tbuckley/cabot-search huggingface dataset:
Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis
Authors: H W Jones, R Bailey, Z Zhang, K A Dunne, D R Blake, N L Cox, C J Morris, P G Winyard
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To investigate the thrombin inhibitory capacity of antithrombin III in the inflamed human joint. <h3>METHODS</h3> Thrombin inhibitory capacity was measured, using a kinetic spectophotometric method, in matched plasma and synovial fluid samples of patients with rheumatoid arthritis (n=22) and osteoarthritis (n=16), together with normal control plasma samples (n=13). In the same samples, the concentration of antithrombin III was also determined by the method of radial immunodiffusion. The combination of these measurements allowed the calculation of the specific thrombin inhibitory capacity of these samples. <h3>RESULTS</h3> An increased concentration of antithrombin III in rheumatoid compared with osteoarthritic synovial fluid was noted (p&lt;0.05). However, there was a significant depression in the specific activity of antithrombin III in rheumatoid synovial fluid when compared with matched plasma samples (p&lt;0.001) or with osteoarthritic synovial fluid (p&lt;0.05). <h3>CONCLUSION</h3> In rheumatoid synovial fluid the thrombin inhibitory capacity of antithrombin III is disproportionately depressed relative to the concentration of antithrombin III, indicating the inactivation of antithrombin III in the rheumatoid joint.
White Matter Abnormalities in Patients With Obsessive-Compulsive Disorder and Their First-Degree Relatives
Authors: Lara Menzies, Guy B. Williams, Samuel R. Chamberlain, Cinly Ooi, Naomi Fineberg, John Suckling, Barbara J. Sahakian, Trevor W. Robbins, Ed T. Bullmore
Journal: American Journal of Psychiatry (2008)

Objective: Obsessive-compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysconnectivity of large-scale brain systems. The extent of white matter abnormalities in OCD is unknown, and the genetic basis of this disorder is poorly understood. The authors used diffusion tensor imaging, a magnetic resonance imaging technique, for examining white matter abnormalities in brain structure through quantification of water diffusion, to confirm whether white matter abnormalities exist in OCD. They also explored whether such abnormalities occur in healthy first-degree relatives of patients, indicating they may be endophenotypes representing increased genetic risk for OCD. Method: The authors used diffusion tensor imaging to measure fractional anisotropy of white matter in 30 patients with OCD, 30 unaffected first-degree relatives, and 30 matched healthy comparison subjects. Regions of significantly abnormal fractional anisotropy in patients in relation to healthy comparison subjects were identified by permutation tests. The authors assessed whether these abnormalities were also evident in the first-degree relatives. A secondary region-of-interest analysis was undertaken to assess the extent of replication between our data and previous relevant literature. Results: Patients with OCD demonstrated significantly reduced fractional anisotropy in a large region of right inferior parietal white matter and significantly increased fractional anisotropy in a right medial frontal region. Relatives also exhibited significant abnormalities of fractional anisotropy in these regions. Conclusions: These findings indicate that OCD is associated with white matter abnormalities in parietal and frontal regions. Similar abnormalities in unaffected first-degree relatives suggest these may be white matter endophenotypes for OCD.
Osteogenesis Imperfecta: Psychological Function
Authors: MARTIN REITE, KEITH DAVIS, CLIVE SOLOMONS, JOHN OTT
Journal: American Journal of Psychiatry (1972)

Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue that is characterized by multiple fractures, severe deformities, and disturbances of growth that frequently result in dwarfism. A study of 12 children with OI found them to be unusually well adjusted and of at least normal intelligence. The authors hypothesize that the generalized metabolic energy disturbance associated with the disease, perhaps specifically an alteration in cyclic AMP metabolism, might affect the patient's psychological functioning, or affective "tone," in a beneficial and/or protective manner.
Safety and Efficacy of Darbepoetin Alfa in Previously Untreated Extensive-Stage Small-Cell Lung Cancer Treated With Platinum Plus Etoposide
Authors: Robert Pirker, Rodryg A. Ramlau, Wolfgang Schuette, Petr Zatloukal, Irene Ferreira, Tom Lillie, Johan F. Vansteenkiste
Journal: Journal of Clinical Oncology (2008)

