tbuckley/cabot-search huggingface dataset:
Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer
Authors: Caroline Lohrisch, Charles Paltiel, Karen Gelmon, Caroline Speers, Suzanne Taylor, Jeff Barnett, Ivo A. Olivotto
Journal: Journal of Clinical Oncology (2006)

Purpose To determine if time to start of adjuvant chemotherapy after curative surgery influences survival in early-stage breast cancer. Patients and Methods A retrospective review was conducted of 2,594 patients receiving adjuvant chemotherapy for stage I and II breast cancer between 1989 and 1998 at the British Columbia Cancer Agency. Relapse-free survival (RFS) and overall survival (OS) were compared among patients grouped by time from definitive curative surgery to start of adjuvant chemotherapy (≤ 4 weeks, &gt; 4 to 8 weeks, &gt; 8 to 12 weeks, and &gt;12 to 24 weeks). Results RFS and OS were similar for women starting chemotherapy up to 12 weeks after surgery. OS hazard ratio (univariate) for initiation of chemotherapy more than 12 weeks compared with 12 weeks or less after surgery was 1.5 (95% CI, 1.07 to 2.10; P = .017). Five-year OS rates were 84%, 85%, 89%, and 78%, (log-rank P = .013); RFS rates were 74%, 79%, 82%, and 69% (log-rank P = .004) for patients starting chemotherapy 4 weeks or fewer, more than 4 to 8 weeks, more than 8 to 12 weeks, and more than 12 to 24 weeks after surgery, respectively. In multivariate analysis, independent prognostic factors were grade, size, nodal status, estrogen receptor, age, and lymphatic and/or vascular invasion. Initiation of adjuvant chemotherapy more than 12 weeks from surgery remained significantly associated with inferior survival, with a hazard ratio of 1.6 (95% CI, 1.2 to 2.3; P = .005). Conclusion This retrospective analysis suggests that adjuvant chemotherapy is equally effective up to 12 weeks after definitive surgery but that RFS and OS appear to be compromised by delays of more than 12 weeks after definitive surgery.
Cutaneous lesions as the presenting sign of acute graft-versus-host disease following liver transplantation
Authors: M. Schmuth, W. Vogel, G. Weinlich, R. Margreiter, P. Fritsch, N. Sepp
Journal: British Journal of Dermatology (1999)

Acute graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation but is only rarely observed after solid organ transplantation. We describe a 68-year-old man who developed a maculopapular eruption 7 days following orthotopic liver transplantation for cirrhosis with malignant transformation due to haemochromatosis. At day 20, the patient complained of nausea, vomiting, diarrhoea and fever. Skin biopsy revealed a lymphocytic infiltrate at the dermoepidermal interface, vacuolization of basal cells and epidermal dyskeratosis. Immunohistochemistry showed HLA-DR and intercellular adhesion molecule-1 expression of lesional keratinocytes. HLA-typing of peripheral blood lymphocytes demonstrated circulating lymphocytes of donor origin. Endoscopy revealed extensive erosions of the oesophagus, stomach and duodenum that on histology disclosed multifocal loss of crypts, lymphocytic infiltrates and epithelial cell death. A diagnosis of acute GVHD was made, and high-dose immunosuppressive therapy with azathioprine and methylprednisolone was instituted. The skin and gastrointestinal symptoms subsided within 4 weeks, but the patient died from severe infectious complications 105 days after transplantation. We conclude that acute GVHD is a rare but potentially fatal complication of liver transplantation. Skin lesions are an early sign of acute GVHD and thus represent an important tool for early diagnosis.
Long-Chain Monounsaturated Fatty Acids and Incidence of Congestive Heart Failure in 2 Prospective Cohorts
Authors: Fumiaki Imamura, Rozenn N. Lemaitre, Irena B. King, Xiaoling Song, Lyn M. Steffen, Aaron R. Folsom, David S. Siscovick, Dariush Mozaffarian
Journal: Circulation (2013)

Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown.We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2±5.2 years) in the Cardiovascular Health Study (CHS; 1992-2006) and 3577 middle-aged adults (mean age, 54.1±5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987-2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95% confidence interval, 1.02-1.76) and 1.57 (95% confidence interval, 1.11-2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95% confidence interval, 1.23-2.50) and 1.92 (95% confidence interval, 1.22-3.03) for 24:1, respectively (P for trend ≤0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard.Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans.
Opacities of the middle and upper lobes in combination
Authors: B. T. Le Roux
Journal: Thorax (1971)

