tbuckley/cabot-search huggingface dataset:
Invasive pulmonary procedures with biopsy can be performed without inducing metabolic activity
Authors: Pradeesh Sivapalan, Sara Colella, Klaus Richter Larsen, Bente Krogsgaard Schaadt, Paul Frost Clementsen
Journal: European Respiratory Journal (2014)

Introduction   Fluorine 18 fluorodeoxyglucose positron emission tomography computer tomography (PET-CT) has a high sensitivity in detection of malignancy in patients suspected of lung cancer, but is not specific. Also inflammatory reactions can result in metabolic activity. It is presumed, that procedures with biopsies will also result in false positive results. Therefore, PET CT is normally performed  prior  to taking biopsies.   Aim   To investigate if invasive pulmonary procedures with biopsies from benign lesions can be followed by PET negative results, in other words  to find out, if a biopsy can be made without inducing PET activity.    Methods   We searched in a three year period for patients suspected of lung cancer having (1) PET CT performed  after  biopsy, (2) interval 1 – 5 days and (3) PET negative results in sites biopsied with the finding of normal tissue.   Results   Eighty-three patients fulfilled (1), twenty of these also (2) and eight also (3). In these 8 patients, the PET negative findings were seen after bronchoscopy with forceps biopsy in 3 patients, after CT guided lung biopsy (18 G needle) in 2 patients and after EBUS-TBNAB (22 G) from chest lymph nodes in 3 patients. PET positive findings demonstrated malignancy or other abnormal tissue, if biopsied.   Conclusion   Invasive pulmonary procedures with biopsy do not necessarily result in PET activity. Therefore, PET positive results should always be taken seriously even shortly after taking biopsies.   Reference   Kobayashi Ket al. Radiographics 2012; 32(5): 1483-501.
Dihydropyrimidine Dehydrogenase Activity in 150 Healthy Japanese Volunteers and Identification of Novel Mutations
Authors: Kenichiro Ogura, Tomokazu Ohnuma, Yoshiyuki Minamide, Atsuhiro Mizuno, Takahito Nishiyama, Satoru Nagashima, Mitsutaka Kanamaru, Akira Hiratsuka, Tadashi Watabe, Toshihiko Uematsu
Journal: Clinical Cancer Research (2005)

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme catalyzing the metabolic degradation of the anticancer drug 5-fluorouracil (5-FU). Population studies of DPD activity in peripheral blood mononuclear cells (PBMC) were reported in healthy volunteers and cancer patients. Although these studies were done in mainly Caucasian and African American populations, only a little information is available for a Japanese population.One hundred fifty healthy Japanese volunteers were screened for a population distribution of PBMC-DPD activity. Genetic analysis of a volunteer with very low DPD activity was carried out by reverse transcriptase-PCR and genomic sequencing. Bacterially expressed recombinant mutant DPD proteins were purified and characterized.Mean and median values of PBMC-DPD activity for 5-FU reduction in the study population were 0.173 and 0.166 nmol/min/mg protein, respectively. A 57-year-old female volunteer (proband in this study) had very low DPD activity (0.014 nmol/min/mg protein) with a very low level of expression of DPD protein. Two novel nucleotide substitutions, at nucleotide positions 1097 (1097G > C) and 2303 (2303C > A), resulting in amino acid substitutions at positions 366 (G366A) and 768 (T768K), respectively, were identified. The G366A mutation caused not only a marked decrease in the affinity of the enzyme to cofactor NADPH but also reduced Vmax for 5-FU-reducing activity to approximately 0.5. T768K mutant lost its activity much faster than did wild DPD.We found one healthy volunteer (0.7% of the population) with very low PBMC-DPD activity due to heterozygosity for a mutant allele of the DPYD gene in a population of 150 Japanese.
Relationship Over Time Between Psychological Distress and Physical Activity in Colorectal Cancer Survivors
Authors: Suzanne K. Chambers, Brigid M. Lynch, Joanne Aitken, Peter Baade
Journal: Journal of Clinical Oncology (2009)

