tbuckley/cabot-search huggingface dataset:
Approach to the diagnostics of early carbon metabolism disorders and diabetes mellitus 2 type in COPD patients
Authors: Viasheslav Kobylyanskiy, Elena Soyustova, Tatyna Turusina, Gulnara Babadzhanova, Elena Musalevskay, Yury Suntsov
Journal: European Respiratory Journal (2013)

Aim . Perfection of carbon metabolism disorder (CMD) diagnostics in patients with COPD and bronchial asthma (BA), considering the hypothesis that COPD play significant role in CDM development.

Methods . Confirmed diabetes mellitus 2 type (DM2) prevalence in 350 COPD and 247 BA patients was studied as well as COPD and BA prevalence in 400 patients with DM2 within the age limit up to 60. Actual DM2 prevalence was studied using standard peroral glucose tolerant rest in 80 COPD patients of the same age with and without obesity (18 and 62 patients respectively) in whom fasting blood glucose level was normal. Population parameters of the registered DM2 prevalence (3%), COPD (2.6%), BA (6.1%) and actual prevalence of DM2 (15.3%) were used as controls. Results . COPD patients showed confirmed DM2 prevalence more three times higher than in controls (p 0.05), while in BA patients it was significantly lower than in controls (p<0.001). Actual DM2 prevalence in COPD patients was also significantly higher comparing with the corresponding control values independent on presence or absence of obesity, 2 and 1.5 tames respectively. COPD patients without obesity and patients with obesity but without COPD showed no significant difference (p<0.05 and p<0.001).

Conclusion . 1. COPD is a significant risk factor in glucose tolerance and DM2 disorders development. 2. Sugar burden in COPD patients improves CMD diagnostics in COPD patients independent on fasting blood glucose level.

3 . BA is not involved in DM2 development.
The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC): Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness Method
Authors: Vineet Chopra, Scott A. Flanders, Sanjay Saint, Scott C. Woller, Naomi P. O'Grady, Nasia Safdar, Scott O. Trerotola, Rajiv Saran, Nancy Moureau, Stephen Wiseman, Mauro Pittiruti, Elie A. Akl, Agnes Y. Lee, Anthony Courey, Lakshmi Swaminathan, Jack LeDonne, Carol Becker, Sarah L. Krein, Steven J. Bernstein
Journal: Annals of Internal Medicine (2015)

Use of peripherally inserted central catheters (PICCs) has grown substantially in recent years. Increasing use has led to the realization that PICCs are associated with important complications, including thrombosis and infection. Moreover, some PICCs may not be placed for clinically valid reasons. Defining appropriate indications for insertion, maintenance, and care of PICCs is thus important for patient safety. An international panel was convened that applied the RAND/UCLA Appropriateness Method to develop criteria for use of PICCs. After systematic reviews of the literature, scenarios related to PICC use, care, and maintenance were developed according to patient population (for example, general hospitalized, critically ill, cancer, kidney disease), indication for insertion (infusion of peripherally compatible infusates vs. vesicants), and duration of use (≤5 days, 6 to 14 days, 15 to 30 days, or ≥31 days). Within each scenario, appropriateness of PICC use was compared with that of other venous access devices. After review of 665 scenarios, 253 (38%) were rated as appropriate, 124 (19%) as neutral/uncertain, and 288 (43%) as inappropriate. For peripherally compatible infusions, PICC use was rated as inappropriate when the proposed duration of use was 5 or fewer days. Midline catheters and ultrasonography-guided peripheral intravenous catheters were preferred to PICCs for use between 6 and 14 days. In critically ill patients, nontunneled central venous catheters were preferred over PICCs when 14 or fewer days of use were likely. In patients with cancer, PICCs were rated as appropriate for irritant or vesicant infusion, regardless of duration. The panel of experts used a validated method to develop appropriate indications for PICC use across patient populations. These criteria can be used to improve care, inform quality improvement efforts, and advance the safety of medical patients.
Effects of α1-antitrypsin on neutrophil extracellular traps formation
Authors: Eileen Frenzel, Elena Korenbaum, Thomas Köhnlein, Tobias Welte, Sabina Janciauskiene
Journal: European Respiratory Journal (2012)