A placebo-controlled, double-blind, randomized, phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival.Darbepoetin alpha (300 microg) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy (carboplatin plus etoposide or cisplatin plus etoposide) plus 3 weeks after the last dose of chemotherapy. Patients with disease progression were observed until death or until all patients completed their end-of-study visit and 496 deaths had occurred. The two coprimary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival; statistical testing of survival was done if change in hemoglobin was significant at P < .05.The study enrolled 600 patients. Patients' hemoglobin levels dropped due to the myelosuppressive chemotherapy; however, treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo (P < .001). There was no statistically significant difference in overall survival between the treatment groups (hazard ratio [HR], 0.93; 95% CI, 0.78 to 1.11; P = .431). As expected, darbepoetin alpha was associated with a higher incidence of thromboembolic events (darbepoetin alpha, 9%; placebo, 5%). The transfusion risk was lower in the darbepoetin versus placebo group (HR, 0.40; 95% CI, 0.29 to 0.55).The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha; however, they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia.
Re: Sunscreen Use and Duration of Sun Exposure: a Double-Blind, Randomized Trial
Authors: K. Hemminki, V. J. Bykov, J. A. Marcusson
Journal: JNCI Journal of the National Cancer Institute (1999)

Background: In epidemiologic studies, sunscreen use is associated with increased risk of cutaneous melanoma, basal cell skin cancer, and higher numbers of nevi. It has been proposed that sunscreens may encourage prolonged sun exposure because they delay sunburn occurrence. We examined whether, under habitual conditions of sunscreen use, the sun-protection factor (SPF) had an influence on sun-exposure duration. Methods: Before the 1997 summer holidays, we randomly assigned 87 French and Swiss participants who were 18-24 years of age to receive an SPF 10 or an SPF 30 sunscreen. Neither medical personnel nor study participants were aware of their sunscreen assignment. Participants were asked to complete daily records of their sun exposure. To avoid influencing the recreational sun-exposure habits of the study participants, no recommendation was made about sun exposure or sun protection. Furthermore, participants were told that the trial end point was the number of pigmented skin lesions before and after the holidays. One subject was lost to follow-up. All statistical tests were two-sided. Results: The SPF 10 (n = 44) and SPF 30 (n = 42) groups had equivalent mean holiday durations (19.4 days versus 20.2 days) and mean quantities of sunscreen used (72.3 g versus 71.6 g). The mean cumulative sun exposures for the two groups were 58.2 hours and 72.6 hours, respectively (P = .011). The mean daily durations of sunbathing were 2.6 and 3.1 hours, respectively (P = .0013), and, for outdoor activities, they were 3.6 and 3.8 hours, respectively (P = .62). There was no difference in sunburn experience between the two groups. Conclusions: Use of higher SPF sunscreen seems to increase the duration of recreational sun exposure of young white Europeans.
Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study
Authors: S. F. Olsen
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To determine the relation between intake of seafood in pregnancy and risk of preterm delivery and low birth weight. <b>Design:</b> Prospective cohort study. <b>Setting:</b> Aarhus, Denmark. <b>Participants:</b> 8729 pregnant women. <b>Main outcome measures:</b> Preterm delivery and low birth weight. <b>Results:</b> The occurrence of preterm delivery differed significantly across four groups of seafood intake, falling progressively from 7.1% in the group never consuming fish to 1.9% in the group consuming fish as a hot meal and an open sandwich with fish at least once a week. Adjusted odds for preterm delivery were increased by a factor of 3.6 (95% confidence interval 1.2 to 11.2) in the zero consumption group compared with the highest consumption group. Analyses based on quantified intakes indicated that the working range of the dose-response relation is mainly from zero intake up to a daily intake of 15 g fish or 0.15 g n-3 fatty acids. Estimates of risk for low birth weight were similar to those for preterm delivery. <b>Conclusions:</b> Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. In women with zero or low intake of fish, small amounts of n-3 fatty acids—provided as fish or fish oil—may confer protection against preterm delivery and low birth weight. <h3>What is already known on this topic</h3> Long chain n-3 fatty acids in amounts above 2 g a day may delay spontaneous delivery and prevent recurrence of preterm delivery Large studies have not been carried out to determine to what extent low consumption of n-3 fatty acids is a risk factor for preterm delivery The dose-response relation has not been described <h3>What this study adds</h3> Low consumption of fish seems to be a strong risk factor for preterm delivery and low birth weight in Danish women This relation is strongest below an estimated daily intake of 0.15 g long chain n-3 fatty acids or 15 g fish
Human Papillomavirus Vaccines and Prevention of Cervical Cancer
Authors: Kathrin U. Jansen, Alan R. Shaw
Journal: Annual Review of Medicine (2004)

