tbuckley/cabot-search huggingface dataset:
Different Impact of Biomarkers as Mortality Predictors among Diabetic and Nondiabetic Patients Undergoing Hemodialysis
Authors: Berthold Hocher, Reinhard Ziebig, Claudia Altermann, Rolfdieter Krause, Gernot Asmus, Claus-Michael Richter, Torsten Slowinski, Pranav Sinha, Hans-H Neumayer
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Diabetic patients undergoing hemodialysis demonstrate much worse survival rates than do nondiabetic patients undergoing hemodialysis. To search for risk predictors, a prospective cohort study was performed with 245 hemodialysis patients, including 84 with diabetes mellitus, for 2 yr. C-reactive protein, troponin T (TnT), total, HDL, LDL, and lipoprotein(a) cholesterol, apoA2, apoB, triglyceride, fibrinogen, D-dimer, albumin, and creatinine levels and clinical characteristics at the time of entry were recorded. Survival rates were compared with Kaplan-Meier and Cox regression analyses. Forty-three diabetic patients and 30 nondiabetic patients died. Among diabetic patients, oliguria (&lt;200 ml/d) (relative risk, 3.24; 95% confidence interval, 1.63 to 6.41; <i>P</i> = 0.001), elevated C-reactive protein levels (relative risk, 2.57; 95% confidence interval, 1.06 to 6.18; <i>P</i> = 0.035), and elevated D-dimer levels (relative risk, 2.36; 95% confidence interval, 1.11 to 5.01; <i>P</i> = 0.025) predicted all-cause mortality rates. Oliguria was by far the most important predictor, particularly for infectious disease-related death (relative risk, 23.35; 95% confidence interval, 2.60 to 209.97; <i>P</i> = 0.005). Among nondiabetic patients, elevated TnT levels (relative risk, 4.00; 95% confidence interval, 1.58 to 10.10; <i>P</i> = 0.003), elevated D-dimer levels (relative risk, 3.45; 95% confidence interval, 1.27 to 9.33; <i>P</i> = 0.015), and low cholesterol levels (relative risk, 3.61; 95% confidence interval, 1.34 to 9.71; <i>P</i> = 0.011) predicted all-cause mortality rates. Subdivision of the causes of death among nondiabetic patients revealed that TnT levels predicted cardiovascular mortality rates (relative risk, 5.38; 95% confidence interval, 1.11 to 26.10; <i>P</i> = 0.037) and infectious disease-related mortality rates (relative risk, 12.02; 95% confidence interval, 1.42 to 191.96; <i>P</i> = 0.023). In conclusion, mortality predictors among patients undergoing hemodialysis differed substantially between diabetic and nondiabetic patients. Strategies to reduce mortality rates should consider these differences. E-mail: berthold.hocher@charite.de
Utility of emergency, telephone-based national surveillance for Hantavirus pulmonary syndrome. Hantavirus Task Force
Authors: J. W. Tappero
Journal: JAMA (1996)

On May 27,1993, in response to the outbreak investigation of newly recognizedHantaviruspulmonary syndrome (HPS) in the Four Corners states (New Mexico, Arizona, Utah, and Colorado), the Centers for Disease Control and Prevention established a national surveillance case definition for severe, unexplained respiratory disease to determine the extent of HPS throughout the United States. A toll-free telephone hotline number was instituted to provide updated information about unexplained respiratory illness and to serve as a passive mechanism for reporting suspected cases. Clinical information was obtained from callers reporting suspected cases, and diagnostic specimens and medical record reviews were requested from health care providers. From June 3 through December 31, 1993, the hotline received 21 443 telephone inquiries; callers identified 280 suspected cases living outside the Four Corners states with at least one specimen available for diagnostic testing. By December 31, 1993, 21 confirmed cases (age range, 14 to 58 years) residing in 11 states outside the Four Corners region had been identified. This passive surveillance system was successful in rapidly identifying the widespread sporadic geographic distribution for HPS cases throughout the United States and could serve as a model for similar emergencies. Expanding and coordinating surveillance systems for the early detection, tracking, and evaluation of emerging infections is a critical component of disease prevention.  (JAMA. 1996;275:398-400)
Expression of Fused in sarcoma mutations in mice recapitulates the neuropathology of FUS proteinopathies and provides insight into disease pathogenesis
Authors: Christophe Verbeeck, Qiudong Deng, Mariely DeJesus-Hernandez, Georgia Taylor, Carolina Ceballos-Diaz, Jannet Kocerha, Todd Golde, Pritam Das, Rosa Rademakers, Dennis W Dickson, Thomas Kukar
Journal: Molecular Neurodegeneration (2012)

