tbuckley/cabot-search huggingface dataset:
Quantification of left-to-right atrial shunting and defect size after balloon mitral commissurotomy using biplane transesophageal echocardiography, color flow Doppler mapping, and the principle of proximal flow convergence.
Authors: DRittoo, G RSutherland, T RShaw
Journal: Circulation (1993)

BACKGROUNDThe flow convergence region (FCR), a zone of progressive laminar velocity acceleration, can be imaged by color Doppler proximal to stenotic and regurgitant orifices. Theoretically, FCR proximal to a discrete circular and planar orifice consists of concentric hemispheric shells of equal and accelerating velocities centered at the orifice. According to the continuity principle, flow rate across any of these isovelocity surfaces equals flow rate through the orifice. The aim of this study was to investigate whether these principles could be applied to quantify left-to-right shunting and the size of atrial septal defects after balloon mitral commissurotomy.METHODS AND RESULTSBiplane transesophageal echocardiography (TEE) with color flow imaging was performed on 36 consecutive patients (mean age, 57 +/- 16 years; range, 14-78 years) immediately before and within 24 hours of balloon (Inoue, n = 33; Mansfield, n = 3) mitral commissurotomy. Left-to-right atrial shunting was detected by TEE in 33 patients...
Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure.
Authors: MPacker, NMedina, MYushak
Journal: Circulation (1984)

To determine the hemodynamic and clinical effects of long-term positive inotropic stimulation on the myocardium, we treated 31 patients with severe chronic heart failure with oral amrinone (600 mg daily) and performed invasive hemodynamic studies during short- and long-term treatment with the drug. Stroke volume and stroke work indexes increased markedly during the first 48 hr of therapy (p less than .01) but returned to pretreatment values after 2 to 10 weeks; upon drug withdrawal, both variables deteriorated rapidly to values significantly lower than those observed before treatment with amrinone (p less than .01), despite similar values for left ventricular filling pressure, mean arterial pressure, and systemic vascular resistance. This pattern of response indicated that progression of the underlying heart disease had occurred during treatment with amrinone and contributed importantly to its failure to produce long-term benefits. Progression of left ventricular dysfunction was associated with a progress...
Native collaterals in the development of collateral circulation after chronic coronary stenosis in mongrel dogs.
Authors: FSchwarz, H OWagner, MSesto, MHofmann, WSchaper, WKübler
Journal: Circulation (1982)

The response of native collateral circulation to chronic stenosis of the left circumflex coronary artery (LCx) was studied in 17 mongrel dogs. Stenosis restricted reactive hyperemia of the LCx without affecting resting flow. Regional myocardial blood flow was measured by the tracer microsphere technique. Coronary collateral blood flow to the LCx was determined during maximal reactive hyperemia of the left anterior descending branch before and 5 weeks after implantation of a fixed LCx stenosis in the open-chest preparation. The protective effect of collaterals was tested by LCx ligation 5 weeks after implantation of stenosis. Presence of acute myocardial infarction was determined by nitroblue tetrazolium staining. Eleven dogs had a myocardial infarction (group A), but six dogs showed no evidence of infarction at autopsy (group B). In group A, collateral flow and minimal coronary resistance of the LCx bed changed little after LCx stenosis, from 12 to 15 ml/min/100 g and from 10.5 to 10.0 mm Hg/ml/min/100 g,...
Healthy <i>versus</i> inflamed lung environments differentially affect mesenchymal stromal cells
Authors: Sara Rolandsson Enes, Thomas H. Hampton, Jayita Barua, David H. McKenna, Claudia C. dos Santos, Eyal Amiel, Alix Ashare, Kathleen D. Liu, Anna D. Krasnodembskaya, Karen English, Bruce A. Stanton, Patricia R.M. Rocco, Michael A. Matthay, Daniel J. Weiss
Journal: European Respiratory Journal (2021)

Background Despite increased interest in mesenchymal stromal cell (MSC)-based cell therapies for acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and our understanding of the potential in vivo mechanisms of MSC actions in ARDS remains limited. ARDS is driven by an acute severe innate immune dysregulation, often characterised by inflammation, coagulation and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined. Aim The aim of this study was to comparatively assess how the inflammatory environment present in ARDS lungs versus the lung environment present in healthy volunteers alters MSC behaviour. Methods Clinical-grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties, including viability, levels of expression of inflammatory cytokines, gene expression, cell surface human leukocyte antigen expression, and activation of coagulation and complement pathways. Results Pro-inflammatory, pro-coagulant and major histocompatibility complex (self-recognition) related gene expression was markedly upregulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. These changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples. Conclusion These data provide new insights into how hMSCs behave in healthy versus inflamed lung environments, and strongly suggest that the inflamed environment in ARDS induces hMSC responses that are potentially beneficial for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.
Serum creatine kinase MM isoenzyme sub-bands after acute myocardial infarction in man.
Authors: R LMorelli, C JCarlson, BEmilson, D RAbendschein, ERapaport
Journal: Circulation (1983)

