tbuckley/cabot-search huggingface dataset:
Estimating the Delay Between Onset and Diagnosis of Type 2 Diabetes From the Time Course of Retinopathy Prevalence
Authors: Massimo Porta, Giulia Curletto, Dario Cipullo, Roberta Rigault de la Longrais, Marina Trento, Pietro Passera, Anna Viola Taulaigo, Sabrina Di Miceli, Antonella Cenci, Paola Dalmasso, Franco Cavallo
Journal: Diabetes Care (2014)

OBJECTIVE By correlating known diabetes duration with the prevalence of retinopathy, more than 10 years have been estimated to lapse between the onset and diagnosis of type 2 diabetes. Such calculations, however, assumed a linear model, included stages of retinopathy not specific to diabetes, and allowed 5 years for retinopathy to occur after the onset of diabetes. We calculated the duration of undiagnosed type 2 diabetes in outpatients screened for retinopathy in a hospital-based diabetes clinic after correcting these assumptions. RESEARCH DESIGN AND METHODS Diabetic patients (n = 12,074; 35,545 fundus examinations) were stratified into younger onset (YO; age at onset &amp;lt;30 years) or older onset (OO; age at onset ≥30 years), insulin treated (IT) or not IT (NIT), and with mild/more severe diabetic retinopathy (AnyDR) or moderate/more severe diabetic retinopathy (ModDR). The best-fitting equation correlating known duration among the OO-NIT group with the prevalence of ModDR was used to extrapolate time from appearance of retinopathy to diagnosis of type 2 diabetes. Time for retinopathy to develop after diabetes was calculated from the equation correlating the duration among the YO-IT group with appearance of ModDR. RESULTS There were 1,719 patients in the OO-NIT group with AnyDR and 685 with ModDR and 756 in the YO-IT group with AnyDR and 385 with ModDR. A linear model showed ModDR appeared 2.66 years before diagnosis among those in the OO-NIT group. A quadratic model suggested that ModDR appeared 3.29 years after diagnosis among those in the YO-IT group. The resulting estimate was 6.05 years (2.66 + 3.29) between the onset and diagnosis of diabetes, compared with 13.36 years using standard criteria. CONCLUSIONS Using best-fitting models and stratifying by glucose-lowering treatment and severity of retinopathy substantially lowers the estimated duration of undiagnosed type 2 diabetes.
A case of epidermolysis bullosa acquisita with clinical features of Brunsting-Perry pemphigoid showing an excellent response to colchicine
Authors: Noriko Tanaka, Teruki Dainichi, Bungo Ohyama, Shinichiro Yasumoto, Takashi Oono, Keiji Iwatsuki, Susanne Elfert, Anja Fritsch, Leena Bruckner-Tuderman, Takashi Hashimoto
Journal: Journal of the American Academy of Dermatology (2009)
THE NATURE OF THE RENAL CIRCULATORY CHANGES IN CHRONIC CONGESTIVE FAILURE AS REFLECTED BY RENAL TUBULAR MAXIMAL FUNCTIONS 12
Authors: J. Grossman, R. E. Weston, J. P. Halperin, L. Leiter
Journal: Journal of Clinical Investigation (1950)

