tbuckley/cabot-search huggingface dataset:
Treatment failure in pneumonia: impact of antibiotic treatment and cost analysis
Authors: S.R. Ott, B.M. Hauptmeier, C. Ernen, P.M. Lepper, E. Nüesch, M.W. Pletz, J. Hecht, T. Welte, T.T. Bauer
Journal: European Respiratory Journal (2011)

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after &gt;72h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean± sd age 69.6±16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4±7.3 days versus 9.8±4.2 days; p&lt;0.001) and increased median treatment costs (€2,206 versus €1,284; p&lt;0.001). 596 (48.2%) patients received MFX and witnessed less TF (10.9% versus 20.6%; p&lt;0.001). After controlling for confounders in multivariate analysis, adjusted risk of TF was clearly reduced in MFX as compared with β-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI 0.27–0.68) and was more comparable with a β-lactam plus macrolide combination (BLM) (OR 0.68, 95% CI 0.38–1.21). In hospitalised CAP, TF is frequent and leads to prolonged hospital stay and increased treatment costs. Initial treatment with MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment costs.
Glycemic Load, Carbohydrate Intake, and Risk of Colorectal Cancer in Women: A Prospective Cohort Study
Authors: P. D. Terry, M. Jain, A. B. Miller, G. R. Howe, T. E. Rohan
Journal: JNCI Journal of the National Cancer Institute (2003)

Mounting evidence suggests that high circulating levels of insulin might be associated with increased colorectal cancer risk. The glycemic effects of diets high in refined starch may increase colorectal cancer risk by affecting insulin and/or insulin-like growth factor-I levels. We examined the association between dietary intake and colorectal cancer risk in a cohort of 49 124 women participating in a randomized, controlled trial of screening for breast cancer in Canada. Linkages to Canadian mortality and cancer databases yielded data on mortality and cancer incidence up to December 31, 2000. During an average 16.5 years of follow-up, we observed 616 incident cases of colorectal cancer (436 colon cancers, 180 rectal cancers). Rate ratios for colorectal cancer for the highest versus the lowest quintile level were 1.05 (95% confidence interval [CI] = 0.73 to 1.53; P(trend) =.94) for glycemic load, 1.01 (95% CI = 0.68 to 1.51; P(trend) =.66) for total carbohydrates, and 1.03 (95% CI = 0.73 to 1.44; P(trend) =.71) for total sugar. Our data do not support the hypothesis that diets high in glycemic load, carbohydrates, or sugar increase colorectal cancer risk.
Results of a preclinical randomized controlled multicenter trial (pRCT): Anti-CD49d treatment for acute brain ischemia
Authors: Gemma Llovera, Kerstin Hofmann, Stefan Roth, Angelica Salas-Pérdomo, Maura Ferrer-Ferrer, Carlo Perego, Elisa R. Zanier, Uta Mamrak, Andre Rex, Hélène Party, Véronique Agin, Claudine Fauchon, Cyrille Orset, Benoît Haelewyn, Maria-Grazia De Simoni, Ulrich Dirnagl, Ulrike Grittner, Anna M. Planas, Nikolaus Plesnila, Denis Vivien, Arthur Liesz
Journal: Science Translational Medicine (2015)

Numerous treatments have been reported to provide a beneficial outcome in experimental animal stroke models; however, these treatments (with the exception of tissue plasminogen activator) have failed in clinical trials. To improve the translation of treatment efficacy from bench to bedside, we have performed a preclinical randomized controlled multicenter trial (pRCT) to test a potential stroke therapy under circumstances closer to the design and rigor of a clinical randomized control trial. Anti-CD49d antibodies, which inhibit the migration of leukocytes into the brain, were previously investigated in experimental stroke models by individual laboratories. Despite the conflicting results from four positive and one inconclusive preclinical studies, a clinical trial was initiated. To confirm the preclinical results and to test the feasibility of conducting a pRCT, six independent European research centers investigated the efficacy of anti-CD49d antibodies in two distinct mouse models of stroke in a centrally coordinated, randomized, and blinded approach. The results pooled from all research centers revealed that treatment with CD49d-specific antibodies significantly reduced both leukocyte invasion and infarct volume after the permanent distal occlusion of the middle cerebral artery, which causes a small cortical infarction. In contrast, anti-CD49d treatment did not reduce lesion size or affect leukocyte invasion after transient proximal occlusion of the middle cerebral artery, which induces large lesions. These results suggest that the benefits of immune-targeted approaches may depend on infarct severity and localization. This study supports the feasibility of performing pRCTs.
Fatigue in chronic cholestasis
Authors: P Milkiewicz
Journal: Gut (2004)

