tbuckley/cabot-search huggingface dataset:
Preferential inhibition of IKr by MCI-154, a putative cardiotonic Ca2+ sensitizer, in guinea pig atrial cells
Authors: K Eto
Journal: Cardiovascular Research (1998)

To define the electrophysiologic mechanism(s) by which MCI-154, a putative Ca2+ sensitizer, produces a positive inotropic response without a positive chronotropic response, we examined effects of MCI-154 on the action potential of atrial preparations and the membrane currents of atrial myocytes.The action potentias were recorded from left atrial and sinoatrial node preparations of guinea pigs by the use of standard microelectrode techniques. The whole-cell membrane currents were recorded from enzymatically-dissociated guinea pig atrial myocytes using conventional patch clamp techniques.In isolated left atria, MCI-154 increased the developed tension in a concentration-dependent manner. MCI-154 at concentrations of 10 and 100 microM increased the action potential duration (APD) in left atria stimulated at 0.5 Hz. In sinoatrial node preparations MCI-154 at a concentration of 100 microM produced a negative chronotropic response and prolonged APD. In single right atrial myocytes, MCI-154 at concentrations of 10 and 100 microM failed to increase the inward L-type Ca2+ current, but decreased the delayed rectifier K+ current (IK) in a concentration-dependent manner. MCI-154 decreased IK elicited by short depolarizing pulses more markedly than that induced by long depolarizing pulses. In addition, MCI-154 produced only a little inhibition of IK in the presence of E-4031, a specific blocker of rapidly activating component of IK (IKr).MCI-154 preferentially blocks IKr and the inhibitory action on IKr may be partly involved in the negative chronotropic and positive inotropic responses in atrial preparations.
Association Between Physician Time-Unlimited vs Time-Limited Internal Medicine Board Certification and Ambulatory Patient Care Quality
Authors: John Hayes, Jeffrey L. Jackson, Gail M. McNutt, Brian J. Hertz, Jeffrey J. Ryan, Scott A. Pawlikowski
Journal: JAMA (2014)

American Board of Internal Medicine (ABIM) initiatives encourage internists with time-unlimited certificates to recertify. However, there are limited data evaluating differences in performance between internists with time-limited or time-unlimited board certification.To determine whether there are differences in primary care quality between physicians holding time-limited or time-unlimited certification.Retrospective analysis of performance data from 1 year (2012-2013) at 4 Veterans Affairs (VA) medical centers. Participants were internists with time-limited (n = 71) or time-unlimited (n = 34) ABIM certification providing primary care to 68,213 patients. Median physician panel size was 610 patients (range, 19-1316), with no differences between groups (P = .90).Ten primary care performance measures: colorectal screening rates; diabetes with glycated hemoglobin (HbA1c level) less than 9.0%; diabetes with blood pressure less than 140/90 mm Hg; diabetes with low-density lipoprotein cholesterol (LDL-C) level less than 100 mg/dL; hypertension with blood pressure less than 140/90 mm Hg; thiazide diuretics used in multidrug hypertensive regimen; atherosclerotic coronary artery disease and LDL-C level less than 100 mg/dL; post-myocardial infarction use of aspirin; post-myocardial infarction use of β-blockers; congestive heart failure (CHF) with use of angiotensin-converting enzyme (ACE) inhibitor.After adjustment for practice site, panel size, years since certification, and clustering by physician, there were no differences in outcomes for patients cared for by internists with time-limited or time-unlimited certification for any performance measure: colorectal screening (odds ratio [OR], 0.95 [95% CI, 0.89-1.01]); diabetes with HbA1c level less than 9.0% (OR, 0.96 [95% CI, 0.74-1.2]); blood pressure control (OR, 0.99 [95% CI, 0.69-1.4]); LDL-C level less than 100 mg/dL (OR, 1.1 [95% CI, 0.79-1.5]); hypertension with blood pressure less than 140/90 mm Hg (OR, 1.0 [95% CI, 0.92-1.2]); thiazide use (OR, 1.0 [95% CI, 0.8-1.3]); atherosclerotic coronary artery disease with LDL-C level less than 100 mg/dL (OR, 1.1 [95% CI, 0.75-1.7]); post-myocardial infarction use of aspirin (OR, 0.98 [95% CI, 0.58-1.68]) or β-blockers (OR, 1.0 [95% CI, 0.57-1.9]); CHF with use of ACE inhibitor (OR, 0.98 [95% CI, 0.61-1.6]).Among internists providing primary care at 4 VA medical centers, there were no significant differences between those with time-limited ABIM certification and those with time-unlimited ABIM certification on 10 primary care performance measures. Additional research to examine the difference in patient outcomes among holders of time-limited and time-unlimited certificates in non-VA and nonacademic settings and the association with other ABIM goals may help clarify the potential benefit of Maintenance of Certification participation.
Isolated Rabbit Working Heart Function During Progressive Inhibition of Myocardial SERCA Activity
Authors: Elspeth B. Elliott, Allen Kelly, Godfrey L. Smith, Christopher M. Loughrey
Journal: Circulation Research (2012)

