tbuckley/cabot-search huggingface dataset:
Faecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae is common 12 months after infection and is related to strain factors
Authors: E. Titelman, C.M. Hasan, A. Iversen, P. Nauclér, M. Kais, M. Kalin, C.G. Giske
Journal: Clinical Microbiology and Infection (2014)

We aimed to determine the duration of faecal carriage of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae (EPE) in patients with clinical infection caused by an EPE, to study host strains during carriage, and to identify factors associated with prolonged carriage. Patients (n = 61) were followed with faecal samples and questionnaires about antimicrobial treatment and risk factors for EPE, 1, 3, 6 and 12 months after EPE infection. The EPE isolates were subjected to ESBL genotyping, epidemiological typing with pulsed-field gel electrophoresis and PCR-based replicon typing. Escherichia coli isolates were analysed with PCR for phylogrouping, detection of pabB (ST131) and virulence content. Patient-related and strain-related variables were compared for carriers and non-carriers at 12 months. Carriage of EPE was observed in 51 of 61 (84%) patients after 1 month, 36 of 61 (66%) after 3 months, 31 of 61 (55%) after 6 months and 26 of 61 (43%) after 12 months. Of the 26 carriers at 12 months, five had previous negative samples. In 17 of 61 patients, ESBL was found in a new bacterial species and/or strain during carriage. Among E. coli, 14 of 49 belonged to the international clone ST131. Phylogroup B2 and CTX-M-gr.-9 were associated with being carriers at 12 months (OR 4.3, 95% CI 1.1-16.3 and OR 6.4, 95% CI 1.3-30.9, respectively). In conclusion, EPE carriage is common 12 months after infection and persisting carriage may be associated with E. coli phylogroup B2 and CTX-M-gr.-9. The host strain frequently changes throughout carriage and negative samples do not imply eliminated carriage.
Changes in Gene Expression Associated With Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Juliane Hannemann, Hendrika M. Oosterkamp, Cathy A.J. Bosch, Arno Velds, Lodewyk F.A. Wessels, Claudette Loo, Emiel J. Rutgers, Sjoerd Rodenhuis, Marc J. van de Vijver
Journal: Journal of Clinical Oncology (2005)

Purpose At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens. Patients and Methods Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy. Results Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy. Conclusion No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.
A quality-of-life measure for adults with primary ciliary dyskinesia: QOL–PCD
Authors: Jane S. Lucas, Laura Behan, Audrey Dunn Galvin, Adrianne Alpern, Anjana M. Morris, Mary P. Carroll, Michael R. Knowles, Margaret W. Leigh, Alexandra L. Quittner
Journal: European Respiratory Journal (2015)

Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL–PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL–PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL–PCD has been translated into other languages and is awaiting psychometric testing.
Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent
Authors: T Watanabe, K Higuchi, A Kobata, H Nishio, T Tanigawa, M Shiba, K Tominaga, Y Fujiwara, N Oshitani, T Asahara, K Nomoto, K Takeuchi, T Arakawa
Journal: Gut (2007)

Background: Enterobacteria and cytokines both play roles in the pathophysiology of NSAID-induced enteropathy. Toll-like receptor (TLR) 4 recognises lipopolysaccharide (LPS), resulting in activation of an inflammatory cascade via the accessory protein MyD88. Aims: To investigate role of TLR4 in inflammatory responses in indomethacin-induced enteropathy. Methods: Indomethacin was administered p.o. to non-fasting rats and mice to induce small intestinal damage. The extent of such damage was evaluated by measuring the injured area stained dark blue with Evans blue. Rats were given antibiotics (ampicillin, aztreonam or vancomycin) p.o., or intraperitoneal LPS (a TLR4 ligand) or neutralising antibodies against neutrophils, tumour necrosis factor (TNF)-α, or monocyte chemotactic protein (MCP)-1. Furthermore, the intestinal ulcerogenicity of indomethacin was examined in TLR4-mutant, TLR4−/−, and MyD88−/− mice. Results: Indomethacin induced small intestinal damage with an increase in expression of TNF-α and MCP-1 in both rats and mice. Antibodies against neutrophils, TNF-α and MCP-1 inhibited the damage by 83%, 67% and 63%, respectively, in rats. Ampicillin and aztreonam also inhibited this damage, and decreased the number of Gram-negative bacteria in the small intestinal contents of the rat. However, vancomycin, which exhibited no activity against Gram-negative bacteria, had no preventive effect against this damage. Administration of LPS 1 h after indomethacin aggravated the damage, whereas LPS pretreatment inhibited it with reduction of expression of TLR4 and cytokines. In TLR4-mutant mice, the damage and cytokine expression were markedly inhibited. TLR4−/− and MyD88−/− mice were also resistant to the damage. Conclusions: Indomethacin may injure the small intestine through a TLR4/MyD88-dependent pathway.
Hypothyroidism associated with mixed connective tissue disease and its response to steroid therapy.
Authors: R H Withrington, M H Seifert
Journal: Annals of the Rheumatic Diseases (1981)

