tbuckley/cabot-search huggingface dataset:
Prevalence of COPD by disease severity in men and women in relation to smoking in northern Vietnam
Authors: Hoàng Thi Lâm, Linda Ekerljung, Nguyen Van Doàn, Nguyen Van Tuong, Eva Rönmark, Kjell Larsson, Bo Lundbäck
Journal: European Respiratory Journal (2012)

Background: The prevalence of COPD and its risk factor pattern varies between different areas of the world. The aim of this study was to investigate the prevalence of COPD by disease severity in men and women and risk factors for COPD in northern Vietnam.  Methods: From all 5782 responders to a questionnaire survey, a randomly selected sample of 1500 subjects was invited to a clinical follow-up study. The methods included a structured interview using a modified GA2LEN study questionnaire for registration of symptoms and possible determinants of disease. Spirometry was performed before and after bronchodilation. The age distribution of the sample was 23-72 years.  Results: Of 684 subjects attending, 565 completed acceptable spirometric measurements. The prevalence of COPD defined by the GOLD criteria was 7.1%; in men 10.9% and in women 3.9% (p=0.002). Of those 3.4% had a mild disease, 2.8% a moderate and 0.9% a severe disease. In ages >50 years, 23.5% of men and 6.8% of women had COPD. Among smokers aged >60 years (all men), 47.8% had COPD. None of the women with COPD had been smokers. Increasing age, smoking and male sex were the dominating risk factors, although male sex lost its significance in a multivariate setting.  Conclusions: The prevalence of COPD among adults in northern Vietnam was 7.1% and was considerably higher among men than women. The prevalence increased considerably with age. Increasing age and smoking, the latter among men only, were the most important determinants of COPD.
Effectiveness of Amiodarone in Resistant Arrhythmias1
Authors: Arthur Hollman, Phyllis M Holt
Journal: Journal of the Royal Society of Medicine (1980)

Amiodarone is used in the treatment of previously drug-resistant supraventricular and ventricular arrhythmias. We report our experience with amiodarone in 8 patients. Five patients had paroxysmal atrial flutter, one had paroxysmal atrial fibrillation, one had supraventricular tachycardia, and one ventricular tachycardia. Considerable improvement, both objectively and subjectively, was observed in all patients. Side effects were as follows: all patients had corneal microdeposits, one developed left bundle branch block which resolved on stopping amiodarone, and one reported constipation and abdominal pains. Six patients have been treated for 10–28 months; 3 developed tolerance at 4–14 months after the introduction of amiodarone therapy, but symptoms improved with increased dosage. It is important to watch for the development of tolerance to this drug.
Metabolic Effects of Allopurinol and Allo-Xanthine
Authors: R. W. Rundles
Journal: Annals of the Rheumatic Diseases (1966)

An additional comment regarding the origin of allopurinol may now be appropriate.This new type of agent, which many investigators have found to be uniquely useful in the treatment of gout, secondary hyperuricaemia, and hyperuricosuria, is a product of the programme of study of antimetabolites relating to purines and pyrimidines undertaken by Hitchings and Elion (1954) more than 20 years ago.In the early 1950s, two thiopurine compounds of major importance were first synthesized in their laboratory: thioguanine (TG) and 6-mercaptopurine (6-MP).Biological tests showed that both compounds were effective as antipurines and anti-tumour and anti- leukaemic activities were soon demonstrated (Clarke, Philips, Sternberg, and Stock, 1954).During the following years, as the range of clinical usefulness of the thiopurines was explored, many investigators studied their mechanism of action.This turned out to be complicated, since many interrelated bio- chemical effects were produced.In the search for better agents, several hundred related compounds were synthesized and subjected to biological study.Thiopurines with different substituents on the sulphur atom proved to have variable and unpre- dictable effects in animal species and in man (Elion, Callahan, Hitchings, Rundles, and Laszlo, 1962).Comparative studies of drug metabolism were under- taken to explain these discrepancies (Elion, Callahan, Rundles, and Hitchings, 1963b; Hitchings, 1963).One particular finding relating to the degradation of 6-MP led to the present somewhat tangential line of investigation.When therapeutic doses of 6-MP were given to man, 5 to 7 per cent. of the free compound was ordinarily excreted in the urine within a few hours, while 25 to 30 per cent. of the compound was oxidized to the inert metabolite 6-thiouric acid
Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Renal Cancer
Authors: Inmaculada Ibanez de Caceres, Essel Dulaimi, Amanda M. Hoffman, Tahseen Al-Saleem, Robert G. Uzzo, Paul Cairns
Journal: Cancer Research (2006)