Intermittency of glomerular activity in man has not been demonstrated (1).Therefore, functional changes in the renal hemodynamics of human sub- jects generally have been attributed to proportional changes in the flow to all nephrons.Thus, the well-es'tablished decrease of glomerular filtration rate and renal blood flow in chronic congestive failure (2, 3) has been considered a result of in- adequate cardiac output and secondary renal vaso- constriction, occurring without reduction in the mass of functioning tubules.Since the decrease in filtration reduces the quantity of electrolyte delivered to tubules normally adapted to handle a larger load (4, 5), it has been postulated that the resulting glomerulo-tubular imbalance contributes significantly to the salt and water retention of congestive failure.Recent studies from this and other laboratories (6, 7) indicate, however, that despite the mark- edly increased renal A-V oxygen difference, there is a significant reduction in renal oxygen con- sumption in chronic congestive failure.Although this could represent a diffuse depression of parenchymal metabolism, resulting from generalized renal ischemia and hypoxia, an alternative hypothesis exists.In the light of Trueta's demonstra- tion of an intrarenal vascular shunting mechanism in other species (8), this lower oxygen consumption may reflect an intrarenal diversion of blood away from the cortex, bypassing entire nephrons and thereby diminishing the functional mass of actively metabolizing parenchyma.Such a shunt- ing mechanism would result in a decrease in func- tioning tubules, proportionate to the reduced filtration, and thus would minimize the role of
Is Pulse Pressure Useful in Predicting Risk for Coronary Heart Disease?
Authors: Stanley S. Franklin, Shehzad A. Khan, Nathan D. Wong, Martin G. Larson, Daniel Levy
Journal: Circulation (1999)

Background —Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. Methods and Results —We studied 1924 men and women between 50 and 79 years of age at baseline with no clinical evidence of CHD and not taking antihypertensive drug therapy. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relations between blood pressure components and CHD risk over a 20-year follow-up. The association with CHD risk was positive for SBP, DBP, and PP, considering each pressure individually; of the 3, PP yielded the largest χ 2 statistic. When SBP and DBP were jointly entered into the multivariable model, the association with CHD risk was positive for SBP (HR, 1.22; 95% CI, 1.15 to 1.30) and negative for DBP (HR, 0.86; 95% CI, 0.75 to 0.98). Four subgroups were defined according to SBP levels (&lt;120, 120 to 139, 140 to 159, and ≥160 mm Hg). Within each subgroup, the association with CHD risk was negative for DBP and positive for PP. A cross-classification of SBP-DBP levels confirmed these results. Conclusions —In the middle-aged and elderly, CHD risk increased with lower DBP at any level of SBP≥120 mm Hg, suggesting that higher PP was an important component of risk. Neither SBP nor DBP was superior to PP in predicting CHD risk.
Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study
Authors: C. Borg, T. André, G. Mantion, F. Boudghène, F. Mornex, P. Maingon, A. Adenis, D. Azria, M. Piutti, O. Morsli, J.F. Bosset
Journal: Annals of Oncology (2014)
Inducible Podocyte-Specific Gene Expression in Transgenic Mice
Authors: Tetsuya Shigehara, Concepcion Zaragoza, Chagriya Kitiyakara, Hideko Takahashi, Huiyan Lu, Marcus Moeller, Lawrence B. Holzman, Jeffrey B. Kopp
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The podocyte plays a key role in glomerular function and glomerular disease. To facilitate studies of podocyte function, we have developed a transgenic mouse model with inducible expression in the podocyte. The tetracycline-inducible transgenic system facilitates gene expression with restricted cellular distribution and tight temporal control. Recently, Bujard and colleagues have developed a functionally improved reverse tetracycline–controlled transcriptional activator (rtTA) with substantially lower background in the off state (the absence of tetracycline) and greater inducibility in the on state (the presence of tetracycline). We used the human podocin (NPHS2) gene promoter to control expression of the rtTA cassette and bred these mice with a reporter mouse line that contains the cytomegalovirus minimal promoter and tetO promoter elements together with LacZ, encoding β-galactosidase. Dual transgenic mice, bearing both podocin-rtTA and tetO-LacZ transgenes, had no detectable expression in kidney or other organs in the absence of tetracycline. Administration of tetracycline in the drinking water was associated with podocyte expression of β-galactosidase, in a fashion that was time dependent (maximal at 1 wk) and dose-dependent (maximal at 2 mg/ml). Podocyte expression was confirmed in two ways: histochemical staining for β-galactosidase and double-immunostaining using the podocyte marker WT-1 and β-galactosidase. This transgenic system should aid future investigations of podocyte function. E-mail: [email protected]
Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis
Authors: Silvia Fargion, Anna Ludovica Fracanzani, Alberto Piperno, Mario Braga, Roberta D'Alba, Guido Ronchi, Gemino Fiorelli
Journal: Hepatology (1994)