The case is reported of a 49-year-old housewife who presented with arthralgia and severe Raynaud9s phenomenon. A diagnosis of mixed connective tissue disease (MCTD) was made on the basis of the clinical picture and serological findings. During the course of her disease she developed hypothyroidism. She was started on prednisolone to control the symptoms of the MCTD, and after this her thyroid function returned to normal despite her never having had any thyroid replacement therapy. There is reported evidence that Hashimoto9s thyroiditis responds to systemic steroid preparations, but we can find no report of hypothyroidism in MCTD having a similar response.
Phase I clinical and pharmacokinetic studies of the taxoid derivative RPR 109881A administered as a 1-hour or a 3-hour infusion in patients with advanced solid tumors
Authors: C. Sessa, C. Cuvier, S. Caldiera, J. Bauer, S. Van den Bosch, C. Monnerat, D. Semiond, D. Pérard, A. Lebecq, M. Besenval, M. Marty
Journal: Annals of Oncology (2002)
The Nuclear Transcription Factor κB/bcl-2 Pathway Correlates with Pathologic Complete Response to Doxorubicin-Based Neoadjuvant Chemotherapy in Human Breast Cancer
Authors: Thomas A. Buchholz, Amit K. Garg, Nitin Chakravarti, Bharat B. Aggarwal, Francisco J. Esteva, Henry M. Kuerer, S. Eva Singletary, Gabriel N. Hortobagyi, Lajos Pusztai, Massimo Cristofanilli, Aysegul A. Sahin
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Molecular factors involved in apoptosis may affect breast cancer response to chemotherapy. Herein, we studied the nuclear factor κB (NF-κB)/bcl-2 pathway to determine whether or not activation of this antiapoptotic pathway was associated with a poor response of human breast cancer to anthracycline-based neoadjuvant chemotherapy. Experimental Design: We studied 82 human breast cancer samples from patients treated with neoadjuvant doxorubicin-based chemotherapy and studied whether or not nuclear location of the transcription factor NF-κB was associated with expression of bcl-2 and bax and whether or not expression of these proteins correlated with chemotherapy response. Protein expression was measured with immunohistochemical staining. A dedicated breast cancer pathologist who was unaware of the clinical outcome data dichotomized the slides as positive or negative based on the presence or absence of cytoplasmic staining for bcl-2 and bax or nuclear staining for NF-κB. Results: Sixty-one percent of the tumors were positive for bcl-2, 85% were positive for bax, and 16% were positive for NF-κB. All bcl-2-positive tumors were also bax positive (P &amp;lt; 0.0001) and all NF-κB-positive tumors were both bcl-2 positive (P = 0.001) and bax positive (P = 0.113). Eleven of the 82 patients (13%) had a pathologic complete response (pCR) to chemotherapy. Patients with positive staining tumors for any of the markers less commonly achieved a pCR to chemotherapy than those with negative tumor staining. The pCR rates were NF-κB positive 0% (0 of 13) versus NF-κB negative 13% (11 of 69; P = 0.130); bcl-2 positive 4% (2 of 49) versus bcl-2 negative 27% (9 of 33; P = 0.004); and bax positive 6% (4 of 69) versus bax negative 58% (7 of 12; P &amp;lt; 0.001). Conclusion: We conclude that nuclear localization of NF-κB correlates with bcl-2 and bax expression and that the NF-κB/bcl-2 pathway may be associated with a poor response to neoadjuvant doxorubicin-based chemotherapy.
Retracing Evolution of Red Fluorescence in GFP-Like Proteins from Faviina Corals
Authors: S. F. Field, M. V. Matz
Journal: Molecular Biology and Evolution (2009)

Proteins of the green fluorescent protein family represent a convenient experimental model to study evolution of novelty at the molecular level. Here, we focus on the origin of Kaede-like red fluorescent proteins characteristic of the corals of the Faviina suborder. We demonstrate, using an original approach involving resurrection and analysis of the library of possible evolutionary intermediates, that it takes on the order of 12 mutations, some of which strongly interact epistatically, to fully recapitulate the evolution of a red fluorescent phenotype from the ancestral green. Five of the identified mutations would not have been found without the help of ancestral reconstruction, because the corresponding site states are shared between extant red and green proteins due to their recent descent from a dual-function common ancestor. Seven of the 12 mutations affect residues that are not in close contact with the chromophore and thus must exert their effect indirectly through adjustments of the overall protein fold; the relevance of these mutations could not have been anticipated from the purely theoretical analysis of the protein's structure. Our results introduce a powerful experimental approach for comparative analysis of functional specificity in protein families even in the cases of pronounced epistasis, provide foundation for the detailed studies of evolutionary trajectories leading to novelty and complexity, and will help rational modification of existing fluorescent labels.
Osteoporosis is not a specific complication of primary biliary cirrhosis (PBC)
Authors: A Floreani
Journal: Gut (2002)