Fatigue is probably the most intriguing symptom affecting patients with chronic cholestatic disorders, in particular those with primary biliary cirrhosis. It is postulated that fatigue in patients with primary biliary cirrhosis may be associated with morphological abnormalities of the central nervous system secondary to accumulation of manganese. However, we are still far from understanding this complex issue.
Alcohol and Breast Cancer
Authors: Keith W. Singletary, Susan M. Gapstur
Journal: JAMA (2001)

The association of alcohol consumption with increased risk for breast cancer has been a consistent finding in a majority of epidemiologic studies during the past 2 decades. Herein, we summarize information on this association from human and animal investigations, with particular reference to epidemiologic data published since 1995. increased estrogen and androgen levels in women consuming alcohol appear to be important mechanisms underlying the association. Other plausible mechanisms include enhanced mammary gland susceptibility to carcinogenesis, increased mammary carcinogen dna damage, and greater metastatic potential of breast cancer cells, processes for which the magnitude likely depends on the amount of alcohol consumed. Susceptibility to the breast cancer-enhancing effect of alcohol may also be affected by other dietary factors (such as low folate intake), lifestyle habits (such as use of hormone replacement therapy), or biological characteristics (such as tumor hormone receptor status). Additional progress in understanding alcohol's enhancing effect on breast cancer will depend on a better understanding of the interactions between alcohol and other risk factors and on additional insights into the multiple biological mechanisms involved.
Minor histocompatibility antigen-specific cytotoxic T cell lines, capable of lysing human hematopoietic progenitor cells, can be generated in vitro by stimulation with HLA-identical bone marrow cells.
Authors: W A Marijt, W F Veenhof, A Brand, E Goulmy, W E Fibbe, R Willemze, J J van Rood, J H Falkenburg
Journal: The Journal of Experimental Medicine (1991)

Recipient-antidonor alloreactivity before HLA genotypically identical bone marrow transplantation (BMT) between donor-recipient pairs that are negative in the mixed lymphocyte reaction (MLR), the cell-mediated lympholysis (CML) assay, and the lymphocyte crossmatch was not detectable in the majority of cases, using recipient peripheral blood lymphocytes (PBL) collected before BMT as responder cells and donor PBL as stimulator cells. However, when donor bone marrow mononuclear cells (BMMNC) instead of PBL were used as stimulator cells, we could detect donor-specific alloreactivity in 7 of 10 HLA genotypically identical donor-recipient pairs. To demonstrate that this alloreactivity was minor histocompatibility (mH) antigen specific and not directed against HLA class I splits or variants, two cytotoxic T lymphocyte (CTL) lines were tested in further detail against phytohemagglutinin (PHA) blasts from pairs of HLA genotypically identical siblings positive for the HLA class I restriction molecule. Both CTL lines recognized mH antigens, as illustrated by the differential recognition of PHA blasts of one of the two siblings from several pairs. The potential role of these mH antigen-specific CTLs in bone marrow graft rejection was demonstrated by the mH antigen-specific growth inhibition of hematopoietic progenitor cells from the original bone marrow donor and from HLA class I restriction molecule-positive individuals who expressed the mH antigens on their PBL and BMMNC. Our assay can be used in HLA genotypically identical BMT to detect a recipient-antidonor response, directed against cellularly defined mH antigens expressed on donor HPC, BMMNC, and PBL, before transplantation.
Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study
Authors: A. Scherpereel, T. Berghmans, J. J. Lafitte, B. Colinet, M. Richez, Y. Bonduelle, A. P. Meert, X. Dhalluin, N. Leclercq, M. Paesmans, L. Willems, J. P. Sculier
Journal: European Respiratory Journal (2010)

