tbuckley/cabot-search huggingface dataset:
Chronology and Pattern of Human Chromosome Replication. V. Blood Leukocytes of Chronic Myelocytic Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Toshio Sofuni, Yasumoto Kikuchi, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1967)

Results of autoradiographic studies performed on cultured blood cells of Ph1-positive patients with chronic myelocytic leukemia (6 females and 2 males) indicated that: 1) phytohemagglutinin P (PHA) stimulated the incorporation of tritiated thymidine into the chromosomes of normal (diploid) blood leukocytes, possibly by shortening their G2 period; 2) PHA did not affect the incorporation pattern in Ph1-positive leukocytes, though there were a few exceptions; 3) the Ph1 was probably not characterized by a unique replicatory pattern, since its labeling did not differ radically from that of the autosomes of group G; 4) the chronology of the late-replicating chromosomes, particularly that of one X chromosome in female cells, was retained in the leukemic leukocytes, including those with an aneuploid mode; and 5) there may be some deviation from the chronology of chromosome replication, because some cells that had an aneuploid chromosome constitution and were Ph1-positive showed very late replication of one autosome of group C besides the late-replicating X. In general, however, the chromosomal replicatory pattern in Ph1-positive cells, including those with an aneuploid makeup, appeared not to differ substantially from that of the normal lymphocytes in the blood of the subjects studied.
A prospective study of factors predicting postoperative pulmonary complications (PPC) in patients undergoing non-cardiothoracic surgery under general anaesthesis (GA)
Authors: Kaleem Ullah Toori, Jahangir Sarwar Khan, Syed Waqar Hussain
Journal: European Respiratory Journal (2012)

Introduction:  PPC after non-cardiothoracic surgery are common and can adversely effect morbidity, mortality and length of hospital stay. Knowledge as reagrds factors predicting PPC in our local setting is imperfect.   Aims & Objectives:  To study factors predicting PPC in our setting.   Methods : Prospective study of consecutive 404 patients undergoing non-cardiothoracic surgery under GA with tracheal intubation from Jan 2009 to Dec 2010. Chi-square was used for univariate analysis and forward stepwise logistic regression for multivariate analysis.   Results:  The mean age was 36±18 years with 54% males. 22% were smokers, and mean BMI was 23±4.5 kg/m 2  with 35% overweight & obese. 4% of subjects had chronic lung conditons while 23% had non-pulmonary chronic conditions. 70% of the surgeries were done electively and the mean duration of GA was 78±44 min. The overall PPC rate was 8%; atelactasis (48%) followed by bronchospasm (25%) and pneumonia (16%) being the commonest complications. The mean duration of hospital stay was significantly longer in patients with PPC (11±9 days, p   Conclusion:  PPC after non-cardiaothoracic surgery are common and lead to increased morbidity and prolonged hospital stay in our setting. We identified pre-existing chest disease, prolonged anaesthesia and emergency surgery as significant predictors of PPC.
No Disadvantage in Outcome of Using Matched Unrelated Donors as Compared With Matched Sibling Donors for Bone Marrow Transplantation in Children With Acute Lymphoblastic Leukemia in Second Remission
Authors: Ulla M. Saarinen-Pihkala, Göran Gustafsson, Olle Ringdén, Carsten Heilmann, Anders Glomstein, Gudmar Lönnerholm, Jonas Abrahamsson, Albert N. Bekassy, Henrik Schroeder, Lotta Mellander
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT) using either matched sibling donors or unrelated donors (URDs). PATIENTS AND METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in 2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off therapy. The preparative regimens were cyclophosphamide plus total-body irradiation ± antithymocyte/antilymphocyte globulin, busulfan plus cyclophosphamide ± antithymocyte/antilymphocyte globulin, or cytarabine plus total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and 28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the posttransplantation 5-year event-free survival was 39% versus 54% (P = .4), the estimated posttransplantation relapse rate was 76% versus 40% (P = not significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD) was 38% versus 64% (P &lt; .05) and was 14% versus 32% (P &lt; .10) for severe (grade 3 to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P &lt; .05) and was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD groups. CONCLUSION: BMT with matched URD allografts offers at least equal survival for children with ALL in 2CR, as compared with allografts from matched sibling donors. URD allografts were not associated with a higher toxic mortality rate, although both acute and chronic GVHD were more frequent with URD. Indications for using matched URD allografts in ALL 2CR can be considered the same as for using matched sibling donors.
Crystal structure of<i>Porphyromonas gingivalis</i>peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis
Authors: Anna B Montgomery, Jolanta Kopec, Leela Shrestha, Marie-Laetitia Thezenas, Nicola A Burgess-Brown, Roman Fischer, Wyatt W Yue, Patrick J Venables
Journal: Annals of the Rheumatic Diseases (2015)