Hypomagnesaemia due to malabsorption is not always responsive to oral magnesium oxide supplementation aloneWe read with interest the Gut File report by Dr Ross and colleagues of hypomagnesaemia due to malabsorption, eventually responding to oral magnesium oxide supplementation (Gut 2001;48:857-8).Our experience however has been different.For the past seven years we have managed a 65 year old woman with short bowel syndrome (right hemicolectomy for Duke's C colorectal carcinoma and thereafter a terminal ileal resection for abscess formation).High ileostomy output was initially difficult to manage (after excluding infection, secreting gut hormone tumours by normal hormone levels, and despite dietary and pharmacological modifications).Clinical signs of hypomagnesaemia and hypocalcaemia ensued.An initial trial with magnesium glycerophosphate (September 1992 to December 1993) was insufficient to sustain her serum magnesium levels requiring frequent "top ups" of intravenous magnesium. 1In December 1993, she was switched to magnesium oxide supplementation but despite this the frequency of intravenous magnesium "top ups" were not reduced.Compliance was not deemed to be an issue with our patient.Since then we have managed this woman while still taking magnesium oxide supplements with almost 3-6 monthly (fig 1) intravenous magnesium replacement through a peripheral line and have avoided insertion of a Hickman line and all its associated complications. 2 While we agree that a trial of magnesium oxide is prudent and until the pharmacokinetics are better understood, this preparation may not be sufficient, especially in patients with extensive resection of the small bowel, as demonstrated in our patient.
Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy
Authors: H Kosugi, M Towatari, S Hatano, K Kitamura, H Kiyoi, T Kinoshita, M Tanimoto, T Murate, K Kawashima, H Saito, T Naoe
Journal: Leukemia (1999)
Baseline Chest Radiograph for Lung Cancer Detection in the Randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Authors: Martin M. Oken, Pamela M. Marcus, Ping Hu, Thomas M. Beck, William Hocking, Paul A. Kvale, Jill Cordes, Thomas L. Riley, Stephen D. Winslow, Steven Peace, David L. Levin, Philip C. Prorok, John K. Gohagan
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was initiated in 1992 to examine cause-specific mortality reduction from screening for these four cancers in men and women. We report lung cancer detection results of the baseline screening round. Methods: Of the 154 942 participants enrolled, who were aged 55–74 years with no history of PLCO cancers, 77 465 were randomly assigned to the intervention arm. Current or former smokers and never smokers in this arm received an initial single-view posterior-anterior chest radiograph. Results: In the initial screen, 5991 (8.9%, 95% confidence interval [CI] = 8.7% to 9.2%) of radiographs were suspicious for lung cancer: 8.2% (95% CI = 7.9% to 8.5%) for women and 9.6% (95% CI = 9.3% to 10.0%) for men. Rates were highest for older age groups and for smokers. Among those 5991 participants with a positive screen, 206 (3.4%, 95% CI = 3.0% to 3.9%) underwent biopsy examination, 126 (61.2%, 95% CI = 54.5% to 67.8%) of whom were diagnosed with lung cancer within 12 months of the screen (59 in women and 67 in men). The positive predictive value was 2.1% (95% CI = 1.7% to 2.5%), and 1.9 lung cancers were detected per 1000 screens. Among these cancers, 44% (95% CI = 35% to 52%) were stage I non–small-cell lung cancer. High rates of lung cancer were found in current smokers (6.3 per 1000 screens) and in former smokers who had smoked within the past 15 years (4.9 per 1000 screens). The lung cancer detection rate among never smokers was 0.4 per 1000 screens; this group accounted for 11% (95% CI = 5.6% to 16.6%) of the cancers identified. Conclusions: In the baseline screen, nearly half the cancers were stage I. Whether this experience results in a reduction in lung cancer mortality is yet to be seen.
Comparison of tuberculin test and Diaskintest® in the diagnosis of tuberculosis in children
Authors: Natalia Korneva, Anna Starshinova, Julia Ovchinnikova, Irina Dovgaliuk, Peter Yablonskiy
Journal: European Respiratory Journal (2013)