The diagnosis of bronchial carcinoma was confirmed in 8 of 17 patients who presented with the radiographic appearances of a combination of right upper and middle lobar opacification. In 9 patients the cause of the combination of lobar shadows was inflammatory, in 2 destructive. This experience serves to emphasize that the investigation of lobar and segmental shadows, in whatever combination, must, at an early stage, include bronchoscopy.
Effect of an acute oral protein load on renal acidification in healthy humans and in patients with chronic renal failure.
Authors: N G de Santo, G Capasso, G Malnic, P Anastasio, L Spitali, A D'Angelo
Journal: Journal of the American Society of Nephrology (1997)

The effect of a meat load on the renal handling of acid-base balance was studied in ten healthy subjects (GFR by inulin clearance = 98.5 +/- 8.14 ml.min-1.1.73 m-2) and in ten patients affected by chronic renal failure (CRF) (GFR = 39.9 +/- 5.3 ml.min-1.1.73 m-2). After the meat load (2 g.kg-1 body weight of cooked unsalted red meat), GFR increased by 26.9% (peak value) over baseline in healthy subjects and by 32% in CRF patients. The acid-base status of the healthy subjects was in the normal range, whereas the CRF patients disclosed a slight metabolic acidosis. After a meat load, there was, in the healthy subjects, an increase in the filtered load of bicarbonate coupled to an enhanced tubular reabsorption and urinary excretion. The time course between bicarbonate load and urinary excretion was coincident. In CRF patients, the increase of bicarbonate tubular load after the meal was associated with an increase in tubular reabsorption but not in urinary excretion of this anion. The relationship between bicarbonate load and reabsorption was linear in both groups up to the highest filtered loads. Baseline titratable acidity (TA) and ammonium (NH4+) excretion (expressed per ml GFR) were increased in CRF patients as compared with control subjects, but no changes were found after the meat load in both groups in these experimental conditions. The data indicate that the renal tubules contribute to the maintenance of acid-base balance both in healthy subjects and in CRF patients by reabsorbing most of the additional bicarbonate load. The transient, but significant, increase in bicarbonate excretion observed in healthy subjects could be related to the increased tubular load of bicarbonate. In CRF patients, tubular bicarbonate reabsorption was more complete, possibly because of the stimulation of H+ secretion by the mild metabolic acidosis. TA and NH4+ did not participate in tubular compensation of the increased buffer load.
Hypertension and adherence to physical activity programs--a sticky matter!
Authors: Garry L R Jennings
Journal: British Journal of Sports Medicine (2009)

The public is informed on lifestyle from many sources. In contrast to drug therapy, consumers do not necessarily recognise their physician as being the most authoritative source of information on physical activity. While some physicians are naturally gifted in effecting behavioural change in patients, many of us are not and the track record of obtaining long-term adherence to healthy lifestyle measures is not good. The media provides advice on numerous effective and ineffective lifestyle measures, much of which derive from vested interests. In this context, it is not surprising that physicians have difficulty in getting patients to take up useful lifestyle measures in hypertension and that a bewildered community has decided that medical researchers cannot make their minds up on which lifestyle measures are worthwhile (table 1).

View this table:

Table 1 
The important ingredients to implementing any lifestyle measure in hypertension



Nevertheless, the benefits of success in improving physical activity levels in hypertension are great. The possibility of shifting the frequency distribution of blood pressure in the whole population through physical activity and of achieving the challenging present-day targets for blood pressure by supplementing drug therapy is a major incentive.

Research on efficacy of physical activity and other lifestyle measures has generally focussed on the effect of a single intervention, independent of others. However, single lifestyle interventions are almost unknown in real life. Increase in physical activity is always associated with altered diet.1 A fundamental difference to drug prescription, therefore, is that the recommendation of an apparently simple lifestyle change is always a multiple intervention involving significant effects on daily life. Choosing suitable interventions is therefore the first step, and the challenge of inducing and maintaining change is such that efforts should not be wasted on useless and unproven measures. The scientific framework for contemporary recommendations on physical activity for hypertension has …
Granulomatous lipophagic panniculitis and temporal arteritis in a patient with cryptogenic chronic active hepatitis.
Authors: J E Naschitz, D Yeshurun, J Barth, I Misselevitch, J H Boss
Journal: Annals of the Rheumatic Diseases (1992)

An elderly woman receiving long term treatment with prednisone and azathioprine for cryptogenic chronic active hepatitis developed granulomatous lipophagic panniculitis and temporal arteritis. The lymphoplasmahistiocytic inflammatory reaction pattern is common to this patient9s three diseases. It is suggested that an aberration of the defence mechanisms, immunological or otherwise, is responsible for this unusual occurrence. The triple association of chronic active hepatitis, granulomatous panniculitis and temporal arteritis has not been reported previously.
Asthma mortality and death certification in Northern Ireland.
Authors: S C Wright, A E Evans, D G Sinnamon, J MacMahon
Journal: Thorax (1994)