Cervical cancer and precancerous cervical lesions constitute a major problem in women's health. Every year 470,000 cases of cervical cancer are diagnosed worldwide, and about half the women afflicted will die. In the United States alone, approximately 14,000 cases of cervical cancer are diagnosed each year despite the availability of screening and access to high-quality gynecological care. With the confirmation that cervical cancer is caused by an infectious agent, human papillomavirus, the possibility of fighting this disease with either prophylactic or therapeutic vaccination arose. This review describes advances in vaccine development and very promising first results for prophylactic vaccination against cervical cancer.
The new definition of acute kidney injury in patients with cirrhosis: a critical look
Authors: Carlos Noronha Ferreira, Teresa Rodrigues, Helena Cortez-Pinto, Fátima Serejo, Fernando Ramalho, Paula Alexandrino, José Velosa
Journal: Gut (2012)

In the paper ‘Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis’ Florence Wong and co-authors have attempted to improve the definition of renal dysfunction in liver cirrhosis.1 The Working Party Statement (WPS) defines acute kidney injury as all causes of acute deterioration of renal function as indicated by an increase in serum creatinine (SeCr) of >50% from baseline or a rise in SeCr of ≥0.3 mg/dl in <48 h.1

We aimed at analysing and comparing the incidence and clinical significance of acute renal dysfunction (ARD) at hospital admission defined by the WPS and the conventional cut-off value of …
Effects of Stress on Decision-Making Deficits in Formerly Heroin-Dependent Patients After Different Durations of Abstinence
Authors: Xiao-li Zhang, Jie Shi, Li-yan Zhao, Li-li Sun, Jun Wang, Gui-bin Wang, David H. Epstein, Lin Lu
Journal: American Journal of Psychiatry (2011)

Drug abuse is associated with substantial impairments in decision making. However, little is known about the time course of changes in decision-making ability after abstinence or about the effects of stress on decision making in individuals recovering from heroin dependence after different durations of abstinence.First, the authors assessed decision-making performance with the original card version of the Iowa Gambling Task in formerly heroin-dependent patients who had been abstinent for 3, 7, 15, or 30 days or 3, 6, 12, or 24 months. Second, patients who had been abstinent from heroin for 15 or 30 days or 3, 12, or 24 months were challenged with acute stress induced by the Trier Social Stress Test. Third, the β-adrenoceptor antagonist propranolol (40 mg) was administered 1 hour before stress to those who had been abstinent for 30 days or 12 or 24 months.The short-term abstinence groups (3-30 days) performed worse on the Iowa Gambling Task compared with the long-term abstinence groups (3-24 months). Psychosocial stress unmasked a latent impairment in decision making in the 24-month abstinence group, which seemed to perform identically to healthy comparison subjects in the absence of stress. Propranolol blocked the stress-induced impairment of decision making, which was seen only in the formerly heroin-dependent patients.Stress can exacerbate an already existing impairment of decision making or unmask a latent one in individuals recovering from heroin dependence. The β-adrenergic blockade reduces this effect and might hold promise for treatment of substance use disorders.
High-dose chemotherapy and stem-cell rescue in the treatment of high-risk breast cancer: prognostic indicators of progression-free and overall survival.
Authors: G Somlo, J H Doroshow, S J Forman, T Odom-Maryon, J Lee, W Chow, V Hamasaki, L Leong, R Morgan, K Margolin, J Raschko, S Shibata, M Tetef, Y Yen, J Simpson, A Molina
Journal: Journal of Clinical Oncology (1997)

PURPOSE To examine the predictive value of tumor- and treatment-specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS Between June 1989 and September 1994, 114 patients with HRBC (stage II with &gt; or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high-grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.
Prevalence and Predictors of Psychological Distress Among Women With Ovarian Cancer
Authors: Tina R. Norton, Sharon L. Manne, Stephen Rubin, John Carlson, Enrique Hernandez, Mitchell I. Edelson, Norman Rosenblum, David Warshal, Cynthia Bergman
Journal: Journal of Clinical Oncology (2004)