Abstract Aberrant promoter hypermethylation is a common mechanism for inactivation of tumor suppressor genes in cancer cells. To generate a global profile of genes silenced by hypermethylation in renal cell cancer (RCC), we did an expression microarray-based analysis of genes reactivated in the 786-0, ACHN, HRC51, and HRC59 RCC lines after treatment with the demethylating drug 5-aza-2 deoxycytidine and histone deacetylation inhibiting drug trichostatin A. Between 111 to 170 genes were found to have at least 3-fold up-regulation of expression after treatment in each cell line. To establish the specificity of the screen for identification of genes, epigenetically silenced in cancer cells, we validated a subset of 12 up-regulated genes. Three genes (IGFBP1, IGFBP3, and COL1A1) showed promoter methylation in tumor DNA but were unmethylated in normal cell DNA. One gene (GDF15) was methylated in normal cells but more densely methylated in tumor cells. One gene (PLAU) showed cancer cell–specific methylation that did not correlate well with expression status. The remaining seven genes had unmethylated promoters, although at least one of these genes (TGM2) may be regulated by RASSF1A, which was methylated in the RCC lines. Thus, we were able to show that up-regulation of at least 6 of the 12 genes examined was due to epigenetic reactivation. The IGFBP1, IGFBP3, and COL1A1 gene promoter regions were found to be frequently methylated in primary renal cell tumors, and further study will provide insight into the biology of the disease and facilitate translational studies in renal cancer. (Cancer Res 2006; 66(10): 5021-8)
Cohort characteristics and chronic lung allograft dysfunction (CLAD) adjudication in a FP-7 funded project, systems prediction of CLAD (SysCLAD)
Authors: Christophe Pison, Angela Koutsokera, Adrien Tissot, Karine Botturi, Christian Benden, John-David Aubert, Antoine Roux, Martine Reynaud-Gaubert, Romain Kessler, Sacha Mussot, Claire Dromer, Véronique Boussaud, Jean-François Mornex, Olivier Brugière, Marcel Dahan, Christiane Knopp, Florian Ernst, Andreas Fritz, Gustavo Olivera-Botello, Kévin Deplanche, Charles Auffray, Pierre-Joseph Royer, Michel Sève, Antoine Magnan, Laurent Nicod
Journal: European Respiratory Journal (2014)

Background : CLAD including restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS)is the main limitation in long-term survival after lung transplantation (LT); no predictive model of CLAD exists.   Methods : SysCLAD is a prospective study of LT in 14 centers by merging STCS 3  and COLT 1  prospective cohorts including “clinicome”, environmental pollution, lung microbiome, exome sequencing, blood and BAL proteomics, blood transcriptomics and immunological assays collected at months 6 and 12 post LT to identify signature or biomarkers that will predict CLAD by year-3 post LT by a systems medicine approach (Pison  et al.  Eur Respir J 2014;43:689). Based on FEV 1 , FVC, TLC, FEV 1 /FCV, clinical files and CT (Verleden  et al . JHLT 2014;33:127), a SysCLAD multidisciplinary adjudication committee held 3 times in 2013 identified by year-3, 4 phenotypes: stable, BOS, RAS and mix-RAS as RAS with an obstructive ventilatory defect.   Results:  between 2008 and 2013, 1 050 LT recipients were included. The first 425 patients were analysed: 51% male, 45±16 yrs old, 32±17 months follow-up, survival at 1, 2, 3, 4 and 5-year of 88, 82, 78, 76, 69% respectively. Among the 143 reaching 3 years alive we identified 83 stables, 38 BOS, 16 RAS and 6 mixed RAS cases, as a “novel” phenotype.   Conclusion : By 2013, 1050 LT within 14 clinical centres were included in SysCLAD with a complete data base allowing to define 4 robust phenotypes by year-3 post LT: stable, BOS, RAS, mixed RAS, essential step in SysCLAD to promote a prediction within year-1 post LT before any decline in lung function. Funds from VLM, PHRC, STCS, FP-7.
Measles, mumps, and rubella (MMR) vaccine and autism
Authors: L. Smeeth, A. J Hall, L. C Rodrigues, X. Huang, P. G Smith, E. Fombonne, M. Edwardes, M. Baltzan, F E. Yazbak, J. A Kaye, M. d. M. Melero-Montes, H. Jick
Journal: BMJ (2001)