Using an isoelectric-focusing (IEF) method developed to quantitate MM isoenzyme-creatine kinase (CK) sub-band activity, we identified a reproducible time-varying pattern of these sub-bands in the serum of eight patients with acute myocardial infarction (MI). Our observations are consistent with the view that MM3-CK (the M2-CK dimer, the pure gene product) is converted intravascularly to MM2-CK, and then to MM1-CK (the M1-CK dimer, the pure postsynthetic sub-band). The MM3-CK reaches a peak first, 16 hours after infarction, followed by MM2-CK, and then by MM1-CK. The MM3-CK is the dominant sub-band in normal myocardium; there is much less MM2-CK and virtually no MM1-CK. The MM3-CK sub-band peak may indicate the time at which enzyme ceases to be released from the injured myocardium. The ratio MM3-CK:MM1-CK rises within 6 hours after onset of chest pain from a baseline of 0.38 and peaks 10 hours after MI. The peak ratio was between 1.1 and 4.2, and the value correlated with the time when total CK activity pe...
Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Björk-Shiley prosthesis.
Authors: FSchwarz, WFlameng, FLangebartels, MSesto, PWalter, MSchlepper
Journal: Circulation (1979)

Postoperative survival and left ventricular function were studied in 128 patients who underwent isolated aortic valve replacement by the Bjork-Shiley valve between 1973 and 1977. The average follow-up was 2.1 years. Patients with associated coronary artery disease or mitral valve disease were excluded. Preoperative ejection fraction ranged from 15-84%. Forty-two patients were restudied by cardiac catheterization 9.1 +/- 1.1 months (mean +/- SEM) after valve replacement. The hospital mortality was 11%. Preoperative type of valve lesion, functional class, cardiothoracic ratio, and ejection fraction (EF) had no significant effect on postoperative survival up to 4 years. After operation, left ventricular mass (LVMI) and peak systolic wall stress (PSWS) fell significantly, while EF and mean normalized systolic ejection rate (MNSER) increased in aortic stenosis and in aortic insufficiency. Neither in aortic stenosis nor in aortic insufficiency was there a significant relation between preoperative ejection fract...
Endoscopic Ultrasound-Guided Radiofrequency Ablation For Treatment Of Benign Insulinoma
Authors: C Svoboda, T Pachofszky, N Mitrovits, J Stimakovits, A Schleischitz, A Püspök
Journal: Endoscopy (2021)

Aims An insulinoma is a rare functional neuroendocrine tumor of the pancreas (pNETs) with an incidence of approximately 1/250.000, the majority (90 %) is benign. Insulinomas count to the small pNETs, therefore their detection with conventional imaging (CT, MRI) is sometimes unrewarding. Endoscopic ultrasound (EUS) can detect up to 95 %, consequently should be imaging technique of choice. Surgical resection (tumor enucleation or limited pancreatic resection) is currently standard of care for solitary insulinoma. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) as a minimally invasive and local ablative procedure was described as feasible treatment approach with a low periprocedural complications risk in selected patients in the last few years.
Cholangioscopy With Electrohydraulic Lithotripsy (EHL) for Post-Cholecystectomy Mirizzi Syndrome
Authors: A Sioulas, M Spinou, K Papadaki, I Scotiniotis
Journal: Endoscopy (2021)

Α 48-year-old man with a history of laparoscopic cholecystectomy presented with right upper quadrant pain and jaundice. Magnetic Resonance Cholangiopancreatography showed a cystic duct stump stone causing proximal dilation of the biliary system, with normal distal common bile duct (CBD) diameter.
Responses to inflation of vagal afferents with endings in the lung of dogs.
Authors: M PKaufman, G AIwamoto, J HAshton, S SCassidy
Journal: Circulation Research (1982)

