tbuckley/cabot-search huggingface dataset:
Incidence of Stroke Before and After Dialysis Initiation in Older Patients
Authors: Anne M. Murray, Stephen Seliger, Kamakshi Lakshminarayan, Charles A. Herzog, Craig A. Solid
Journal: Journal of the American Society of Nephrology (2013)

The incidence of stroke is substantially higher among hemodialysis patients than among patients with earlier stages of CKD, but to what extent the initiation of dialysis accelerates the risk for stroke is not well understood. In this cohort study, we analyzed data from incident hemodialysis and peritoneal dialysis patients in 2009 who were at least 67 years old and had Medicare as primary payer. We noted whether each of the 20,979 hemodialysis patients initiated dialysis as an outpatient (47%) or inpatient (53%). One year before initiation, the baseline stroke rate was 0.15%-0.20% of patients per month (ppm) for both outpatient and inpatient initiators. Among outpatient initiators, stroke rates began rising approximately 90 days before initiation, reached 0.5% ppm during the 30 days before initiation, and peaked at 0.7% ppm (8.4% per patient-year) during the 30 days after initiation. The pattern was similar among inpatient initiators, but the stroke rate peaked at 1.5% ppm (18% per patient-year). For both hemodialysis groups, stroke rates rapidly declined by 1-2 months after initiation, fluctuated, and stabilized at approximately twice the baseline rate by 1 year. Among the 620 peritoneal dialysis patients, stroke rates were slightly lower and variable, but approximately doubled after initiation. In conclusion, these data suggest that the process of initiating dialysis may cause strokes. Further studies should evaluate methods to mitigate the risk for stroke during this high-risk period.
Familial hypercholesterolaemia commonly presents with Achilles tenosynovitis
Authors: D Beeharry
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Patients with heterozygous familial hypercholesterolaemia (HeFH) develop tendon xanthomata (TX), most commonly in their Achilles tendons. Even before tendons are chronically enlarged, tenosynovitis may occur and medical advice be sought. Untreated HeFH carries a high risk of premature coronary heart disease, which can be ameliorated by early diagnosis. <b>Objective:</b> To determine the prevalence of episodes of Achilles tendon pain in HeFH before its diagnosis. <b>Methods:</b> Patients with definite HeFH (Simon Broome criteria) attending a lipid clinic were identified. They completed a questionnaire asking about symptoms relating to their Achilles tendons. Unaffected spouses or cohabiting partners served as controls. <b>Results:</b> 133 patients (47% men) and 87 controls (51% men) participated. TX had been recognised by the referring physicians in &lt;5% of cases. However, 62 (46.6% (95% confidence interval (CI) 38.1 to 55.1)) patients had experienced one or more episodes of pain in one or both Achilles tendons lasting &gt;3 days, whereas only 6 (6.9% (1.6 to 12.2)) controls had done so (difference p&lt;0.001; likelihood ratio 6.75). Typically, in the patients with HeFH the pain lasted 4 days (median). It was described as severe or very severe in 24/62 (38.7% (30.4 to 47.0)) patients with HeFH, but never more than moderate in controls. 35 (26.3% (18.8 to 33.8)) patients with HeFH had consulted a doctor about Achilles tendon pain, but in no case had this led to a diagnosis of HeFH. None of the controls had consulted a doctor. <b>Conclusions:</b> Measurement of serum cholesterol in patients presenting with painful Achilles tendon could lead to early diagnosis of HeFH.
Tricuspid Insufficiency
Authors: CHARLES E. HANSING, GEORGE G. ROWE
Journal: Circulation (1972)

