tbuckley/cabot-search huggingface dataset:
Neurotransmitter depletion compromises the ability of indirect-acting amines to provide inotropic support in the failing human heart.
Authors: J DPort, E MGilbert, PLarrabee, PMealey, KVolkman, RGinsburg, R EHershberger, JMurray, M RBristow
Journal: Circulation (1990)

To test the hypothesis that cardiac norepinephrine depletion related to heart failure alters contractile responses to beta-adrenergic agonists with a component of indirect action (acting by release of neuronal norepinephrine), we examined the inotropic potential of several pharmacologically distinct beta-agonists. Contractile responses to the nonselective beta-agonist isoproterenol, the beta 2-selective agonist zinterol, and the direct- and indirect-acting agonists dopamine and dopexamine were compared in isolated right ventricular trabeculae removed from failing, nonfailing innervated, and previously transplanted and, therefore, denervated nonfailing human hearts. In failing hearts, the contractile response to isoproterenol was significantly lower (41%) than that in nonfailing innervated hearts. The responses to the mixed agonists dopamine and dopexamine were even more attenuated in failing hearts, to a level 76-90% lower than those of nonfailing innervated hearts. In denervated, previously transplante...
Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure-volume relationships.
Authors: D AKass, W LMaughan, Z MGuo, AKono, KSunagawa, KSagawa
Journal: Circulation (1987)

We examined the quantitative influence of carefully controlled alterations in end-diastolic volume and afterload resistance on multiple simultaneously determined ejection and isovolumetric phase indexes of left ventricular contractile function in 23 isolated supported canine ventricles. The influence of load change on each index was compared with its sensitivity to inotropic stimulation, and this sensitivity was in turn contrasted to the response of the end-systolic pressure-volume relationship (ESPVR). Experimental data demonstrated various degrees of load sensitivity among the indexes, with a generally curvilinear relationship between load and index response for both preload and afterload alterations. The curvilinear nature of these relationships meant that over a select range of loading, many indexes demonstrated relative load independence. They also often displayed greater sensitivity to inotropic change than the ESPVR, and both factors help explain their enduring clinical utility. To further explore ...
Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial
Authors: Ling Qu, Xiaochun Liang, Guoqing Tian, Gaili Zhang, Qunli Wu, Xiumei Huang, Yazhong Cui, Yuling Liu, Zhufang Shen, Changqing Xiao, Yingfen Qin, Heng Miao, Yongyan Zhang, Ziling Li, Shandong Ye, Xuezhi Zhang, Jing Yang, Guiwen Cao, Yi Li, Gangyi Yang, Ji Hu, Xiaoyue Wang, Zhengfang Li, Yukun Li, Xiuzhen Zhang, Guangde Zhang, Li Chen, Wenjin Hua, Ming Yu, Chunyan Lu, Xiaomei Zhang, Hong Jiang
Journal: Diabetes Care (2021)

OBJECTIVE This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS After treatment for 24 weeks, the change in HbA1c was –0.93% (95% CI –1.03 to –0.83) (–10.2 mmol/mol [–11.3 to –9.1]) and –0.87% (–0.99 to –0.76) (–9.5 mmol/mol [–10.8 to –8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was –0.05% (95% CI –0.18 to 0.07) (–0.5 mmol/mol [–2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P &amp;gt; 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P &amp;lt; 0.01), but no differences for AEs or SAEs between the two groups were observed (P &amp;gt; 0.05). CONCLUSIONS SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.
Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation
Authors: Markus Guba, Karl-Walter Jauch
Journal: New England Journal of Medicine (2008)

BackgroundImmunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients.This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. MethodsWe randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus.The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation.Secondary end points included acute rejection and allograft survival. ResultsThe mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute).The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), lowdose cyclosporine (24.0%), or low-dose sirolimus (37.2%).Allograft survival differed significantly among the four groups (P = 0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%).Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%). ConclusionsA regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction.(ClinicalTrials.govnumber, NCT00231764.)
Abstract 12966: Clinical Aspects and Prognosis of Elderly Patients with Brugada Syndrome
Authors: Tsukasa Kamakura, Kohei Ishibashi, Ikutaro Nakajima, Koji Miyamoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Takeshi Aiba, Wataru Shimizu, Hiroshi Takaki, Toshihisa Anzai, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa, Shiro Kamakura, Kengo Kusano
Journal: Circulation (2013)

