tbuckley/cabot-search huggingface dataset:
The effects of right atrial and ventricular pacing on the auscultatory findings in patients with mitral valve prolapse.
Authors: W DTowne, S HRahimtoola, M ZSinno, H SLoeb, K MRosen, R MGunnar
Journal: Circulation (1975)

Fifteen patients with midsystolic clicks associated with mitral valve prolapse were studied in order to assess changed in ausculatatory findings produced by pacing-induced variations in cardiac rate, rhythm, and conduction. As the heart rate was increased in stepwise intervals to the maximum possible extent by right atrial pacing (RAP) in 14 patients, the interval between the Q wave and the click (Q-C) decreased in all cases (21 plus or minus msec/10 beats/min; P smaller than 0.001). In two patients, RAP at rates of and above 118 and 159 per minute, respectively, resulted in disappearance of the click. During right ventricular pacing (RVP) without evidence of atrioventricular (A-V) dissociation on the surface ECG in ten patients, the click was inaudible at all pacing rates in three instances. In all seven of the cases in which the click was audible at the lowest rate of RVP with VA conduction, Q-C was greater and C-S2 less than that in sinus rhythm. As the rate of RVP was increased, Q-C was noted to decre...
Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial
Authors: Claire-Louise Murphy, Eithne Murphy, Trevor Duffy, Miriam O'Sullivan, Maurice Barry
Journal: Annals of the Rheumatic Diseases (2013)

We read with interest the paper regarding the efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial.1 We note the exclusion criteria included secondary knee osteoarthritis. On review of the results section, it appears that many of the patients, the randomised and the intention-to-treat groups, for example, the strontium 1 g/day group, strontium 2 g/day group and placebo group, were either overweight or …
The effect of aortic valve replacement on survival.
Authors: FSchwarz, PBaumann, JManthey, MHoffmann, GSchuler, H CMehmel, WSchmitz, WKübler
Journal: Circulation (1982)

We retrospectively studied 252 operated and 47 unoperated patients with isolated aortic valve disease. Aortic valve replacement (AVR) was recommended to all patients based on clinical and hemodynamic data. Preoperative hemodynamic and angiographic data were similar in operated and unoperated cohorts. Seventy-one percent of patients received a Bjork-Shiley prosthesis. Operative mortality was 7% for the entire surgical series. For patients with predominant aortic stenosis (AS), survival at 3 years was 87% in operated and 21% in unoperated patients (p less than 0.001). For patients with predominant aortic insufficiency (AI), the 5-year survival rate was 86% in operated and 87% in unoperated patients (NS). AVR improved long-term survival in patients with AS who had normal or impaired left ventricular (LV) function. In patients with AI and normal LV function, survival was not improved after AVR, but those with LV dysfunction who were operated on tended to survive longer (NS). Long-term survival of unoperated p...
Dialysis arthropathy: complication of long term treatment with haemodialysis.
Authors: E A Brown, I R Arnold, P E Gower
Journal: BMJ (1986)

Twenty eight patients who had received haemodialysis for more than 10 years were reviewed to establish the incidence of joint problems. Only six patients had no joint symptoms, one had avascular necrosis, one had had recent septic arthritis, and four had hyperparathyroidism. The remaining 16 patients had no evidence of hyperparathyroidism yet had an arthropathy causing pain and stiffness in many joints, particularly the shoulders. Ten of these 16 patients had a recurrent carpal tunnel syndrome requiring repeated surgical decompressions, which resulted in only partial improvement. Of the eight patients who had received dialysis for more than 15 years, seven had this "dialysis arthropathy" and six had recurrent carpal tunnel syndrome. Dialysis arthropathy is a common and often severe and disabling complication of long term treatment with haemodialysis. The cause is not known, but amyloid was found in a synovial biopsy specimen from one patient.
Prevalence of Barrett’s Esophagus in a South European Country:A Multicentre, Cross-Sectional Study
Authors: I Marques de Sá, C Leal, J Silva, D Falcão, C Felix, C Nascimento, P Boal Carvalho, H Vasconcelos, I Pedroto, C Chagas, M Cravo, J Cotter, P Sharma, M Dinis-Ribeiro
Journal: Endoscopy (2021)