The clinical diagnosis of the presence and severity of tricuspid insufficiency is difficult and is complicated by the transient nature of this abnormality as well as its usual occurrence in subjects with other valve disease. This paper presents correlative hemodynamic data from 100 consecutive catheterized patients with valvular heart disease in 90 of whom the presence of tricuspid insufficiency was sought by the indicator-dilution technic. Tricuspid regurgitation was present in 28 of the 90 patients. Subjects were grouped into 20 controls without tricuspid insufficiency and those with mild, moderate, and severe tricuspid insufficiency. The hemodynamics of these groups were compared by the analysis of variance to determine which parameters relate most closely to tricuspid insufficiency. The results are interpreted to confirm that tricuspid insufficiency results from those factors which overdistend the right side of the heart, and by permitting blood to escape retrograde from the right ventricle serves as a safety valve preventing progressive overload of the pulmonary circulation.
Angiopoietin-2 Functions as a Tie2 Agonist in Tumor Models, Where It Limits the Effects of VEGF Inhibition
Authors: Christopher Daly, Alexandra Eichten, Carla Castanaro, Elizabeth Pasnikowski, Alexander Adler, Alshad S. Lalani, Nicholas Papadopoulos, Alastair H. Kyle, Andrew I. Minchinton, George D. Yancopoulos, Gavin Thurston
Journal: Cancer Research (2012)

The angiopoietins Ang1 (ANGPT1) and Ang2 (ANGPT2) are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase Tie2 (TEK) and regulate angiogenesis. Ang1 activates Tie2 to promote blood vessel maturation and stabilization. In contrast, Ang2, which is highly expressed by tumor endothelial cells, is thought to inhibit Tie2 activity and destabilize blood vessels, thereby facilitating VEGF-dependent vessel growth. Here, we show that the inhibition of tumor xenograft growth caused by an Ang2-specific antibody (REGN910) is reversed by systemic administration of the Tie2 agonist Ang1. These results indicate that Ang2 blockade inhibits tumor growth by decreasing Tie2 activity, showing that Ang2 is a Tie2 activator. REGN910 treatment of tumors resulted in increased expression of genes that are repressed by Tie2 activation, providing further evidence that REGN910 inhibits Tie2 signaling. Combination treatment with REGN910 plus the VEGF blocker aflibercept reduced tumor vascularity and tumor perfusion more dramatically than either single agent, resulting in more extensive tumor cell death and more potent inhibition of tumor growth. Challenging the prevailing model of Ang2 as a destabilizing factor, our findings indicate that Ang2 plays a protective role in tumor endothelial cells by activating Tie2, thereby limiting the antivascular effects of VEGF inhibition. Thus, blockade of Ang2 might enhance the clinical benefits currently provided by anti-VEGF agents. .
Identification of common allergenic structures in mugwort and ragweed pollen☆☆☆★★★
Authors: Reinhold Hirschwehr, Claudia Heppner, Susanne Spitzauer, Wolfgang R. Sperr, Peter Valent, Uwe Berger, Friedrich Horak, Siegfried Jäger, Dietrich Kraft, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (1998)
Lymphocytes are detrimental during the early innate immune response against <i>Listeria monocytogenes </i>
Authors: Javier A. Carrero, Boris Calderon, Emil R. Unanue
Journal: The Journal of Experimental Medicine (2006)

Mice deficient in lymphocytes are more resistant than normal mice to Listeria monocytogenes infection during the early innate immune response. This paradox remains unresolved: lymphocytes are required for sterilizing immunity, but their presence during the early stage of the infection is not an asset and may even be detrimental. We found that lymphocyte-deficient mice, which showed limited apoptosis in infected organs, were resistant during the first four days of infection but became susceptible when engrafted with lymphocytes. Engraftment with lymphocytes from type I interferon receptor–deficient (IFN-αβR−/−) mice, which had reduced apoptosis, did not confer increased susceptibility to infection, even when the phagocytes were IFN-αβR+/+. The attenuation of innate immunity was due, in part, to the production of the antiinflammatory cytokine interleukin 10 by phagocytic cells after the apoptotic phase of the infection. Thus, immunodeficient mice were more resistant relative to normal mice because the latter went through a stage of lymphocyte apoptosis that was detrimental to the innate immune response. This is an example of a bacterial pathogen creating a cascade of events that leads to a permissive infective niche early during infection.
Differential regulation of matrix metalloproteinases and their inhibitors in human glomerular epithelial cells in vitro.
Authors: J Martin, R Steadman, J Knowlden, J Williams, M Davies
Journal: Journal of the American Society of Nephrology (1998)