Periodontitis (PD) is a known risk factor for rheumatoid arthritis (RA) and there is increasing evidence that the link between the two diseases is due to citrullination by the unique bacterial peptidylarginine deiminase (PAD) enzyme expressed by periodontal pathogen Pophyromonas gingivalis (PPAD). However, the precise mechanism by which PPAD could generate potentially immunogenic peptides has remained controversial due to lack of information about the structural and catalytic mechanisms of the enzyme.By solving the 3D structure of PPAD we aim to characterise activity and elucidate potential mechanisms involved in breach of tolerance to citrullinated proteins in RA.PPAD and a catalytically inactive mutant PPAD(C351A) were crystallised and their 3D structures solved. Key residues identified from 3D structures were examined by mutations. Fibrinogen and α-enolase were incubated with PPAD and P. gingivalis arginine gingipain (RgpB) and citrullinated peptides formed were sequenced and quantified by mass spectrometry.Here, we solve the crystal structure of a truncated, highly active form of PPAD. We confirm catalysis is mediated by the following residues: Asp130, His236, Asp238, Asn297 and Cys351 and show Arg152 and Arg154 may determine the substrate specificity of PPAD for C-terminal arginines. We demonstrate the formation of 37 C-terminally citrullinated peptides from fibrinogen and 11 from α-enolase following incubation with tPPAD and RgpB.PPAD displays an unequivocal specificity for C-terminal arginine residues and readily citrullinates peptides from key RA autoantigens. The formation of these novel citrullinated peptides may be involved in breach of tolerance to citrullinated proteins in RA.
Health promotion and cancer screening services for African refugee women
Authors: J. K. Carroll, R. Epstein, K. Fiscella, E. Volpe, P. Jean-Pierre, G. Morrow
Journal: Journal of Clinical Oncology (2006)

6101 Background: Previous work has shown that refugee women do not receive adequate preventive healthcare services, especially cancer screening. To identify factors that could affect the provision of cancer screening services to African Somali refugee women living in Rochester, NY, we assessed beliefs these women have about health promotion, access to care and use of preventive healthcare services. Methods: Individual in-depth interviews were conducted on a community-based sample of 34 resettled Somali-born women who were older than 18 years. Interviews were audiotaped and transcribed verbatim. A professional interpreter listened to all audiotaped interviews to check accuracy of transcription and translation. Content was analyzed by a multidisciplinary team using a grounded theory approach. Results: Median age of the women was 27 years. Length of residence in US was two months to nine years. For these women, health maintenance for acute survival took precedence over long-term prevention of disease. All women were familiar with basic health promotion practices, immunizations and routine medical examinations, and participants used both US-based and traditional techniques to prevent illness. Most women (71%, n=24), recognized the importance of maintaining good hygiene (59%, n=20) understood the need to have an adequate source of safe food and water, (74%, n=25) saw the need for access to a regular source of healthcare and (65%, n=22) acknowledged the need to function well at home. Few women understood cancer prevention services. Only three (9%) women recognized that the purpose of the Papanicalaou test was to screen for cervical cancer. Only six women (18%) recognized mammography (either the term or the procedure) and all of them were English-speaking, had lived in the US five years or longer, and had worked in the healthcare field. Conclusions: While traditional beliefs about health promotion did not appear to impede delivery of most preventive services, and participants understood prevention of infectious disease, their familiarity with cancer and cancer screening services was poor. Future health promotion programs need to increase refugee women’s knowledge about these services while building on other positive health-promoting beliefs. Supported by AHRQ 5R03HS014105 and NCI 1R25CA102618 No significant financial relationships to disclose.
Amyloid Neuropathy Following Domino Liver Transplantation
Authors: Pierre R. Bourque, Sharmi Shafi, Gerard H. Jansen, Arleigh McCurdy, Jodi Warman Chardon
Journal: JAMA Neurology (2016)

Amyloid Neuropathy Following Domino Liver Transplantation: Response to DiflunisalThe transmission of systemic transthyretin amyloidosis through domino liver transplantation, using a donor liver graft from a patient with familial amyloid neuropathy (FAP), was first described in 2005. 1 This complication had not been expected, given that the onset of neurologic symptoms in cases of inherited amyloidosis typically occurs in the age range of 25 to 40 years.Accelerated deposition of amyloid in these types of liver recipients may be facilitated by the presence of amyloid fibrils in the donor liver, which act as a template for amyloidogenesis.We present a case with an unusually short latency of symptomatic onset in which therapy with diflunisal may have helped stabilize neuropathy and nephropathy while the patient waited for another liver transplant.
Qualitative research and<i>The BMJ</i>
Authors: Elizabeth Loder, Trish Groves, Sara Schroter, Jose G Merino, Wim Weber
Journal: BMJ (2016)