Neutrophils belong to the innate immune response and are essential for elimination of invading pathogens. Apart from phagocytosis and secretion of anti-microbials, neutrophils are also capable of producing neutrophil extracellular traps (NETs) to kill pathogens extracellularly (NETosis). Neutrophil elastase (NE) is a critical initiator of NETosis and also is one of the main components of NETs. The acute phase protein α 1 -Antitrypsin (AAT) is a potent inhibitor for NE released from the activated neutrophils. Therefore, we asked a question if AAT inhibits NETosis?  We induced NETosis in neutrophils isolated from healthy donors by applying phorbol myristate acetate (PMA, 10 ng/ml) alone or together with purified AAT protein (1 mg/ml). To our surprise, AAT did not inhibit NETs formation but make the structures less adherent to the surface. Remarkably, using anti-AAT antibodies we detected AAT in the NETs either separately or in co-localization with elastase. In the next set of experiments, we isolated neutrophils from emphysema patient with inherited ZZ (Glu342 Lys) AAT deficiency before and after AAT augmentation therapy. In response to PMA, neutrophils isolated before augmentation therapy formed NETs similar to those observed in healthy donors. However, after augmentation therapy, NETs contained large cell aggregates some of which were detached from the specimen. Again, exogenous AAT did not inhibit NETs.  We suggest that an increased risk for development of chronic obstructive pulmonary disease (COPD) in subjects with inherited AAT deficiency results from both-increased elastase activity and uncontrolled NETosis.
The monocyte-dependent immune response to bacterial infections is systemically suppressed in COPD
Authors: Jürgen Knobloch, Susanne Panek, Sarah Yanik, Sandra Körber, Paul Bürger, David Jungck, Marcus Peters, Andrea Koch
Journal: European Respiratory Journal (2014)

Rationale: Smokers and COPD patients are abnormally susceptible to bacterial infections, which exacerbate COPD. Targeting the causative molecular defects could reduce exacerbation rates. In response to bacterial airway infections, circulating monocytes enter the lung and contribute to infection defense by releasing cytokines.  Hypothesis: Monocyte responses to pathogen-associated molecular patterns (PAMPs) of gram-positive bacteria are impaired in smokers/COPD.  Methods: Pure peripheral blood monocytes of never-smokers (NS), smokers without (S) and with COPD (n=10/10/14) were stimulated in concentration-response experiments with gram-positive PAMPs (peptidoglycan, PGN; lipoteichoic acid, LTA; lipopeptide amiA) or  S. aureus  (SaE) or  S. pneumoniae  (SpE) extract. TNFα, GM-CSF, IL-8 and PAMP receptors (NOD2, TLR2) were measured by ELISA, qRT-PCR, Western Blot.  Results: All PAMPs/extracts induced TNFα, GM-CSF and IL-8 but not NOD2 or TLR2. PGN/SaE/SpE-induced TNFα releases were reduced in S and COPD compared to NS, correlated positively to FEV1 but negatively to packyears (all p  Discussion: The innate immune response to bacteria is suppressed by smoking and in COPD because monocyte cytokine responses to gram-positive PAMPs are impaired - possibly due to systemic NOD2 reduction. This might explain the increased susceptibility of S and COPD to bacterial infections. Targeting PAMP-associated signaling might reduce exacerbation rates.
2000 Update of Recommendations for the Use of Tumor Markers in Breast and Colorectal Cancer: Clinical Practice Guidelines of the American Society of Clinical Oncology*
Authors: Robert C. Bast, Peter Ravdin, Daniel F. Hayes, Susan Bates, Herbert Fritsche, John M. Jessup, Nancy Kemeny, Gershon Y. Locker, Robert G. Mennel, Mark R. Somerfield
Journal: Journal of Clinical Oncology (2001)

