tbuckley/cabot-search huggingface dataset:
Validation of Current Practice and a near Patient Testing Method for Oral-Anticoagulant Control in General Practice
Authors: David A Seamark, Susan Backhouse, Paul Barber, John Hichens, Richard Lee, Roy Powell
Journal: Journal of the Royal Society of Medicine (1997)

When oral anticoagulant control is monitored in general practice, venous blood samples are usually transported to a central laboratory for determination of international normalized ratio (INR). An alternative is near patient testing by a commercial method. In a rural general practice 27 km from a central haematology laboratory, whole blood samples were drawn from patients receiving oral anticoagulants and analysed by three methods: after centrifugation, plasma separated and frozen in liquid nitrogen, transported to the laboratory, thawed and immediately analysed (control); courier transport of citrated sample to the laboratory for analysis (routine); near patient testing of whole blood sample (NPT). Maximum temperature achieved and time to analysis for routine samples were recorded. 306 complete sets of data were obtained. Comparison between the routine method and the control method revealed acceptable agreement. On multiple regression analysis, maximum temperature achieved did not contribute to differences observed but time to analysis of over 5 hours did make a significant contribution. Comparison between the NPT method and control method showed acceptable agreement, with persistent under-recording by the NPT method. The routine method for INR determination was validated as robust and reproducible with the proviso that needle-to-analysis time should be kept below 5 hours. The NPT method was valid under conditions of normal general practice. Strict quality control of NPT methods is essential if performance is to be comparable with that of established methods.
PML/RARα-Regulated miR-181a/b Cluster Targets the Tumor Suppressor RASSF1A in Acute Promyelocytic Leukemia
Authors: Daniela Bräuer-Hartmann, Jens-Uwe Hartmann, Alexander Arthur Wurm, Dennis Gerloff, Christiane Katzerke, Maria Vittoria Verga Falzacappa, Pier Giuseppe Pelicci, Carsten Müller-Tidow, Daniel G. Tenen, Dietger Niederwieser, Gerhard Behre
Journal: Cancer Research (2015)

In acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA) treatment induces granulocytic maturation and complete remission of leukemia. microRNAs are known to be critical players in the formation of the leukemic phenotype. In this study, we report downregulation of the miR-181a/b gene cluster in APL blasts and NB4 leukemia cells upon ATRA treatment as a key event in the drug response. We found that miR-181a/b expression was activated by the PML/RARα oncogene in cells and transgenic knock-in mice, an observation confirmed and extended by evidence of enhanced expression of miR-181a/b in APL patient specimens. RNA interference (RNAi)-mediated attenuation of miR-181a/b expression in NB4 cells was sufficient to reduce colony-forming capacity, proliferation, and survival. Mechanistic investigations revealed that miR-181a/b targets the ATRA-regulated tumor suppressor gene RASSF1A by direct binding to its 3'-untranslated region. Enforced expression of miR-181a/b or RNAi-mediated attenuation of RASSF1A inhibited ATRA-induced granulocytic differentiation via regulation of the cell-cycle regulator cyclin D1. Conversely, RASSF1A overexpression enhanced apoptosis. Finally, RASSF1A levels were reduced in PML/RARα knock-in mice and APL patient samples. Taken together, our results define miR-181a and miR-181b as oncomiRs in PML/RARα-associated APL, and they reveal RASSF1A as a pivotal element in the granulocytic differentiation program induced by ATRA in APL.
Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey
Authors: M M Weissman, J S Markowitz, R Ouellette, S Greenwald, J P Kahn
Journal: American Journal of Psychiatry (1990)

Follow-up studies of psychiatric patients with panic disorder have shown an abnormally high mortality rate in men due to cardiovascular and cerebrovascular events. The authors report that in the New Haven portion of the Epidemiologic Catchment Area program the risk for stroke in persons with lifetime diagnoses of panic disorder was over twice that in persons with other psychiatric disorders or no psychiatric disorder. After adjustments for demographic differences between groups, the risk was even higher. While the results should be interpreted cautiously because of the small sample and absence of medical examinations, these findings are consistent with clinical studies showing an association between panic disorder and cardiovascular/cerebrovascular events.
An Italian, observational, multicenter trial in female COPD patients: Preliminary data on the women reality in the MISTRAL study
Authors: Pietro Schino, Alberto Carrassi, Giosuè Catapano, Francesco Ventrella, Evren Karayel, Marta Bartezaghi, Francesco Sergio
Journal: European Respiratory Journal (2014)