Aims The identification of Barrett’s esophagus (BE) with detection and treatment of dysplasia is essential to prevent adenocarcinoma. Therefore, the determination of BE prevalence is important to define screening and subsequent surveillance strategies. However, precise estimates on BE prevalence from several European countries are lacking. We aimed to determine BE prevalence in Portugal.
Alterations in the human oral and gut microbiomes and lipidomics in COVID-19
Authors: Zhigang Ren, Haiyu Wang, Guangying Cui, Haifeng Lu, Ling Wang, Hong Luo, Xinhua Chen, Hongyan Ren, Ranran Sun, Wenli Liu, Xiaorui Liu, Chao Liu, Ang Li, Xuemei Wang, Benchen Rao, Chengyu Yuan, Hua Zhang, Jiarui Sun, Xiaolong Chen, Bingjie Li, Chuansong Hu, Zhongwen Wu, Zujiang Yu, Quancheng Kan, Lanjuan Li
Journal: Gut (2021)

To characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile. We collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity. Oral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery. This study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.
Secular decline in death rates due to ischemic heart disease in Mexican Americans and non-Hispanic whites in Texas, 1970-1980.
Authors: M PStern, B SBradshaw, C WEifler, D SFong, H PHazuda, MRosenthal
Journal: Circulation (1987)

Although the decline in ischemic heart disease mortality is now entering its third decade, there has been no definitive information on the experience of Mexican Americans, the nation's second largest minority group. Earlier studies carried out in the 1970s were hampered by the unavailability of satisfactory population data beyond 1970. In the present study we have used 1970 and 1980 census data to compute death rates in Mexican Americans and non-Hispanic whites from Texas for the periods 1969-1971 and 1979-1981. All four sex-ethnic groups showed statistically significant declines in death rates due to all causes, due to total ischemic heart disease, and due to acute myocardial infarction between 1969-1971 and 1979-1981. Declines in the latter two causes of death were least marked in Mexican American men. This sex-ethnic group was also the only one that failed to show a decline in death rates due to chronic ischemic heart diseases. The fact that Mexican Americans have been shown to be less well informed ab...
Rate-related suppression and facilitation of conduction in isolated canine cardiac Purkinje fibers.
Authors: R FGilmour, J JSalata, D PZipes
Journal: Circulation Research (1985)

Previous studies have shown that antegrade conduction through damaged His Purkinje tissue may be suppressed following rapid ventricular pacing (overdrive suppression of conduction). We studied this phenomenon using isolated Purkinje fibers placed in a three-chamber bath. Superfusates for the left, middle, and right segments of the fiber were altered to produce action potentials that resembled those of normal bundle branch, damaged His bundle, and normal His bundle, respectively. To produce anisotropic conduction, the left segment of the fiber was adjusted to be three to four times longer than the right segment. Pacing the right segment at intermediate rates produced maximal action potential amplitude in the middle segment and 1:1 right-to-left conduction, whereas pacing at faster or slower rates reduced action potential amplitude and produced block. Pacing the left segment at fast or slow rates also reduced action potential amplitude in the middle segment, but conduction was maintained (anisotropy). After...
Release of histamine by sympathetic nerve stimulation in the guinea pig heart and modulation of adrenergic responses. A physiological role for cardiac histamine
Authors: S SGross, Z GGuo, RLevi, W HBailey, A AChenouda
Journal: Circulation Research (1984)

Histamine has been reported to attenuate adrenergic responses in cardiovascular tissues. In guinea pig atria preloaded with [3H]norepinephrine, histamine diminishes the field stimulation-induced efflux of radioactivity; this effect has been attributed to an inhibition of norepinephrine release from nerve endings. To assess the possible physiological relevance of these findings, we have reinvestigated the effects of histamine on cardiac sympathetic responses and on the release of endogenous norepinephrine in the guinea pig heart isolated with its intact sympathetic innervation. Heart rate, left ventricular contractile force, and perfusion pressure all increased with increasing frequencies of sympathetic nerve stimulation (2-8 Hz). Histamine (3 X 10(-8) to 3 X 10(-7) M) caused dose-dependent attenuation of the responses to sympathetic stimulation. The ability of histamine to modulate nerve stimulation-induced norepinephrine overflow into the coronary effluent was dependent on whether the heart had been prel...
Obituary for Robert Schrier
Authors: Tomas Berl
Journal: Journal of the American Society of Nephrology (2021)