Purpose To identify the prevalence of psychological distress among women with ovarian cancer and to examine the association between these symptoms of distress and demographic and medical variables. Patients and Methods Participants were 143 women with ovarian cancer. Forty-eight percent of participants had been diagnosed with advanced-stage disease (stage III or IV) and most (80%) were currently receiving treatment. Psychological distress was assessed with the following measures: the Beck Depression Inventory, the Mental Health Inventory, the Impact of Events Scale, and a questionnaire regarding mental health service use. Results Approximately one fifth of women reported moderate to severe levels of distress, and more than half reported high stress responses to their cancer and its treatment. Most participants (60%) were not using any mental health services or psychotropic medications. There was also evidence to suggest that younger patients, patients with more advanced or recurrent disease, and patients who had more recently been diagnosed with ovarian cancer experienced greater psychological distress. Conclusion These findings indicate that psychological distress and high stress responses to cancer are prevalent among women with ovarian cancer, suggesting they should be carefully evaluated to determine whether treatment for these symptoms is warranted.
Peroxisome proliferator-activated receptor- reduces inflammation and vascular leakage in a murine model of acute lung injury
Authors: M. B. Schaefer, A. Pose, J. Ott, M. Hecker, A. Behnk, R. Schulz, N. Weissmann, A. Günther, W. Seeger, K. Mayer
Journal: European Respiratory Journal (2008)

Acute lung injury (ALI) still represents a major cause of morbidity and mortality in intensive care units. Beneficial effects have been described after activation of the peroxisome proliferator-activated receptor (PPAR)-α by fibrates such as WY 14,643 (WY) in inflammatory models. In the present study, the impact of WY was investigated in a model of endotoxin (lipopolysaccharide; LPS)-induced ALI in mice. Intratracheal LPS challenge dose-dependently resulted in leukocyte invasion, protein leakage and release of tumour necrosis factor-α as well as macrophage inflammatory protein-2, prostaglandin E 2 and thromboxane B 2 into the alveolar space after 8 and 24 h. Lung ventilator compliance was reduced at both time-points. In isolated perfused mouse lungs, platelet-activating factor (PAF) induced an acute increase in pulmonary artery pressure ( P pa ) and in capillary filtration coefficient ( K fc ). WY significantly improved all features of ALI in vivo and blunted the increase in K fc in isolated perfused mice lungs. In mice with genetic deletion of PPAR-α, all characteristics of ALI, P pa , and K fc were not significantly different from wild-type mice but WY failed to improve ALI and PAF-induced increase in K fc . Activation of peroxisome proliferator-activated receptor-α by WY 14,643 reduced acute lung injury and vascular leakage. Fibrates may possess beneficial effects in acute pulmonary diseases beyond their lipid-lowering capability.
An X-Linked Haplotype of Neandertal Origin Is Present Among All Non-African Populations
Authors: V. Yotova, J.-F. Lefebvre, C. Moreau, E. Gbeha, K. Hovhannesyan, S. Bourgeois, S. Bedarida, L. Azevedo, A. Amorim, T. Sarkisian, P. H. Avogbe, N. Chabi, M. H. Dicko, E. S. Kou' Santa Amouzou, A. Sanni, J. Roberts-Thomson, B. Boettcher, R. J. Scott, D. Labuda
Journal: Molecular Biology and Evolution (2011)

Recent work on the Neandertal genome has raised the possibility of admixture between Neandertals and the expanding population of Homo sapiens who left Africa between 80 and 50 Kya (thousand years ago) to colonize the rest of the world. Here, we provide evidence of a notable presence (9% overall) of a Neandertal-derived X chromosome segment among all contemporary human populations outside Africa. Our analysis of 6,092 X-chromosomes from all inhabited continents supports earlier contentions that a mosaic of lineages of different time depths and different geographic provenance could have contributed to the genetic constitution of modern humans. It indicates a very early admixture between expanding African migrants and Neandertals prior to or very early on the route of the out-of-Africa expansion that led to the successful colonization of the planet.
Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.
Authors: D Rice, S Barone
Journal: Environmental Health Perspectives (2000)

Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.