The extent to which sarcoplasmic reticulum Ca(2+)ATPase (SERCA) activity alone determines left ventricular (LV) pump function is unknown.To correlate SERCA activity with hemodynamic function of rabbit LV during thapsigargin perfusion.Isolated rabbit hearts were perfused in working heart configuration, and LV pump function was assessed using a pressure-volume catheter. Rapid and complete (>95%) inhibition of SERCA was associated with a moderate decrease in cardiac function (to 70%-85% of control). Further decrease in cardiac function to 50%-75% of control occurred over the next ≈ 30 minutes despite no detectable further inhibition of SERCA activity. Analysis of the 20 seconds prior to pump failure revealed a rapid decrease in end diastolic volume. Intermediate levels of SERCA function (≈ 50% of control) had only minor hemodynamic effects. Parallel experiments in field-stimulated isolated ventricular cardiomyocytes monitored intracellular Ca(2+) and cell shortening. On perfusion with thapsigargin, Ca(2+) transient amplitude and cell shortening fell to ≈ 70% of control followed by increased diastolic Ca(2+) concentration and diastolic cell shortening to achieve a new steady state.The relationship between SERCA activity and LV function in the rabbit is highly nonlinear. In the short term, only moderate effects on LV pump function were observed despite almost complete (>95%) reduction in SERCA activity. The terminal decline of function was associated with sudden sustained increase in diastolic tone comparable to the sustained contraction observed in isolated cardiomyocytes. Secondary increases of intracellular Ca(2+) and Na(+) following complete SERCA inhibition eventually limit contractile function and precipitate LV pump failure.
Nephrotoxicity with Cisplatin and Antihypertensive Medications
Authors: MAURIE MARKMAN
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 February 1982Nephrotoxicity with Cisplatin and Antihypertensive MedicationsMAURIE MARKMAN, M.D., DONALD L. TRUMP, M.D.MAURIE MARKMAN, M.D.Search for more papers by this author, DONALD L. TRUMP, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-2-257_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with interest the article by Blachley and Hill (1) reviewing renal and electrolyte abnormalities associated with cisplatin. We have recently cared for a patient in whom renal failure followed administration of cisplatin and antihypertensive medications used to treat marked elevation of blood pressure that occurred during cisplatin-induced emesis.A 58-year-old man with metastatic bladder cancer was treated with cisplatin, 70 mg/m2body surface area, intravenously, after hydration with normal saline, 0.9% NaC1 at 150 mL/h for 12 h. In addition, mannitol, 12.5 g intravenously, was administered immediately before the cisplatin infusion. The patient had a...References1. BLACHLEYHILL JJ. Renal and electrolyte disturbances associated with cisplatin. Ann Intern Med. 1981;95:628-32. LinkGoogle Scholar2. CVITKOVICSPAULDINGBETHUNE EJV. Improvement of cis-dichlorodiammineplatinum (NSC 119875): therapeutic index in an animal model. Cancer. 1977;39:1357-61. CrossrefMedlineGoogle Scholar3. PERAZOOKHARDER MBH. Effects of mannitol or furosemide diuresis on the nephrotoxicity and physiological disposition of cis-dichlorodiammineplatinum-(II) in rats. Cancer Res. 1979;39:1269-79. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Johns Hopkins Oncology Center Baltimore, MD 21205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClinical and Experimental Nephrotoxicity of Cancer Chemotherapeutic AgentsCumulative renal tubular damage associated with cisplatin nephrotoxicityHypertension after Metoclopramide 1 February 1982Volume 96, Issue 2Page: 257-257KeywordsBladder cancerBlood pressureBody surface areaMannitolRenal failureSaline solutions Issue Published: 1 February 1982 PDF downloadLoading ...
Abstract 1314: Estrogen receptor-α is activated in breast ductal epithelial cells by CCN5 in CCN5-conditional tri-transgenic mice
Authors: Monami Majumder, Snigdha Banerjee, Smita Mehta, Archana De, Kakali Dhar, Ossama Tawfik, Melissa A. Larson, Sushanta K. Banerjee
Journal: Cancer Research (2011)

