tbuckley/cabot-search huggingface dataset:
Are Depressive Symptoms a Risk Factor for Mortality in Elderly Japanese American Men?: The Honolulu-Asia Aging Study
Authors: Junji Takeshita, Kamal Masaki, Iqbal Ahmed, Daniel J. Foley, Yuan Qing Li, Randi Chen, Daryl Fujii, G. Webster Ross, Helen Petrovitch, Lon White
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study determined the influence of depressive symptoms on subsequent mortality of all causes. METHOD: The Honolulu Heart Program, established in 1965, is a prospective, community-based cohort of Japanese American men living in Hawaii. The analysis was based on 3,196 Japanese American men aged 71–93 at the time of the fourth examination in 1991–1993. Depressive symptoms were measured by use of an 11-question version of the Centers for Epidemiologic Studies Depression Scale questionnaire. All-cause mortality data were available for 6 years of follow up. Data were analyzed on the basis of presence or absence of chronic diseases. RESULTS: The overall prevalence of frequent depressive symptoms was 9.9%. Age-adjusted mortality rates at 3 years were 48.0 and 30.3 per 1,000 person-years for the depressed and nondepressed groups, respectively. At 6 years, the rates were 54.1 (depressed) and 41.5 (nondepressed) per 1,000 person-years. After adjustment for age, marital status, and antidepressant use, the relative risk for all-cause mortality associated with depressive symptoms was 1.53 for 3-year and 1.27 for 6-year mortality. Among participants who were healthy (without cognitive impairment, coronary heart disease, stroke, diabetes, or cancer), the association between depressive symptoms and mortality was greater (relative risk of 2.30 and 1.57 for 3- and 6-year mortality, respectively). Among participants with chronic disease, there were no significant associations between depressive symptoms and mortality. CONCLUSIONS: Depressive symptoms are a risk factor for mortality in elderly people, particularly in physically healthy individuals.
Achilles tendons in people with type 2 diabetes show mildly compromised structure: an ultrasound tissue characterisation study
Authors: Suzan de Jonge, Robert Rozenberg, Bruno Vieyra, Henk J Stam, Henk-Jan Aanstoot, Harrie Weinans, Hans T M van Schie, Stephan F E Praet
Journal: British Journal of Sports Medicine (2015)

Musculotendinous overuse injuries are prevalent in people with type 2 diabetes. Non-enzymatic glycosylation of collagen resulting in tendon stiffening may play a role. In this case-control study we determined whether patients with diabetes had poorer ultrasonographic structure in their Achilles tendons compared to age-matched controls.People with type 1 diabetes or type 2 diabetes, and age-matched controls, had computerised ultrasound tissue characterisation of both Achilles tendons. In contiguous ultrasonographic images of the tendon, echopatterns were quantified and categorised into four echo-types. Tendon abnormality was quantified as sum of echo-types III+IV. Furthermore, skin autofluorescence (AF) of the forearm (AF-value) was gathered.Twenty four type 2 diabetes patients, 24 controls, 24 type 1 diabetes patients and 20 controls were included. AF-value was higher in type 1 diabetes (1.55±0.17) than in their controls (1.39±0.18, p<0.001) and in type 2 diabetes (2.28±0.38) compared to their controls (1.84±0.32, p<0.001) Achilles tendons of type 2 diabetes patients contained more echo-types III+IV (14.1±7.9%) than matched controls (8.0±5.4%, p<0.001). There was a trend towards a difference in echo-types III+IV between type 1 diabetes patients (9.5±5.3%) and their controls (6.5±3.7%, p=0.055). In a stepwise linear regression analysis, body mass index (BMI) was moderately associated with tendon abnormality in patients with diabetes and controls (β=0.393, p<0.001).Type 2, and possibly type 1, diabetes patients showed poorer ultrasonographic Achilles tendon structure that may be a risk factor for tendinopathy. Although markers for accumulation of advanced glycation end products were elevated in both diabetes populations, only BMI was associated with these abnormalities.NTR2209.
Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension
Authors: Ferdinando C. Sasso, Ornella Carbonara, Marcello Persico, Dario Iafusco, Teresa Salvatore, Rosanna D’Ambrosio, Roberto Torella, Domenico Cozzolino
Journal: Diabetes Care (2002)