To identify factors that might be useful as prognostic indexes for the risk of hepatocellular carcinoma in Italian patients with genetic hemochromatosis, 152 homozygotes were studied prospectively for 1 to 229 mo. Factors that were considered in estimating the risk of developing hepatocellular carcinoma were age, sex, cirrhosis (Child class), HBsAg, antibodies to HBsAg, antibodies to HBcAg, hepatitis C antibodies, alcohol abuse and the amount of iron removed during therapeutic phlebotomy to produce iron depletion. At diagnosis, cirrhosis was present in 97 patients and absent in 55. During follow-up, hepatocellular carcinoma developed in 28 of the 97 patients with cirrhosis but in none of those without. Among patients with cirrhosis, the cumulative probability of being free of hepatocellular carcinoma at 10 yr was 70%. For patients with and without HBsAg the probabilities of being free of liver cancer at 10 yr were, respectively, 54% and 75%; for those with and without history of alcoholism, 58% and 78%; and for those younger and older than 55 yr, 90% and 54%. In patients with cirrhosis, multivariate analysis using proportional-hazards (Cox) regression found that the only factors contributing significantly to the estimation of a prognostic index were age, presence of HBsAg and alcohol abuse. Age over 55 yr increased the relative risk of hepatocellular carcinoma 13.3-fold (p < 0.001), the presence of HBsAg increased it 4.9-fold (p < 0.02) and alcohol abuse increased it 2.3-fold (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Enoxaparin for the Prevention of Venous Thromboembolism Associated With Central Vein Catheter: A Double-Blind, Placebo-Controlled, Randomized Study in Cancer Patients
Authors: Melina Verso, Giancarlo Agnelli, Sergio Bertoglio, Franco C. Di Somma, Francesco Paoletti, Walter Ageno, Mario Bazzan, Pasquale Parise, Roberto Quintavalla, Emanuele Naglieri, Armando Santoro, Davide Imberti, Mariella Sorarù, Stefano Mosca
Journal: Journal of Clinical Oncology (2005)

The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE.In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications.Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period.In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.
Systemic vasculitis or not? That is the question
Authors: V. Kontogiannis, M. Havlat, J. S Lowe, R. J Powell
Journal: Annals of the Rheumatic Diseases (1999)

The study presented in this article is about the role played by imagination when national and international organisations convey the idea of a dystopian crisis involved in the real transition to a postantibiotic era. The present is an era that can be defined as a time when no new antibiotics are discovered or developed, and existing antibiotics simultaneously become less effective since bacteria develop resistance against the active substances. Today, antibiotic resistance is an international fact; thousands of people die every year in Europe and the USA as a result of bacteria that have become resistant. Then, imagination can conjure up a different and a much more dystopian future. This article stems from a public debate concerning the global increase of antibiotic resistance; and will examine how the concept of fantasy and imagination is central in picturing such a future crisis in society. The article's empirical basis mainly consists of reports from global and Swedish organisations, dating from the 1990s and onwards. These fantasies show that our society has a strong urge to always try to understand and explain present time and to identify how 'our' era relates to the past as well as the future. The concept of crisis plays an important role in these fantasies, it is key to use it when thinking about change. The analysis builds on texts and illustrations from global organisations like the WHO and also national authorities in Sweden that aim to convey the science behind the challenge. The aim is to develop a theoretical and empirical understanding, from the perspective of cultural analysis, of how fantasy and crisis are linked when the future is conceived.
Gain-of-function mutations in <i>interleukin-7 receptor-α</i> (<i>IL7R</i>) in childhood acute lymphoblastic leukemias
Authors: Chen Shochat, Noa Tal, Obul R. Bandapalli, Chiara Palmi, Ithamar Ganmore, Geertruy te Kronnie, Gunnar Cario, Giovanni Cazzaniga, Andreas E. Kulozik, Martin Stanulla, Martin Schrappe, Andrea Biondi, Giuseppe Basso, Dani Bercovich, Martina U. Muckenthaler, Shai Izraeli
Journal: The Journal of Experimental Medicine (2011)