To update the 1997 clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials.Six tumor markers for colorectal cancer and eight for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In addition to carcinoembryonic antigen (CEA) and CA 15-3, CA 27.29 was also considered among the serum tumor markers for breast cancer.In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used.A computerized literature search from 1994 to March 1999 was performed.The same values for use, utility, and levels of evidence were used by the committee.The same benefit, harms, and costs were used.Changes were recommended (see Appendix).The updated recommendations were validated by external review by the American Society of Clinical Oncology's (ASCO's) Health Services Research Committee and by ASCO's Board of Directors.American Society of Clinical Oncology.
The effect of obesity on the bronchial hyperresponsiveness of asthmatic children
Authors: Nikolaos Karampatakis, Myrofora Goutaki, Eleni Kotanidou, Assimina Galli-Tsinopoulou, Maria Eboriadou, Katerina Haidopoulou
Journal: European Respiratory Journal (2013)

Introduction

Obesity associated asthma has been proposed as a distinct phenotype but the links between asthma and obesity are unclear. Bronchial Hyperresponsiveness (BHR) is a cardinal feature of asthma.

Objectives

The objective of this study was to evaluate BHR in obese asthmatic children in comparison with asthmatic chlidren of normal weight and obese non asthmatic children of prepubertal age.

Methods

We have studied 35 children of pre-pubertal age (6-11 yrs) divided in three groups. The first group consisted of 7 obese asthmatic children (BMI>95th percentile, according to the United States Centers for Disease Control and Prevention-CDC- growth charts for children 2 years and older), the second group consisted of 14 normal-weight asthmatic children and the third group consisted of 14 obese but not asthmatic children. As asthmatic, we categorized the children with a doctor-diagnosed asthma. To all children, airway function (spirometry) and BHR (inhaled dry powder mannitol) tests were performed, after being depleted from corticosteroid medication for a period of at least three weeks.

Results

We found a significant difference (p<0.001) between the BHR measurements of the children in the obese-asthmatic group and those of the normal-weight asthmatic group and the obese but not asthmatic group. The PD15 (Provoking Dose of mannitol, required to cause a 15% fall in FEV1) measurements were significantly lower in obese-asthmatic children.

Conclusion

Obesity seems to have a boosting effect on the Bronchial Hyperresponsiveness of asthmatic children. Addressing obesity could be a therapeutic measure.
Coeliac disease: it takes three to tango!
Authors: Y VAN DE WAL
Journal: Gut (2000)

