tbuckley/cabot-search huggingface dataset:
Diagnostic Testing Following Fecal Occult Blood Screening in the Elderly
Authors: J. D. Lurie, H. G. Welch
Journal: JNCI Journal of the National Cancer Institute (1999)

Screening with a fecal occult blood test (FOBT) has been shown to reduce colorectal cancer mortality in controlled trials. Recently, Medicare approved payment for FOBT screening. We evaluated the pattern of diagnostic testing following the initial FOBT in elderly Medicare beneficiaries. Such follow-up testing would in the long run influence both the cost and the benefit of widespread use of FOBT.Using Medicare's National Claims History System, we identified 24 246 Americans 65 years old or older who received FOBT at physician visits between January 1 and April 30, 1995. Prior to FOBT, these people had no evidence of any conditions for which FOBT might be used diagnostically. We examined relevant diagnostic testing in this cohort during the subsequent 8 months and determined what proportion of those received an evaluation recommended by the American College of Physicians.For every 1000 Medicare beneficiaries who received FOBT, 93 (95% confidence interval = 89-96 per 1000) had positive findings and relevant testing in the subsequent 8 months. Of these, 34% had the recommended evaluation of either colonoscopy or flexible sigmoidoscopy with an air-contrast barium enema. Another 34% received a partial colonic evaluation with either flexible sigmoidoscopy or a barium enema. The remaining 32% received other gastrointestinal (GI) testing without evaluation of the colonic lumen: computed tomography or magnetic resonance imaging of the abdomen (15%), upper GI series (10%), carcinoembryonic antigen (7%), and upper endoscopy (2%). Restricting the analysis to testing performed within 2 months of the initial FOBT yielded similar results.Following FOBT, many Medicare beneficiaries get further diagnostic testing, but only a small proportion receives the recommended evaluation. With this pattern of practice, population screening is likely to be more costly and less effective than estimated from controlled trials.
A Comparison of Diabetes Education Administered Through Telemedicine Versus in Person
Authors: Roberto E. Izquierdo, Paul E. Knudson, Suzanne Meyer, Joann Kearns, Robert Ploutz-Snyder, Ruth S. Weinstock
Journal: Diabetes Care (2003)

To determine whether diabetes education can be provided as effectively through telemedicine technology as through in-person encounters with diabetes nurse and nutrition educators.A total of 56 adults with diabetes were randomized to receive diabetes education in person (control group) or via telemedicine (telemedicine group) and were followed prospectively. The education consisted of three consultative visits with diabetes nurse and nutrition educators. The in-person and telemedicine groups were compared using measures of glycemic control (HbA(1c)) and questionnaires to assess patient satisfaction and psychosocial functioning as related to diabetes. Outcome measures were obtained at baseline, immediately after the completion of diabetes education, and 3 months after the third educational visit.Patient satisfaction was high in the telemedicine group. Problem Areas in Diabetes scale scores improved significantly with diabetes education (adjusted P < 0.05, before vs. immediately after education and 3 months after education), and the attainment of behavior-change goals did not differ between groups. With diabetes education, HbA(1c) improved from 8.6 +/- 1.8% at baseline to 7.8 +/- 1.5% immediately after education and 7.8 +/- 1.8% 3 months after the third educational visit (unadjusted P < 0.001, P = 0.089 adjusted for BMI and age), with similar changes observed in the telemedicine and in-person groups.Diabetes education via telemedicine and in person was equally effective in improving glycemic control, and both methods were well accepted by patients. Reduced diabetes-related stress was observed in both groups. These data suggest that telemedicine can be successfully used to provide diabetes education to patients.
A New Look at Platelet-Derived Growth Factor in Renal Disease
Authors: Ju[Combining Diaeresis]rgen Floege, Frank Eitner, Charles E. Alpers
Journal: Journal of the American Society of Nephrology (2007)