Abstract Background Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) can cause familial and sporadic amyotrophic lateral sclerosis (ALS) and rarely frontotemproal dementia (FTD). FUS accumulates in neuronal cytoplasmic inclusions (NCIs) in ALS patients with FUS mutations. FUS is also a major pathologic marker for a group of less common forms of frontotemporal lobar degeneration (FTLD), which includes atypical FTLD with ubiquitinated inclusions (aFTLD-U), neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD). These diseases are now called FUS proteinopathies, because they share this disease marker. It is unknown how FUS mutations cause disease and the role of FUS in FTD-FUS cases, which do not have FUS mutations. In this paper we report the development of somatic brain transgenic (SBT) mice using recombinant adeno-associated virus (rAAV) to investigate how FUS mutations lead to neurodegeneration. Results We compared SBT mice expressing wild-type human FUS (FUS WT ), and two ALS-linked mutations: FUS R521C and FUS Δ14 , which lacks the nuclear localization signal. Both FUS mutants accumulated in the cytoplasm relative to FUS WT . The degree of this shift correlated with the severity of the FUS mutation as reflected by disease onset in humans. Mice expressing the most aggressive mutation, FUS Δ14 , recapitulated many aspects of FUS proteinopathies, including insoluble FUS, basophilic and eosiniphilic NCIs, and other pathologic markers, including ubiquitin, p62/SQSTM1, α-internexin, and the poly-adenylate(A)-binding protein 1 (PABP-1). However, TDP-43 did not localize to inclusions. Conclusions Our data supports the hypothesis that ALS or FTD-linked FUS mutations cause neurodegeneration by increasing cyotplasmic FUS. Accumulation of FUS in the cytoplasm may retain RNA targets and recruit additional RNA-binding proteins, such as PABP-1, into stress-granule like aggregates that coalesce into permanent inclusions that could negatively affect RNA metabolism. Identification of mutations in other genes that cause ALS/FTD, such as C9ORF72, sentaxin, and angiogenin, lends support to the idea that defective RNA metabolism is a critical pathogenic pathway. The SBT FUS mice described here will provide a valuable platform for dissecting the pathogenic mechanism of FUS mutations, define the relationship between FTD and ALS-FUS, and help identify therapeutic targets that are desperately needed for these devastating neurodegenerative disorders.
Naltrexone and Cognitive Behavioral Therapy for the Treatment of Outpatient Alcoholics: Results of a Placebo-Controlled Trial
Authors: R F Anton, D H Moak, L R Waid, P K Latham, R J Malcolm, J K Dias
Journal: American Journal of Psychiatry (1999)