Increased physical activity in patients with colorectal cancer is related to improved recurrence-free and overall survival. Psychological distress after cancer may place patients at risk of reduced physical activity, but paradoxically may also act as a motivator for lifestyle change. The relationship between psychological distress and physical activity after cancer over time has not been described.A prospective survey of 1,966 (57% response) colorectal cancer survivors assessed the psychological distress variables of anxiety, depression, somatization, and cancer threat appraisal as predictors of physical activity at 5, 12, 24, and 36 months postdiagnosis; 978 respondents had valid data for all time points.Higher somatization was associated with greater physical inactivity (relative risk ratio [RRR] = 1.12; 95% CI, 1.1 to 1.2) and insufficient physical activity (RRR = 1.05; 95% CI, 0.90 to 1.0). Respondents with a more positive appraisal of their cancer were significantly (P = .031) less likely to be inactive (RRR = 0.95; 95% CI, 0.90 to 1.0) or insufficiently active (RRR = 0.96). Fatigued and obese respondents and current smokers were more inactive. Respondents whose somatization increased between two time periods were less likely to increase their physical activity over the same period (P < .001). Respondents with higher anxiety at one time period were less likely to have increased their activity at the next assessment (P = .004). There was no association between depression and physical activity.Cancer survivors who experience somatization and anxiety are at greater risk of physical inactivity. The lack of a clear relationship between higher psychological distress and increasing physical activity argues against distress as a motivator to exercise in these patients.
Endothelial Nitric Oxide Synthase Deficiency Produces Accelerated Nephropathy in Diabetic Mice
Authors: Hui John Zhao, Suwan Wang, Huifang Cheng, Ming-zhi Zhang, Takamune Takahashi, Agnes B. Fogo, Matthew D. Breyer, Raymond C. Harris
Journal: Journal of the American Society of Nephrology (2006)

Functionally significant polymorphisms in endothelial nitric oxide synthase (eNOS) and reduced vascular eNOS activity have been associated with increased human diabetic nephropathy (DN), but the pathogenic role of eNOS deficiency in the development of DN has not yet been confirmed. This study characterizes the severity of DN in eNOS(-/-) mice that were backcrossed to C57BLKS/J db/db mice. Although the severity of hyperglycemia was similar to C57BLKS/J db/db mice, by 26 wk, eNOS(-/-) C57BLKS/J db/db mice exhibited dramatic albuminuria, arteriolar hyalinosis, increased glomerular basement membrane thickness, mesangial expansion, mesangiolysis, and focal segmental and early nodular glomerulosclerosis. Even more remarkable, eNOS(-/-) C57BLKS db/db exhibited decreases in GFR to levels <50% of that in eNOS(+/+) C57BLKS db/db, as confirmed by increased serum creatinine. In summary, eNOS(-/-) db/db mice provide the most robust model of type II DN that has been described to date and support a role for deficient eNOS-derived NO production in the pathogenesis of DN.
Mitomycin C in combination with capecitabine or biweeklyhigh-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial
Authors: G.V. Kornek, B. Schuell, F. Laengle, T. Gruenberger, M. Penz, K. Karall, D. Depisch, F. Lang, W. Scheithauer
Journal: Annals of Oncology (2004)
Simpson's Paradox and the Impact of Different <i>DNMT3A</i> Mutations on Outcome in Younger Adults With Acute Myeloid Leukemia
Authors: Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, Alan K. Burnett, Robert K. Hills, David C. Linch
Journal: Journal of Clinical Oncology (2015)

To evaluate the impact of DNMT3A mutations on outcome in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.
Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients
Authors: J. Czyż, R. Dziadziuszko, W. Knopińska-Postuszuy, A. Hellmann, Ł. Kachel, J. Hołowiecki, J. Goździk, J. Hansz, A. Avigdor, A. Nagler, M. Osowiecki, J. Walewski, P. Mensah, W. Jurczak, A. Skotnicki, M. Sędzimirska, A. Lange, W. Sawicki, K. Sułek, M. Wach, A. Dmoszyńska, A. Kuś, T. Robak, K. Warzocha
Journal: Annals of Oncology (2004)
Cytokines in pathogenesis of pulmonary tuberculosis
Authors: T.S. Basek, A.V. Elkin, B.E. Knoring, M.E. Kobak, Y.V. Kirillov
Journal: European Respiratory Journal (2011)