A response to Greenhalgh and colleagues’ appeal for more

Trish Greenhalgh and colleagues argue persuasively that qualitative research is important.1 Why, they ask, has The BMJ , once a champion of qualitative research, seemingly turned away from it? They appeal to the journal to publish one qualitative research paper a month and in other ways confirm a commitment to qualitative research. In the past, qualitative research was a higher priority for The BMJ than it is now, so we understand why the community of qualitative researchers does not like our change in emphasis. And yet, despite the extensive discussion within and outside The BMJ that this letter has provoked, we are not persuaded that we should make the major changes requested.

The BMJ does not have quotas for specific types of research and we do not intend to establish them. We believe it is reasonable to consider study design, research questions, and limitations when …
Phase I clinical and pharmacokinetic (PK) study of gemcitabine (GEM) given by hepatic arterial infusion (HAI)
Authors: C. Vangroeningen, R. Honeywell, G. Peters, A. Laan, R. Ruyter, H. Pinedo, G. Giaccone
Journal: Journal of Clinical Oncology (2005)

3697 Background: GEM HAI may be more effective and less toxic than iv GEM in patients (pts) with liver metastases and because of the high activity of cytidine deaminase in the liver hepatic extraction can be expected. Methods: The maximum tolerated dose (MTD) and side effects of GEM HAI were determined, and PK were compared with PK after GEM iv at the same dose schedule in the same pts. A 24-hr infusion was used because a better effect was seen with GEM prolonged administration. GEM PK was analysed by LC-APCI-MS-MS, which also enabled to evaluate changes in normal metabolites such as deoxycytidine. Difluorodeoxyuridine (dFdU) was analyzed by HPLC. Results: 13 pts, 9 male and 4 female, median age 60 years, with liver metastases (7 colorectal, 3 hepatocellular, 2 pancreas, 1 bile ducts) were given GEM as a 24 hrs HAI, weekly x 3, q 4 weeks. This was preceded by iv GEM given either the first or second administration. Three dose levels were tested: 75 (4 pts) [1 pt not evaluable], 135 (3 pts), and 180 mg/m2 (6 pts). Thrombocytopenia was the most frequent toxicity, and was dose limiting at the highest dose level (grade [gr] 3; 1 pt, gr 4; 2 pts). Non-hematological toxicity was mild: gr 1–2 flu-like symptoms and nausea/vomiting occurred in 7 pts. No objective responses were recorded, but the 3 pts with hepatocellular carcinoma and the pt with bile duct carcinoma had stable disease for 8–12 months. Peak plasma concentrations of GEM by HAI increased from 26 to 125 nM by increasing dose. The average AUC’s (nmol/l x hr) after HAI/iv were 697/3861, 1229/5043, and 2293/5061, for 75, 135 and 180 mg/m2, respectively, resulting in a hepatic clearance of GEM of 0.82, 0.77 and 0.48, respectively, indicating saturated extraction by the liver when GEM dose is escalated. The PK profile of dFdU was not different between HAI and iv GEM and peak plasma concentrations increased linearly from 4 to 12 uM with dose escalation. Deoxycytidine concentration increased 3-fold from 75 to 180 mg/m2. Conclusions: (1) in the present schedule the MTD of HAI GEM is 180 mg/m2, (2) thrombocytopenia is the dose-limiting toxicity, (3) saturation of liver extraction at the higher HAI GEM dose explains the comparable MTD and toxicity observed with the same schedule of iv GEM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Oncology Lilly Oncology Lilly Oncology
Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease
Authors: Stephen G. Ellis, Dean J. Kereiakes, D. Christopher Metzger, Ronald P. Caputo, David G. Rizik, Paul S. Teirstein, Marc R. Litt, Annapoorna Kini, Ameer Kabour, Steven O. Marx, Jeffrey J. Popma, Robert McGreevy, Zhen Zhang, Charles Simonton, Gregg W. Stone
Journal: New England Journal of Medicine (2015)

In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes.In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year.Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13).In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).
Second interim analysis of the Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib (GIDEON): Sorafenib dosing and safety in U.S. patients.
Authors: Anthony B. El-Khoueiry, Bilal Piperdi, Alec Goldenberg, Allen Lee Cohn, Jeff H. Geschwind, Jorge A. Marrero, Arun Sanyal, Alan Paul Venook
Journal: Journal of Clinical Oncology (2012)