The PDGF system, comprising four isoforms (PDGF-A, -B, -C, and -D) and two receptor chains (PDGFR-alpha and -beta), plays important roles in wound healing, atherosclerosis, fibrosis, and malignancy. Components of the system are expressed constitutively or inducibly in most renal cells. They regulate a multitude of pathophysiologic events, ranging from cell proliferation and migration to extracellular matrix accumulation, production of pro- and anti-inflammatory mediators, tissue permeability, and regulation of hemodynamics. Genetic deletion of PDGF-B or PDGFR-beta results in an absent glomerular mesangium, whereas PDGF-C and PDGFR-alpha contribute to the formation of the renal cortical interstitium. Almost all experimental and human renal diseases are characterized by altered expression of components of the PDGF system. Infusion or systemic overexpression of PDGF-B or -D induces prominent mesangioproliferative changes and renal fibrosis. Intervention studies identified PDGF-C as a mediator of renal interstitial fibrosis and PDGF-B and -D as key factors involved in mesangioproliferative disease and renal interstitial fibrosis. These data establish PDGF as one of the best characterized growth factors in renal disease and the most potent stimulus of mesangial cell proliferation currently identified. Accordingly, targeted intervention against the various PDGF isoforms offers a promising novel therapeutic approach to renal disease.
Burst Emergence of Intracellular Ca <sup>2+</sup> Waves Evokes Arrhythmogenic Oscillatory Depolarization via the Na <sup>+</sup> –Ca <sup>2+</sup> Exchanger
Authors: Katsuji Fujiwara, Hideo Tanaka, Hiroki Mani, Takuo Nakagami, Tetsuro Takamatsu
Journal: Circulation Research (2008)

Intracellular Ca 2+ waves (CaWs) of cardiomyocytes are spontaneous events of Ca 2+ release from the sarcoplasmic reticulum that are regarded as an important substrate for triggered arrhythmias and delayed afterdepolarizations. However, little is known regarding whether or how CaWs within the heart actually produce arrhythmogenic membrane oscillation because of the lack of data confirming direct correlation between CaWs and membrane potentials ( V m ) in the heart. On the hypothesis that CaWs evoke arrhythmogenic oscillatory depolarization when they emerge synchronously and intensively in the heart, we conducted simultaneous fluorescence recording of intracellular Ca 2+ ([Ca 2+ ] i ) dynamics and V m of ventricular myocytes on subepicardial surfaces of Langendorff-perfused rat hearts using in situ dual-view, rapid-scanning confocal microscopy. In intact hearts loaded with fluo4/acetoxymethyl ester and RH237 under perfusion with cytochalasin D at room temperature, individual myocytes exhibited Ca 2+ transients and action potentials uniformly on ventricular excitation, whereas low-K + –perfused (2.4 mmol/L) hearts exhibited CaWs sporadically between Ca 2+ transients without discernible membrane depolarization. Further [Ca 2+ ] i loading of the heart, produced by rapid pacing and addition of isoproterenol, evoked triggered activity and subsequent oscillatory V m , which are caused by burst emergence of CaWs in individual myocytes. Such arrhythmogenic membrane oscillation was abolished by ryanodine or the Na + –Ca 2+ exchanger inhibitor SEA0400, indicating an essential role of CaWs and resultant Na + –Ca 2+ exchanger–mediated depolarization in triggered activity. In summary, we demonstrate a mechanistic link between intracellular CaWs and arrhythmogenic oscillatory depolarizations in the heart. Our findings provide a cellular perspective on abnormal [Ca 2+ ] i handling in the genesis of triggered arrhythmias in the heart.
RETRACTED ARTICLE: Extranuclear ERα is associated with regression of T47D PKCα-overexpressing, tamoxifen-resistant breast cancer
Authors: Bethany Perez White, Mary Ellen Molloy, Huiping Zhao, Yiyun Zhang, Debra A. Tonetti
Journal: Molecular Cancer (2013)