Asthma mortality has been rising in many western countries for largely unknown reasons. One cause could be change in certification practice. This study was designed to investigate the accuracy of death certification in Northern Ireland for the years 1981-4 and, in addition, to assess the reliability of trends observed in asthma death registration from 1957 to 1985.The following death certificates were obtained for the years 1981-4: those mentioning asthma (all age groups), chronic obstructive airway disease, emphysema, or chronic bronchitis, but only where the decreased was 55 years or less. Information was collected from medical records, questionnaires to the general practitioner, and interviews with a close relative of the decreased. Death as a result of asthma was confirmed or otherwise by a panel and the confirmed deaths were compared with those registered. The numbers of deaths from asthma for the years 1957-85 were obtained from the offices of the Northern Ireland Registrar General.A total of 174 deaths from asthma was identified; 123 (70.7%) had been registered, while the remainder had been coded under another diagnosis. The annual number of confirmed deaths differed little from the figures of the Registrar General. A sharp increase in the annual number of deaths from asthma was observed, beginning in 1977, following a decline in the mid 1970s.During the years 1981-4 death certification for asthma was found to be inaccurate. The number of false positive registrations was balanced by the number of false negatives, suggesting that the registered totals reflect actual asthma mortality.
Successful use of high dose rate brachytherapy for non-malignant bronchial obstruction
Authors: M R Kramer
Journal: Thorax (2001)

High dose rate (HDR) endobronchial brachytherapy is a palliative treatment for symptomatic airway obstruction by malignant tumours. We report a novel use of HDR brachytherapy for treating non-malignant bronchial obstruction. The patient had a metal stent placed in a reconstructed airway after a bronchial tear to ensure patency. Granulation tissue formation in and around the stent caused symptomatic occlusion of the airway, necessitating multiple laser applications. A single treatment of HDR brachytherapy (1000 cGy) was delivered following laser therapy. The patient remains well 15 months after treatment with no evidence of recurrent granulation tissue formation on bronchoscopy. HDR brachytherapy is an effective treatment for non-malignant airway obstruction.
The <i>MET</i> Oncogene Is a Functional Marker of a Glioblastoma Stem Cell Subtype
Authors: Francesca De Bacco, Elena Casanova, Enzo Medico, Serena Pellegatta, Francesca Orzan, Raffaella Albano, Paolo Luraghi, Gigliola Reato, Antonio D'Ambrosio, Paola Porrati, Monica Patanè, Emanuela Maderna, Bianca Pollo, Paolo M. Comoglio, Gaetano Finocchiaro, Carla Boccaccio
Journal: Cancer Research (2012)

The existence of treatment-resistant cancer stem cells contributes to the aggressive phenotype of glioblastoma. However, the molecular alterations that drive stem cell proliferation in these tumors remain unknown. In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma. Met expression was almost absent from neurospheres expressing the signature of the classical subtype and was mutually exclusive with amplification and expression of the EGF receptor (EGFR) gene. Met-positive and Met-negative neurospheres displayed distinct growth factor requirements, differentiated along divergent pathways, and generated tumors with distinctive features. The Met(high) subpopulation within Met-pos neurospheres displayed clonogenic potential and long-term self-renewal ability in vitro and enhanced growth kinetics in vivo. In Met(high) cells, the Met ligand HGF further sustained proliferation, clonogenicity, expression of self-renewal markers, migration, and invasion in vitro. Together, our findings suggest that Met is a functional marker of glioblastoma stem cells and a candidate target for identification and therapy of a subset of glioblastomas.
Reduced carotid atherosclerosis in asthmatic patients treated with inhaled corticosteroids
Authors: M. Otsuki, A. Miyatake, K. Fujita, T. Hamasaki, S. Kasayama
Journal: European Respiratory Journal (2010)

Although inflammation is an important component of atherosclerosis, it is unknown whether inhaled corticosteroids (ICS) as anti-inflammatory drugs prevent atherosclerosis. In the present study, carotid atherosclerosis was evaluated by ultrasonography in 150 asthmatic patients who had been regularly treated with ICS, and in 150 matched nonasthmatic controls, with an assessment of atherosclerotic risk factors. Carotid intima-media thickness was significantly lower in the asthmatic patients than in the controls. The prevalence of carotid plaque tended to be lower in the asthmatic patients than in the controls. Defined carotid atherosclerosis was diagnosed in 51 of the asthmatic patients, who were older, with a higher prevalence of males, a higher prevalence of dyslipidaemia and a lower mean daily dose of ICS than the 99 patients without carotid atherosclerosis. Stepwise multiple logistic regression analysis identified age, male sex and dyslipidaemia as positive risk factors for carotid atherosclerosis. The mean daily dose of ICS was a negative risk factor. Carotid atherosclerosis is reduced in asthmatic patients treated with ICS compared with matched controls. This study suggests that ICS may have protective effects against atherosclerosis.
Influence of dietary fat on duodenal resistance to acid.
Authors: A Lugea, A Salas, F Guarner, J R Malagelada
Journal: Gut (1993)