Introduction  Clinical management of COPD patients (pts) can be influenced by whether the pts are frequent or non-frequent exacerbators (FE or NFE, respectively) depending on history of exacerbations in the previous year. Evidence suggests that females are at a higher risk of developing COPD vs male pts. The ongoing MISTRAL study was designed to describe the changes in COPD treatment management between the FE or NFE COPD pts9 phenotypes and genders. Here, we present the description of female population on the first 217 entered pts of the MISTRAL study.  Methods  The MISTRAL study is an Italian, 3-year, multicenter, longitudinal, prospective, observational cohort study to evaluate pharmacological management of FE and NFE. Pts are defined as FE and NFE, if they had a previous year history of ≥2 and 0 or 1 exacerbations, respectively (GOLD 2011). Male and female COPD pts aged ≥40yrs with a smoking history of ≥10 pack-years were enrolled.  Results  Of the 1500 planned pts, 217 were included in the first 6 months of enrollment. Among these, 18.4% were women and 81.6% were men. In particular, 55% and 63.1% of the enrolled women and men were non-frequent exacerbators, respectively.  Conclusion  The preliminary data show a pattern in which the percentage of women affected by COPD that is lower than the expected. No relevant differences between exacerbators distribution was observed.  Reference:  1. Donaldson et al Respiratory research 2013, 14:79  2. Viegi, Respiration 2001, 68:4-19  3. GOLD 2011. http://www.goldcopd.com
Capecitabine vs. capecitabine + trastuzumab in patients with HER2-positive metastatic breast cancer progressing during trastuzumab treatment: The TBP phase III study (GBG 26/BIG 3–05)
Authors: G. Von Minckwitz, C. Zielinski, E. Maarteense, P. Vogel, M. Schmidt, H. Eidtmann, T. Cufer, F. E. de Jongh, M. Kaufmann, S. Loibl
Journal: Journal of Clinical Oncology (2008)

1025 Background: There is uncertainty, if trastuzumab treatment should be continued beyond progression (TBP). Methods: Patients (pts) with HER-2 positive, locally advanced or metastatic breast cancer that progressed during treatment with trastuzumab with or without adjuvant and/or 1st-line metastatic chemotherapy were prospectively randomized to capecitabine (X; 2,500 mg/m² on days 1–14, q21) or X plus continuation of trastuzumab (XH; 6 mg/kg, q3w). The primary end point was TTP. With registration of lapatinib, the slowly accruing trial was closed prematurely. Results: Between 01/04 and 05/07 156 pts (X=78; XH=78) were randomized and stratified according to pre-treatment: taxane/trastuzumab as 1st-line therapy (111 pts), taxanes/trastuzumab as adjuvant therapy (3 pts), trastuzumab alone or without taxanes as 1st-line treatment (42 pts). 75 (48.1%) pts were pre-treated with anthracyclines. 119 (76.3%) showed visceral metastasis. Current analysis (median follow-up 11.8 months) revealed a progression-free survival of 5.6 months with 53 events for X and 8.5 months with 48 events for XH (HR=0.71). Brain metastases were observed in 4 (X) and 7 (XH) pts. Overall survival was 19.9 months with 31 events for X and 20.3 months with 26 events in XH (HR=0.79). Crude response rates were 24.6% (X) and 49.1% (XH) and primary progressions were observed in 26.3% (X) and 16% (XH) of patients. Grade III/IV toxicities were (%X/%XH): neutropenia (3.3/6.3), febrile neutropenia (0/0), vomiting (6.0/1.6), diarrhea (20.9/14.8), mucositis (3.0/1.6), hand-foot syndrome (23.9/31.1), nail changes (0/4.9), sensory neuropathy (4.5/3.3), fatigue (6.0/4.9), allergic (3.0/3.3), and cardiac (2.9/4.9). No therapy-related death occurred. Conclusions: Preliminary results of the TBP study suggest a higher efficacy but similar toxicity for continuing trastuzumab beyond trastuzumab progression when 2nd-line chemotherapy with capecitabine is initiated. Final efficacy analysis will be performed in March 2008. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche Roche Roche
Blood Transfusion and 30-Day Mortality in Patients With Coronary Artery Disease and Anemia Following Noncardiac Surgery
Authors: Robert H. Hollis, Brandon A. Singletary, James T. McMurtrie, Laura A. Graham, Joshua S. Richman, Carla N. Holcomb, Kamal M. Itani, Thomas M. Maddox, Mary T. Hawn
Journal: JAMA Surgery (2015)