Abstract Background Prior to the introduction of tamoxifen, high dose estradiol was used to treat breast cancer patients with similar efficacy as tamoxifen, albeit with some undesirable side effects. There is renewed interest to utilize estradiol to treat endocrine resistant breast cancers, especially since findings from several preclinical models and clinical trials indicate that estradiol may be a rational second-line therapy in patients exhibiting resistance to tamoxifen and/or aromatase inhibitors. We and others reported that breast cancer patients bearing protein kinase C alpha (PKCα)- expressing tumors exhibit endocrine resistance and tumor aggressiveness. Our T47D:A18/PKCα preclinical model is tamoxifen-resistant, hormone-independent, yet is inhibited by 17β-estradiol (E2) in vivo . We previously reported that E2-induced T47D:A18/PKCα tumor regression requires extranuclear ERα and interaction with the extracellular matrix. Methods T47D:A18/PKCα cells were grown in vitro using two-dimensional (2D) cell culture, three-dimensional (3D) Matrigel and in vivo by establishing xenografts in athymic mice. Immunofluoresence confocal microscopy and co-localization were applied to determine estrogen receptor alpha (ERα) subcellular localization. Co-immunoprecipitation and western blot were used to examine interaction of ERα with caveolin-1. Results We report that although T47D:A18/PKCα cells are cross-resistant to raloxifene in cell culture and in Matrigel, raloxifene induces regression of tamoxifen-resistant tumors. ERα rapidly translocates to extranuclear sites during T47D:A18/PKCα tumor regression in response to both raloxifene and E2, whereas ERα is primarily localized in the nucleus in proliferating tumors. E2 treatment induced complete tumor regression whereas cessation of raloxifene treatment resulted in tumor regrowth accompanied by re-localization of ERα to the nucleus. T47D:A18/neo tumors that do not overexpress PKCα maintain ERα in the nucleus during tamoxifen-mediated regression. An association between ERα and caveolin-1 increases in tumors regressing in response to E2. Conclusions Extranuclear ERα plays a role in the regression of PKCα-overexpressing tamoxifen-resistant tumors. These studies underline the unique role of extranuclear ERα in E2- and raloxifene-induced tumor regression that may have implications for treatment of endocrine-resistant PKCα-expressing tumors encountered in the clinic.
Tibial and femoral cartilage changes in knee osteoarthritis
Authors: F M Cicuttini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>BACKGROUND</h3> Despite the increasing interest in using knee cartilage volume as an outcome measure in studies of osteoarthritis (OA), it is unclear what components of knee cartilage will be most useful as markers of structure in the tibiofemoral (TF) joint. <h3>OBJECTIVE</h3> To compare the changes that occur in femoral and tibial cartilage volume in normal and osteoarthritic knees and how they relate to radiological grade. <h3>METHODS</h3> 82 subjects (44 female, 38 male, age range 35–69 years) with a spectrum of radiological knee OA were examined. Each subject had femoral and tibial cartilage volume in the medial and lateral TF joint determined from T<sub>1</sub> weighted fat saturated magnetic resonance images of the knee. Radiological grade of OA was determined from standing knee radiographs. <h3>RESULTS</h3> There was strong correlation between femoral and tibial cartilage volume measured in both the medial (<i>R</i>=0.75, p&lt;0.001) and lateral TF joint (<i>R</i>=0.77, p&lt;0.001). Similar correlations persisted when those with normal and those with OA joints were examined separately at both the medial and lateral TF joint. For each increase in radiological grade of joint space narrowing (0–3), there was a mean (SD) reduction in tibial cartilage volume of 1.00 (0.32) ml in the medial compartment and 0.53 (0.25) ml in the lateral compartment, after adjusting for differences in bone size. Similar changes were seen in the femoral cartilage. <h3>CONCLUSIONS</h3> The amounts of tibial and femoral cartilage are strongly related. It may be that for TF joint disease, measuring tibial cartilage alone may be adequate, given that measurements of the total femoral cartilage are less reproducible and the difficulties inherent in identifying the most appropriate component of femoral cartilage to measure.
NKT cells and the hedgehog pathway: an unhealthy marriage in non-alcoholic fatty liver disease?
Authors: Mariana Verdelho Machado, Helena Cortez-Pinto
Journal: Gut (2012)

In the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH), the hedgehog (Hh) pathway has recently been implicated, with a new target gene, osteopontin (OPN), being a candidate in the coordination of inflammation and fibrosis development.1 This pathway, which is critical in embryogenesis, can be activated in adult life in the context of tissue regeneration. It has been suggested that dying and injured hepatocytes, such as ballooned hepatocytes,2 against a background of lipotoxicity, can produce Hh that will then act on inflammatory cells such as natural killer T (NKT) cells3 and on progenitor cells in such a way as to promote growth and hepatocyte differentiation, maintaining the liver mass.1 Unfortunately, it also acts on stellate cells inducing a profibrogenic phenotype.1