The opiate antagonist drug naltrexone has been shown in a few studies with limited sample sizes to be effective when combined with psychosocial therapies for the treatment of alcohol dependence. The goal of this study was to obtain additional information regarding its efficacy in pertinent alcoholic populations and with a well-defined therapy.In this study, 131 recently abstinent alcohol-dependent outpatients were treated with 12 weekly sessions of manual-guided cognitive behavioral therapy and either 50 mg/day of naltrexone (N = 68) or placebo (N = 63) (with riboflavin added as a marker of compliance) in a double-blind, randomized clinical trial. Alcohol consumption, craving, adverse events, and urinary riboflavin levels were assessed weekly. Levels of blood markers of alcohol abuse were also ascertained during the trial.The study completion, therapy participation, and medication compliance rates in the trial were high, with no differences between treatment groups. Naltrexone-treated subjects drank less, took longer to relapse, and had more time between relapses. They also exhibited more resistance to and control over alcohol-related thoughts and urges, as measured by a subscale of the Obsessive Compulsive Drinking Scale. Over the study period, 62% of the naltrexone group did not relapse into heavy drinking, in comparison with 40% of the placebo group.Motivated individuals with moderate alcohol dependence can be treated with greater effectiveness when naltrexone is used in conjunction with weekly outpatient cognitive behavioral therapy. Naltrexone increases control over alcohol urges and improves cognitive resistance to thoughts about drinking. Thus, the therapeutic effects of cognitive behavioral therapy and naltrexone may be synergistic.
Usefulness of Sniff Nasal Pressure in Patients with Neuromuscular or Skeletal Disorders
Authors: DANIELA STEFANUTTI, MARIE-ROSE BENOIST, PIERRE SCHEINMANN, MICHÈLE CHAUSSAIN, JEAN-WILLIAM FITTING
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Inspiratory muscle strength is an important variable in patients with neuromuscular or skeletal disorders. It is usually assessed by measuring maximal inspiratory pressure (Pi max), but this test may prove difficult for some patients, and low values may originate from incomplete effort or air leaks. We assessed the usefulness of the novel sniff nasal pressure (Pnsn) test in 126 patients with a neuromuscular or a skeletal disorder, aged 5 to 49 yr. Pnsn was measured in an occluded nostril during maximal sniffs performed through the contralateral nostril. All patients performed the Pnsn maneuver easily, whereas 10 young and weak patients with neuromuscular disorders could not perform the Pi max maneuver. Data were analyzed for the 116 patients who could perform both tests (92 patients with neuromuscular and 24 with skeletal disorders). When expressed as percents of the predicted values, Pnsn was similar to Pi max in patients with neuromuscular disorders (54 ± 25% predicted [mean ± SD] versus 52 ± 24% predicted), and was higher than Pi max in patients with skeletal disorders (70 ± 25% predicted versus 61 ± 27% predicted, p < 0.05). Pnsn appeared to be the main determinant of VC in patients with neuromuscular disorders, whereas the Cobb angle and Pi max were the main determinants of VC in patients with skeletal disorders. We conclude that inspiratory muscle strength can be easily assessed with Pnsn in children and adults with various neuromuscular and skeletal disorders. This new muscular parameter appears particularly useful in neuromuscular disorders, in which it represents a major determinant of VC.
Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice
Authors: Iker Uriarte, Maite G Fernandez-Barrena, Maria J Monte, Maria U Latasa, Haisul C Y Chang, Simone Carotti, Umberto Vespasiani-Gentilucci, Sergio Morini, Eva Vicente, Axel R Concepcion, Juan F Medina, José Juan G Marin, Carmen Berasain, Jesus Prieto, Matías A Avila
Journal: Gut (2013)