No treatment is recommended for patients with malignant mesothelioma (MM) failing after first-line cisplatin-based chemotherapy. <i>In vitro</i> data suggested that valproic acid, a histone deacetylase inhibitor (HDACi), had a proapoptotic effect and synergised with doxorubicin to induce apoptosis in MM cells. Our primary end-point was to determine response rate of combined valproic acid and doxorubicin in patients with unresectable MM failing after platinum-based chemotherapy. Treatment consisted of doxorubicin (60 mg·m<sup>-2</sup>) plus valproic acid. An interim analysis for response rate was planned after the first 16 registered patients. All the cases were centrally reviewed. From July 2006 to March 2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status (PS) ≥80 (76%) and an epithelioid subtype (80%). There were seven partial responses (response rate 16%; 95% CI 3–25%), all in patients with PS 80–100. The best disease control rate was 36% (95% CI 22–51%). Two toxic deaths were observed (febrile neutropenia and cerebral thrombotic event), both in patients with poor PS (60–70). Valproic acid, an HDACi, plus doxorubicin appeared an effective chemotherapy regimen in good PS (80–100) patients with refractory or recurrent MM, for which no standard therapy was available.
Limited CD4+ T-cell renewal in early HIV-1 infection: Effect of highly active antiretroviral therapy
Authors: Sylvain Fleury, Rob J. De Boer, G. Paolo Rizzardi, Katja C. Wolthers, Sigrid A. Otto, Craig C. Welbon, Cecilia Graziosi, Christian Knabenhans, Hugo Soudeyns, Piere-Alexander Bart, Serge Gallant, Jean-Marc Corpataux, Michel Gillet, Pascal Meylan, Pierre Schnyder, Jean-Yves Meuwly, William Spreen, Michel P. Glauser, Frank Miedema, Giuseppe Pantaleo
Journal: Nature Medicine (1998)
Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline Modifications
Authors: Xavier Duval, François Delahaye, François Alla, Pierre Tattevin, Jean-François Obadia, Vincent Le Moing, Thanh Doco-Lecompte, Marie Celard, Claire Poyart, Christophe Strady, Catherine Chirouze, Michelle Bes, Emmanuelle Cambau, Bernard Iung, Christine Selton-Suty, Bruno Hoen
Journal: Journal of the American College of Cardiology (2012)
Effectiveness of Hyperbaric Oxygen During Fractionated Irradiation of a Transplanted Mouse Tumor
Authors: Anthony E. Howes
Journal: JNCI Journal of the National Cancer Institute (1974)

A study was made of the response of C3H/He mouse mammary tumors to 10 equal fractions of 137CS γ-rays given under air or high-pressure oxygen breathing (O2, 30 psi) conditions; O2, 30 psi also was given for the first or second half of treatment to determine the extent of the presence of hypoxic cells during each segment. Both latter forms of treatment produced tumor responses similar to those obtained when O2, 30 psi, was given for all 10 treatments, which indicated the presence of large numbers of hypoxic cells at all stages of irradiation. By a cell survival model it was deduced that the extent of transfer of cells from a hypoxic to an oxygenated status was greater during the second half of treatment than the first, under both airbreathing and O2, 30 psi, breathing conditions.
Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a comparison using life-table methods.
Authors: R D Situnayake, K A Grindulis, B McConkey
Journal: Annals of the Rheumatic Diseases (1987)

Life-table analysis was applied to the records of 317 patients with rheumatoid arthritis (RA) treated with sulphasalazine (SAS), 201 treated with sodium aurothiomalate (gold), and 163 with penicillamine. They comprised all those treated in our department with these drugs between January 1973 and July 1984. Risks of treatment termination for all reasons were similar for each drug at five years (gold 92%, penicillamine 83%, SAS 81%). The risk of treatment termination due to inefficacy was less for gold (29.5%) than for penicillamine (38.1%) or sulphasalazine (41.2%). Adverse effects, however, led to withdrawal of gold in 57%, penicillamine in 41.2%, and SAS in 37%; the most effective drugs appeared most toxic. Serious adverse effects were much more common in association with gold (17.4%) and penicillamine (12.3%) than with SAS (1.6%). Sulphasalazine appears as well tolerated over long periods in RA as gold or penicillamine and is associated with fewer serious adverse effects; of these drugs, it might therefore be considered the agent of first choice.
Dispensation of long-acting agonists with or without inhaled corticosteroids, and risk of asthma-related hospitalisation: a population-based study
Authors: M. Sadatsafavi, L. D. Lynd, C. A. Marra, J. M. FitzGerald
Journal: Thorax (2013)