On the night of January 23, 2021, the world of internal medicine, and particularly nephrology, lost one of its most towering figures, Dr. Robert W. Schrier. For much of the second half of the twentieth century and the first decade of the twenty-first century, he was one of the most recognized and
Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies
Authors: Mihaela Aldea, Fabrice Andre, Aurelien Marabelle, Semih Dogan, Fabrice Barlesi, Jean-Charles Soria
Journal: Cancer Discovery (2021)

Resistance to anticancer therapies includes primary resistance, usually related to lack of target dependency or presence of additional targets, and secondary resistance, mostly driven by adaptation of the cancer cell to the selection pressure of treatment. Resistance to targeted therapy is frequently acquired, driven by on-target, bypass alterations, or cellular plasticity. Resistance to immunotherapy is often primary, orchestrated by sophisticated tumor-host-microenvironment interactions, but could also occur after initial efficacy, mostly when only partial responses are obtained. Here, we provide an overview of resistance to tumor and immune-targeted therapies and discuss challenges of overcoming resistance, and current and future directions of development. SIGNIFICANCE: A better and earlier identification of cancer-resistance mechanisms could avoid the use of ineffective drugs in patients not responding to therapy and provide the rationale for the administration of personalized drug associations. A clear description of the molecular interplayers is a prerequisite to the development of novel and dedicated anticancer drugs. Finally, the implementation of such cancer molecular and immunologic explorations in prospective clinical trials could de-risk the demonstration of more effective anticancer strategies in randomized registration trials, and bring us closer to the promise of cure.
Controlled trial of chlorpromazine as antisecretory agent in patients with cholera hydrated intravenously.
Authors: G H Rabbani, W B Greenough, J Holmgren, B Kirkwood
Journal: BMJ (1982)

A randomised controlled trial was conducted to investigate the ability of chlorpromazine to reduce intestinal secretion in cholera. Chlorpromazine had reduced loss of intestinal fluid in animals with diarrhoea induced by cholera toxin, and in a preliminary study the drug had reduced purging in patients with cholera. Forty-six adults with cholera were included in the randomised trial. Of these, 34 were treated with chlorpromazine (1 mg/kg or 4 mg/kg either by mouth or intramuscularly) and 12 served as controls. After treatment with the drug there was a significantly greater reduction in the rate of fluid loss in the treated patients than in the controls during the first (p less than 0.005), second (p less than 0.05), and fourth (p less than 0.01) eight-hour periods, but not during the third eight-hour period; the dose of 4 mg/kg was only marginally more effective than 1 mg/kg. The effect of chlorpromazine was strikingly biphasic, with one peak during the first eight hours and another 24-32 hours after administration. Chlorpromazine also significantly reduced the duration of diarrhoea, frequency of vomiting, and amount of intravenous fluid required. The drug induced mild sedation and no hypotension in these well-hydrated patients. These findings confirm the effectiveness of chlorpromazine in reducing fluid loss in cholera. A sedative effect, however, especially in children, may limit its usefulness and requires further study.
ERCP By Rendez-Vous Technique
Authors: Z Tammouch, A Zazour, A El Mekkaoui, W Khannoussi, G Kharrasse, Z Ismaili
Journal: Endoscopy (2021)

A 87-year-old woman, followed for suspicion of cholangiocarcinoma of the middle part of the CBD. Admitted for the management of cholangitis evolving for 2 weeks. Clinically she was altered, febrile and icteric with epigastric tenderness. Abdominal CT scan show a dilatation of CBD and IHBD at19 mm upstream of a locally advanced lesion in biliopancreatic area .Liver tests were perturbed with an inflammatory syndrome. The patient underwent 3 failed ERCP due to the presence of a very tight stenosis in the middle CBD not crossed by ERCP material. Thus, we performed an endoscopic drainage using the Rendezvous technique.
T-Cell Receptors
Authors: Jane F. Desforges
Journal: New England Journal of Medicine (1985)