The present study examines the effect of transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta (IL-1beta) on the regulation of gelatinase A, gelatinase B, tissue inhibitor of metalloproteinase-I (TIMP-I) and TIMP-II in human glomerular epithelial cells (GEC). The addition of TGF-beta1 resulted in the increased production and secretion of both gelatinase A (72-kD type IV collagenase) and gelatinase B (92-kD type IV collagenase), in a dose- and time-dependent manner. In contrast, the addition of IL-1beta to GEC resulted in the stimulation of secretion of gelatinase B but not gelatinase A. When the secretion of the regulatory inhibitors was examined, IL-1beta or TGF-beta1 both resulted in an increased secretion of TIMP-I, whereas the secretion of TIMP-II was downregulated. Such results demonstrate an independent and opposite regulation of the enzymes and their inhibitors. Of particular interest was the observation of the differential regulation of gelatinase A and its specific inhibitor TIMP-II (which binds to the latent form of this enzyme) in response to TGF-beta1. These results for the first time indicate that in human GEC, matrix metalloproteinases (MMP), as well as their specific inhibitors, are independently regulated by different cytokines. MMP and their regulatory tissue inhibitors (TIMP) play an important role in tissue remodeling. The results of the present study serve to emphasize both the complex regulation of matrix metabolism in the glomerulus and the potential pathologic role of an imbalance between the proteinases and their inhibitors in various forms of glomerular disease.
Combination Chemotherapy in Advanced Hodgkin's Disease
Authors: EMIL FREI
Journal: Annals of Internal Medicine (1973)

One hundred and seventy-eight patients with stages III and IV Hodgkin's disease were treated with combination chemotherapy (mechlorethamine, vincristine [Oncovin®], procarbazine, and prednisone [MOPP]). The complete remission rate for all patients was 66%. After 6 months of MOPP treatment, patients in complete remission were randomly allocated either to continued MOPP treatment every 2 months for a total of 18 months (maintained remission) or to no further treatment (unmaintained remission). The relapse rate was significantly less in the patients in maintained remission, whether plotted from time of randomization or from end of MOPP treatment. Thus 75% of the maintained patients were in complete remission 3 years after the start of the study, compared with 46% for the unmaintained patients. Eighty percent of patients entering complete remission were alive at 4 years, and there was no difference between the maintained and unmaintained groups. This lack of difference was caused largely by more effective secondary treatment in patients receiving only six courses of MOPP. The anatomical distribution of sites of relapse correlated highly with the anatomical distribution of major pretreatment sites of involvement.
Peripheral Muscle Wasting in Chronic Obstructive Pulmonary Disease
Authors: RICHARD DEBIGARÉ, CLAUDE H. CÔTÉ, FRANÇOIS MALTAIS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Peripheral muscle wasting is a common finding in advanced chronic obstructive pulmonary disease (COPD) and several other chronic diseases. Although muscle wasting has long been recognized by clinicians (1), its relevance to patients' outcome and management has been overlooked. There is a renewed interest in this problem in respiratory and other chronic diseases as recent advances in clinical research have confirmed the negative impact of muscle wasting on patient survival (2, 3). At the same time, exciting and innovative research in molecular biology is improving our understanding of how muscle mass is maintained (4, 5). Effective treatment for muscle wasting has yet to be developed, but there is now evidence, from animal and human studies, that muscle mass may he manipulated with success in wasting disorders (4). As a result of this research, new molecules specifically targeted at maintaining or increasing muscle mass in patients with COPD or other chronic conditions should become available in the future. In this pulmonary perspective, the clinical significance of muscle wasting associated with COPD will he briefly reviewed, taking into account the knowledge obtained from the study of other chronic diseases. Based upon new developments in molecular biology, possible mechanisms leading to muscle wasting and potential therapeutic strategies will be presented as well as suggestions for future research. It is not the scope of the present study to provide a complete review of the literature on peripheral muscle function in COPD, which can be found elsewhere (6, 7).
Nomograms to Predict Pathologic Complete Response and Metastasis-Free Survival After Preoperative Chemotherapy for Breast Cancer
Authors: Roman Rouzier, Lajos Pusztai, Suzette Delaloge, Ana M. Gonzalez-Angulo, Fabrice Andre, Kenneth R. Hess, Aman U. Buzdar, Jean-Remi Garbay, Marc Spielmann, Marie-Christine Mathieu, W. Fraser Symmans, Peter Wagner, David Atallah, Vicente Valero, Donald A. Berry, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2005)