Editor—Kaye et al undertook an ecological study comparing the time trend in measles, mumps, and rubella (MMR) vaccine coverage with the time trend in diagnoses of autism.1 They found a marked increase in the incidence of codes for autism in children's electronic general practice records over 11 years.
In vitro antibacterial activity of moxifloxacin against hospital isolates: a multicentre study
Authors: C.-J. Soussy, J. Nguyen, F. Goldstein, H. Dabernat, A. Andremont, R. Leclercq, H. Drugeon, P. Cavallo, H. Chardon, J. Etienne, Y. Rio, P. Courvalin
Journal: Clinical Microbiology and Infection (2003)
Non–High-Density Lipoprotein Cholesterol, Guideline Targets, and Population Percentiles for Secondary Prevention in 1.3 Million Adults
Authors: Mohamed B. Elshazly, Seth S. Martin, Michael J. Blaha, Parag H. Joshi, Peter P. Toth, John W. McEvoy, Mohammed A. Al-Hijji, Krishnaji R. Kulkarni, Peter O. Kwiterovich, Roger S. Blumenthal, Steven R. Jones
Journal: Journal of the American College of Cardiology (2013)
TOLL-erating cardiac hypertrophy following pressure overload
Authors: R VANOORT, L DEWINDT
Journal: Cardiovascular Research (2005)

See article by Ha et al.  [4]  (pages 224–234) in this issue.  Ah, broken is the golden bowl! the spirit flown forever! Let the bell toll!–a saintly soul floats on the Stygian river; …And I!–to-night my heart is light!–no dirge will I upraise, But waft the angel on her flight with a Paean of old days! –Excerpted from “Lenore”, by Edgar Allen Poe (1831)

Sensing and defeating microbial infections are essential to the survival of metazoan species and contingent upon the reliable detection of pathogens, which are characterized by rapid evolution and molecular heterogeneity. Multicellular species have developed two overall strategies to kill and remove parasites, to send them “ floating on the Stygian river ” (after the river Styx in Hades , the underworld, in Greek mythology), as alluded to in the poem “ Lenore ” from Edgar Allen Poe: an innate versus an adaptive immune recognition system. The first line of defense (the innate system) is limited to the recognition of evolutionarily conserved pathogen motifs, molecular patterns that are unique to the microbial world and invariable among classes of pathogens. In contrast, the adaptive system involves dynamic adaptation (e.g. antibody generation) to unique epitopes on pathogens in the environment. Induction of the innate immune system is fast (usual within hours) and depends upon targets of pattern recognition, p athogen- a ssociated m olecular p atterns or PAMPs that are recognized by p attern r ecognition r eceptors (PRRs) [1].