ACE inhibitors delay the progression from incipient to overt diabetic nephropathy and reduce albumin excretion rate (AER), independently of blood pressure. Angiotensin II type 1 receptor antagonists produce similar effects on microalbuminuria and mean arterial pressure. The aim of this study was to evaluate the effect of irbesartan on microalbuminuria and blood pressure in hypertensive and normotensive type 2 diabetic patients.Sixty-four microalbuminuric hypertensive (group 1) and 60 microalbuminuric normotensive (group 2) type 2 diabetic male patients, matched for age, BMI, HbA(1c), and diabetes duration, were enrolled. Each group was divided into two subgroups receiving either irbesartan (150 mg b.i.d. orally) or placebo for 60 days. After 15 days of washout, irbesartan was given to the subgroups who had received the placebo, and vice versa, in a randomized double-blind crossover study.In microalbuminuric hypertensive type 2 diabetic subjects, irbesartan reduced 24-h mean systolic and diastolic pressure and AER. In microalbuminuric normotensive type 2 diabetic patients, irbesartan reduced AER.These results indicate the beneficial effects of irbesartan on AER in type 2 diabetic subjects, independently of its antihypertensive effects.
Isolation and Characterization of the Mannose Receptor From Human Liver Potentially Involved in the Plasma Clearance of Tissue–Type Plasminogen Activator
Authors: Marlies Otter, PETRA Žočková, Johan Kuiper, Theo J.C. Van Berkel, Marrie M. Barrett-Bergshoeff, Dingeman C. Rijken
Journal: Hepatology (1992)

Various studies have shown that mannose receptors rapidly eliminate glycoproteins and microorganisms bearing high mannose-type carbohydrate chains from the blood circulation. The purpose of this study was to characterize the mannose receptor in the liver, which in vivo is involved in the rapid clearance of tissue–type plasminogen activator from the circulation. Human liver membranes were solubilized in Triton X–100, and the solution was applied to a tissue–type plasminogen activator Sepharose column. Bound proteins were eluted with ethylenediaminetetraacetate (10 mmol/L). A second, similar purification step rendered a single liver protein of 175,000 daltons. A combination of ligand blotting and a chromogenic assay for tissue–type plasminogen activator demonstrated that the identified liver protein is a mannose receptor because it bound tissue–type plasminogen activator, this tissue–type plasminogen activator binding being fully inhibited by 0.2 mol/L D–mannose. Western–blot analysis revealed that the isolated liver protein is immunologically identical to the human mannose receptor from placenta. Treatment of the liver protein and the placenta mannose receptor with trypsin yielded the same pattern of proteolytic degradation products as identified on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We conclude that the physiologically relevant mannose receptor for tissue–type plasminogen activator clearance isolated from human liver is immunologically and structurally similar to or identical with the human mannose receptor isolated from placenta. (Hepatology 1992;16:54-59.)
REGULATION OF PLATELET FUNCTIONS BY P2 RECEPTORS
Authors: Christian Gachet
Journal: The Annual Review of Pharmacology and Toxicology (2005)

▪ Abstract The main role of blood platelets is to ensure primary hemostasis, which is the maintenance of vessel integrity and cessation of bleeding upon injury. While playing a major part in acute arterial thrombosis, platelets are also involved in inflammation, atherosclerosis, and angiogenesis. ADP and ATP play a crucial role in platelet activation, and their receptors are potential targets for antithrombotic drugs. The ATP-gated cation channel P2X 1 and the two G protein–coupled ADP receptors, P2Y 1 and P2Y 12 , selectively contribute to platelet aggregation and formation of a thrombus. Owing to its central role in the growth and stabilization of a thrombus, the P2Y 12 receptor is an established target of antithrombotic drugs such as clopidogrel. Studies in P2Y 1 and P2X 1 knockout mice and selective P2Y 1 and P2X 1 antagonists have shown that these receptors are also attractive targets for new antithrombotic compounds. The potential role of platelet P 2 receptors in the involvement of platelets in inflammatory processes is also discussed.
Human Papillomavirus Genotyping and p16 Expression As Prognostic Factors for Patients With American Joint Committee on Cancer Stages I to III Carcinoma of the Anal Canal
Authors: Eva Serup-Hansen, Dorte Linnemann, Wojciech Skovrider-Ruminski, Estrid Høgdall, Poul Flemming Geertsen, Hanne Havsteen
Journal: Journal of Clinical Oncology (2014)