Coeliac disease: it takes three to tango!Coeliac disease (CD), the most common food sensitive enteropathy in humans, is caused by permanent intolerance for dietary gluten. 1 2 Typical symptoms include chronic diarrhoea, abdominal distension, and failure to thrive.These symptoms are the result of a lesion in the upper small bowel characterised by (sub)total villous atrophy, hypertrophic crypts, an increased number of interepithelial lymphocytes, and a chronic inflammatory response of the lamina propria lymphocytes.IgA antibodies against endomysium are specific indicators of CD. 3 4 Yet CD is considered to be primarily a T cell mediated disease because the majority of patients express the HLA-DQ2 [DQ( 1*0501, 1*02)], and/or -DQ8 [DQ( 1*03, 1*0302)] molecules 5 6 ; gluten specific HLA-DQ restricted T cells are present at the site of the lesion in the gut 7 and withdrawal of gluten stops the disease process. 2 The identity of potentially disease inducing, gluten derived T cell stimulatory peptides, however, was unknown until recently.Here we briefly discuss recent work which sheds light on the requirements for an optimal interaction between gluten, HLA-DQ, and T cells, requirements which explain the association of CD with HLA-DQ2/8. Specificity of the humoral immune responseCD patients generally have high serum levels of antigliadin antibodies.A more specific indicator for the disease, however, is the presence of antiendomysium antibodies. 3 4Recently, these antibodies have been found to be specific for the enzyme tissue transglutaminase (tTG). 8tTG is a ubiquitous protein that belongs to a family of structurally and functionally related calcium dependent enzymes.These enzymes cross link proteins by catalysing the formation of isopeptide bonds between carboxamide groups of glutamine residues and amino groups of lysine residues. 9 103][14] Identification of tTG as an autoantigen 8 has fuelled novel concepts about the pathogenesis of CD.Schuppan and colleagues 15 have suggested that anti-tTG antibodies could play a direct role in the pathogenesis of CD as tTG is required for activation of transforming growth factor (TGF-). 14 It was proposed that the observed lack of diVerentiation of villous epithelium in CD patients could be a result of an excess of locally produced anti-tTG antibodies as this would block tTG and thus activation of TGF-required for epithelial diVerentiation.Others have suggested that presentation of tTG derived peptides could lead to activation of autoreactive T cells. 16Finally, it has been suggested that because of the high glutamine content of gliadin, tTG could be involved in the generation of gliadin-tTG complexes thus giving rise to novel epitopes. 17As discussed previously, 17 the latter hypothesis is particularly attractive as such novel epitopes could play a role in breaking oral tolerance to both tTG and gluten and thus explain the appearance of antiendomysium antibodies that are characteristic of CD.In addition, recent work has on August 19,
Second Cancers Among Long-Term Survivors of Hodgkin’s Disease Diagnosed in Childhood and Adolescence
Authors: Catherine Metayer, Charles F. Lynch, E. Aileen Clarke, Bengt Glimelius, Hans Storm, Eero Pukkala, Timo Joensuu, Flora E. van Leeuwen, Mars B. van’t Veer, Rochelle E. Curtis, Eric J. Holowaty, Michael Andersson, Tom Wiklund, Mary Gospodarowicz, Lois B. Travis
Journal: Journal of Clinical Oncology (2000)

To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences.We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994.A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale.Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.
Endoscopic Therapy of Esophageal Premalignancy and Early Malignancy
Authors: Thomas B. Nealis, Kay Washington, Rajesh N. Keswani
Journal: Journal of the National Comprehensive Cancer Network (2011)

Esophageal adenocarcinoma (EAC) is an often deadly cancer with a rising incidence in Western countries. Chronic gastroesophageal reflux disease is associated with the metaplastic transformation of normal squamous epithelium to premalignant specialized intestinal metaplasia within the esophagus (Barrett's esophagus). Barrett's esophagus may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD), or even EAC. Although nondysplastic Barrett's esophagus progresses to EAC at a rate of 0.5% per year, rates of progression for true LGD and HGD are significantly higher. Treatment is mandatory for HGD and may be appropriate in select patients with nondysplastic Barrett's esophagus and many with LGD. Thus, accurate pathologic assessment is necessary before considering endoscopic therapy. Previously, only esophagectomy was offered to patients with HGD or EAC. However, esophagectomy has significant morbidity and mortality, and therefore endoscopic therapies have been advocated for early Barrett's neoplasia. These methods include endoscopic mucosal resection (EMR) and ablative techniques. Ablation techniques include argon plasma coagulation, multipolar electrocoagulation, laser therapy, photodynamic therapy, radiofrequency ablation, and cryotherapy. Of these, radiofrequency ablation has experienced the greatest adoption for the treatment of dysplastic Barrett's esophagus because of excellent published outcomes. The use of EMR to resect suspicious areas or raised lesions is mandatory to provide histology. In contrast, ablation techniques such as radiofrequency ablation have been shown to effectively eradicate large areas of dysplastic tissue with relative ease but do not allow for histologic assessment of the treated area. Combination EMR with radiofrequency ablation is thus advocated to resect visible lesions via EMR (providing histology) and ablate the remainder of the Barrett's esophagus. As always, the appropriate treatment is best determined after careful discussion with patients in a multidisciplinary environment. However, endoscopic therapy offers an attractive alternative to esophagectomy for early Barrett's neoplasia.
Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants.
Authors: A Majlis, W C Pugh, M A Rodriguez, W F Benedict, F Cabanillas
Journal: Journal of Clinical Oncology (1997)