<h3>Background</h3> The role of long-acting β-agonists (LABA) added to inhaled corticosteroids (ICS) in the management of asthma is extensively debated. We thought to assess the risk of asthma-related hospitalisation in individuals who regularly filled prescriptions for ICS+LABA compared to those who regularly filled prescriptions for ICS alone or LABA alone, and compared to those who did not regularly fill such medications. <h3>Methods</h3> Using administrative health databases of the province of British Columbia (BC), Canada, from 1997 to 2012, we conducted a nested case-control analysis of a cohort of asthma patients. Cases were defined as those who experienced asthma-related hospitalisation after the first year of their entry into the cohort. For each case, up to 20 controls were matched based on age, sex, date of cohort entry, and several measures of asthma severity. We categorised individuals as regularly exposed, irregularly exposed, or non-exposed to ICS alone, LABA alone, or ICS+LABA based on dispensation records in the past 12 months. The primary outcome measures were the rate ratio (RR) of the asthma-related hospitalisation among categories of regular exposure. <h3>Results</h3> 3319 cases were matched to 43 023 controls. The RR for regular dispensation of ICS+LABA was 1.14 (95% CI 0.93 to 1.41) compared with regular dispensation of ICS alone and 0.45 (95% CI 0.29 to 0.70) compared with regular dispensation of LABA alone. Those who regularly dispensed LABA had to dispense an ICS for at least three quarters of a year to reduce their risk to that of those who did not dispense LABA. <h3>Conclusions</h3> Regular dispensation of ICS+LABA was not associated with an increased risk of asthma-related hospitalisation compared with regular dispensation of ICS alone. Adherence to ICS in patients who regularly receive ICS+LABA seems to be an important factor in the prevention of adverse asthma-related outcomes.
Spiking of Contemporary Human Template DNA with Ancient DNA Extracts Induces Mutations Under PCR and Generates Nonauthentic Mitochondrial Sequences
Authors: C. M. Pusch
Journal: Molecular Biology and Evolution (2004)

Proof of authenticity is the greatest challenge in palaeogenetic research, and many safeguards have become standard routine in laboratories specialized on ancient DNA research. Here we describe an as-yet unknown source of artifacts that will require special attention in the future. We show that ancient DNA extracts on their own can have an inhibitory and mutagenic effect under PCR. We have spiked PCR reactions including known human test DNA with 14 selected ancient DNA extracts from human and nonhuman sources. We find that the ancient DNA extracts inhibit the amplification of large fragments to different degrees, suggesting that the usual control against contaminations, i.e., the absence of long amplifiable fragments, is not sufficient. But even more important, we find that the extracts induce mutations in a nonrandom fashion. We have amplified a 148-bp stretch of the mitochondrial HVRI from contemporary human template DNA in spiked PCR reactions. Subsequent analysis of 547 sequences from cloned amplicons revealed that the vast majority (76.97%) differed from the correct sequence by single nucleotide substitutions and/or indels. In total, 34 positions of a 103-bp alignment are affected, and most mutations occur repeatedly in independent PCR amplifications. Several of the induced mutations occur at positions that have previously been detected in studies of ancient hominid sequences, including the Neandertal sequences. Our data imply that PCR-induced mutations are likely to be an intrinsic and general problem of PCR amplifications of ancient templates. Therefore, ancient DNA sequences should be considered with caution, at least as long as the molecular basis for the extract-induced mutations is not understood.
Cancer converts tobacco lobbyist: Victor L. Crawford goes on the record. Interview by Andrew A. Skolnick
Authors: V. L. Crawford
Journal: JAMA (1995)