Cholestasis is associated with increased liver injury and morbidity after partial hepatectomy (PH), yet bile acids (BAs) are emerging as important mediators of liver regeneration. Fibroblast growth factor 15 (Fgf15, human FGF19) is a BA-induced ileum-derived enterokine that governs BA metabolism. We evaluated the relevance of Fgf15 in the preservation of BA homeostasis after PH and its potential role in the regenerative process.Liver regeneration after PH was studied in Fgf15 (-/-) and Fgf15 (+/+) mice. The effects of the BA sequestrant cholestyramine and adenovirally delivered Fgf15 were examined in this model. The role of Fgf15 in BA-induced liver growth was tested in Fgf15 (-/-) mice upon cholic acid (CA) feeding. The direct mitogenic effect of Fgf15 was evaluated in cultured mouse hepatocytes and cholangiocytes.Fgf15 (-/-) mice showed marked liver injury and mortality after PH accompanied by persistently elevated intrahepatic BA levels. Cholestyramine feeding and adenovirally delivered Fgf15 reduced BA levels and significantly prevented this lethal outcome. Fgf15 also reduced mortality after extensive hepatectomy in Fgf15(+/+) animals. Liver growth elicited by CA feeding was significantly diminished in Fgf15 (-/-) mice. Proliferation of hepatocytes and cholangiocytes was also noticeably reduced in CA-fed Fgf15 (-/-) mice. Fgf15 induced intracellular signalling and proliferation of cultured hepatocytes and cholangiocytes.Fgf15 is necessary to maintain BA homeostasis and prevent liver injury during liver regeneration. Moreover, Fgf15 is an essential mediator of the liver growth-promoting effects of BA. Preoperative administration of this enterokine to patients undergoing liver resection might be useful to reduce damage and foster regeneration.
Inhibition of the von Willebrand (VWF)–collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons
Authors: Dongmei Wu, Karen Vanhoorelbeke, Nancy Cauwenberghs, Muriel Meiring, Hilde Depraetere, Harry F. Kotze, Hans Deckmyn
Journal: Blood (2002)
Snoring, asthma and sleep disturbance in Britain: a community-based survey
Authors: MF Fitzpatrick, K Martin, E Fossey, CM Shapiro, RA Elton, NJ Douglas
Journal: European Respiratory Journal (1993)

A questionnaire was sent to a random sample of adults in eight locations throughout Britain, to investigate the prevalence of snoring, asthma and sleep complaints in community-based British adult. Of the 1,478 respondents (831 females, 647 males; mean +/- SD age 45 +/- 18 yrs), 37% reported snoring at least occasionally, and 11% reported snoring on at least four nights per week (frequent snorers). Frequent snorers reported spending less time asleep at night, falling asleep accidentally during the day more often, taking planned daytime naps, and falling asleep whilst driving or operating machinery more often than the other respondent. Using ordinal logistic regression analysis to allow for the age and sex of the respondents, both accidental daytime sleep and planned daytime naps were commoner in frequent snorers than other respondents. Six percent of all respondents and 6% of those aged under 40 yrs reported that they had asthma (asthmatics). Seven percent of respondents aged less than 40 yrs reported wheezing on three or more occasions per year, and had been prescribed oral or inhaled bronchodilators (young wheezers). More than 80% of the asthmatic respondents of all ages, and young wheezers, reported waking at night with wheeze at least occasionally, and more than 30% of each group reported this symptom frequently. A larger proportion of asthmatics and young wheezers reported that their night-time sleep was unrefreshing, and that they had too little sleep at night than the other respondents.(ABSTRACT TRUNCATED AT 250 WORDS)
Time-Dependent Impact of Diabetes on Mortality in Patients After Major Lower Extremity Amputation
Authors: Andrea Icks, Marsel Scheer, Stephan Morbach, Jutta Genz, Burkhard Haastert, Guido Giani, Gerd Glaeske, Falk Hoffmann
Journal: Diabetes Care (2011)

OBJECTIVE To estimate the impact of diabetes on mortality in patients after first major lower extremity amputation (LEA). RESEARCH DESIGN AND METHODS Using claims data of a nationwide statutory health insurance, we assessed all deaths in a cohort of all 444 patients with a first major LEA since 2005 (71.8% male; mean age 69.1 years; 58.3% diabetic; 43% with amputation above the knee) up to 2009. Using Cox regression, we estimated the time-dependent hazard ratios to compare patients with and without diabetes. RESULTS The cumulative 5-year mortality was 68% in diabetic and 59% in nondiabetic individuals. In the first course, mortality was lower in diabetic compared with nondiabetic patients. Later, the diabetes risk increased yielding crossed survival curves after 2 to 3 years (time dependency of diabetes; P = 0.003). Age- and sex-adjusted hazard ratios for diabetes were as follows: 0–30 days: 0.50 [95% CI 0.31–0.84]; 31–60 days: 0.60 [0.25–1.41]; 61 days to 6 months: 0.75 [0.38–1.48]; &amp;gt;6–12 months: 1.27 [0.63–2.53]; &amp;gt;12–24 months: 1.65 [0.88–3.08]; &amp;gt;24–36 months: 2.02 [0.80–5.09]; and &amp;gt;36–60 months: 1.91 [0.70–5.21]. The pattern was similar in both sexes. In the full model, significant risk factors for mortality were age (1.05; 1.03–1.06), amputation above the knee (1.50; 1.16–1.94), and quartile category 3 or 4 of the number of prescribed medications (1.64; 1.12–2.40 and 1.76; 1.20–2.59). Further adjustment for comorbidity did not alter the results. CONCLUSIONS In this population-based study, we found a time-dependent mortality risk of diabetes following first major LEA, which may be in part a result of a healthier lifestyle in diabetic patients or the access to specific treatment structures in diabetic individuals.
BRCA2 and Nucleophosmin Coregulate Centrosome Amplification and Form a Complex with the Rho Effector Kinase ROCK2
Authors: Hui-Feng Wang, Katsuya Takenaka, Akira Nakanishi, Yoshio Miki
Journal: Cancer Research (2010)

