ARDS)
Authors: A Dushianthan, R Cusack, V Goss, MPW Grocott, AD Postle
Journal: Thorax (2012)

<h3>Introduction and Aims</h3> ARDS is a significant health burden. Mortality still remains high between 30–50%. Surfactant is a mixture of phospholipids and proteins. Phosphatidylcholines (PC) account for 80% of total phospholipids. PC16:0/16:0 is the main PC with surface tension reducing characteristics. Surfactant abnormalities are well recognised in patients with ARDS However, replacement strategies remain unhelpful in improving mortality. Existing diagnostic definitions fail to identify a homogeneous population and this lack of phenotyping of patients according to surfactant biology may in part explain the absence of therapeutic benefit. The aims of this study are to assess surfactant PC kinetics by the incorporation of <i>methyl</i>-D<sub>9</sub>-choline in patients with ARDS. <h3>Methods</h3> ARDS patients were identified according to American European Consensus Conference (AECC) criteria. Patients were infused with 3.6mg/kg <i>methyl</i>-D9-choline. Small volume bronchoalveolar lavages were performed via a fibre optic bronchoscope at serial time points. Healthy volunteers were used as controls. The phospholipid fraction was extracted and analysed by triple quadrupole electrospray ionisation mass spectrometry. <h3>Results</h3> Ten patients and nine healthy controls were recruited. The endogenous PC composition consisted primarily of PC16:0/16:0, PC16:0/18:1 and PC18:0/18:2. There was significant reduction in the relative proportion of endogenous PC16:0/16:0 in patients. Compared to healthy controls, newly synthesised deuteriated PC16:0/16:0 was much lower in patients (26%) than controls (47%). Total <b>surfactant PC</b> D<sub>9</sub><b>-</b>incorporation was linear until 48 hours (0.019%/h, r<sup>2</sup>=0.9734, P&lt;0.05) and reached its maximum at 48 hours (0.93±0.15%). Steady state of incorporation was achieved between 48–96 hours. There was ∼80% increase in the fractional D<sub>9</sub> labelling in patients at 48 hours compared to healthy controls. Total <b>plasma PC</b> D<sub>9</sub>-incorporation was linear until 24 hours (0.032%/h, r<sup>2</sup>=0.9825, P&lt;0.05) and reached its maximum (0.755±0.056%) at 24 hours. Linear decline in enrichment was noted after 24 hours at a rate of 0.003% per hour (r<sup>2</sup>=0.9915, P&lt;0.05). The total surfactant PC D<sub>9</sub>-incorporation was much higher for patients at 24 hours and 48 hours reflecting increased synthetic rate. <h3>Conclusions</h3> By labelling surfactant PC precursors, it is possible to study surfactant kinetics in patients with ARDS. The methodology may be utilised to phenotype patients according to alveolar surfactant kinetics prior to replacement strategies.
The Vateriaii Segment and the Phantom Ampulla
Authors: Marvin L. Daves
Journal: JAMA (1962)

THE DUODENAL END of the biliary and pancreatic drainage systems constitutes the "Vaterian segment." At first, our understanding of the anatomy of the distal biliary and pancreatic ducts was poor and constituted a legitimate handicap to discussions of pathology and pursuit of therapeusis. We would like to call attention to the accurate anatomy which now has been established, point out that persistent use of an archaic concept and loose use of otherwise accurate terms perpetuate a discouraging degree of confusion, and make a plea for the modernization of our talk and writing concerning the Vaterian segment. In the first half of the eighteenth century, a German anatomist named Abraham Vater investigated the anatomy of the confluence of the biliary and pancreatic ducts. His work is preserved for us in the third volume of Albert Haller's<i>Disputalionum Anatomicarum Selectarum.</i>Excerpts from Vater's dissertation pertinent to this discussion are reproduced in the
Prior Coronary Artery Bypass Surgery and Risk of Death Among Patients With Ischemic Left Ventricular Dysfunction
Authors: George D. Veenhuyzen, Steven N. Singh, Dorothea McAreavey, Brent J. Shelton, Derek V. Exner
Journal: Circulation (2001)