Syn et al 4 further showed that NKT cells are responsive to Hh, and also are themselves a major source of Hh, inducing OPN production in an autocrine and paracrine fashion, thus being crucial in promoting fibrogenesis in NASH. The authors evaluated wild-type and knockout mice with NKT cell depletion, either knockout for the specific junction J α …
A Phase I Study of Intravenous Oncolytic Reovirus Type 3 Dearing in Patients with Advanced Cancer
Authors: Laura Vidal, Hardev S. Pandha, Timothy A. Yap, Christine L. White, Katie Twigger, Richard G. Vile, Alan Melcher, Matt Coffey, Kevin J. Harrington, Johann S. DeBono
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine the safety and feasibility of daily i.v. administration of wild-type oncolytic reovirus (type 3 Dearing) to patients with advanced cancer, assess viral excretion kinetics and antiviral immune responses, identify tumor localization and replication, and describe antitumor activity. Experimental Design: Patients received escalating doses of reovirus up to 3 × 1010 TCID50 for 5 consecutive days every 4 weeks. Viral excretion was assessed by reverse transcription-PCR and antibody response by cytotoxicity neutralization assay. Pretreatment and post-treatment tumor biopsies were obtained to measure viral uptake and replication. Results: Thirty-three patients received 76 courses of reovirus from 1 × 108 for 1 day up to 3 × 1010 TCID50 for 5 days, repeated every four weeks. Dose-limiting toxicity was not seen. Common grade 1 to 2 toxicities included fever, fatigue, and headache, which were dose and cycle independent. Viral excretion at day 15 was not detected by reverse transcription-PCR at 25 cycles and only in 5 patients at 35 cycles. Neutralizing antibodies were detected in all patients and peaked at 4 weeks. Viral localization and replication in tumor biopsies were confirmed in 3 patients. Antitumor activity was seen by radiologic and tumor marker (carcinoembryonic antigen, CA19.9, and prostate-specific antigen) evaluation. Conclusions: Oncolytic reovirus can be safely and repeatedly administered by i.v. injection at doses up to 3 × 1010 TCID50 for 5 days every 4 weeks without evidence of severe toxicities. Productive reoviral infection of metastatic tumor deposits was confirmed. Reovirus is a safe agent that warrants further evaluation in phase II studies.
Alemtuzumab is effective against severe chronic lymphocytic leukaemia-associated paraneoplastic pemphigus
Authors: R. Bech, J. Baumgartner-Nielsen, N.A. Peterslund, T. Steiniche, M. Deleuran, F. d'Amore
Journal: British Journal of Dermatology (2013)

Alemtuzumab (ALZ) is a monoclonal antibody used in the treatment of a variety of lymphoproliferative diseases, primarily chronic lymphocytic leukaemia (CLL). Paraneoplastic pemphigus (PNP) is a severe mucocutaneous disease, which can occur in association with B-cell malignancies. A correct diagnosis of PNP relies on distinct clinical and histopathological features, and the demonstration, by direct immunofluorescence, of intercellular and basement membrane IgG deposits in the affected tissue. PNP is often refractory to immunosuppressive drugs and frequently has a fatal outcome. We report three cases where sustained remissions of both PNP and CLL were induced by ALZ. In one of these cases, ALZ was able to reinduce a sustained remission of PNP at the reappearance of the disorder years after the primary treatment. In all cases, the PNP diagnosis was confirmed by immunofluorescence. In conclusion, ALZ should be considered as a treatment option in severe CLL-associated PNP. Patients should be carefully selected and receive appropriate infectious prophylaxis before, during and after ALZ treatment, due to the risk of opportunistic infections secondary to combined disease- and drug-induced immunosuppression.
Ubiquitous and Kidney-Specific Subunits of Vacuolar H+-ATPase Are Differentially Expressed during Nephrogenesis
Authors: Franc[COMBINING CEDILLA]ois Jouret, Céline Auzanneau, Huguette Debaix, Ge-Hong Sun Wada, Chrystel Pretto, Etienne Marbaix, Fiona E. Karet, Pierre J. Courtoy, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2005)