Introduction:  The present work is devoted to relative research of some cytokines (IL-1β, IL-8, IL-2, TNF-α) at the tuberculosis patients with the subsequent evaluation of their role in pathogenesis of various forms of pulmonary tuberculosis.   Aim:  The aim of the study is to assess the severity of immune system disorders in patients with progressive forms of tuberculosis   Materials and methods:  The clinical and immunological inspection is executed at 193 patients with active pulmonary tuberculosis.   Results:  At infiltrative tuberculosis the high level of production IL-1β and IL-8 was combined with the maximal stimulation index of IL-1β and TNF-α, but low stimulation index of IL-8. Production of IL-2 exceeded the patients with more serious forms of a tuberculosis - disseminated and caseous pneumonia. Fibro-cavernousis tuberculosis was characterized by more intensive production of IL-2, low serumal contents of IL-1β, TNF-α and lower activity of IL-8. The level of inflammatory cytokines production (IL-1β and TNF-α), alongside with a low index of their stimulation is characteristic for a disseminated tuberculosis, that testifies to a state of hyper activation of immunocompetent cells. In caseous pneumonia, alongside with the maximal reduced of IL-1β, TNF-α and IL-2, the highest index of stimulation IL-1β and TNF-α was marked.   Conclusion:  The received data testify to the highest degree of an activation of cells of cytophagous in patients with infiltrative tuberculosis, and their expressed functional incompetence in caseous pneumonia. The down stroke of production not only IL-2, but also IL-1β alongside with a high level of IL-8, corresponds to the extremely serious state of the patients.
Clinical and Metabolic Efficacy of Glutamine-supplemented Parenteral Nutrition after Bone Marrow Transplantation
Authors: Thomas R. Ziegler, Lorraine S. Young, Kathleen Benfell, Marc Scheltinga, Kari Hortos, Rancy Bye, Frank D. Morrow, Danny O. Jacobs, Robert J. Smith, Joseph H. Antin, Douglas W. Wilmore
Journal: Annals of Internal Medicine (1992)

▪ Objective: To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation. ▪ Design: Double-blind, randomized, controlled clinical trial. ▪ Setting: University teaching hospital. ▪ Patients: Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies. ▪ Intervention: Parenteral nutrition was initiated the day after bone marrow transplantation (day 1). The experimental solution was supplemented with L-glutamine (0.57 g/kg body weight per day) and provided estimated requirements for energy and protein. The control solution was a standard, glutamine-free, isonitrogenous, isocaloric formula. ▪ Measurements: Nitrogen balance was determined between days 4 and 11 in the initial 23 patients. The incidence of clinical infection and microbial colonization, time until bone marrow engraftment, indices of clinical care, and other data related to hospital morbidity were recorded for all patients. ▪ Results: The glutamine-supplemented patients (n = 24) were clinically similar to the controls (n = 21) at entry. Nutrient intake was similar in both groups; however, nitrogen balance was improved in the glutamine-supplemented patients relative to the controls (- 1.4 ± 0.5 g/d compared with - 4.2 ± 1.2; P = 0.002). Fewer experimental patients developed clinical infection (three compared with nine in the control group; P = 0.041), and the incidence of microbial colonization was also significantly reduced. Hospital stay was shortened in patients receiving glutamine supplementation (29 ± 1 d compared with 36 ± 2 d; P = 0.017). ▪ Conclusion: Patients receiving glutamine-supplemented parenteral nutrition after bone marrow transplantation had improved nitrogen balance, a diminished incidence of clinical infection, lower rates of microbial colonization, and shortened hospital stay compared with patients receiving standard parenteral nutrition. These effects occurred despite no differences between groups in the incidence of fever, antibiotic requirements, or time to neutrophil engraftment.
Beta-adrenergic receptor stimulation increases unloaded shortening velocity of skinned single ventricular myocytes from rats.
Authors: K T Strang, N K Sweitzer, M L Greaser, R L Moss
Journal: Circulation Research (1994)