Abstract Estrogen receptor-alpha (ER-α) is localized in the nuclei of approximately 3-7% of normal resting breast epithelial cells with a higher proportion in lobular cells than in ductal. This number is significantly increased in atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), pure intraductal carcinoma, and intraductal carcinoma with invasive duct carcinoma. Despite having this information for last 15 years, it is still uncertain how ER-α is activated in the nuclei of breast epithelial cells. CCN5/WISP-2, a member of the CCN (Cysteine-rich61/Connective Tissue Growth Factor/Nephroblastoma overexpressed) family of growth factors, is becoming an increasingly important focus in breast cancer research. CCN5/WISP-2 is a two-faced signaling molecule and plays differently in breast carcinogenesis under different micro-environmental setups. Our previous studies have shown that the transcriptional and translational activation of the WISP-2/CCN5 gene is a characteristic of estrogen receptor positive non-invasive breast tumor cell lines. Expression of the WISP-2/CCN5 gene was virtually undetected in non-transformed mammary epithelial cells. Moreover, multiple studies suggest a fine tune between CCN5 signaling and ER-α pathways, but this has not yet been fully elucidated. The main objective of this work was to establish the effect of excessive activation of CCN5 on the ER-α signaling. To do so, we generated a tri-transgenic inducible mouse model that overexpresses CCN5 under the Doxycycline (dox) environment. After the confirmation of the conditional expression of CCN5 in a mammary-specific and dox-dependent manner, morphology as well as the status of ER-α was evaluated. We found that induced expression of CCN5 by Dox in breast epithelial cells significantly increased ER-α expression and activity along with no morphological changes. Collectively, these studies indentify CCN5 as a regulator of ER-α in breast epithelial cells in a tri-transgenic mouse model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1314. doi:10.1158/1538-7445.AM2011-1314
Clinical studies with silymarin: Fibrosis progression is the end point
Authors: Detlef Schuppan, Eckhart G. Hahn
Journal: Hepatology (2001)

We read with interest the report by Angulo et al. 1 on 27 patients with primary biliary cirrhosis (PBC) who did not respond biochemically to ursodeoxycholic acid (UDCA).In a noncontrolled one-armed study the authors investigated the effect of adding oral silymarin for 1 year to the standard regimen with UDCA.Since silymarin did not alter alkaline phosphatase, bilirubin, aspartate transaminase, albumin, or the Mayo risk score, they concluded that silymarin is not effective in patients with PBC who do not respond to UDCA and that further controlled trials of silymarin in PBC are not warranted.We would take issue with several aspects of the study.1.The patients were at an early clinical stage of the disease, in which the Mayo score has limited prognostic value.3][4][5][6][7] If one chooses to argue that 1 year is sufficient, then the finding of no progression of disease could be interpreted as evidence for a beneficial effect of silymarin.3][4][5][6][7] Since progression of fibrosis ultimately determines the prognosis of PBC, fibrosis-related parameters should be monitored, including sequential histology, aminoterminal procollagen type III peptide, collagen IV, hyaluronic acid, and others. 8.
Not all those who wander are lost
Authors: T. Greenhalgh
Journal: BMJ (2010)