Background: Little is known about the clinical characteristics and prognosis of elderly patients with Brugada syndrome (BrS). Methods and Results: This study included 60 patients (mean age 71.3±5.4...
Block of sodium current by heptanol in voltage-clamped canine cardiac Purkinje cells.
Authors: W LNelson, J CMakielski
Journal: Circulation Research (1991)

Heptanol blocks sodium current (INa) in nerve, but its effects on cardiac INa have not been well characterized. Block of INa by heptanol was studied in 16 internally perfused voltage-clamped cardiac Purkinje cells at reduced Na+ (45 mM outside, 0 mM inside). Heptanol block of peak sodium conductance was well described by a single-site binding curve with half block at 1.3 mM (20 degrees C) and showed no use dependence. With 1.5 mM heptanol, block increased slightly by 0.7%/degrees C from 10 degrees C to 27 degrees C. With 3.0 mM heptanol, steady-state availability shifted by 9.4 +/- 1.3 mV (n = 6) in the hyperpolarizing direction, and steady-state activation shifted by 8.3 +/- 2.2 mV (n = 5) in the depolarizing direction, thus closing off the INa window current. Heptanol also decreased the time to peak and accelerated the decay of INa. Similar results were found with octanol at lower concentrations. These alcohols have important effects on cardiac INa at concentrations used in studies for cellular unco...
Concordance for coronary risk factors among spouses.
Authors: D LSackett, G DAnderson, RMilner, MFeinleib, W BKannel
Journal: Circulation (1975)

Values for several coronary risk factors, including systolic and diastolic blood pressure, serum cholesterol, triglycerides, blood glucose, uric acid, hemoglobin, weight, vitral capacity and cigarette smoking have been found to be similar among spouses in the Framingham Study. However, longitudinal analyses show that this spouse concordance does not increase over a twelve-year observation period, suggesting that it has arisen through the marriage of similar people rather than through the sharing of a common marital environment. Apparent conflicts between cross-sectional and longitudinal findings have been resolved by showing that spouses who were concordant at the begining of the study are more likely to survive to later exams, while discordant spouse pairs tend to be dissolved through the death of one of their members.
Iontophoretic transmyocardial drug delivery. A novel approach to antiarrhythmic drug therapy.
Authors: BAvitall, JHare, GZander, CBockoff, PTchou, MJazayeri, MAkhtar
Journal: Circulation (1992)

BACKGROUNDAntiarrhythmic drugs often fail to achieve therapeutic effects without toxic systemic levels. Direct transport of drugs into the myocardium may circumvent this problem and may also provide new insights into antiarrhythmic drug effect on arrhythmogenic tissues. In a canine model, procainamide (PA) was delivered iontophoretically using pulsed current synchronized with the ventricular depolarization via an implantable defibrillator patch electrode that was modified to contain a 3.6-ml chamber. Myocardial tissue concentrations of PA were evaluated in 7-day myocardial infarcts (n = 16) that were exposed to 10 minutes of iontophoretic PA delivery and compared with passive diffusion (n = 5) and intravenous (n = 16) PA. These dogs were followed for 3 hours. The infarcted tissue PA levels were compared with normal myocardium. Coronary and systemic blood levels of PA, effective refractory period (ERP), diastolic threshold, and efficacy of ventricular tachycardia (VT) suppression were evaluated throughout ...
Age-associated alterations in viscoelastic properties of canine aortic strips.
Authors: F CYin, H ASpurgeon, C HKallman
Journal: Circulation Research (1983)