Three experimental diets were prepared from a standard formula plus pure oleic, linoleic, or eicosapentaenoic acid (2% by weight). Mucosal resistance to acid was tested in anaesthetised rats fed the experimental diets for at least four weeks (60 rats per diet) by duodenal infusion of HCl (200 to 700 mumol) 30 minutes after pretreatment with either saline or 100 mumol HCl (used as a mild irritant). Rats were killed one hour after the test and the duodenal damage was assessed 9blindly9 using a combined macroscopic and histological score. Differences were tested by analysis of covariance of the dose-response curves. Mucosal resistance was similar in the three groups when the acid challenge was given after saline pretreatment. Resistance to acid in all three groups was significantly increased by previous exposure to 100 mumol HCl (p &lt; 0.01). Interestingly, rats fed a linoleic or eicosapentaenoic supplemented diet after pretreatment with HCl developed significantly higher resistance to acid than those fed the diet with oleic acid (p &lt; 0.05). Pretreatment with indomethacin suppressed the difference between diets. In conclusion, dietary polyunsaturated fatty acids enhance duodenal resistance to acid by potentiation of adaptive cytoprotection.
Wnt11 inhibits epithelial-mesenchymal transition induced by TGFb1 in human type II alveolar epithelial cells
Authors: Domokos Bartis, Vijay D'Souza, Judit E. Pongracz, David R. Thickett
Journal: European Respiratory Journal (2012)

Increased activity of TGFβ1 plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Alveolar type II cells (ATII) undergo EMT expressing mesenchymal markers when exposed to a high concentration of TGFβ1 in both in vitro and in vivo models. Mesenchymal signals might contribute to the differentiation and regeneration of pulmonary epithelium. Wnt11 is a secreted glycoprotein known to be expressed in the mesenchyme of the embryonic lung.  We constructed a 3-dimensional (3D) human tissue model of primary human pulmonary cells to mimic epithelial-mesenchymal interactions in the lung. Our results indicate that human lung fibroblasts are a source of Wnt11 in the lung tissue model. ATII cells isolated from human lung samples were treated with recombinant TGFβ1 and/or Wnt11. Expression levels of the EMT markers N-cadherin, Vimentin, alpha smooth musle actin (αSMA) and SLUG were determined by qPCR and immunofluorescence. We found that Wnt11 inhibits EMT induced by TGFβ1 in ATII monolayers and in 2D and 3D ATII+fibroblast co-cultures. Wnt11 treatment resulted in decreased expression of EMT markers compared to TGFβ1 treated cell cultures.  We propose that the pulmonary mesenchyme might contribute to the homeostasis of epithelial cells by secreting Wnt11. The finding that effects of TGFβ1 can be antagonized by Wnt11 may mark it as a potential therapeutic target in the fibrotic diseases of lung.
Ornithine Decarboxylase-1 Polymorphism, Chemoprevention With Eflornithine and Sulindac, and Outcomes Among Colorectal Adenoma Patients
Authors: J. A. Zell, C. E. McLaren, W.-P. Chen, P. A. Thompson, E. W. Gerner, F. L. Meyskens
Journal: JNCI Journal of the National Cancer Institute (2010)

The ornithine decarboxylase-1 (ODC1) polymorphism at position +316 affects binding by transcriptional activators and repressors and modulates the risk of metachronous colorectal adenomas, particularly in association with aspirin use. We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma patients in a randomized phase III trial were genotyped for ODC1. We used Wilcoxon rank sums tests on non-normally distributed continuous variables across two genotype groups, χ(2) or Fisher exact test to assess the association between baseline categorical variables and genotype group, and log binomial regression for the primary (adenoma recurrence) and secondary outcomes (tissue polyamine response, cardiovascular toxicity, gastrointestinal toxicity, and ototoxicity). All statistical tests were two-sided. In binomial regression models with variables age, sex, race, aspirin use, treatment, and ODC1 genotype, treatment was the only statistically significant factor associated with differences in adenoma recurrence or tissue polyamine response. A statistically significant interaction was detected between ODC1 genotype and treatment with respect to adenoma recurrence (placebo group: GG, 50%, AA/GA: 34%; treatment group: GG, 11%, AA/GA, 21%; P(interaction) = .038). Excess ototoxicity was observed among ODC1 AA patients receiving treatment, but the interaction of genotype and treatment on ototoxicity was not statistically significant (P = .45).