302 Background: Sorafenib (SOR) is the first systemic therapy to improve survival in patients (pts) with advanced hepatocellular carcinoma (HCC). GIDEON is a global, prospective, noninterventional study to evaluate SOR safety in pts with unresectable HCC in real-life practice. We present results from the second interim analysis, describing SOR dosing in US pts. Methods: From Jan 2009 – Nov 2010, 326 pts were enrolled in 92 US centers and followed ≥4 months, with 313 pts evaluable for safety. Demographics, initial dose, treatment duration (TD), dose modifications (mods), treatment interruptions (TIs), and adverse events (AEs) were analyzed in pts with complete data available. Results: Initial SOR dose was 400 mg/d in 106 pts (34%) and 800 mg/d in 177 pts (57%). Thirty (10%) pts received alternate doses or had incomplete data. Most pts were male (400 mg/d: 75%; 800 mg/d: 80%). Age distribution was similar between groups (400 mg/d: 59% &lt;65 yr and 41% &gt;65 yr; 800 mg/d: 64% &lt;65 yr and 36% &gt;65 yr). In 400 mg/d vs 800 mg/d groups respectively, ECOG PS was 0/1/2 in 19%/49%/16% vs 34%/35%/12%, and Child-Pugh (CP) status was A/B/C in 32%/35%/7% (26% unevaluable) vs 42%/29%/6% (21% unevaluable). Median TD was 9.8 wks (&lt;4 wks in 22%, &gt;4-12 wks in 40%, and &gt;12 wks in 39%) in the 400 mg/d group and 13.2 wks (&lt;4 wks in 17%, &gt;4-12 wks in 29%, and &gt;12 wks in 53%) in the 800 mg/d group. Dose mods and TIs occurred in 49% (37% due to AE) and 35%, and 57% (36% due to AE) and 38% of 400 mg/d vs 800 mg/d pts, respectively. See table for safety data. Conclusions: While statistical comparisons were not made, PS or CP status may impact initial SOR dose selection. Other baseline characteristics did not affect this decision. Frequencies of dose mods, TIs, and AEs were similar between dosing groups. Limitations of an observational study must be considered. Clinical judgment remains important in choosing initial SOR dose. [Table: see text]
KL-6 serum levels in adult cystic fibrosis patients
Authors: Federico Piffer, Andrea Airoldi, Marta Di Pasquale, Giovanna Pizzamiglio, Maddalena Zanardelli, Samantha Galbiati, Barbara Dallari, Francesco Blasi
Journal: European Respiratory Journal (2011)

Introduction:  Cystic fibrosis (CF) is a chronic lung disease with a typical obstructive pulmonary pattern. KL-6 is a high molecular weight glycoprotein, whose serum level are related to alveolar epithelium damage particularly in interstitial lung diseases; its role is not clear in CF patients.   Objective:  To compare C-reactive protein (CRP) and Kl-6 levels in adult CF patients requiring intravenous antibiotic therapy or pulmonary exacerbation.   Methods:  Prospective observational study of adult CF patients admitted with pulmonary exacerbation to CF Adult Unit of Policlinico Hospital, Milan between November 2009 and February 2010. Kl-6 and CRP serum levels were measured on admission, at day 7 and day 14 of intravenous therapy. Clinical and functional data were collected.   Results:  13 patients were analyzed (mean age 33 yrs, range 24-44, 6 women). Mean FEV1 was 49% of predicted (range 25-70). KL-6 levels seemed to show a trend similar to CRP9s during hospitalisation, with early increase and late decrease of the mean values.   Conclusion:  These preliminary data show that KL-6 could be an useful biomarker in the follow-up of pulmonary exacerbation of adult CF patients. Further studies in greater cohorts are needed in order to confirm these data.
Urinary Bisphenol A Levels in Young Men: Association with Reproductive Hormones and Semen Quality
Authors: Tina Harmer Lassen, Hanne Frederiksen, Tina Kold Jensen, Jørgen Holm Petersen, Ulla N. Joensen, Katharina M. Main, Niels E. Skakkebaek, Anders Juul, Niels Jørgensen, Anna-Maria Andersson
Journal: Environmental Health Perspectives (2014)

Background: Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent.Objectives: We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population.Methods: Our study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography–tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors.Results: We found that 98% of the men had detectable urinary levels of BPA. Median (5th–95th percentiles) BPA concentration was 3.25 ng/mL (0.59–14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile (ptrend ≤ 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (–6.7 percentage points, 95% CI: –11.76, –1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results.Conclusions: The pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic–pituitary–gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.Citation: Lassen TH, Frederiksen H, Jensen TK, Petersen JH, Joensen UN, Main KM, Skakkebaek NE, Juul A, Jørgensen N, Andersson AM. 2014. Urinary bisphenol A levels in young men: association with reproductive hormones and semen quality. Environ Health Perspect 122:478–484; http://dx.doi.org/10.1289/ehp.1307309