<h3>Introduction</h3> The widespread prevalence of type 2 diabetes (T2D) not only influences patients’ daily lives but also has an economic impact on society. Increasing physical activity and a healthy diet can delay the progression of T2D. Although there are evidence-based recommendations on diet and physical activity, patients with T2D have difficulties implementing them. An appropriate lifestyle intervention can address this problem. <h3>Methods and analysis</h3> This study is based on the need to develop an intervention that helps patients to establish behavioural changes in order to achieve glycaemic control. The intervention will be evaluated in a monocentric, open-label, pragmatic, two-arm randomised controlled trial with a sample ratio of 1:1 and a parallel design. This superiority study will be conducted in Switzerland. All enrolled patients (n=90) will receive the standard medical treatment for T2D. The intervention group will receive personal health coaching by telephone and access to a smartphone and web application for 1 year. The control group will receive access to the application for 1 year and a one-time written diet and exercise recommendation. The primary outcomes are objectively measured physical activity and glycated haemoglobin. Secondary outcomes are self-reported physical activity, nutrition, cognitive mediators of changes in sport-related behaviour, blood values, medication and nutritional supplements, anthropometric data, quality of life, neuropathy and cost-effectiveness. All outcomes will be measured at baseline, at 27 weeks after inclusion and at 54 weeks after inclusion. The recruitment of participants and the measurements will be completed after 2 years. Linear mixed-effects models will be applied for each outcome variable to analyse the intervention effects. <h3>Ethics and dissemination</h3> This study was approved by the Ethics Committee North-western and Central Switzerland in February 2021 (ref: 2020-02755). All participants will be required to provide written informed consent. The results will be published in international peer-reviewed journals. <h3>Trial registration number</h3> ISRCTN79457541.
Increased Neutrophil Elastase Activity in Cigarette Smokers
Authors: JEFFREY I. WEITZ
Journal: Annals of Internal Medicine (1987)

We compared plasma levels of the neutrophil elastase-derived fibrinopeptide A-alpha-1-21 in healthy cigarette smokers with those in nonsmokers. The mean A-alpha-1-21 concentration was fivefold higher (95% confidence interval [Cl], 3.0 to 9.6) in ten cigarette smokers than in 20 healthy nonsmokers (2.0 nmol/L compared with 0.4 nmol/L; p < 0.0001). To evaluate the acute effect of smoking on enzyme activity, a second group of ten smokers was studied. After refraining from smoking for 12 hours, each person smoked three cigarettes. The mean A-alpha-1-21 level in the second group of smokers was not different from that in the first group of smokers (1.8 nmol/L compared with 2.0 nmol/L) but was fivefold higher (95% Cl, 2.6 to 8.7) than that in the nonsmokers (1.8 nmol/L compared with 0.4 nmol/L; p < 0.0001). After smoking three cigarettes, subjects had a twofold elevation (95% Cl, 1.6 to 3.5) in the mean A-alpha-1-21 concentration (from 1.8 nmol/L to 4.1 nmol/L; p = 0.002). Our data show that cigarette smoking perturbs the in-vivo elastase-antielastase balance and thus may produce lung disease through this mechanism.
Observations on THE USE OF RADON SEEDS IN THE TREATMENT OF CARCINOMA
Authors: H. S. Souttar
Journal: BMJ (1930)

THi uise of radiumni emanation ini the form of seeds presents -ery conlsidlerable advaiatages in practice and, f ly collsln prctce ad or nea.rl two ve'ars I lhave adopte(d it wh-enever p-ossible, to the exclusion of other methods.-Iiitie-coullse of that timlie I have developed certain mnodifications iin teclhn-ique wlich I have founid advantagreous, and altlhough it i.s obvious that observationis on cases treated over so slhort a period can-onily be of a tentative nature, I feel that they ma'y not be devoid of interest.Radoni, or radiuLm emianation, is a lheavy gas of atomic weightt 222, anld it is formed by tile decav of radiulmi at an-absolutely constanit rate1 which is independenit of thle physical conlditioni of the radium, its solutioni, temperature, or-pressure.Radon itself decays, but by the end of a olloltll, if unltdisturbed, tlie r:adiium and(I its emaniation lhave virtually reaclhed a state of equiilibrium, w-heni thie produc-
Cardiovascular and renal function of angiotensin II type-2 receptors
Authors: O JOHREN
Journal: Cardiovascular Research (2004)