Many studies have delineated the changes in the elastic properties of arterial tissue as a function of age. Despite the fact that viscoelasticity is a prominent feature of these tissues, there is little information or characterization of age-associated changes in viscoelastic properties, over a wide range of smooth muscle activation, particularly in nonhuman tissue where atherosclerosis is not a confounding factor. In the present study, using small sinusoidal length perturbations, we determined the dynamic stiffness properties across a wide range of lengths (stretch ratios from 100 to 135%) and frequencies (from 0.25 to 35 Hz) in strips excised from ascending and descending aortas from six young (2 to 4-year-old) and 12 senescent (10- to 13-year-old) beagles. Studies were performed with the smooth muscle fully activated with calcium and norepinephrine, as well as fully inactivated with cyanide, iodoacetate, and dinitrophenol. There was a cubic nonlinear dependence of stiffness modulus on length only in se...
Pulmonary parenchymal tissue volume measurements in graded degrees of pulmonary edema in dogs.
Authors: F LGlauser, A FWilson, LCarothers, JHigi, DWhite, JDavis
Journal: Circulation Research (1975)

We investigated the accuracy and the sensitivity of a modification of the acetylene inhalation technique for the determination of lung tissue volume (Vt) during various grades of hemodynamic pulmonary edema in 23 dogs. After base-line acetylene measurements were obtained, intravascular driving force (pulmonary wedge pressure minus intravascular colloid osmotic pressure) was varied between -8 and +71 mm Hg by the inflation of an intra-aortic ballon and the infusion of isotonic saline. After 30 minutes at this new driving force, four timed acetylene samples were again collected. Vt (when factored by alveolar volume, VA) increased from base line to 0.23 plus or minus 0.07 ml/ml between a driving force of 0 and + 17 mm Hg. This same change in Vt/VA was accompanied by an increase in the lung wet weight-dry weight ratio from 3.84 plus or minus 0.31 to 5.2 plus or minus 0.25. Vt was 271 plus or minus ml compared with an actual lung wet weight of 288 plus or minus 57 g; Vt tended to overestimate lung wet weight i...
Midterm results after the arterial switch operation for transposition of the great arteries with intact ventricular septum: clinical, hemodynamic, echocardiographic, and electrophysiologic data.
Authors: GWernovsky, T JHougen, E PWalsh, G FSholler, S DColan, S PSanders, I AParness, J FKeane, J EMayer, R AJonas
Journal: Circulation (1988)

Although the short-term results of atrial level repair of transposition of the great arteries (TGA) are satisfactory, longer follow-up has disclosed a significant incidence of systemic right ventricular dysfunction and rhythm disturbances. The arterial switch operation (ASO) may represent a major improvement by restoring the left ventricle as the systemic ventricle and avoiding extensive atrial surgery. We have prospectively evaluated 49 consecutive survivors of ASO for TGA with intact ventricular septum (IVS) by clinical examination, echocardiography, cardiac catheterization, ambulatory electrocardiographic monitoring, and invasive electrophysiologic studies. The mean length of follow-up has been 29 +/- 14 (SD) months after surgery. All children are currently asymptomatic and on no medications. Severe supravalvular pulmonary stenosis (greater than 60 mm Hg) was present in five children, all of whom have undergone reoperation. No patient has severe supravalvular aortic obstruction. Mild degrees of suprava...
Humanized skeletal muscle in MYF5/MYOD/MYF6-null pig embryos
Authors: Geunho Maeng, Satyabrata Das, Sarah M. Greising, Wuming Gong, Bhairab N. Singh, Stefan Kren, Daniel Mickelson, Erik Skie, Ohad Gafni, Jacob R. Sorensen, Cyprian V. Weaver, Daniel J. Garry, Mary G. Garry
Journal: Nature Biomedical Engineering (2021)
Selective inhibition by des-1-Asp-8-lle-angiotensin ii of the steroidogenic response to restricted sodium intake in the rat.
Authors: C ASarstedt, E DVaughan, M JPeach
Journal: Circulation Research (1975)

