tbuckley/cabot-search huggingface dataset:
Sickness absence as a global measure of health: evidence from mortality in the Whitehall II prospective cohort study
Authors: M. Kivimaki
Journal: BMJ (2003)

To examine the association between sickness absence and mortality compared with associations between established health indicators and mortality.Prospective cohort study. Medical examination and questionnaire survey conducted in 1985-8; sickness absence records covered the period 1985-98.20 civil service departments in London.6895 male and 3413 female civil servants aged 35-55 years.All cause mortality until the end of 1999.After adjustment for age and grade, men and women who had more than five medically certified absences (spells > 7 days) per 10 years had a mortality 4.8 (95% confidence interval 3.3 to 6.9) and 2.7 (1.5 to 4.9) times greater than those with no such absence. Poor self rated health, presence of longstanding illness, and a measure of common clinical conditions comprising diabetes, diagnosed heart disease, abnormalities on electrocardiogram, hypertension, and respiratory illness were all associated with mortality--relative rates between 1.3 and 1.9. In a multivariate model including all the above health indicators and additional health risk factors, medically certified sickness absence remained a significant predictor of mortality. No linear association existed between self certified absence (spells 1-7 days) and mortality, but the findings suggest that a small amount of self certified absence is protective.Evidence linking sickness absence to mortality indicates that routinely collected sickness absence data could be used as a global measure of health differentials between employees. However, such approaches should focus on medically certified (or long term) absences rather than self certified absences.
Serum IgE in non‐atopic adults and in dermatitis patients
Authors: L. Peltonen, V. K. Havu, L. Mattila
Journal: Allergy (1988)

Total serum IgE was determined with the PRIST® technique, and specific reaginic antibodies against 10 allergens were measured in 163 healthy adults with no personal or family history of symptoms indicative of atopy (Group A). 103 non‐atopic adults with a family history of atopic diseases were similarly investigated (Group B). When all subjects who at the second interview presented with a history of atopic symptoms and those with positive RAST results were excluded, the geometric mean serum IgE value for Group A was 14.5 (SD = 2) ‐ 94.4 U/ml and for Group B 14.4 (SD = 2) ‐ 130.2 U/ml. There was no significant difference in the IgE values between men and women. Subjects under 40 years of age had significantly higher IgE values than subjects over 40 years. In the series of 276 dermatitis patients the geometric mean IgE value for the men was significantly higher (46.8) than for the women (28.8 U/ml). There was a highly significant difference in the mean serum IgE levels between the patients with a personal history of atopic diseases and the other patients. Patients with present atopic disease had significantly higher mean IgE values than those with past atopic disease while no significant difference was discernible in the mean IgE levels between the non‐atopic patients from atopic families and those with no personal and family atopy. Three years later, total serum IgE was controlled in subjects with initial IgE levels &gt; 100 U/ml. During this time, eight subjects had developed an atopic disease. In most cases, there were only slight variations in the IgE values.
Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo
Authors: J BECHLAURSEN, S BOESGAARD, H ENGHUSENPOULSEN, J ALDERSHVILE
Journal: Cardiovascular Research (1996)

Nitroglycerin (NTG) is metabolized to nitric oxide (NO) in vascular smooth muscle cells. It is currently not clear whether prolonged exposure to NTG and tolerance development directly affects endogenous NO-mediated vasodilation in vivo. This study investigates NO-mediated vasodilation in conscious chronically catheterized rats before and after development of nitrate tolerance. The effect of the thiol compound N-acetylcysteine (NAC), which may affect NTG responsiveness, was also studied.Nitrate tolerance was induced by a 72-h intravenous infusion of NTG and confirmed by a 65-68% reduction in the hypotensive response to NTG (P < 0.05). The hypotensive effects of acetylcholine (ACh) and sodium nitroprusside, (SNP) and possible NAC-mediated changes in the responses to these compounds were examined in nontolerant and nitrate-tolerant rats. Furthermore, the hypertensive response to the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) was measured.Nitrate tolerance was associated with a significantly attenuated hypotensive response to ACh (before 24 +/- 1 mmHg; after 17 +/- 2 mmHg, n = 7, P < 0.05). Similarly, the response to SNP was reduced from 32 +/- 1 mmHg to 26 +/- 3 mmHg (n = 7, P < 0.05). NTG-vehicle (placebo) did not affect the response to ACh and SNP (P > 0.05). NAC augmented the effect of NTG, ACh and SNP in both nontolerant and nitrate-tolerant animals (P < 0.05). The hypertensive response to L-NAME (n = 8), was reduced by 67% (from 34 +/- 6 mmHg to 11 +/- 1 mmHg, P < 0.05) after induction of nitrate tolerance.The results suggest (1) that nitrate tolerance in vivo is associated with cross tolerance to NO-mediated vasodilation produced by both exogenous and endogenous nitrovasodilators and (2) that also responses to nitrovasodilator agents other than NTG are improved by the addition of NAC.
Rheumatological Hand and Finger Symptoms
Authors: E Jonsson
Journal: Annals of the Rheumatic Diseases (1949)