While all of the well-known cardiovascular and renal effects of angiotensin II (ANG) are attributed to the ANG type-1 (AT(1)) receptor, much less is known about the function of ANG type-2 (AT(2)) receptors. This review focuses on progress made in AT(2) receptor research over the past 10 years mainly enabled by the availability of AT(2) receptor-deficient mice. Two general mechanisms regarding AT(2) receptor-mediated actions emerge from recent experiments. Firstly, AT(2) receptor stimulation inhibits growth and promotes apoptosis, an important mechanism during development and tissue remodeling. Secondly, ANG stimulates the release of nitric oxide (NO)/cGMP via AT(2) receptor activation, as described in the aorta, heart, and kidney. This effect appears to be indirectly mediated by the modulation of bradykinin release. Thus, activation of AT(2) receptors may be potentially protective and appears to oppose the effects mediated by AT(1) receptors. The question whether AT(2) receptors are activated in patients with elevated ANG levels when treated with AT(1) receptor antagonists and whether these effects are relevant awaits further clarification.
The Association between Blood Lead Levels and Osteoporosis among Adults—Results from the Third National Health and Nutrition Examination Survey (NHANES III)
Authors: James R. Campbell, Peggy Auinger
Journal: Environmental Health Perspectives (2007)

BackgroundOsteoporosis is a reduction in bone mass sufficient to increase the risk of fracture. Lead exposure during childhood may be a risk factor for low bone mineral density (BMD). Basic-science research demonstrates that lead exposure is associated with a decrease in BMD in animals. However, human studies are limited.ObjectiveOur objective was to conduct a secondary analysis of a national database to explore the association between lead exposure and osteoporosis in adult humans.MethodsIn this study we used data from the Third National Health and Nutrition Examination Survey (NHANES III). We analyzed subjects who were ≥ 50 years of age. A concurrent venous blood lead level defined lead exposure. The primary outcome variable was the BMD of the total hip. We conducted analyses on four groups: non-Hispanic white men, non-Hispanic white women, African-American men, and African-American women. We conducted bivariate analyses between covariates known to be associated with bone density (i.e., age, body mass index, calcium intake, ethanol/tobacco consumption, physical activity, socioeconomic status) and the total hip BMD. The significant covariates were introduced into analysis of covariance to determine the association between BMD and blood lead level tercile.ResultsThe adjusted mean total hip BMD among non-Hispanic white males with a blood lead level in the lowest tercile versus the highest tercile was 0.961 g/cm2 and 0.934 g/cm2, respectively (p &lt; 0.05). We also found a similar association among white females, but the difference was marginally significant (0.05 &lt; p &lt; 0.10).ConclusionsWe found a significant inverse association between lead exposure and BMD, but only among white subjects. However, because of the cross-sectional design of NHANES, we cannot make inferences about the temporal sequence of this association. With the large number of adults who had lead exposure in the past and the morbidity associated with osteoporosis, further inquiry is necessary on the possible casusal association between lead exposure and osteoporosis in humans.
Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice
Authors: Gina Balciunaite, Marcel P. Keller, Egle Balciunaite, Luca Piali, Saulius Zuklys, Yves D. Mathieu, Jason Gill, Richard Boyd, Daniel J. Sussman, Georg A. Holländer
Journal: Nature Immunology (2002)
Polyostotic Fibrous Dysplasia as a Mimic of Bony Metastatic Disease
Authors: D. N. JONES, M MARION
Journal: Clinical Nuclear Medicine (1991)

A 40-year-old woman, with recently diagnosed ductal carcinoma in situ of the breast, received a chest radiograph as a baseline study. Multiple bilateral, asymmetric expansile rib lesions were seen, and bony metastatic disease was suggested. The patient had no pain and was constitutionally well. She was referred for whole-body bone scanning which revealed abnormal increased uptake in the skull, facial bones, mandible, spine, ribs, pelvis, and femora. The initial suggestion of widespread bony metastatic disease was opposed by the marked relative unilateral involvement of the skull and facial bones. Radiologic correlation revealed the typical findings of polyostotic fibrous dysplasia. This case highlights the potential pitfalls in interpretation of bone scanning where widespread abnormal areas of increased uptake are seen, particularly in the context of suspected malignancy. Polyostotic fibrous dysplasia and Paget's disease may mimic closely the appearance of bony metastatic disease. In these instances, the distribution of radionuclide uptake and the clinical and radiologic correlation are helpful in determining the etiology.