During the past 25 years, we have gradually come to comprehend the underlying order of the complex family of lymphocytes.The first area to be clarified was the growth and differentiation of B lymphocytes, the source of antibodies. At the earliest stage of development of a B cell, the gene segments encoding for the immunoglobulins produced by the cell begin to form unique combinations, which are rearranged from their germ-line configuration. This genetic system contains many different coding regions, from which a single segment is selected for the V (variable) region and another for the D (diverse) region in the . . .
Two-dimensional echocardiographic diagnosis of left-atrial thrombus in rheumatic heart disease. A clinicopathologic study.
Authors: N KShrestha, F LMoreno, F VNarciso, LTorres, H BCalleja
Journal: Circulation (1983)

Two-dimensional echocardiographic studies were performed in 293 patients with rheumatic heart disease who underwent open-heart mitral valve surgery during an 18-month period. Diagnostic confirmation of a left atrial thrombus was based on direct inspection of the left atrium during surgery and histopathologic examination. Two-dimensional echocardiographic recordings were reviewed. Of the 293 patients, 33 had left atrial thrombi by two-dimensional echocardiographic criteria. This diagnosis was confirmed at surgery and histopathologic study in 30 (specificity 98.8%). A thrombus was not found in three patients. In 21 other patients, left atrial thrombi were present but were not detected by two-dimensional echocardiography (sensitivity 58.8%). Ten of these 21 had thrombi in the left atrial cavity. In 11 patients, thrombi were located in the left atrial appendage, all of which were missed by two-dimensional echocardiography. Excluding these 11 left atrial appendage thrombi, the sensitivity of two-dimensional ec...
Platelet aggregation in aortic and coronary venous blood in patients with and without coronary disease. 3. Role of tachycardia stress and propranolol.
Authors: JMehta, PMehta, C JPepine
Journal: Circulation (1978)

We studied 16 patients with coronary artery disease (CAD) to evaluate platelet aggregation in blood samples withdrawn simultaneously from the aorta and coronary sinus. At rest, mean platelet aggregation in coronary venous blood was significantly lower than that in aortic blood. Platelet counts in coronary venous blood were also lower than in the aortic blood in each of the six CAD patients in whom counts were done. Platelet aggregation was lower in seven patients who were taking propranolol than in the remaining nine who were not taking propranolol. During tachycardia stress, platelet aggregation increased in all patients, but the magnitude of increase was greater in patients not taking propranolol. In four other patients without CAD, platelet aggregation and counts were also studied in the same fashion and were similar in both the aortic and coronary venous blood. These data suggest that in certain CAD patients, platelet consumption or destruction within atherosclerotic vasculature may occur. Propranolol...
Marked reduction in myocardial infarct size due to prolonged infusion of an antioxidant during reperfusion.
Authors: L DHorwitz, P VFennessey, R HShikes, YKong
Journal: Circulation (1994)

BACKGROUNDThere has been controversy about whether early reperfusion of myocardial infarcts causes further necrosis mediated by reactive oxygen species or other mechanisms. Unequivocal evidence that therapeutic agents given only during reperfusion can prevent, rather than delay or modify, injury has been sparse. Failure to account for variables, such as collateral blood flow, that influence infarct size independently and attempts to measure infarct size too early in reperfusion may have limited the sensitivity and specificity of some previous studies.METHODS AND RESULTSAfter 90 minutes of coronary occlusion and 48 hours of reperfusion in a canine model, we examined the effect on infarct size of intravenous infusion of N-(2-mercaptopropionyl)-glycine (MPG), a diffusible antioxidant. Infarct size and region at risk were measured by post-mortem dual perfusion with triphenyl tetrazolium chloride and Evans blue dyes, and regional myocardial blood flow was measured with radioactive microspheres. Infusion of MPG...
Mitral valve prolapse in short-term experimental coronary occlusion: a possible mechanism of ischemic mitral regurgitation.
Authors: CTei, TSakamaki, P MShah, SMeerbaum, SKondo, KShimoura, ECorday
Journal: Circulation (1983)