The Toll-like receptor (TLR) family is … 

*Corresponding author. Email address: dewindt{at}niob.knaw.nl
Survival in Early Breast Cancer Patients Is Favorably Influenced by a Natural Humoral Immune Response to Polymorphic Epithelial Mucin
Authors: S. von Mensdorff-Pouilly, A.A. Verstraeten, P. Kenemans, F.G. M. Snijdewint, A. Kok, G.J. Van Kamp, M.A. Paul, P.J. Van Diest, S. Meijer, J. Hilgers
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P = .0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P = .0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P = .026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.
SK-216, an inhibitor of plasminogen activator inhibitor-1, limits tumor growth and lung metastasis formation probably through the reduction of tumor angiogenesis
Authors: Takeshi Masuda, Noboru Hattori, Kousuke Hamai, Shin Akita, Tadashi Senoo, Hiroshi Iwamoto, Shinichiro Ohshimo, Masashi Kanehara, Nobuhisa Ishikawa, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Nobuoki Kohno
Journal: European Respiratory Journal (2011)

Introduction:  Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of plasminogen activators, is known to be involved in tumor progression.   Objectives:  To investigate whether a PAI-1 inhibitor, SK-216, can limit tumor growth and lung metastasis formation.   Methods:  C57BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma (LLC) cells and tumor volume (mm 3 ) was measured twice a week until 2 weeks after the inoculation. The numbers of lung tumors were also counted 21 days after the injection of LLC cells through the tail vein. The mice were given either water or SK-216 (500 p.p.m.) in drinking water. In addition, the sections of tumor were stained with CD31 antibody, and the number of CD31-positive vessels was counted in three random microscopic fields per section.   Results:  The volumes of subcutaneous tumors 14 days after the inoculation of LLC cells were significantly smaller in SK-216-treated group than those in control group (mean ± SD; 1566±515.9 and 2354.3±559.3, respectively; p=0.018). The numbers of lung surface tumors were significantly lower in SK-216-treated group than those in control group (3.3±4.1 and 12.1±7.3, respectively; p=0.02). The numbers of CD31-positive vessels in subcutaneous or lung tumor sections were significantly lower in SK-216-treated group than those in control group (subcutaneous tumor; 60.5±15.9/field and 78.7±21.8/field, respectively, p=0.004: lung tumor; 24.0±7.9/field and 44.8±4.4/field, respectively, p=0.002).   Conclusion:  These results suggest that SK-216 limits tumor growth and lung metastasis formation probably through the reduction of tumor angiogenesis.
Activation of the ribosomal protein L13 gene in human gastrointestinal cancer
Authors: Yasushi Sasaki, Toshihisa Kobayashi, Hiroaki Mita, Minoru Toyota, Hiromu Suzuki, Kohzoh Imai, Yasuhisa Shinomura, Takashi Tokino
Journal: Clinical Cancer Research (2006)

A22   Although ribosomal proteins are major components of ribosomes, recent data have shown them to have extraribosomal functions apart from the ribosome and protein biosynthesis. In our earlier study we showed that ribosomal protein L13 mRNA was upregulated in response to DNA damage in hamster cells. We report here that L13 is activated in human gastrointestinal cancers. We also examined the biological role of L13 on human cancer cells. Knocking down L13 expression by small interfering RNA (siRNA) resulted in drastic attenuation of cancer cell growth with significant G1 and G2/M arrest of the cell cycle. Moreover, L13 siRNA significantly enhanced the cellular sensitivity to certain DNA damaging agents and, concordantly, L13-overexpressing cells demonstrated greater chemoresistance compared to parent cells, suggesting an inverse correlation between L13 expression and chemosensitivity. By using semiquantitative RT-PCR, we analyzed expression of L13 in freshly resected cancer tissue of the stomach, colorectum, and liver. Upregulation of L13 mRNA expression was observed in 10 (28%) of 36 stomach, 19 (41%) of 46 colorectal, and 5 (20%) of 25 liver cancer tissue samples compared to adjacent normal tissue samples. We also found that increased expression of the L13 gene was correlated with clinical staging in stomach cancers. Importantly, we discovered that L13 expression was inversely related to p53 mutational status in primary gastric cancer, and siRNA-mediated L13 suppression resulted in robust induction of p53 protein. These findings suggest that L13 plays an essential role in the progression of some gastrointestinal malignancies by numbing the p53 pathway, thus allowing tumorigenic growth in the presence of wild-type p53.
Performance of Wells Score for Deep Vein Thrombosis in the Inpatient Setting
Authors: Patricia C. Silveira, Ivan K. Ip, Samuel Z. Goldhaber, Gregory Piazza, Carol B. Benson, Ramin Khorasani
Journal: JAMA Internal Medicine (2015)