Interleukin-7 receptor α (IL7R) is required for normal lymphoid development. Loss-of-function mutations in this gene cause autosomal recessive severe combined immune deficiency. Here, we describe somatic gain-of-function mutations in IL7R in pediatric B and T acute lymphoblastic leukemias. The mutations cause either a serine-to-cysteine substitution at amino acid 185 in the extracellular domain (4 patients) or in-frame insertions and deletions in the transmembrane domain (35 patients). In B cell precursor leukemias, the mutations were associated with the aberrant expression of cytokine receptor-like factor 2 (CRLF2), and the mutant IL-7R proteins formed a functional receptor with CRLF2 for thymic stromal lymphopoietin (TSLP). Biochemical and functional assays reveal that these IL7R mutations are activating mutations conferring cytokine-independent growth of progenitor lymphoid cells. A cysteine, included in all but three of the mutated IL-7R alleles, is essential for the constitutive activation of the receptor. This is the first demonstration of gain-of-function mutations of IL7R. Our current and recent observations of mutations in IL7R and CRLF2, respectively suggest that the addition of cysteine to the juxtamembranous domains is a general mechanism for mutational activation of type I cytokine receptors in leukemia.
Effects of Alcohol on Hepatic Transport of Proteins
Authors: E Baraona, C S Lieber
Journal: Annual Review of Medicine (1982)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Low-Gradient, Low-Flow Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction
Authors: Christophe Tribouilloy, Dan Rusinaru, Sylvestre Maréchaux, Anne-Laure Castel, Nicolas Debry, Julien Maizel, Romuald Mentaverri, Said Kamel, Michel Slama, Franck Lévy
Journal: Journal of the American College of Cardiology (2015)
Pulmonary toxicity with mefloquine
Authors: E. Undry, F. Bailly, M. Dusmet, P. Schnyder, R. Lemoine, J.W. Fitting
Journal: European Respiratory Journal (2001)

This report presents a case of acute lung injury developing within hours after administration of mefloquine for a low-level <i>Plasmodium falciparum</i> malaria, which was persistent despite halofantrine therapy. Extensive microbiological investigation remained negative and video-assisted thoracoscopic lung biopsy demonstrated diffuse alveolar damage. The evolution was favourable without treatment. This is the second report of acute lung injury and diffuse alveolar damage caused by mefloquine. Glucose-;6-;phosphate dehydrogenase deficiency was present in the former case and was thought to contribute to the lung injury. However, glucose-phosphate dehydrogenase was normal in the present case, suggesting that it is not a predisposing condition to the lung injury.
Egg Consumption and Risk of Type 2 Diabetes in Men and Women: Response to Djousse et al.
Authors: Leslie Citrome, Richard I. G. Holt
Journal: Diabetes Care (2009)

Djousse et al. (1) found that intake of seven or more eggs per week was associated with a 58% increased risk of type 2 diabetes in men and 77% in women after adjustment for potential confounders compared with that in subjects who denied any egg consumption. Two important caveats need to be made explicit.