Experimental coronary occlusions were carried out in 12 closed-chest dogs to investigate the functional anatomic characteristics of the mitral valve complex during acute myocardial ischemia. Two-dimensional echocardiography was used to assess left ventricular function, the mitral valve complex, and left atrial size. Presence of mitral regurgitation was assessed by left ventricular contrast echocardiography. Thirty-seven coronary occlusions of up to 10 min in duration were carried out in proximal or distal locations in the left anterior descending and the left circumflex coronary arteries. Mitral regurgitation, which was mild in severity as judged by a small rise in pulmonary artery wedge pressures, was observed in 15 of 37 brief coronary occlusion experiments. Mitral valve prolapse was noted in all 15 experiments, as well as in four additional studies in which mitral regurgitation was not seen. The development of experimental mitral valve prolapse was explained by measurements that demonstrated a relative...
Cascaded amplification of intracellular oxidative stress and reversion of multidrug resistance by nitric oxide prodrug based-supramolecular hydrogel for synergistic cancer chemotherapy
Authors: Jimin Zhang, Meigui Deng, Xiaoguang Shi, Chuangnian Zhang, Xiongwei Qu, Xiuli Hu, Weiwei Wang, Deling Kong, Pingsheng Huang
Journal: Bioactive Materials (2021)

• Supramolecular hydrogel was facilely developed by self-assembly of NO prodrug conjugated hydrogelator sequence. • The locoregionally sustained NO release from the hydrogel could be triggered by intracellular over-expressed GSH/GST. • NO could effectively reverse the P-gp mediated MDR effect and facilitate the intracellular accumulation of DOX. • This type of stimuli-sensitive NO delivery platform holds great potential for combating drug-resistance cancer.
Photodynamic Therapy: Photodynamic Therapy Directed by Three‐Photon Active Rigid Plane Organic Photosensitizer (Adv. Healthcare Mater. 7/2021)
Authors: Hongzhi Cao, Bin Fang, Jiejie Liu, Yu Shen, Jie Shen, Pan Xiang, Qin Zhou, Senio Campos De Souza, Dandan Li, Yupeng Tian, Lei Luo, Zhongping Zhang, Xiaohe Tian
Journal: Advanced Healthcare Materials (2021)

In article number 2001489 by Xiaohe Tian, Dandan Li, and co-workers, a novel rigid planar organic photosensitizer is designed and used for three-photon photodynamic therapy. The concentration of lower dark toxicity can burst superior phototoxicity. After co-incubation with cells, it targets mitochondria and lipid droplets, and generates reactive oxygen species (ROS) under 940nm three-photon laser irradiation to induce cell death and achieve excellent photodynamic therapy effects.
Cationic amphiphiles prevent calcium leak induced by ATP depletion in myocardial cells.
Authors: J RClague, J APost, G ALanger
Journal: Circulation Research (1993)

Excessive calcium influx is important in the irreversible injury of cardiac myocytes and other cell types. The mechanism is unknown, but possibilities include L-type channels, Na(+)-Ca2+ exchange, sarcolemmal (SL) defects, and calcium leak channels. In this study, metabolic inhibition was used to induce ATP depletion and augmented calcium influx in cultured cardiac myocytes. Inhibition of the L-type calcium channel and Na(+)-Ca2+ exchanger had no significant effect on the calcium leak. There was no significant lactate dehydrogenase release, indicating that the leak did not occur through major SL defects. No alterations in the asymmetric distribution of SL phospholipids were demonstrated. Phospholipid rearrangements were therefore not responsible. The leak was unaffected by 0.5 mM cadmium and 1 microM nifedipine but was augmented by 50 microM nifedipine, characteristics in common with calcium leak channels. Insertion of the cationic amphiphiles dodecyltrimethylammonium bromide or polymyxin B sulfate into t...
Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? No
Authors: V. Lawton
Journal: BMJ (2009)

<b>Ben Goldacre</b> (doi:10.1136/bmj.b4949) argues that the financial interests of drug companies lead to distorted evidence, but <b>Vincent Lawton</b> believes that adequate safeguards exist to keep bias in check