<h3>Importance</h3> Although liberal blood transfusion thresholds have not been beneficial following noncardiac surgery, it is unclear whether higher thresholds are appropriate for patients who develop postoperative myocardial infarction (MI). <h3>Objective</h3> To evaluate the association between postoperative blood transfusion and mortality in patients with coronary artery disease and postoperative MI following noncardiac surgery. <h3>Design, Setting, and Participants</h3> Retrospective cohort study involving Veterans Affairs facilities from January 1, 2000, to December 31, 2012. A total of 7361 patients with coronary artery disease who underwent inpatient noncardiac surgery and had a nadir postoperative hematocrit between 20% and 30%. Patients with significant bleeding, including any preoperative blood transfusion or transfusion of greater than 4 units during the intraoperative or postoperative setting, were excluded. Mortality rates were compared using both logistic regression and propensity score matching. Patients were stratified by postoperative nadir hematocrit and the presence of postoperative MI. <h3>Exposure</h3> Initial postoperative blood transfusion. <h3>Main Outcomes and Measures</h3> The 30-day postoperative mortality rate. <h3>Results</h3> Of the 7361 patients, 2027 patients (27.5%) received at least 1 postoperative blood transfusion. Postoperative mortality occurred in 267 (3.6%), and MI occurred in 271 (3.7%). Among the 5334 patients without postoperative blood transfusion, lower nadir hematocrit was associated with an increased risk for mortality (hematocrit of 20% to &lt;24%: 7.3%; 24% to &lt;27%: 3.7%; and 27% to 30%: 1.6%;<i>P</i> &lt; .01). In patients with postoperative MI, blood transfusion was associated with lower mortality, for those with hematocrit of 20% to 24% (odds ratio, 0.28; 95% CI, 0.13-0.64). In patients without postoperative MI, transfusion was associated with significantly higher mortality for those with hematocrit of 27% to 30% (odds ratio, 3.21; 95% CI, 1.85-5.60). <h3>Conclusions and Relevance</h3> These findings support a restrictive postoperative transfusion strategy in patients with stable coronary artery disease following noncardiac surgery. However, interventional studies are needed to evaluate the use of a more liberal transfusion strategy in patients who develop postoperative MI.
NK-DC crosstalk controls the autopathogenic Th17 response through an innate IFN-γ–IL-27 axis
Authors: Wai Po Chong, Nicholas van Panhuys, Jun Chen, Phyllis B. Silver, Yingyos Jittayasothorn, Mary J. Mattapallil, Ronald N. Germain, Rachel R. Caspi
Journal: The Journal of Experimental Medicine (2015)

IFN-γ is a pathogenic cytokine involved in inflammation. Paradoxically, its deficiency exacerbates experimental autoimmune encephalomyelitis, uveitis, and arthritis. Here, we demonstrate using IFN-γ−/− mice repleted with IFN-γ+/+ NK cells that innate production of IFN-γ from NK cells is necessary and sufficient to trigger an endogenous regulatory circuit that limits autoimmunity. After immunization, DCs recruited IFN-γ-producing NK cells to the draining lymph node and interacted with them in a CXCR3-dependent fashion. The interaction caused DCs to produce IL-27, which in turn enhanced IFN-γ production by NK cells, forming a self-amplifying positive feedback loop. IL-10, produced by the interacting cells themselves, was able to limit this process. The NK-DC–dependent IL-27 inhibited development of the adaptive pathogenic IL-17 response and induced IL-10–producing Tr1-like cells, which ameliorated disease in an IL-10-dependent manner. Our data reveal that an early NK-DC interaction controls the adaptive Th17 response and limits tissue-specific autoimmunity through an innate IFN-γ–IL-27 axis.
Life-span perspective of susceptibility to tobacco smoking in men and women
Authors: Toril Mørkve Knudsen, Roy Miodini Nilsen, Trude Duelien Skorge, Cecilie Svanes
Journal: European Respiratory Journal (2012)