The vacuolar H(+)-ATPase (V-ATPase) is a ubiquitous multisubunit pump that is responsible for acidification of intracellular organelles. In the kidney, a particular form of V-ATPase, made of specific subunits isoforms, has been located at the plasma membrane of intercalated cells (IC). Mutations in genes encoding IC-specific subunits cause infant distal renal tubular acidosis (dRTA), suggesting that the segmental distribution of these subunits is acquired at birth or during early infancy. However, the comparative ontogeny of the IC-specific versus the ubiquitous subunits of V-ATPase and the mechanisms involved in their segmental expression remain unknown. Real-time reverse transcription-PCR, in situ hybridization, immunoblotting, immunostaining, and subcellular fractionation analyses characterized the expression and distribution of V-ATPase subunits, transcription factors, and differentiation markers during mouse nephrogenesis. Ubiquitous A, E1, B2, G1, and C1 subunits showed an early (embryonic day 13.5 [E13.5]) and stable expression throughout nephrogenesis, followed by a slight increase around birth. The developmental pattern of a1 was bimodal, with early induction, gradual decrease during organogenesis, and neonatal increase. These patterns contrasted with the later (from E15.5) and progressive expression of IC-specific a4, B1, G3, and C2 subunits, after the induction of the forkhead transcription factor Foxi1. From E15.5, Foxi1 mRNA was detected in IC, where it co-distributed with B1 in late nephrogenesis. Immunostaining showed that the distribution of ubiquitous E1 and B2 was acquired from E15.5, whereas a4 was located in IC during late nephrogenesis. Subcellular fractionation showed that in both fetal and mature (cortex and medulla) kidneys, E1 and a4 were located in endosomes. These data demonstrate a differential expression and a coordinate regulation of IC-specific versus ubiquitous V-ATPase subunits during nephrogenesis. They provide new insights into the complex regulation of V-ATPase subunits, the maturation of IC along the nephron, and the pathophysiology of hereditary dRTA.
Neighborhood Poverty and Racial Differences in ESRD Incidence
Authors: Nataliya Volkova, William McClellan, Mitchel Klein, Dana Flanders, David Kleinbaum, J. Michael Soucie, Rodney Presley
Journal: Journal of the American Society of Nephrology (2007)

Poverty is associated with increased risk of ESRD, but its contribution to observed racial differences in disease incidence is not well-defined. To explore the contribution of neighborhood poverty to racial disparity in ESRD incidence, we analyzed a combination of US Census and ESRD Network 6 data comprising 34,767 patients that initiated dialysis in Georgia, North Carolina, or South Carolina between January 1998 and December 2002. Census tracts were used as the geographic units of analysis, and the proportion of the census tract population living below the poverty level was our measure of neighborhood poverty. Incident ESRD rates were modeled using two-level Poisson regression, where race, age and gender were individual covariates (level 1), and census tract poverty was a neighborhood covariate (level 2). Neighborhood poverty was strongly associated with higher ESRD incidence for both blacks and whites. Increasing poverty was associated with a greater disparity in ESRD rates between blacks and whites, with the former at greater risk. This raises the possibility that blacks may suffer more from lower socioeconomic conditions than whites. The disparity persisted across all poverty levels. The reasons for increasingly higher ESRD incidence among US blacks as neighborhood poverty increases remain to be explained.
Hospital admissions of adults with community-acquired pneumonia in Portugal between 2000 and 2009
Authors: Filipe Froes, António Diniz, Margarida Mesquita, Margarida Serrado, Baltazar Nunes
Journal: European Respiratory Journal (2012)

Recent studies in the USA and northern Europe have shown an increase in community-acquired pneumonia (CAP). In southern Europe, this increase has not yet been documented. We carried out a retrospective analysis from encoded information from the Portuguese database for hospital admissions that included all individuals aged ≥18 years, with a primary diagnosis of pneumonia, who were discharged between 2000 and 2009. We excluded patients infected with HIV, individuals immunocompromised as a result of anti-cancer or immunosuppressive treatment, and transplant recipients. Of the 294 027 admissions for CAP, 56% were male. The mean age was 73.1 years and the median age 77 years. Between 2000 and 2009, there was a 5% increase in the average age of patients admitted with CAP. Admissions for CAP represented 3.7% of total admissions of adult patients. The average annual rate of hospital admissions for adults with CAP was 3.61 per 1000 total population, rising to 13.4 for those aged ≥65 years. Between 2000-2004 and 2005-2009 the average annual rate of hospital admission for CAP per 1000 population increased by 28.2%. Hospital admissions for CAP in Portugal increased between 2000 and 2009. It has grown consistently over time, varying according to age with males over-represented.
A prognostic model for predicting the disappearance of left atrial thrombi among candidates for percutaneous transvenous mitral commissurotomy
Authors: Songkwan Silaruks, Bandit Thinkhamrop, Wirote Tantikosum, Chaiyasith Wongvipaporn, Pyatat Tatsanavivat, Virat Klungboonkrong
Journal: Journal of the American College of Cardiology (2002)