Angiotensin III (des-1-Asp-angiotensin II) is a potent steriodogenic agent in many species. The effects of the heptapeptide in the adrenal zona glomerulosa are resistant to blockade by C-terminally substituted analogues of angiotensin II (1-Sar-8-Ile- or 1-Sar-8-Ala-octapeptides). For this reason, the effects of 7-Ile-angiotensin III, a C-terminally substituted analogue of the heptapeptide, and 1-Sar-8-Ile-angiotensin II on aldosterone biosynthesis in rabbit adrenal cortical cell suspensions and on urinary aldosterone excretion in sodium-deprived rats were studied. In the vitro studies, 7-Ile-angiotensin III was a better antagonist of angiotensin II- or angiotensin III-induced steroidogenesis than was 1-Sar-8-Ile-angiotensin II. In the rats, subcutaneously administered 1-Sar-8-Ile-angiotensin II (0.9 mumoles/kg) produced prolonged blockade of the pressor responses to exogenous angiotensin II. 70Ile-angiotensin III (0.9 mumoles/kg) had no effect on resting blood pressure or on blood pressure responses to a...
Appropriate sensing of ventricular fibrillation after failed shocks in a transvenous cardioverter-defibrillator system.
Authors: J REllis, D TMartin, F JVenditti
Journal: Circulation (1994)

BACKGROUNDReduction in R-wave amplitude immediately after defibrillation shocks in an integrated shock/sense transvenous cardioverter-defibrillator (TCD) lead system has prompted concerns regarding adequate sensing after failed shocks. We therefore studied redetection characteristics for ventricular fibrillation after unsuccessful defibrillation shocks in a TCD system to determine if these observations have clinical relevance.METHODS AND RESULTSFifty patients with this shock/sense TCD lead system underwent conversion testing of their TCD at several time intervals. There were a total of 142 failed shocks events recorded, including 10, 15, 70, and 47 events at implantation, predischarge, and 2- and 6-month testing, respectively. Initial detection time (IDT) and redetection time (RDT) for ventricular fibrillation were measured from event markers for all unsuccessful defibrillation shocks. To assess the effect of failed shocks on electrogram quality, 54 failed shock episodes were evaluated in 37 of the 50 pat...
The ultra-connected generation would like to disconnect now
Authors: Julie Cassan, Agathe Claude, Mariuca de Hillerin, Audrey Fontaine, Paige Goodwin, Emily Halstead, Maya-Lhanze Lama, Yanis M'zali, Kim Paulin, Leonard Raimbault, Robin Tocqueville-Perrier, Riya Verma, Chloe Villaret
Journal: The Lancet (2021)
Left ventricular mass and subsequent blood pressure changes among middle-aged men in rural and urban Japanese populations.
Authors: HIso, MKiyama, MDoi, NNakanishi, AKitamura, YNaito, SSato, MIida, MKonishi, TShimamoto
Journal: Circulation (1994)

BACKGROUNDIt has been suggested that echocardiographically determined left ventricular mass (LVM) is useful in the prediction of hypertension. To examine the relation between LVM and subsequent blood pressure (BP) change, a 6- to 8-year follow-up was conducted in adult Japanese men.METHODS AND RESULTSLVM was determined by M-mode echocardiography using the American Society of Echocardiography formula among 354 normotensive men aged 30 to 59 years from a rural community (n = 193) and from urban companies (n = 161) in Japan between 1979 and 1983. BP was remeasured 6 to 8 years after baseline in 148 rural men (77%) and 127 urban men (79%). For men whose BP was remeasured, the mean +/- SD LVM index (LVM/body surface area [g/m2]) at baseline was 117 +/- 22 in rural men and 99 +/- 15 in urban men (the difference, P < .001). For both populations, LVM index was positively associated with age and physical activity but not with body mass index. Associations of LVM index with usual alcohol intake and initial BPs were...
The effects of atrial fibrillation on atrial pressure-volume and flow relationships.
Authors: C WWhite, R EKerber, H RWeiss, M LMarcus
Journal: Circulation Research (1982)