To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis-free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram.Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model.The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of > or = 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02).Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.
Alzheimer's Disease: A Medical Companion
Authors: B. Woods
Journal: BMJ (1995)

Alistair Burns, Robert Howard, William Pettit Blackwell Science, pounds sterling19.50, pp 159 ISBN 0 632 03731 8

Alzheimer's disease is rarely out of the news these days, whether through the revelations of public figures such as Ronald Reagan or Lord Wilson being affected (or not, in the case of Ernest Saunders) or the furore over the decision not to license tacrine for use in the United Kingdom. Public awareness has risen dramatically over the past decade, and Professor Burns and his colleagues have produced an authoritative, attractive, well designed monograph which should help general practitioners to keep abreast of the many developments influencing the diagnosis and management of patients …
Prepregnancy Dietary Protein Intake, Major Dietary Protein Sources, and the Risk of Gestational Diabetes Mellitus
Authors: Wei Bao, Katherine Bowers, Deirdre K. Tobias, Frank B. Hu, Cuilin Zhang
Journal: Diabetes Care (2013)

Dietary protein is an important modulator of glucose metabolism. However, studies regarding the association between dietary protein intake and gestational diabetes mellitus (GDM) risk are sparse. This study was to examine the association.Our study included 21,457 singleton pregnancies reported among 15,294 participants of the Nurses' Health Study II cohort between 1991 and 2001. Included pregnancies were free of chronic diseases before pregnancy or previous GDM. Generalized estimating equations were used to estimate the relative risks (RRs) and 95% CIs.After adjustment for age, parity, nondietary and dietary factors, and BMI, multivariable RRs (95% CIs) comparing the highest with lowest quintiles were 1.49 (1.03-2.17) for animal protein intake and 0.69 (0.50-0.97) for vegetable protein intake. The substitution of 5% energy from vegetable protein for animal protein was associated with a 51% lower risk of GDM (RR [95% CI], 0.49 [0.29-0.84]). For major dietary protein sources, multivariable RRs (95% CIs) comparing the highest with the lowest quintiles were 2.05 (1.55-2.73) for total red meat and 0.73 (0.56-0.95) for nuts, respectively. The substitution of red meat with poultry, fish, nuts, or legumes showed a significantly lower risk of GDM.Higher intake of animal protein, in particular red meat, was significantly associated with a greater risk of GDM. By contrast, higher intake of vegetable protein, specifically nuts, was associated with a significantly lower risk. Substitution of vegetable protein for animal protein, as well as substitution of some healthy protein sources for red meat, was associated with a lower risk of GDM.
Gene Expression Signature and the Prediction of Ulcerative Colitis–Associated Colorectal Cancer by DNA Microarray
Authors: Toshiaki Watanabe, Takashi Kobunai, Etsuko Toda, Takamitsu Kanazawa, Yoshihiro Kazama, Junichiro Tanaka, Toshiaki Tanaka, Yoko Yamamoto, Keisuke Hata, Tetsu Kojima, Tadashi Yokoyama, Tsuyoshi Konishi, Yoshihiro Okayama, Yoshikazu Sugimoto, Toshinori Oka, Shin Sasaki, Yohichi Ajioka, Tetsuichiro Muto, Hirokazu Nagawa
Journal: Clinical Cancer Research (2007)

Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients.Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group).By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor-related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8% and 98.1%, respectively.These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.
Predictive Value of D-Dimer Test for Recurrent Venous Thromboembolism After Anticoagulation Withdrawal in Subjects With a Previous Idiopathic Event and in Carriers of Congenital Thrombophilia
Authors: Gualtiero Palareti, Cristina Legnani, Benilde Cosmi, Lelia Valdré, Barbara Lunghi, Francesco Bernardi, Sergio Coccheri
Journal: Circulation (2003)

Background— We have shown that normal D-dimer levels obtained after the discontinuation of oral anticoagulant treatment (OAT) has a high negative predictive value for recurrent venous thromboembolism (VTE). The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE in subjects with a previous unprovoked event who are either carriers of inherited thrombophilia or not. Methods and Results— We prospectively evaluated 599 patients (301 males) with a previous VTE episode. They were repeatedly examined for D-dimer levels after OAT withdrawal and were screened for inherited thrombophilic alterations. Alterations were detected in 130 patients (21.7%), factor V Leiden (70 patients; 2 of whom were homozygotes) and prothrombin mutation (38 patients) were the most prevalent ones. Recurrent events were recorded in 58 subjects (9.7%) during a follow-up of 870.7 patient-years. Altered D-dimer levels at 1 month after OAT withdrawal were associated with a higher rate of subsequent recurrence in all subjects investigated, especially in those with an unprovoked qualifying VTE event (hazard ratio, 2.43; 95% confidence interval, 1.18 to 4.61) and in those with thrombophilia (hazard ratio, 8.34; 95% confidence interval, 2.72 to 17.43). The higher relative risk for recurrence of altered D-dimer was confirmed by multivariate analysis after adjustment for other risk factors. The negative predictive value of D-dimer was 92.9% and 95.8% in subjects with an unprovoked qualifying event or with thrombophilia, respectively. Conclusions— D-dimer levels measured 1 month after OAT withdrawal have a high negative predictive value for recurrence in subjects with unprovoked VTE who are either carriers or not carriers of congenital thrombophilia.
THE PRESERVATION OF VIRULENT TREPONEMA PALLIDUM AND TREPONEMA PERTENUE IN THE FROZEN STATE; WITH A NOTE ON THE PRESERVATION OF FILTRABLE VIRUSES
Authors: Thomas B. Turner
Journal: The Journal of Experimental Medicine (1938)

1. A simple method for freezing and maintaining tissue specimens in a mixture of solid carbon dioxide and 95 per cent ethyl alcohol at a temperature approximating -78 degrees C. is described. 2. When frozen and maintained at this temperature Treponema pallidum and Treponema pertenue, upon thawing, exhibited normal morphology and motility and their virulence for rabbits was not appreciably altered after periods of at least 1 year. This applied to a number of different strains of each organism. The infectivity of material in which treponemes were scant was maintained as well as of material in which they were abundant. 3. At temperatures of -10 degrees C. and -20 degrees C. syphilis treponemes did not survive as long as 2 months. Death of the organism occurred not at the time of freezing but during the maintenance period. 4. Treponemes did not commonly survive freezing and desiccation, although one lot of dried material which contained T. pallidum was infective for rabbits 1 day after desiccation. 5. The viruses of human influenza, yellow fever, and spontaneous encephalomyelitis of mice when frozen and maintained at -78 degrees C. showed substantially the same titer after 6 months as before freezing. 6. Certain practical applications of the method are suggested.