Rheumatological symptoms in hands and fingers occur frequently and are very important in practice, but they have not received the attention in the literature which their significance deserves. Various Hand and Finger SymptomsThe Usual Rheumatoid Arthritic Changes.-Thehand symptoms occurring in ordinary rheumatoid arthritis are typical and well known: swelling of the jbints, muscular atrophy, ulnar deviations, sub- luxations, trophic disorders, etc.A characteristic feature is the symmetric spread of the joint changes.Atypical Arthritic Changes.-An" atypical " form of rheumatoid arthritis has been described by this author (1946).It is characterized by the joint symptoms being asymmetrical.Muscular atrophy and consequent ulnar deviation do not occur to any great extent, nor do " trophic " skin symptoms.From the practical point of view it is important that there is little progressive tendency in these cases.The risk of invalidism is therefore smaller than with the common type of rheumatoid arthritis, despite the fact that the joint changes may be quite pronounced, so that large exudates and destructive changes are present in the interphalangeal joints.The sedimentation rate usually remains low for long periods, with the joint symptoms restricted to hands and feet.Nevertheless, in a few cases exacerbations and progress may be observed.Osteoarthropathia Mutilans.-This is a strange
The Tongue Enables Computer and Wheelchair Control for People with Spinal Cord Injury
Authors: Jeonghee Kim, Hangue Park, Joy Bruce, Erica Sutton, Diane Rowles, Deborah Pucci, Jaimee Holbrook, Julia Minocha, Beatrice Nardone, Dennis West, Anne Laumann, Eliot Roth, Mike Jones, Emir Veledar, Maysam Ghovanloo
Journal: Science Translational Medicine (2013)

Individuals with severe spinal cord injury control a computer and powered wheelchair by using a wireless tongue-operated assistive technology called the Tongue Drive System.
First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: A multicenter phase II study
Authors: V. Georgoulias, N. Androulakis, A.M. Dimopoulos, C. Kourousis, S. Kakolyris, E. Papadakis, F. Apostolopoulou, C. Papadimitriou, A. Vossos, M. Agelidou, P. Heras, S. Tzannes, J. Vlachonicolis, E. Mavromanolakis, D. Hatzidaki
Journal: Annals of Oncology (1998)
cis and trans elements differ among mouse strains with high and low extrahepatic complement factor B gene expression.
Authors: G Garnier, B Ault, M Kramer, H R Colten
Journal: The Journal of Experimental Medicine (1992)