Russia is the country with a high burden of tuberculosis and routine BCG vaccination at birth. Screening of tuberculosis in children by tuberculin skin test (TST) provides low information, because almost all children have positive results of TST.  Objectives. The aim of this study is to compare specificity and sensitivity of tuberculin skin test (TST) vs Diaskintest ® (DST) in diagnosis of tuberculosis in children.  Materials and Methods. 249 patients from 3 to 14 years old (with a mean age 8,7 years) were examined during 2009-2012 at children9s phthisiopulmonology department. All children were divided in two groups: first one – 154 (61.8%) patients with TB and second one – 95(38.2%) healthy children. All patients underwent the TST and DST.  Results: The results of TST and DST in two groups are showed in the table.  The results of TST and DST  TST I group (154) II group (95) DST I group (154) II group (95  Low (  Medium (10-15 mm) 49.3% (76) 55.8% (53)) doubtful 3.5% (5) 15.7% (15)  High (≥15 mm) 44.2% (68) 24.2% (23) positive 80.0% (123) 25.3% (24)  Results demonstrate that specificity and specificity of DST were significantly higher in comparison with TST: sensitivity (80.0% vs 44.4%) and specificity (59.0% vs 20.0%).  Conclusions: It seems that the DST is a more reliable method for the diagnosis of TB in children in comparison with TST.
Pathophysiology of Coronary Artery Disease
Authors: Peter Libby, Pierre Theroux
Journal: Circulation (2005)

During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a “solid-state” stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the “fluid phase” of the blood can also predispose toward ACS. Recent results have established the multiplicity of “high-risk” plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid “stabilization” of other plaques that may produce recurrent events. The concept of “interventional cardiology” must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
Telomere Length Shortening and Alzheimer Disease—A Mendelian Randomization Study
Authors: Yiqiang Zhan, Ci Song, Robert Karlsson, Annika Tillander, Chandra A. Reynolds, Nancy L. Pedersen, Sara Hägg
Journal: JAMA Neurology (2015)

Telomeres are sequences of repetitive nucleotides at the end of the chromosomes, which protect them from fusion with neighboring chromosomes. 1 Observational studies have found associations between shorter telomeres and Alzheimer disease (AD). 2 However, these studies could have residual confounding or reverse causation, making it difficult to draw conclusions on whether telomere length (TL) is causally associated with AD.For the past decades, instrumental variable (IV) analysis has been developed for assessing causality using genetic variants in epidemiological research under the name of mendelian randomization (MR). 3 In the present study, we investigated the causal effect of TL on AD by applying the MR method to summary genome-wide association study (GWAS) data from Codd et al 4 and from the International Genomics of Alzheimer's Project Consortium.
Antiviral Therapy for Cirrhotic Hepatitis C: Association with Reduced Hepatocellular Carcinoma Development and Improved Survival
Authors: Yasushi Shiratori, Yoichi Ito, Osamu Yokosuka, Fumio Imazeki, Ryo Nakata, Naohide Tanaka, Yasuyuki Arakawa, Etsuko Hashimoto, Katsutaro Hirota, Haruhiko Yoshida, Yasuo Ohashi, Masao Omata
Journal: Annals of Internal Medicine (2005)

Although cirrhosis is a major risk factor for development of hepatocellular carcinoma, no definitive prospective analyses have assessed the long-term efficacy of antiviral therapy in cirrhotic patients.To elucidate the role of antiviral therapy in the suppression of liver tumors and survival over a long-term follow-up period.Prospective cohort study.25 clinical centers.345 patients with chronic hepatitis C and cirrhosis enrolled in previous trials.271 patients received 6 to 9 million U of interferon 3 times weekly for 26 to 88 weeks; 74 received no treatment.Blood tests and abdominal ultrasonography were done regularly to detect hepatocellular carcinoma.Hepatocellular carcinoma was detected in 119 patients during a 6.8-year follow-up: 84 (31%) in the interferon-treated group and 35 (47%) in the untreated group. Cumulative incidence of hepatocellular carcinoma among interferon-treated patients was significantly lower than in untreated patients (Cox model: age-adjusted hazard ratio, 0.65 [95% CI, 0.43 to 0.97]; P = 0.03), especially sustained virologic responders. A total of 69 patients died during follow-up: 45 (17%) in the treated group and 24 (32%) in the untreated group. Interferon-treated patients had a better chance of survival than the untreated group (Cox model: age-adjusted hazard ratio, 0.54 [CI, 0.33 to 0.89]; P = 0.02). This was especially evident in sustained virologic responders.This was not a randomized, controlled study. Patients enrolled in the control group had declined to receive interferon treatment even though they were eligible for treatment.Interferon therapy for cirrhotic patients with chronic hepatitis C, especially those in whom the infection had been cured, inhibited the development of hepatocellular carcinoma and improved survival.