Patients with ischemic LV dysfunction are at high risk of sudden death. However, no benefit from prophylactic defibrillator therapy was observed in a group of patients with LV dysfunction undergoing CABG (CABG Patch trial). Thus, the effect of CABG on future risk of sudden death in patients with LV dysfunction is of considerable interest.Mortality and modes of death in 5410 patients with ischemic LV dysfunction who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trials were evaluated. Outcomes of patients with (n=1870, 35%) versus without (n=3540) history of prior CABG were compared, and stratification by baseline ejection fraction (EF) values (<0.25, 0.25 to 0.30, and >0.30) was performed. Prior CABG was associated with a 25% (95% CI, 15% to 36%) reduction in risk of death and a 46% (95% CI, 30% to 58%) reduction in risk of sudden death independent of EF and severity of heart failure symptoms. As baseline EF declined, absolute reduction in risk of sudden death with prior CABG increased (P<0.01). No alteration in risk of death from progressive heart failure was observed with prior CABG. When these results were applied to a group of patients with LV dysfunction who had not undergone prior surgery (Coronary Artery Surgery Study Registry) predicted annual rates of death (8.2%) and sudden death (2.4%) were similar to those observed in the CABG Patch trial (7.9% and 2.3%, respectively).In patients with ischemic LV dysfunction, prior CABG is associated with a significant independent reduction in mortality. These results appear to account for the lack of benefit from defibrillator therapy in the CABG Patch trial.
Extending the Conserved Phylogenetic Core of Archaea Disentangles the Evolution of the Third Domain of Life
Authors: Céline Petitjean, Philippe Deschamps, Purificación López-García, David Moreira, Céline Brochier-Armanet
Journal: Molecular Biology and Evolution (2015)

Initial studies of the archaeal phylogeny relied mainly on the analysis of the RNA component of the small subunit of the ribosome (SSU rRNA). The resulting phylogenies have provided interesting but partial information on the evolutionary history of the third domain of life because SSU rRNA sequences do not contain enough phylogenetic signal to resolve all nodes of the archaeal tree. Thus, many relationships, and especially the most ancient ones, remained elusive. Moreover, SSU rRNA phylogenies can be heavily biased by tree reconstruction artifacts. The sequencing of complete genomes allows using a variety of protein markers as an alternative to SSU rRNA. Taking advantage of the recent burst of archaeal complete genome sequences, we have carried out an in-depth phylogenomic analysis of this domain. We have identified 200 new protein families that, in addition to the ribosomal proteins and the subunits of the RNA polymerase, form a conserved phylogenetic core of archaeal genes. The accurate analysis of these markers combined with desaturation approaches shed new light on the evolutionary history of Archaea and reveals that several relationships recovered in recent analyses are likely the consequence of tree reconstruction artifacts. Among others, we resolve a number of important relationships, such as those among methanogens Class I, and we propose the definition of two new superclasses within the Euryarchaeota: Methanomada and Diaforarchaea.
Mortality after hospital discharge for people with schizophrenia or bipolar disorder: retrospective study of linked English hospital episode statistics, 1999-2006
Authors: U. Hoang, R. Stewart, M. J. Goldacre
Journal: BMJ (2011)

To investigate whether the mortality gap has reduced in recent years between people with schizophrenia or bipolar disorder and the general population.Record linkage study.English hospital episode statistics and death registration data for patients discharged 1999-2006.People discharged from inpatient care with a diagnosis of schizophrenia or bipolar disorder, followed for a year after discharge.Age standardised mortality ratios at each time, comparing the mortality in people with schizophrenia or bipolar disorder with mortality in the general population. Poisson test of trend was used to investigate trend in ratios over time.By 2006 standardised mortality ratios in the psychiatric cohorts were about double the population average. The mortality gap widened over time. For people discharged with schizophrenia, the ratio was 1.6 (95% confidence interval 1.5 to 1.8) in 1999 and 2.2 (2.0 to 2.4) in 2006 (P < 0.001 for trend). For bipolar disorder, the ratios were 1.3 (1.1 to 1.6) in 1999 and 1.9 (1.6 to 2.2) in 2006 (P = 0.06 for trend). Ratios were higher for unnatural than for natural causes. About three quarters of all deaths, however, were certified as natural, and increases in ratios for natural causes, especially circulatory disease and respiratory diseases, were the main components of the increase in all cause mortality.The total burden of premature deaths from natural causes in people with schizophrenia or bipolar disorder is substantial. There is a need for better understanding of the reasons for the persistent and increasing gap in mortality between discharged psychiatric patients and the general population, and for continued action to target risk factors for both natural and unnatural causes of death in people with serious mental illness.
Separation of Cells From a Murine Fibrosarcoma on the Basis of Size. I. Relationship Between Cell Size and Age as Modified by Growth In Vivo or In Vitro23
Authors: D. J. Grdina, L. J. Peters, S. Jones, E. Chan
Journal: JNCI Journal of the National Cancer Institute (1978)