SHAKESPEARE said it in<i>Julius Caesar</i>: "The evil that men do lives after them / The good is oft interred with their bones." Oft, but not always. Sometimes someone who does what many view as wrong has both the time and inclination to make amends. Victor Crawford does not have much time—he is dying of T2, N2c squamous cell stage IV carcinoma of the base of the tongue with pulmonary and bone metastases—but he does have the inclination to undo much of the harm he says he believes he caused as a lobbyist for the tobacco industry. Crawford, an attorney and retired Maryland state legislator who lives in Rockville, Md, worked as a contractual lobbyist for the Tobacco Institute during the late 1980s. He did it for the money, he says, although it wasn't very much. He estimates that he made at least $20 000 during the 6 years he helped
A Phase II Placebo-Controlled Trial of Neoadjuvant Anastrozole Alone or With Gefitinib in Early Breast Cancer
Authors: Ian E. Smith, Geraldine Walsh, Anthony Skene, Antonio Llombart, José Ignacio Mayordomo, Simone Detre, Janine Salter, Emma Clark, Patrick Magill, Mitch Dowsett
Journal: Journal of Clinical Oncology (2007)

Purpose Increased epidermal growth factor receptor (EGFR) expression may promote breast cancer resistance to endocrine therapy. We have therefore investigated whether neoadjuvant gefitinib, an EGFR inhibitor, might overcome biologic and clinical resistance to neoadjuvant anastrozole in a phase II placebo-controlled trial. Patients and Methods Postmenopausal women with stage I to IIIB hormone receptor–positive early breast cancer received anastrozole 1 mg daily for 16 weeks and were randomly assigned at a ratio of 2:5:5 to receive, in addition, gefitinib 250 mg/d orally for 16 weeks: placebo 1 tablet/d orally for 2 weeks and then gefitinib for 14 weeks or placebo for 16 weeks. The primary end point was biologic change in proliferation as measured by Ki67 at 2 and 16 weeks; the main secondary end point was overall objective response (OR). Results Two hundred six women were randomly assigned. Mean changes in Ki67 with anastrozole and gefitinib versus anastrozole alone were −77.4% and −83.6%, respectively, between baseline and 16 weeks (geometric mean ratio = 1.37; 95% CI, 0.79 to 2.39; P = .26), −80.1% and −71.3% between baseline and 2 weeks (geometric mean ratio = 0.70; 95% CI, 0.39 to 1.25; P = .22) and −19.3% and −43% (geometric mean ratio = 1.42; 95% CI, 0.86 to 2.35; P = .16) between 2 and 16 weeks. ORs in the combination and anastrozole alone groups were 48% and 61% (estimated difference = −13.1%; 95% CI, –27.3% to 1.2%), respectively, with a nonsignificant trend against the combination (P = .08) and 48% versus 72% (estimated difference = −24.1%; 95% CI, –45.3% to −2.9%) in the progesterone-receptor–positive subgroup, which was significant (P = .03) and consistent with Ki67 changes. Common treatment-related adverse events included diarrhea, rash, alopecia, dry skin, and nausea. There was no evidence of a pharmacokinetic interaction. Conclusion Addition of gefitinib to neoadjuvant anastrozole had no additional clinical or biologic effect, failing to support our original hypothesis.
Intercollegiate Board for Sport and Exercise Medicine
Authors: Donald A D Macleod
Journal: British Journal of Sports Medicine (2000)

Establishing a new medical discipline in the United Kingdom must meet a series of criteria laid down by the European Medical Specialist Qualification Order, the General Medical Council, and the Specialist Training Authority (STA). Enthusiastic practitioners of sport and exercise medicine must meet the demands of these bodies before the National Health Service medical education unit will recommend that the secretary of state for health should amend schedule 2 of the Specialist Medical Order.

There is a reluctance in the STA to increase the number of specialties. Any proposal to support the recognition of sport and exercise medicine will need to be soundly based and closely argued, demonstrating that an identified need for the specialty can be met by appropriately trained doctors.

Postgraduate medical training in the United Kingdom is based on doctors spending one year as a preregistration house officer followed by a minimum of two years general professional/basic specialty training giving a breadth of experience before the doctor chooses a higher specialty training programme. These supervised programmes vary from a minimum of one year in general practice to four to six years in hospital based or community medicine specialties. Thereafter, the doctor applies to the STA for recognition that his/her training has been completed. This …