Factor B (Bf), an enzyme of the alternative pathway of complement activation, is one of four major histocompatibility complex (MHC) class III genes. To ascertain the genetic mechanism for tissue-specific constitutive and regulated expression of Bf, we sequenced the regulatory regions 5' of the gene from mice of different H-2 MHC haplotypes and assessed trans-acting factors, specific DNA binding nucleoproteins, in liver and kidney. Striking tissue-specific differences in constitutive expression of Bf were demonstrated in mice of H-2f or H-2z haplotypes when compared with H-2d or H-2u (kidney and intestinal Bf in H-2d or H-2u much greater than H-2f or H-2z). These differences correlated with a point nucleotide substitution 3 bp downstream of the upstream Bf initiation site that affects interaction with a DNA binding protein. This and additional cis differences localize the sequence substitutions responsible for previously identified restriction fragment length polymorphisms among inbred mouse strains and also reveal two previously unrecognized polymorphisms generated by SmaI and HinfI digestion. Evidence for differences in trans was found in a comparison of DNA binding nucleoproteins from kidney, but not liver, of B10.PL when compared with B10.M. These data, together with the high degree of sequence homology between human and mouse Bf 5' flanking regions, should prompt a search for polymorphic restriction sites and cis binding elements in the Bf promoter that could serve as markers of human MHC-associated renal pathology and variants in local MHC class III gene expression.
Constitutional and somatic deletions of the Williams-Beuren syndrome critical region in Non-Hodgkin Lymphoma
Authors: David Guenat, Samuel Quentin, Carmelo Rizzari, Catarina Lundin, Tiziana Coliva, Patrick Edery, Helen Fryssira, Laurent Bermont, Christophe Ferrand, Jean Soulier, Christophe Borg, Pierre-Simon Rohrlich
Journal: Journal of Hematology & Oncology (2014)

Here, we report and investigate the genomic alterations of two novel cases of Non-Hodgkin Lymphoma (NHL) in children with Williams-Beuren syndrome (WBS), a multisystem disorder caused by 7q11.23 hemizygous deletion. Additionally, we report the case of a child with NHL and a somatic 7q11.23 deletion. Although the WBS critical region has not yet been identified as a susceptibility locus in NHL, it harbors a number of genes involved in DNA repair. The high proportion of pediatric NHL reported in WBS is intriguing. Therefore, the role of haploinsufficiency of genes located at 7q11.23 in lymphomagenesis deserves to be investigated.
Quantitative Morphology of the Caudate and Putamen in Patients With Cocaine Dependence
Authors: L K Jacobsen, J N Giedd, C Gottschalk, T R Kosten, J H Krystal
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Deficits in dopaminergic function may contribute to hypertrophy of striatal structures associated with typical neuroleptic treatment. In light of a body of research that has associated chronic cocaine use with extrapyramidal symptoms and striatal dopaminergic depletion, the authors looked for evidence of striatal dysmorphology in patients with chronic cocaine dependence. METHOD: Caudate, putamen, and total brain volumes were quantified by means of magnetic resonance imaging in 25 cocaine-dependent and 20 healthy subjects. RESULTS: Normalized caudate and putamen volumes were 3.40% and 9.18% larger, respectively, in the cocaine-dependent subjects. CONCLUSIONS: These observations suggest that deficits in dopaminergic function associated with cocaine dependence may contribute to striatal hypertrophy.
Cytotoxic activity of rheumatoid and normal lymphocytes against allogeneic and autologous synovial cells in vitro.
Authors: M M Griffiths, C B Smith, J R Ward, M R Klauber
Journal: Journal of Clinical Investigation (1976)

The possibility that lymphocytes from patients with rheumatoid arthritis (RA) might be sensitized to RA synovial cell antigens was investigated with a 51Cr release cytotoxicity assay. Peripheral blood lymphocytes from rheumatoid and normal donors were tested for cytotoxic activity against their own synovial cells and against allogeneic rheumatoid and nonrhemuatoid synovial cells. In the allogeneic studies, the degree of cytotoxicity was significantly influenced by the age in culture (passage number) of the synovial target cells (P less than 0.001). When the passage number of the target cells was considered in the analysis, rheumatoid lymphocytes were found to have greater cytotoxic activity than normal lymphocytes against young cultures (low passage number) of both RA and non-RA synovial cells (P = 0.0042). Differences in susceptibility to lysis between RA and non-RA synovial cells were more susceptible to both RA and normal lymphocyte-induced lysis than were non-RA synovial cells (P = 0.0048). No evidence of cytotoxicity was detected when lymphocytes from nine RA patients and two osteoarthritis patients were reacted against their own synovial cells. Although the data demonstrated an increased cytotoxic activity of peripheral blood lymphocytes from some RA patients against allogeneic synovial cells, the fact that this reactivity was seen against both non-RA and RA synovial cells and was not demonstrated against autologous synovial cells argues against the presence of an immunospecific response of RA lymphocytes to RA synovial cell antigens.
Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies
Authors: D.S.M. Chan, A.R. Vieira, D. Aune, E.V. Bandera, D.C. Greenwood, A. McTiernan, D. Navarro Rosenblatt, I. Thune, R. Vieira, T. Norat
Journal: Annals of Oncology (2014)

Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised.We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations.Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29-1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02-1.12) for overweight (BMI 25.0-<30.0) and 1.10 (95% CI 0.92-1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26-2.41) for pre-menopausal and 1.34 (95% CI 1.18-1.53) for post-menopausal breast cancer. For each 5 kg/m(2) increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively.Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer.
Unexplained Fatigue Syndromes in a Multinational Primary Care Sample: Specificity of Definition and Prevalence and Distinctiveness From Depression and Generalized Anxiety
Authors: Petros Skapinakis, Glyn Lewis, Venetsanos Mavreas
Journal: American Journal of Psychiatry (2003)

The authors investigated whether narrow definitions of unexplained fatigue syndromes that require additional minor somatic symptoms are more strongly associated with psychiatric morbidity than wider ones.This was a secondary analysis of the World Health Organization Collaborative Project on Psychological Problems in General Health Care. A total of 5,438 primary care patients from 14 countries were assessed with the Composite International Diagnostic Interview.The prevalence of fatigue syndromes fell from 7.99 to 1.69 as somatic criteria were added. Patients with depression or anxiety were more likely to report unexplained fatigue, but this association was stronger for definitions of unexplained fatigue with more somatic criteria.Definitions of unexplained fatigue syndromes that require more somatic criteria selected more patients with psychiatric disorders in this culturally diverse sample. These findings might have implications for the revision of existing international diagnostic criteria for neurasthenia or chronic fatigue syndrome.
Within-Person Across-Neuropsychological Test Variability and Incident Dementia
Authors: Roee Holtzer
Journal: JAMA (2008)