Purpose Carcinomas of the anal canal are strongly associated with the human papillomavirus (HPV). Expression of p16 is used as a surrogate marker of HPV infection. In a retrospective study, we evaluated HPV genotyping and p16 expression as prognostic markers of overall survival (OS) and disease-specific survival (DSS) in patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to III carcinoma of the anal canal. Patients and Methods HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed by using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone. Results HPV16 was detected in 81.0% of the tumors, followed by HPV33 (5.1%), HPV18 (2.2%), and HPV58 (0.7%). p16 positivity was found in 92.9% of the tumors. In univariable survival analysis, HPV positivity was significantly correlated with improved OS (74% v 52%; P = .036) and DSS (84% v 52%; P = .002), and p16 positivity was significantly correlated with improved OS (76% v 30%; P &lt; .001) and DSS (85% v 30%; P &lt; .001). In multivariable COX analysis that included HPV status, p16 status, sex, T stage, N stage, and treatment, p16 positivity remained an independent prognostic factor for OS (hazard ratio [HR], 0.07; 95% CI, 0.01 to 0.61; P = .016) and DSS (HR, 0.07; 95% CI, 0.01 to 0.53; P = .011). Conclusion p16 positivity is an independent prognostic factor for OS and DSS in patients with AJCC stages I to III carcinoma of the anal canal.
Thrombin Drives Tumorigenesis in Colitis-Associated Colon Cancer
Authors: Brian Turpin, Whitney Miller, Leah Rosenfeldt, Keith Kombrinck, Matthew J. Flick, Kris A. Steinbrecher, Eleana Harmel-Laws, Eric S. Mullins, Maureen Shaw, David P. Witte, Alexey Revenko, Brett Monia, Joseph S. Palumbo
Journal: Cancer Research (2014)

The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. On the basis of evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/- mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge. Similar results were obtained with pharmacologic inhibition of prothrombin expression or inhibition of thrombin proteolytic activity. Detailed longitudinal analyses showed that the role of thrombin in tumor development in CAC was temporally associated with the antecedent inflammatory colitis. However, direct studies of the antecedent colitis showed that mice carrying half-normal prothrombin levels were comparable to control mice in mucosal damage, inflammatory cell infiltration, and associated local cytokine levels. These results suggest that thrombin supports early events coupled to inflammation-mediated tumorigenesis in CAC that are distinct from overall inflammation-induced tissue damage and inflammatory cell trafficking. That prothrombin is linked to early events in CAC was strongly inferred by the observation that prothrombin deficiency dramatically reduced the formation of very early, precancerous aberrant crypt foci. Given the importance of inflammation in the development of colon cancer, these studies suggest that therapeutic interventions at the level of hemostatic factors may be an effective means to prevent and/or impede colitis-associated colon cancer progression.
Quality of life is predictive of survival in patients with unresectable hepatocellular carcinoma
Authors: W. Yeo, F.K.F. Mo, J. Koh, A.T.C. Chan, T. Leung, P. Hui, L. Chan, A. Tang, J.J. Lee, T.S.K. Mok, P.B.S. Lai, P.J. Johnson, B. Zee
Journal: Annals of Oncology (2006)
Additional Use of Glycated Hemoglobin for Diagnosis of Type 2 Diabetes in People Undergoing Coronary Angiography Reveals a Subgroup at Increased Cardiovascular Risk
Authors: Guenther Silbernagel, Marcus E. Kleber, Tanja B. Grammer, Bernhard R. Winkelmann, Bernhard O. Boehm, Winfried März
Journal: Diabetes Care (2011)