To study whether atrial fibrillation might produce local changes in the atrium which could facilitate the tendency of this arrhythmia to become chronic and self-perpetuating, we compared the effect of atrial fibrillation, atrial pacing, and acute volume loading on the perfusion and oxygen consumption of the atrium in anesthetized dogs. Measurement of atrial perfusion with microspheres indicates that during atrial fibrillation, atrial blood flow increases 2- to 3-fold. Right atrial pacing is a significantly less potent metabolic stimulus for atrial vasodilation. Using Doppler velocity recordings of sinus node artery blood flow velocity, a marked increase in velocity is observed within 5 seconds after the initiation of atrial fibrillation. During atrial fibrillation, the sinus node artery reactive hyperemia response is markedly attenuated. Atrial fibrillation acutely decreases atrial distensibility; atrial pressure increased 81 +/- 19% with only a small increase (9.7 +/- 3%) in atrial diameter measured by e...
Renal Excretion of Contrast After a Complicated Ercp: A Rare Complication?
Authors: F Garrido, JC Villa, Á Martínez-Alcalá, C Zaera, A Encinas, AM Mora, E Sacristán, Á Ponferrada
Journal: Endoscopy (2021)

A 22 years old woman came to our Hospital with abdominal pain and choledocolithiasis in abdominal ultrasound. An ERCP was requested, seeing the flow of the constrast throught the ureter during the procedure. A mild acute pancreatitis after ERCP was diagnosed.
Genomic, Transcriptomic, and Proteomic Profiling of Metastatic Breast Cancer
Authors: Argun Akcakanat, Xiaofeng Zheng, Christian X. Cruz Pico, Tae-Beom Kim, Ken Chen, Anil Korkut, Aysegul Sahin, Vijaykumar Holla, Emily Tarco, Gopal Singh, Senthil Damodaran, Gordon B. Mills, Ana Maria Gonzalez-Angulo, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Metastatic breast cancer (MBC) is not curable and there is a growing interest in personalized therapy options. Here we report molecular profiling of MBC focusing on molecular evolution in actionable alterations. Experimental Design: Sixty-two patients with MBC were included. An analysis of DNA, RNA, and functional proteomics was done, and matched primary and metastatic tumors were compared when feasible. Results: Targeted exome sequencing of 41 tumors identified common alterations in TP53 (21; 51%) and PIK3CA (20; 49%), as well as alterations in several emerging biomarkers such as NF1 mutations/deletions (6; 15%), PTEN mutations (4; 10%), and ARID1A mutations/deletions (6; 15%). Among 27 hormone receptor–positive patients, we identified MDM2 amplifications (3; 11%), FGFR1 amplifications (5; 19%), ATM mutations (2; 7%), and ESR1 mutations (4; 15%). In 10 patients with matched primary and metastatic tumors that underwent targeted exome sequencing, discordances in actionable alterations were common, including NF1 loss in 3 patients, loss of PIK3CA mutation in 1 patient, and acquired ESR1 mutations in 3 patients. RNA sequencing in matched samples confirmed loss of NF1 expression with genomic NF1 loss. Among 33 patients with matched primary and metastatic samples that underwent RNA profiling, 14 actionable genes were differentially expressed, including antibody–drug conjugate targets LIV-1 and B7-H3. Conclusions: Molecular profiling in MBC reveals multiple common as well as less frequent but potentially actionable alterations. Genomic and transcriptional profiling demonstrates intertumoral heterogeneity and potential evolution of actionable targets with tumor progression. Further work is needed to optimize testing and integrated analysis for treatment selection.
Arterial reactivity is significantly impaired in normotensive young adults after successful repair of aortic coarctation in childhood.
Authors: H MGardiner, D SCelermajer, K ESorensen, DGeorgakopoulos, JRobinson, OThomas, J EDeanfield
Journal: Circulation (1994)

BACKGROUNDDespite successful repair of coarctation of the aorta in childhood, adult survivors often have hypertension at rest or on exercise, and their life expectancy is shorter than normal because of premature coronary and cerebrovascular disease. This may be related to persistent structural and functional arterial abnormalities after surgery.METHODS AND RESULTSUsing high-resolution ultrasound, we studied the right brachial arteries of 25 normotensive young adults who had undergone successful repair of coarctation in childhood (mean age at repair, 62 months; range, 0 to 167 months, including 8 patients operated on in infancy; mean age at study, 19 years; range, 14 to 27 years) and 50 age- and sex-matched control subjects. We assessed the degree of reactive hyperemia (RH) produced after distal cuff occlusion and release and the changes in arterial diameter in response to RH (with increased flow causing endothelium-dependent dilation) and to glyceryltrinitrate (GTN, an endothelium-independent dilator). Th...