<h3>Context</h3>Neuropsychological tests are used to predict and diagnose dementia. However, to our knowledge, no studies to date have examined whether within-person across-neuropsychological test variability predicts dementia.<h3>Objective</h3>To examine whether within-person across-neuropsychological test variability predicts future dementia.<h3>Design</h3>The Einstein Aging Study (EAS) is a population-based longitudinal study of aging and dementia located in Bronx County, New York. We used Cox proportional hazards models using age as the time scale to estimate hazard ratios (HRs) for performance on individual neuropsychological tests (Free and Cued Selective Reminding Test, Digit Symbol Substitution subtest of the Wechsler Adult Intelligence Scale Revised, and the Vocabulary subtest of the Wechsler Adult Intelligence Scale Revised) and for within-person across-neuropsychological test variability as predictors of incident dementia. Analyses were stratified by sex, and controlled for education and medical illness.<h3>Setting and Participants</h3>A total of 1797 participants (age ≥70 years) enrolled in the EAS between October 1993 and December 2007. Participants seen for the baseline visit only (n = 750), prevalent dementia cases (n = 72), and those with missing follow-up information (n = 78) were excluded. A total of 897 individuals were included in this investigation. Participants had follow-up visits every 12 to 18 months.<h3>Main Outcome Measure</h3>Incident dementia.<h3>Results</h3>Sixty-one cases of incident dementia were identified during follow-up (mean [SD], 3.3 [2.4] years), of which 26 were in the highest quartile of within-person across-neuropsychological test variability. Adjusting for sex, education, and medical illness, variability was associated with incident dementia (HR for 1-point difference in variability, 3.93 [95% confidence interval {CI}, 2.04-7.56]). The association persisted even after adjusting for level of performance on individual neuropsychological tests (HR for 1-point difference in variability, 2.10 [95% CI, 1.04-4.23]). Comparing Cox models using neuropsychological tests with and without within-person across-neuropsychological test variablity showed that the former improved the prediction of dementia. Sensitivity in a model predicting dementia at 1 year also improved when neuropsychological test variability was included.<h3>Conclusions</h3>In this population, within-person across-neuropsychological test variability was associated with development of incident dementia independent of neuropsychological test performance. This finding needs to be confirmed in future studies.
Analysis of Overall Survival in Patients with Nonmetastatic Castration-Resistant Prostate Cancer Treated with Vaccine, Nilutamide, and Combination Therapy
Authors: Ravi A. Madan, James L. Gulley, Jeffrey Schlom, Seth M. Steinberg, David J. Liewehr, William L. Dahut, Philip M. Arlen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We reported previously the first randomized study of any kind in patients with nonmetastatic, castrate-resistant prostate cancer. The study employed vaccine, the hormone nilutamide, and the combined therapy (crossover for each arm) with an endpoint of time to progression. We now report survival analyses at 6.5 years from the initiation of therapy with a median potential follow-up of 4.4 years. Experimental Design: Forty-two patients were randomized to receive either a poxvirus-based prostate-specific antigen (PSA) vaccine or nilutamide. Patients in either arm who developed increasing PSA without radiographic evidence of metastasis could cross over to receive the combined therapies. Results: Median survival among all patients was 4.4 years from date of enrollment. Median survival exhibited a trend toward improvement for patients initially randomized to the vaccine arm (median, 5.1 versus 3.4 years; P = 0.13). Starting from the on-study date, the retrospectively determined subset of 12 patients who initially received vaccine and then later received nilutamide suggested improved survival compared with the 8 patients who began with nilutamide and subsequently were treated with vaccine (median, 6.2 versus 3.7 years; P = 0.045). A subgroup analysis of patients randomized to the vaccine arm versus the nilutamide arm showed substantial improvements in survival if at baseline patients had a Gleason score &amp;lt;7 (P = 0.033) and PSA &amp;lt;20 ng/dL (P = 0.013) or who had prior radiation therapy (P = 0.018). Conclusions: These data indicate that patients with nonmetastatic castration-resistant prostate cancer (D0.5) who receive vaccine before second-line hormone therapy may potentially result in improved survival compared with patients who received hormone therapy and then vaccine. These data also suggest that patients with more indolent disease may derive greater clinical benefit from vaccine alone or vaccine before second-line hormone therapy compared with hormone therapy alone or hormone therapy followed by vaccine. These findings have potential implications for both the design and endpoint analysis of larger vaccine combination therapy trials.
ATM regulates ATR chromatin loading in response to DNA double-strand breaks
Authors: Myriam Cuadrado, Barbara Martinez-Pastor, Matilde Murga, Luis I. Toledo, Paula Gutierrez-Martinez, Eva Lopez, Oscar Fernandez-Capetillo
Journal: The Journal of Experimental Medicine (2006)

DNA double-strand breaks (DSBs) are among the most deleterious lesions that can challenge genomic integrity. Concomitant to the repair of the breaks, a rapid signaling cascade must be coordinated at the lesion site that leads to the activation of cell cycle checkpoints and/or apoptosis. In this context, ataxia telangiectasia mutated (ATM) and ATM and Rad-3–related (ATR) protein kinases are the earliest signaling molecules that are known to initiate the transduction cascade at damage sites. The current model places ATM and ATR in separate molecular routes that orchestrate distinct pathways of the checkpoint responses. Whereas ATM signals DSBs arising from ionizing radiation (IR) through a Chk2-dependent pathway, ATR is activated in a variety of replication-linked DSBs and leads to activation of the checkpoints in a Chk1 kinase–dependent manner. However, activation of the G2/M checkpoint in response to IR escapes this accepted paradigm because it is dependent on both ATM and ATR but independent of Chk2. Our data provides an explanation for this observation and places ATM activity upstream of ATR recruitment to IR-damaged chromatin. These data provide experimental evidence of an active cross talk between ATM and ATR signaling pathways in response to DNA damage.
Evaluation of the cardioprotective effect of dexrazoxane in children treated with anthracycline
Authors: Marcelo G. Paiva, Sergio Petrilli, Adriana Cordovil, Cristiano Machado, Adelaide Arruda, Adan Gil, Valdir Ambrosio, Orlando Campos, Angelo DePaola, Antonio Carvalho
Journal: Journal of the American College of Cardiology (2002)