To study the prognosis of people with newly diagnosed type 2 diabetes as per the American Diabetes Association (ADA) 2010 definition but without diabetes as per the ADA 2009 definition.A total of 2,002 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study without a history of diabetes were studied.During the follow-up of a mean duration ± SD of 7.7 ± 2.0 years, 346 people died (202 cardiovascular deaths). Subjects with type 2 diabetes as per the ADA 2009 definition (n = 468) had significantly increased all-cause and cardiovascular mortality compared with people without diabetes as per the ADA 2010 definition (both P ≤ 0.003). Subjects with type 2 diabetes as per the ADA 2010 definition but without diabetes as per the ADA 2009 definition (n = 150) were at significantly increased risk to die of cardiovascular diseases (P = 0.029).Use of the ADA 2010 diabetes definition may be instrumental in improving cardiovascular risk stratification in people undergoing coronary angiography.
Randomised factorial trial of falls prevention among older people living in their own homes
Authors: L. Day
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To test the effectiveness of, and explore interactions between, three interventions to prevent falls among older people. <b>Design:</b> A randomised controlled trial with a full factorial design. <b>Setting:</b> Urban community in Melbourne, Australia. <b>Participants:</b> 1090 aged 70 years and over and living at home. Most were Australian born and rated their health as good to excellent; just over half lived alone. <b>Interventions:</b> Three interventions (group based exercise, home hazard management, and vision improvement) delivered to eight groups defined by the presence or absence of each intervention. <b>Main outcome measure:</b> Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques. Changes to targeted risk factors were assessed by using measures of quadriceps strength, balance, vision, and number of hazards in the home. <b>Results:</b> The rate ratio for exercise was 0.82 (95% confidence interval 0.70 to 0.97, P=0.02), and a significant effect (P&lt;0.05) was observed for the combinations of interventions that involved exercise. Balance measures improved significantly among the exercise group. Neither home hazard management nor treatment of poor vision showed a significant effect. The strongest effect was observed for all three interventions combined (rate ratio 0.67 (0.51 to 0.88, P=0.004)), producing an estimated 14.0% reduction in the annual fall rate. The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined. <b>Conclusions:</b> Group based exercise was the most potent single intervention tested, and the reduction in falls among this group seems to have been associated with improved balance. Falls were further reduced by the addition of home hazard management or reduced vision management, or both of these. Cost effectiveness is yet to be examined. These findings are most applicable to Australian born adults aged 70–84 years living at home who rate their health as good.
Use of Oral Fluconazole during Pregnancy and the Risk of Birth Defects
Authors: Ditte Mølgaard-Nielsen, Björn Pasternak, Anders Hviid
Journal: New England Journal of Medicine (2013)