Cells from a murine fibrosarcoma (FSa) that had been Induced by 3-methylcholanthrene were separated and synchronized on the basis of cell size by centrifugal elutriation. More than 108 tumor cells were elutriated either immediately following disaggregation of a solid tumor or after 48 hours of incubation in vitro. Among the tumor cells elutriated immediately after disaggregation, the tumor suspension contained up to 32% normal diploid cells. Normal cells were not detected, however, in the suspension obtained after in vitro incubation. Recovery of cells after elutriation was 85%, and cell viability was greater than 95%. Selected fractions of cells were pooled, and average cell volumes were determined. The (modal) size of FSa cells after incubation in vitro for 48 hours increased from 980 to 1,620 μ3. These size differences were also reflected in the size of the cells comprising the pooled elutriated subpopulations. Modal volumes ranged from 740 to 1,300 μ3 for FSa cells separated without prior in vitro incubation as compared with 880-2,150 μ3 for those cells separated with prior in vitro incubation. With the use of the method of flow microfluorometry, the cell cycle parameters and the relative synchrony of each of the separated populations were determined. Cells incubated in vitro for 2 days were more efficiently synchronized than were cells separated immediately following excision of the tumor. The latter situation reflects the heterogeneity of size of cells in the same phase of the division cycle present in the tumor growing in vivo. The increased efficiency of elutriation in separating synchronized cohorts from cell populations incubated in vitro was probably due to the induction of a more homogeneous class of cells as a result of exposure to a uniform environment.
Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults With Chronic Kidney Disease
Authors: Nisha Bansal, Dongjie Fan, Chi-yuan Hsu, Juan D. Ordonez, Greg M. Marcus, Alan S. Go
Journal: Circulation (2012)

Background— Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. Methods and Results— We studied adults with CKD (defined as estimated glomerular filtration rate eGFR &lt;60 mL/min per 1.73 m 2 by the Chronic Kidney Disease Epidemiology Collaboration equation) enrolled in Kaiser Permanente Northern California who were identified between 2002 and 2010 and who did not have previous ESRD or previously documented AF. Incident AF was identified by using primary hospital discharge diagnoses or 2 or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206 229 adults with CKD, 16 463 developed incident AF. During a mean follow-up of 5.1±2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) in comparison with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P &lt;0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in the rate of ESRD (hazard ratio, 1.67; 95% confidence interval, 1.46–1.91). Conclusions— Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.
Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial
Authors: Alan K. Burnett, Robert K. Hills, Donald Milligan, Lars Kjeldsen, Jonathan Kell, Nigel H. Russell, John A.L. Yin, Ann Hunter, Anthony H. Goldstone, Keith Wheatley
Journal: Journal of Clinical Oncology (2010)

Purpose Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. Patients and Methods In this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m 2 ) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival. Results The addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival. Conclusion A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity.
Bacteria-Induced Intestinal Cancer in Mice with Disrupted<b><i>Gpx1</i></b>and<b><i>Gpx2</i></b>Genes
Authors: Fong-Fong Chu, R. Steven Esworthy, Peiguo G. Chu, Jeffrey A. Longmate, Mark M. Huycke, Sharon Wilczynski, James H. Doroshow
Journal: Cancer Research (2004)

Abstract Two glutathione peroxidase (GPX) isozymes, GPX-1 and GPX-2 (GPX-GI), are the major enzymes that reduce hydroperoxides in intestinal epithelium. We have previously demonstrated that targeted disruption of both the Gpx1 and Gpx2 genes (GPX-DKO) results in a high incidence of ileocolitis in mice raised under conventional conditions, which include the harboring of Helicobacter species [non-specific-pathogen-free (non-SPF) conditions]. In this study, we have characterized GPX-DKO mice that have microflora-associated intestinal cancers, which are correlated with increased intestinal pathology/inflammation. We found that GPX-DKO mice raised under germ-free conditions have virtually no pathology or tumors. After colonizing germ-free mice with commensal microflora without any known pathogens (SPF), &amp;lt;9% of GPX-DKO mice develop tumors in the ileum or the colon. However, about one-fourth of GPX-DKO mice raised under non-SPF conditions from birth or transferred from SPF conditions at weaning have predominantly ileal tumors. Nearly 30% of tumors are cancerous; most are invasive adenocarcinomas and a few signet-ring cell carcinomas. On the basis of these results, we conclude that GPX-DKO mice are highly susceptible to bacteria-associated inflammation and cancer. The sensitivity exhibited in these mice suggests that peroxidative stress plays an important role in ileal and colonic pathology and inflammation, which can lead to tumorigenesis.
Selective abrogation of antigen-specific human B cell responses by antigen-ricin conjugates.
Authors: D J Volkman, A Ahmad, A S Fauci, D M Neville
Journal: The Journal of Experimental Medicine (1982)