Firstly, eggs are often consumed as a breakfast food accompanied by other items that are potentially unhealthy, such as bacon and sausage. This may have confounded the reported results, and eggs may have been an innocent bystander. Although consumption of red meat and saturated, trans , and polyunsaturated fatty acids was …
Syncope and Risk of Sudden Death in Hypertrophic Cardiomyopathy
Authors: Paolo Spirito, Camillo Autore, Claudio Rapezzi, Paola Bernabò, Roberto Badagliacca, Martin S. Maron, Sergio Bongioanni, Fabio Coccolo, N.A. Mark Estes, Caterina S. Barillà, Elena Biagini, Giovanni Quarta, Maria Rosa Conte, Paolo Bruzzi, Barry J. Maron
Journal: Circulation (2009)

Background— The prognostic significance of syncope has not been investigated systematically in hypertrophic cardiomyopathy, and treatment strategies have been based largely on intuition and experience. Methods and Results— We assessed the relationship between syncope and sudden death in 1511 consecutive patients with hypertrophic cardiomyopathy. Unexplained (n=153) or neurally mediated (n=52) syncope occurred in 205 patients (14%). Over a 5.6±5.2-year follow-up, 74 patients died suddenly. Relative risk of sudden death was 1.78 (95% confidence interval 0.88 to 3.51, P =0.08) in patients with unexplained syncope and 0.91 (95% confidence interval 0.00 to 3.83, P =1.0) in those with neurally mediated syncope compared with patients without syncope. In multivariable analysis, the temporal proximity of unexplained syncope to initial patient evaluation was independently associated with risk of sudden death ( P =0.006). Patients with unexplained syncope within 6 months before the initial evaluation showed a 5-fold increase in risk compared with patients without syncope (adjusted hazard ratio 4.89, 95% confidence interval 2.19 to 10.94), a relationship that was maintained throughout all age groups (&lt;18, 18 to 39, and ≥40 years). Older patients (≥40 years of age) with remote episodes of syncope (&gt;5 years before initial evaluation) did not show an increased risk of sudden death (adjusted hazard ratio 0.38, 95% confidence interval 0.05 to 2.74). Conclusions— In the present large cohort of patients with hypertrophic cardiomyopathy, unexplained syncope was a risk factor for sudden death. Patients with syncopal events that occurred in close temporal proximity to the initial evaluation showed a substantially higher risk of sudden death than patients without syncope. Older patients with remote syncopal events did not show an increased risk.
Human T-cell Lymphotropic Virus Type I–Associated Adult T-cell Leukemia–Lymphoma: New Directions in Clinical Research
Authors: Kunihiro Tsukasaki, Kensei Tobinai
Journal: Clinical Cancer Research (2014)

Abstract Adult T-cell leukemia–lymphoma (ATL) is a distinct malignancy of regulatory T cell (Treg)/TH2 cells caused by human T-cell lymphotropic virus type I (HTLV-1), with a high frequency of expression of CD3/CD4/CD25/CCR4 and FoxP3 in about half of the cells. However, in primary ATL cells, although expression of the virus, including the Tax oncoprotein, appears just after an in vitro culture, integration sites of the provirus into the host genome are random, and chromosomal/genetic abnormalities are complex. ATL is thus a single disease entity that is caused by HTLV-1 and possesses diverse molecular features. The clinical features and prognosis of ATL vary, and this has led to subtypes classified into four categories: acute, lymphomatous, chronic, and smoldering types, based on lactate dehydrogenase and calcium values and organ involvement. Approximately 15 to 20 million individuals are infected with HTLV-1 worldwide, 1.1 million of whom reside in Japan, and the annual incidence of ATL has been estimated to be approximately 1,000. HTLV-1 infection early in life, mainly from breast feeding, is crucial for the development of ATL. The age-specific occurrence of ATL and complex genome abnormalities that accumulate with disease progression suggest a multistep carcinogenesis model following HTLV-1 infection. Various treatment options are available for ATL and consist of watchful waiting for indolent ATL, intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation for aggressive ATL, and a combination of IFNα and zidovudine for ATL with leukemic manifestation. Several promising new agents, including an anti-CCR4 antibody, are currently undergoing clinical trials associated with translational research. See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.” Clin Cancer Res; 20(20); 5217–25. ©2014 AACR.