In vitro biochemical experiments have suggested that stimulation of beta-adrenergic receptor may increase the rate of crossbridge cycling in mammalian myocardium, but recent attempts to demonstrate a mechanical correlate have yielded conflicting results. To investigate this issue, we measured the effect of isoproterenol (ISO) and cAMP-dependent protein kinase (PKA) on unloaded shortening velocity (Vo). Vo is thought to be determined by the rate-limiting step of the crossbridge cycle, ie, the rate of crossbridge detachment from actin, and is therefore an index of the cycling rate. Single rat ventricular myocytes were enzymatically isolated, incubated in Ringer's solution without (control) or with 0.1 mumol/L ISO, and then rapidly skinned. Some control cells were subsequently treated with 3 micrograms/mL PKA for 40 minutes. Vo was then measured during maximal activation (pCa 4.5) in control, ISO-treated, and PKA-treated cells using the slack-test method. To test the efficacy of the agonist treatments, Ca2+ sensitivity of isometric tension was also assessed for each treatment by determining the [Ca2+] required for half-maximal tension (ie, pCa50). Both ISO and PKA treatment reduced the Ca2+ sensitivity of isometric tension compared with same-day control cells, in agreement with previous studies in intact and in skinned preparations. Vo was increased 38% by ISO treatment and 41% by PKA treatment compared with same-day control cells. 32P autoradiography showed that troponin I and C protein were the principal proteins phosphorylated by PKA treatment. We conclude that beta-adrenergic stimulation increases the rate of crossbridge release from actin, by a mechanism that most likely involves the phosphorylation of troponin I and/or C protein by PKA.
NHS Direct versus general practice based triage for same day appointments in primary care: cluster randomised controlled trial
Authors: David A Richards, Lesley Godfrey, Jane Tawfik, Mike Ryan, Joan Meakins, Evelyn Dutton, Jeremy Miles
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the relative effects on consultation workload and costs of off-site triage by NHS Direct for patients requesting same day appointments compared with usual on-site nurse telephone triage in general practice. <b>Design</b> Cluster randomised controlled trial. <b>Setting</b> Three primary care sites in York, England. <b>Participants</b> 4703 patients: 2452 with practice based triage, 2251 with NHS Direct triage. All consecutive patients making requests for same day appointments during study weeks were eligible for the trial. <b>Main outcome measures</b> Type of consultation after request for same day appointment (telephone, appointment, or visit); time taken for consultation; service use during the month after same day contact; costs of same day, follow up, and emergency care. <b>Results</b> Patients in the NHS Direct group were less likely to have their call resolved by a nurse and were more likely to have an appointment with a general practitioner. Mean total time per patient in the NHS Direct group was 7.62 minutes longer than in the practice based group. Costs were greater in the NHS Direct group—£2.88 (£0.88 to £4.87) per patient triaged—as a result of the difference between the groups in proportions of patients at each final point contact after triage. <b>Conclusions</b> External management of requests for same day appointments by nurse telephone triage through NHS Direct is possible but comes at a higher cost than practice nurse delivered triage in primary care. If NHS Direct could achieve the same proportions of consultation types as practice based triage, costs would be comparable.
Montelukast as a rescue therapy for bronchiolitis obliterans syndrome (BOS) after lung transplantation
Authors: Jens Gottlieb, Hendrik Suhling, Jessica Rademacher, Thomas Fuehner, Tobias Welte
Journal: European Respiratory Journal (2011)

Bronchiolitis Obliterans syndrome-(BOS) is a major cause of mortality and morbidity after lung transplantation (LTx). Montelukast has been shown to be effective in small case series in patients with BOS after LTx and bone marrow transplantation.  A retrospective single center analysis was performed in all LTx-recipients treated with Montelukast since 1.10.2010 as a rescue therapy for progressive BOS. Montelukast was used in a dose of 10 mg daily as a long-term therapy. All patients with at least 3 weeks of therapy were included. Response and progress were defined as a confirmed FEV1 of  110% baseline, respectively. Broncho-alveolar lavage (BAL)-neutrophilia was recorded at baseline.  38 patients (17 female, 31 double LTx recipients, median age 52 years,) were included with a median follow-up was 74 (interquartile 37-95) days. Median FEV1 at baseline was 55 (33-69)% best. Previous BOS treatment consisted of azithromycin in 100% (3 initial responders) and photopheresis (ECP) in 13 (34%, 2 responders). Median neutrophils in BAL at baseline was 20 (9-50)%, 21 (55%) subjects had neutrophils above 15%. Four patients responded to montelukast after 21-66 days, 10 patients were progressive after 20 - 100 days, 4 pts died from respiratory failure during follow up. Neutrophils in BAL was not different between responder and non-responder to montelukast. Response to azithromycin, montelukast or ECP was highly variable. 8 (21%) of progressive BOS pts. responded to any form of therapy.  Montelukast is an additional treatment option in LTx recipients with BOS refractory to other treatment options. BAL-neutrophils did not predict response.
Which 5-ASA?
Authors: J C Mansfield
Journal: Gut (2003)