The feasibility of selectively eliminating human antigen-specific B cell responses by treating cells in vitro with antigen covalently linked to a cell toxin was examined. Tetanus toxoid (TT) was conjugated to the toxin ricin via a thioether linkage. Peripheral blood mononuclear cells from recently immunized subjects were preincubated for 2 h with TT-ricin in the presence of lactose. Antigen was then removed, and the cells from recently immunized subjects were preincubated for 2 h with TT-ricin in the presence of lactose. Antigen was then removed, and the cells were stimulated with pokeweed mitogen to induce antibody production. TT-specific antibody production was completely abrogated by preincubation with TT-ricin but not by TT alone or a mixture of TT and ricin. In contrast, polyclonal immunoglobulin production was not diminished by TT-ricin. This selective abrogation was also seen when B cells alone were preincubated with TT-ricin and a source of T cell help was later provided. T cell blastogenic responses to TT remained intact after TT-ricin exposure. Thus, antigen-toxin conjugates are capable of selectively eliminating specific antibody-producing B cell clones, while leaving intact the remainder of the B cell repertoire.
Neuropathological Substrates of Psychiatric Symptoms in Prospectively Studied Patients With Autopsy-Confirmed Dementia With Lewy Bodies
Authors: Clive G. Ballard, Robin Jacoby, Teodoro Del Ser, M. Nadeem Khan, David G. Munoz, Clive Holmes, Zsuzanna Nagy, Elaine K. Perry, Catherine Joachim, Evelyn Jaros, John T. O’Brien, Robert H. Perry, Ian G. McKeith
Journal: American Journal of Psychiatry (2004)

This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies.The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer's Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer's disease studied prospectively during life.The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy body staging was associated with the presence of persistent visual hallucinations and persistent delusions. All baseline psychiatric features were significantly more frequent in dementia with Lewy bodies than in Alzheimer's disease, as were persistent visual hallucinations, but patients who had dementia with Lewy bodies and severe tangle pathology had a clinical symptom profile more similar to that of Alzheimer's disease patients and were less likely to have neocortical Lewy bodies.The modest proportion of patients with Lewy body dementia and more severe tangle pathology resembled Alzheimer's disease patients clinically. Unlike Alzheimer's disease, dementia with Lewy bodies showed a significant inverse association between tangle burden and psychosis.
Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma
Authors: Nongnuch Sirachainan, Samart Pakakasama, Anannit Visudithbhan, Surang Chiamchanya, Lojana Tuntiyatorn, Mantana Dhanachai, Jiraporn Laothamatas, Suradej Hongeng
Journal: Neuro-Oncology (2008)

The prognosis of children with diffuse intrinsic pontine glioma (DIPG) is very poor. Radiotherapy remains the standard treatment for these patients, but the median survival time is only 9 months. Currently, the use of concurrent radiotherapy with temozolomide (TMZ) has become the standard care for adult patients with malignant gliomas. We therefore investigated this approach in 12 children diagnosed with DIPG. The treatment protocol consisted of concurrent radiotherapy at a dose of 55.8-59.4 Gy at the tumor site with TMZ (75 mg/m(2)/day) for 6 weeks followed by TMZ (200 mg/m(2)/day) for 5 days with cis-retinoic acid (100 mg/m(2)/day) for 21 days with a 28-day cycle after concurrent radiotherapy. Ten of the 12 patients had a clinical response after the completion of concurrent radiotherapy. Seven patients had a partial response, four had stable disease, and one had progressive disease. At the time of the report, 9 of the 12 patients had died of tumor progression, one patient was alive with tumor progression, and two patients were alive with continuous partial response and clinical improvement. The median time to progression was 10.2 +/- 3.0 months (95% confidence interval [CI], 4.2-16.1 months). One-year progression-free survival was 41.7% +/- 14.2%. The median survival time was 13.5 +/- 3.6 months (95% CI, 6.4-20.5 months). One-year overall survival was 58% +/- 14.2%. The patients who had a partial response after completion of concurrent radiotherapy had a longer survival time (p = 0.036) than did the other patients (those with stable or progressive disease). We conclude that the regimen of concurrent radiotherapy and TMZ should be considered for further investigation in a larger series of patients.