BRCA2 germline mutations account for the majority of heredity breast and ovarian cancer. Besides its role in DNA damage repair, BRCA2 also plays an important role in cytokinesis, transcription regulation, and cancer cell proliferation. Recently, we reported that BRCA2 localizes to centrosomes as well as nuclei and the dysfunction of BRCA2 in a centrosome causes abnormalities in cell division. Here, we identified a nucleolar phosphoprotein, nucleophosmin (NPM), as a novel BRCA2-associated protein. We also detected the binding of BRCA2 to ROCK2, an effector of Rho small GTPase. Because it is known that ROCK2 binds to NPM at centrosomes, these 3 proteins may form a complex. NPM-binding region was within amino acids 639-1,000 of BRCA2. Exogenous expression of this BRCA2 region resulted in aberrant centrosome amplification and a high frequency of multinucleated cells. Our results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer.
Matrix metalloproteinase inhibitors in rheumatic diseases
Authors: D R Close
Journal: Annals of the Rheumatic Diseases (2001)

The rheumatic diseases continue to represent a significant healthcare burden in the 21st century. However, despite the best standard of care and recent therapeutic advances it is still not possible to consistently prevent the progressive joint destruction that leads to chronic disability. In rheumatoid arthritis and osteoarthritis this progressive cartilage and bone destruction is considered to be driven by an excess of the matrix metalloproteinase (MMP) enzymes. Consequently, a great number of potent small molecule MMP inhibitors have been examined. Several MMP inhibitors have entered clinical trials as a result of impressive data in animal models, although only one MMP inhibitor, Ro32-3555 (Trocade), a collagenase selective inhibitor, has been fully tested in the clinic, but it did not prevent progression of joint damage in patients with rheumatoid arthritis. The key stages and challenges associated with the development of an MMP inhibitor in the rheumatic diseases are presented below with particular reference to Trocade. It is concluded that the future success of MMP inhibitors necessitates a greater understanding of the joint destructive process and it is hoped that their development may be accompanied with clearer, more practical, outcome measures to test these drugs for, what remains, an unmet medical need.
Medical Assessment of Adverse Health Outcomes in Long-term Survivors of Childhood Cancer
Authors: Maud M. Geenen, Mathilde C. Cardous-Ubbink, Leontien C. M. Kremer, Cor van den Bos, Helena J. H. van der Pal, Richard C. Heinen, Monique W. M. Jaspers, Caro C. E. Koning, Foppe Oldenburger, Nelia E. Langeveld, Augustinus A. M. Hart, Piet J. M. Bakker, Huib N. Caron, Flora E. van Leeuwen
Journal: JAMA (2007)

Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late effect.To assess the total burden of adverse health outcomes (clinical or subclinical disorders ["adverse events"]) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up.Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner.Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (> or =2 severe or > or =1 life-threatening or disabling adverse events) associated with various treatments.Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 [95% confidence interval, 1.62-2.95] and 0.65 [95% confidence interval, 0.46-0.90], respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each).In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.