Aim: Maternal smoking  in utero , age of smoking debut, and pack years, were examined in relation to wheeze, bronchial reactivity (BHR), and other airways symptoms in 5348 male and 5262 female ECRHS participants.  Results: In both men and women, mutually adjusted models showed that wheeze (33%) was statistically significantly associated with maternal smoking  in utero  (men: OR=1.54[1.19-2.00], women: OR=1.53[1.25-1.88]), age of smoking debut (men: p=0.019, women: p  Conclusion: Exposure to tobacco smoking affects adult respiratory health, with women being more susceptible than men to early smoking debut and amount of pack years.  Figure 1. OR for wheeze in relation to age of smoking debut in women and men. Estimated from GAM models.
Matrix metalloproteinase (MMP) -1 and -3 promoter polymorphisms in Bulgarian patients with COPD
Authors: Tatyana Vlaykova, Dimo Dimov, Mateusz Kurzawski, Anna Wajda, Joanna Lapczuk, Vanya Ilieva, Atanas Koychev, Gospodinka Prakova, Marek Drozdzik
Journal: European Respiratory Journal (2011)

COPD is a chronic disease of the lung that is associated with abnormal chronic inflammation in the airways and development of extensive tissue remodeling. MMPs are proteolytic enzymes that play an essential role in tissue remodeling. Polymorphisms in  MMP  gene promoters have been found to alter transcriptional activity. Particularly, 2G allele of -1607insG polymorphism of  MMP1  has been associated with augment transcription of MMP-1, whereas 6A allele of -1171insA polymorphism of  MMP3  – with reduced gene expression.  The aim of our work was to investigate whether the insertion-deletion polymorphisms of  MMP1  (-1607insG) and  MMP3  (-1171insA) have a role as risk factors for developing and progression of COPD. We genotyped 163 Bulgarian patients with COPD and 172 control individuals using PCR-RFLP-based methods.  The analyses showed no significant difference in both  MMP1  and  MMP3  genotype and allele distribution between controls and patients with COPD. We did not find correlation of the genotypes with the age of disease onset, however the COPD patients homozygous for 2G allele (2G/2G) of  MMP1  had, although not significantly, lower values of the spirometric index FEV1% pr. (49.83±14%) compared to the patients with other genotypes (52.37±16, p=0.375). In particular, this difference was higher, reaching a statistical significance, in the subset of patients with smoking history (44.18±13 vs. 50.91±14, p=0.034).  Our data suggest that -1607 2G allele of  MMP1  gene and -1171 6A allele of  MMP3  gene do not represent risk factors for development of COPD, however the homozygous 2G/2G genotype of  MMP1  seems to affect the lung function, especially of smokers, possibly by enhancing  MMP1  gene expression.
Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer.
Authors: D H Lau, J J Crowley, D R Gandara, M B Hazuka, K S Albain, B Leigh, W S Fletcher, K S Lanier, W L Keiser, R B Livingston
Journal: Journal of Clinical Oncology (1998)

PURPOSE A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.
Productivity loss in ever-smoking COPD subjects from a general population
Authors: Rune Nielsen, Ane Johannessen, Per Sigvald Bakke, Ernst Reidar Omenaas, Amund Gulsvik
Journal: European Respiratory Journal (2011)