I read Dr Travis’ therapy update ( Gut2002;51:548–9 [OpenUrl][1][FREE Full Text][2] ) with interest; the topic is timely in a market about to be challenged by new generic mesalazine brands. I note the choice of time dependent mesalazine (Pentasa) but, if mesalazine is to be relied upon exclusively, some evidence suggests Pentasa may not be the best choice. The recent study by Kruis and colleagues1 in the maintenance of remission in ulcerative colitis (UC) found that with Pentasa 1.5 g/day, the six month remission rate was 56.8% compared with 77.5% with balsalazide 3 g twice daily (p=0.045). The assertion that the advantages of the azo bond delivery to the distal colon can be matched by simply increasing the dose of pH dependent (Asacol) or time dependent release (Pentasa) has not been … [1]: {openurl}?query=rft.jtitle%253DGut%26rft.stitle%253DGut%26rft.issn%253D0017-5749%26rft.aulast%253DTravis%26rft.auinit1%253DS%2BP%2BL%26rft.volume%253D51%26rft.issue%253D4%26rft.spage%253D548%26rft.epage%253D549%26rft.atitle%253DWhich%2B5-ASA%253F%26rft_id%253Dinfo%253Apmid%252F12235078%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=gutjnl&resid=51/4/548&atom=%2Fgutjnl%2F52%2F5%2F771.atom
Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography
Authors: Aiden Abidov, Rory Hachamovitch, Alan Rozanski, Sean W. Hayes, Marcia M. Santos, Maria G. Sciammarella, Ishac Cohen, James Gerlach, John D. Friedman, Guido Germano, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2004)
Behavioral testing as a method for assessing risk.
Authors: R E Butcher
Journal: Environmental Health Perspectives (1976)

Behavioral effects have been found to result from the prenatal administration of substances known to be teratogenic to the CNS. These effects occur at dose levels lower than those producing gross malformations and when the agent is administered at times other than that optimal for CNS relevant technique for detecting adverse consequences of prenatal exposure to drugs and chemicals. Behavioral testing, however, also appears to have attributes that dictate a thoughtful approach to its role as a method for assessing risk, and additional research is needed to obtain usable techniques. The need for such research is intensified by the present inability to identify potential behavioral teratogens by means other than laboratory investigation.
Safety of out-patient investigations and management of suspected pulmonary embolism (PE)
Authors: Muhammad Zahid, Micheal O'gara, Irfan Shafiq, Sonia Mehmood, Naveed Bhatti
Journal: European Respiratory Journal (2011)

Introduction:  PE is usually investigated and treated as in-patient but there is growing evidence that significant proportion of patients might be safely managed in the out patient setting with low molecular weight heparin (LMWH).   Aims:  To assess compliance and safety of our hospital pathway for out-patient management of suspected PE.   Methods:  We studied a prospective cohort of patients with suspected PE managed as outpatients using LMHW from the day of presentation untill either the diagnosis of PE was excluded or confirmed. We analysed patients referred to ambulatory care clinic with suspected PE from June 2009 till June 2010. 42 patients met the inclusion criteria. All patients were reviewed in clinic after a V/Q scan or CTPA.   Results:  16 (38%) patients were diagnosed with PE. Average time taken for PE to be diagnosed or excluded was 57 hours. There were no deaths or complications recorded from either PE or LMWH. No significant differences in clinical and physiological parameters were noted except for systolic BP (p 0.043).   Conclusion:  Its probably safe to investigate and treat suspected PE as outpatient in selected clinically stable patients. Larger multi-centre randomised controlled trials are needed to confirm this finding.