The Wells score to determine the pretest probability of deep vein thrombosis (DVT) was validated in outpatient settings, but it is unclear whether it applies to inpatients.To evaluate the utility of the Wells score for risk stratification of inpatients with suspected DVT.A prospective study was conducted in a 793-bed quaternary care, academic hospital using Wells score clinical predictor findings entered by health care professionals in a computerized physician order entry system at the time lower-extremity venous duplex ultrasound studies were ordered. All adult inpatients suspected of having lower-extremity DVT who underwent lower-extremity venous duplex ultrasound studies between November 1, 2012, and December 31, 2013, were included. Patients with DVT diagnosed within the prior 3 months were excluded. For patients undergoing multiple lower-extremity venous duplex ultrasound studies, only the first was included.Our primary outcome was the Wells score's utility for risk stratification among inpatients with suspected DVT as measured by the difference in incidence of proximal DVT among the 3 Wells score categories (low, moderate, and high pretest probability), the discrimination accuracy of the Wells score categories as the area under the receiver operating characteristics curve, the failure rate of Wells score prediction, and the efficiency of the Wells score to exclude DVT.In a study cohort of 1135 inpatients, 137 (12.1%) had proximal DVT. Proximal DVT incidence in low, moderate, and high pretest probability groups was 5.9% (8 of 135), 9.5% (48 of 506), and 16.4% (81 of 494), respectively (P < .001). The area under the receiver operating characteristics curve for the discriminatory accuracy of the Wells score for risk of proximal DVT identified on lower-extremity venous duplex ultrasound studies was 0.60. The failure rate of the Wells score to classify patients with a low pretest probability was 5.9% (95% CI, 3.0%-11.3%); the efficiency was 11.9% (95% CI, 10.1%-13.9%).The Wells score performed only slightly better than chance for discrimination of risk for DVT in hospitalized patients. It had a higher failure rate and a lower efficiency in the inpatient setting compared with that reported in the outpatient literature. Therefore, the Wells score risk stratification is not sufficient to rule out DVT or influence management decisions in the inpatient setting.
Ovarian Failure After Adjuvant Chemotherapy Is Associated With Rapid Bone Loss in Women With Early-Stage Breast Cancer
Authors: Charles L. Shapiro, Judith Manola, Meryl Leboff
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We sought to evaluate the effects of chemotherapy-induced ovarian failure on bone loss and markers of skeletal turnover in a prospective longitudinal study of young women with breast cancer receiving adjuvant chemotherapy. PATIENTS AND METHODS: Forty-nine premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated within 4 weeks of starting chemotherapy (baseline), and 6 and 12 months after starting chemotherapy with dual-energy absorptiometry and markers of skeletal turnover osteocalcin and bone-specific alkaline phosphatase. Chemotherapy-induced ovarian failure was defined as a negative pregnancy test, greater than 3 months of amenorrhea, and a follicle-stimulating hormone ≥ 30 MIU/mL at the 12-month evaluation. RESULTS: Among the 35 women who were defined as having ovarian failure, highly significant bone loss was observed in the lumbar spine by 6 months and increased further at 12 months. The median percentage decrease of bone mineral density in the spine from 0 to 6 months and 6 to 12 months was −4.0 (range, −10.4 to +1.0; P = .0001) and −3.7 (range, −10.1 to 9.2; P = .0001), respectively. In contrast, there were no significant decreases in bone mineral density in the 14 patients who retained ovarian function. Serum osteocalcin and bone specific alkaline phosphatase, markers of skeletal turnover, increased significantly in the women who developed ovarian failure. CONCLUSION: Chemotherapy-induced ovarian failure causes rapid and highly significant bone loss in the spine. This may have implications for long-term breast cancer survivors who may be at higher risk for osteopenia, and subsequently osteoporosis. Women with breast cancer who develop chemotherapy-induced ovarian failure should have their bone density monitored and treatments to attenuate bone loss should be evaluated.