Background:  We aimed to estimate productivity losses of chronic obstructive pulmonary disease (COPD) in hospital- and population-based subjects with spirometric post-bronchodilator COPD, relative to a control group.   Methods:  53 COPD-cases and 107 randomly recruited individuals without COPD were included from a general population. 102 COPD patients were recruited from a hospital register. All participants were ever-smokers, 40-66 yrs of age. In 4 standardized telephone interviews we surveyed the utilization of sick leave and disability pension during one calendar year. Productivity loss was defined as number of days in sick leave or disability pension. The outcomes in a two-part regression approach were any productivity loss (multiple logistic regression) and number of days of lost productivity (multiple linear regression). The latter model excluded subjects without any productivity loss.   Results:  The logistic regression model showed little effect of COPD when we compared the population-based COPD cases to the controls. In the linear regression model the increased productivity loss in population-based subjects with stage II, stage III and stage IV COPD were (95% CI) 73 (22 - 124), 178 (49 - 308) and 249 (33 - 465) days, compared to the controls. In addition, being a woman, a 1-yr increase in age and low education was associated with an increase of 59 (15 - 103), 6 (2 - 10) and 131 (65 - 197) days of productivity loss. Similar results were found for hospital recruited COPD patients.   Conclusion:  The access to sick leave and disability pension was similar in subjects with and without COPD. The volume of these services was considerably higher in subjects with COPD and was also associated with disease severity.
Effects of home environment on respiratory symptoms and lung function in a general population sample in north Italy
Authors: G Viegi, P Paoletti, L Carrozzi, M Vellutini, L Ballerin, P Biavati, G Nardini, F Di Pede, T Sapigni, MD Lebowitz, al. et
Journal: European Respiratory Journal (1991)

Effects of indoor pollution exposure were evaluated in a general population sample (n = 3,289) living in the Po River Delta area. Prevalence rates of chronic cough in men and dyspnoea in women were significantly higher in association with the use of bottled gas (propane) for cooking instead of natural gas (methane). Chronic cough and phlegm in men and dyspnoea in women were significantly associated with the use of a stove for heating. When combining type of heating and fuel used, in men a trend toward higher prevalence rates of chronic cough and phlegm was shown in those with stove or fan heating (regardless of the fuel); in women the trend reached statistical significance for dyspnoea. The relationship between stove (regardless of fuel) and decrease in forced expirograms was statistically significant only in women. In multiple logistic models, accounting for independent effects of age, smoking, pack-years, parents' smoking, socio-economic status, body mass index, significantly increased odds ratios were found in males for the associations of: bottled gas for cooking with cough (1.66) and dyspnoea (1.81); stove for heating with cough (1.44) and phlegm (1.39); stove fuelled by natural gas and fan or stove fuelled other than by natural gas with cough (1.54 and 1.66). In females, significantly increased odds ratios were found only for dyspnoea when associated with bottled gas for cooking (1.45), stove for heating (1.46), stove fuelled by natural gas (1.58), stove or fan fuelled other than by natural gas (1.73).(ABSTRACT TRUNCATED AT 250 WORDS)
Bernard Aloysius Marshall
Authors: A. A. A. Alsop
Journal: BMJ (2015)

Bernard Aloysius Marshall, or Benny as he was known to friends and family, was born in Dundee to Mary and Alexander Marshall. He was the youngest of four children, and he followed in his older brother’s footsteps by studying medicine at St Andrews University. He often played down this achievement and would say, as he looked at the photo of his year group, that “They passed with honours and distinction, whereas I passed with difficulty.” It was in St Andrews that he developed his lifelong love of all sports, and he was …
Vector analysis in partitioning of inspiratory muscle action in dogs
Authors: ME Ward, M Paiva, PT Macklem
Journal: European Respiratory Journal (1992)

We considered the displacements and the pressure changes resulting from isolated contraction of 2 muscles as analogous to 2 vectors and those during simultaneous contraction as resultants. These were resolved into contributing components to calculate the contribution of each muscle group and partition the action of inspiratory muscles. Relative displacements of rib cage (delta RC) and abdomen (delta AB) and changes in transpulmonary (delta PL) and abdominal (delta Pab) pressures were obtained during spontaneous breathing, isolated contraction of rib cage muscle (RCM), diaphragmatic (DI), costal and crural diaphragm and passive inflation in 7 dogs. The diaphragm accounted for 58 +/- 19.8% SD of the chest wall displacement and 90 +/- 6.6% SD of the pressure swings during spontaneous breathing. The costal diaphragm accounted for 61 +/- 28.9% SD of the displacement produced by contraction of the entire diaphragm. Despite wide variability in the action of the diaphragm and its components, all animals breathed close to their relaxation characteristic. We conclude that there are marked differences in the degree of RCM recruitment between dogs in order to prevent chest wall distortions.