Case reports suggest that long-term, high-dose fluconazole treatment for severe fungal infections during pregnancy causes a pattern of birth defects. It is unclear whether commonly used lower doses increase the risk of specific birth defects.In a registry-based cohort of liveborn infants in Denmark, we evaluated first-trimester oral fluconazole exposure and the risk of birth defects overall and of birth defects previously linked to azole antifungal agents.The majority of fluconazole-exposed pregnancies were in women who received common therapeutic doses of 150 mg (56% of pregnancies) or 300 mg (31%). Oral fluconazole exposure was not associated with an increased risk of birth defects overall (210 birth defects among 7352 fluconazole-exposed pregnancies [prevalence, 2.86%] and 25,159 birth defects among 968,236 unexposed pregnancies [prevalence, 2.60%]; adjusted prevalence odds ratio, 1.06; 95% confidence interval [CI], 0.92 to 1.21). In addition, oral fluconazole exposure was not associated with a significantly increased risk of 14 of 15 types of birth defects previously linked to azole antifungal agents: craniosynostosis, other craniofacial defects, middle-ear defects, cleft palate, cleft lip, limb defects, limb-reduction defects, polydactyly, syndactyly, diaphragmatic hernia, heart defects overall, pulmonary-artery hypoplasia, ventricular septal defects, and hypoplastic left heart. A significantly increased risk of tetralogy of Fallot was observed (7 cases in fluconazole-exposed pregnancies [prevalence, 0.10%] as compared with 287 cases in unexposed pregnancies [prevalence, 0.03%]; adjusted prevalence odds ratio, 3.16; 95% CI, 1.49 to 6.71).Oral fluconazole was not associated with a significantly increased risk of birth defects overall or of 14 of the 15 specific birth defects of previous concern. Fluconazole exposure may confer an increased risk of tetralogy of Fallot. (Funded by the Danish Medical Research Council.).
Characteristics of Lung Cancers Detected by Computer Tomography Screening in the Randomized NELSON Trial
Authors: Nanda Horeweg, Carlijn M. van der Aalst, Erik Thunnissen, Kristiaan Nackaerts, Carla Weenink, Harry J. M. Groen, Jan-Willem J. Lammers, Joachim G. Aerts, Ernst T. Scholten, Joost van Rosmalen, Willem Mali, Matthijs Oudkerk, Harry J. de Koning
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek) trial is, with 15,822 participants, the largest European lung cancer computer tomography screening trial. A volumetry-based screening strategy, stringent criteria for a positive screening, and an increasing length of screening interval are particular features of the NELSON trial.To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of screen-detected lung cancers, and to compare this across screening rounds, between sexes, and with other screening trials.All NELSON participants with screen-detected lung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localization were compared between the screening rounds, the sexes, and with other screening trials.In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. Of these lung cancers, 70.8% were diagnosed at stage I and 8.1% at stage IIIB-IV, and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology, or tumor localization across the screening rounds. Women were diagnosed at a significantly more favorable cancer stage than men. Compared with other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV.Despite stringent criteria for a positive screening, an increasing length of screening interval, and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is essential for the effectiveness of our screening strategy. Clinical trial registered with www.trialregister.nl (ISRCTN63545820).
Diagnosis of functional tricuspid insufficiency by pulsed-wave Doppler ultrasound.
Authors: D García-Dorado, S Falzgraf, A Almazán, J L Delcán, L López-Bescós, L Menárguez
Journal: Circulation (1982)

Twenty-four healthy subjects and 33 patients with left-sided valvular heart disease in atrial fibrillation were studied using a pulsed-wave Doppler ultrasound system connected to a 900 two-dimension- al echocardiography device.Systolic turbulence in the right atrium (RAST) was studied, and the ratio of maximum systolic velocity to maximum diastolic velocity ratio (MSV:MDV) was determined in the superior vena cava.In the 33 patients with valvular disease, right ventricular angiography was performed, classify- ing tricuspid insufficiency (TI) in 31 cases as absent, mild or moderate-to-severe.In two cases, right ventricular angiography was inconclusive.In all of the healthy subjects, right atrial flow could be analyzed, and no RAST was found.In the group with valvular heart disease, no interpretable signs of right atrial flow were found in three patients.RAST was found in all 14 palients who had moderate-to-severe TI and in three of seven who had mild TI; none of the patients without TI had RAST (pretest likelihood 68%, sensitivity 81%, specificity 100%, and positive predictive value 100%).No relationship could be demonstrated between the intensity of RAST and the severity of TI.The flow pattern in the superior vena cava could be analyzed in all 57 patients.The MSV:MDV ratio was > 1 in all the healthy subjects and < 1 in the 31 patients.MSV was negligible (MSV < 1:3 MDV) in the 15 patients with moderate-to-severe TI, in four of the seven patients with mild TI, and ir, two of the eight without TI.Using a MSV:MDV < 1:3 to differentiate, sensitivity was 83% and specificity 77%, and the positive predictive value was 90%.Pulsed-wave Doppler ultrasound examination in patients with valvular heart disease is a highly specific means of diagnosing functional TI and is probably useful for identifying patients with severe functional TI.However, sensitivity is lower for mild TI.