Clinical data and histologic material were retrospectively analyzed in 46 cases of previously untreated mantle cell lymphoma (MCL) to more fully characterize the clinical response pattern of these lymphomas and to determine whether growth pattern significantly affected clinical outcome.The histologic pattern was classified as diffuse (61%), nodular (13%), and mantle zone (26%) in accordance with stated criteria.Bone marrow infiltration was detected in 69% of cases; the frequency of involvement correlated with histologic pattern, being most common in diffuse variants and least common in mantle zone variants. Other sites of extranodal involvement were observed in 50% of cases. Cyclin-D1 staining revealed nuclear positivity in 23 of 25 patients (92%) and no difference was observed between the various histologic patterns. Rearrangement at the bcl-1 major translocation cluster (MTC) was detected in seven of 21 cases, without regard for histologic pattern. Complete response rates to doxorubicin-based regimens showed a striking correlation with histologic pattern. Seventy-three percent of patients with a mantle zone pattern attained a complete response compared with only 25% of patients with a nodular pattern and 19% with a diffuse pattern. Three-year survival rates were 100%, 50%, and 55% for patients with mantle zone, nodular, and diffuse histologic patterns, respectively.We conclude that (1) diffuse and nodular MCL are associated with a poor treatment response and a poor overall survival rate; (2) the mantle zone variant exhibits the clinical attributes of a low-grade lymphoma; and (3) the poor survival rates of patients with nodular and diffuse MCL suggest that these variants be classified as intermediate-grade lymphomas. However, the trend of the time to treatment failure curve does not indicate that current regimens can cure MCL.
Cell type– and brain region–resolved mouse brain proteome
Authors: Kirti Sharma, Sebastian Schmitt, Caroline G Bergner, Stefka Tyanova, Nirmal Kannaiyan, Natalia Manrique-Hoyos, Karina Kongi, Ludovico Cantuti, Uwe-Karsten Hanisch, Mari-Anne Philips, Moritz J Rossner, Matthias Mann, Mikael Simons
Journal: Nature Neuroscience (2015)
Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.
Authors: B Fisher, A Brown, E Mamounas, S Wieand, A Robidoux, R G Margolese, A B Cruz, E R Fisher, D L Wickerham, N Wolmark, A DeCillis, J L Hoehn, A W Lees, N V Dimitrov
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine whether preoperative doxorubicin and cyclophosphamide (AC) permits more lumpectomies to be performed and decreases the incidence of positive nodes in women with primary breast cancer. PATIENTS AND METHODS Women (n = 1,523) were randomized to National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18; 759 eligible patients received postoperative AC and 747, preoperative AC. The clinical size of breast and axillary tumors was determined before each of four cycles of AC and before surgery. Tumor response to preoperative therapy was clinically complete (cCR), partial (cPR), stable (cSD), or progressive disease (cPD). Tissue from patients with a cCR was evaluated for a pathologic complete response (pCR). RESULTS Breast tumor size was reduced in 80% of patients after preoperative therapy; 36% had a cCR. Tumor size and clinical nodal status were independent predictors of cCR. Twenty-six percent of women with a cCR had a pCR. Clinical nodal response occurred in 89% of node-positive patients: 73% had a cCR and 44% of those had a pCR. There was a 37% increase in the incidence of pathologically negative nodes. Before randomization, lumpectomy was proposed for 86% of women with tumors &lt; or = 2 cm, 70% with tumors 2.1 to 5.0 cm, and 3% with tumors &gt; or = 5.1 cm. Clinical tumor size and nodal status influenced the physician's decision. Overall, 12% more lumpectomies were performed in the preoperative group; in women with tumors &gt; or = 5.1 cm, there was a 175% increase. CONCLUSION Preoperative therapy reduced the size of most breast tumors and decreased the incidence of positive nodes. The greatest increase in lumpectomy after preoperative therapy occurred in women with tumors &gt; or = 5 cm, since women with tumors less than 5 cm were already lumpectomy candidates. Preoperative therapy should be considered for the initial management of breast tumors judged too large for lumpectomy.