In dogs, inflating the lungs to pressures of 9 cm H2O or less reflexly increases heart rate, whereas inflating the lungs to pressures of 10-30 cm H2O reflexly decreases heart rate. The afferent fibers responsible for the cardioacceleration travel in the vagus nerves and are believed to be pulmonary stretch receptors, whereas the afferent responsible for the deceleration also travel in the vagus nerves, but are believed to be lung C-fibers. To identify the afferents responsible for these effects, we recorded the impulse activity of vagal afferents with endings in the left lung, while we slowly inflated that lung to 30-45 cm H2O. We found that 12 slowly adapting receptors fired at significantly lower inflation pressures than did 10 rapidly adapting receptors (5.8 +/- 1.5 vs. 13.5 +/- 2.2 cm H2O, respectively). We also found that 13 pulmonary C-fibers fired at significantly lower inflation pressures than did 10 bronchial C-fibers (16.4 +/- 1.8 vs 26.5 %/- 2.9 cm H2O, respectively). We conclude that slowly ad...
David Anton: aviation doctor who investigated air crashes and became the first occupational physician with the RNLI
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Photo credit: UX Solutions Prague

David Anton, the Royal National Lifeboat Institution’s first consultant occupational physician, who investigated multiple high profile aeroplane crashes and was a consultant to the US navy and air force, has died at his home at the age of 75.

David Anton was born in London to Tony Anton, a solicitor, and Vera (nee Dobson). He was educated at Strode’s School, Egham, and Solihull School, along with his three younger brothers. His lifelong interest in mountains and the outdoors was sparked by an inspirational teacher who had the class follow the progress of John Hunt’s successful Everest expedition, building a model of the mountain and studying the climbers and their equipment. During Anton’s life, he travelled to many of the world’s great mountain ranges, including Everest base camp, and studied the physiology of survival. He adored his formidable but affable grandfather, Harry Dobson, a retired Grenadier Guard who had fought and been wounded at Ypres. A Yeoman of the Guard, Dobson lived for the rest of his life in a flat at St James’s Palace. As a child, Anton’s parents took him to the Farnborough Air Show, which made a great impression and influenced his career path.

Anton summed this up on his blog in 2019: “I have always been interested in why things go wrong and the physical and mental consequences that follow. I suppose it started when I was a boy. My parents took me to the Farnborough Air Show from a very young age, but we missed the day when John Derry crashed into the crowd, killing 31 people. The aircraft fell where we used to sit. Had we been there we would have …
Malignant Biliary Obstruction Secondary To Metastatic Bladder Cancer - An Uncommon Presentation Of Cholangitis
Authors: D Buckley, RS O’Neill
Journal: Endoscopy (2021)

Correction to: Malignant Biliary Obstruction Secondary To Metastatic Bladder Cancer - An Uncommon Presentation Of CholangitisEndoscopy 2021; 53(S 01): eP331DOI: 10.1055/s-0041-1724823
Initial ventricular activation in left-sided intraventricular conduction defects.
Authors: D SCannom, M GWyman, B NGoldreyer
Journal: Circulation (1980)

Nine patients with ECG evidence of rate-related left bundle branch block (LBBB) were studied using His bundle electrograms, electrograms from the right ventricular (RV) apex and vectorcardiograms recorded as heart rate was increased to produce LBBB. In five patients, when LBBB occurred, initially normal septal activation reversed and the HV intervals increased 10-30 msec, while the H-RVA interval did not change (group 1). Four patients had initially normal QRS duration (90-100 msec) but reversed septal activation (group 2). When LBBB developed there was no shift in either the HV interval or H-RVA interval. Only the QRS complex itself widened to distinguish these patients from group 1. These studies defined ventricular septal activation in normal conduction and in complete LBBB (group 1) and incomplete LBBB (group 2). The conduction patterns of group 1 and 2 patients are similar but are both markedly different from normal.
Degree of revascularization in patients with multivessel coronary disease: a report from the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry.
Authors: G SReeder, D RHolmes, KDetre, TCostigan, S FKelsey
Journal: Circulation (1988)

There is controversy regarding the application of angioplasty to patients with multivessel disease in whom all significant stenoses are not dilated. We analyzed the outcomes of 286 patients with multivessel disease and prior successful angioplasty at a mean follow-up duration of 26.2 months. End points analyzed included death, myocardial infarction, late revascularization, and angina pectoris. After successful angioplasty, 127 patients had no residual stenoses of 70% or greater (group 1) and 159 patients had one or more residual stenoses of 70% or greater (group 2). Because there were significant differences in baseline risk factors between the two groups, a logistic regression model was used to make the necessary adjustments in the analysis. Adjusted estimates of the risk of death, death/myocardial infarction, or presence of angina pectoris did not differ between the two groups. Group 2 patients, however, had more coronary artery bypass surgery during follow-up, while those in group 1 had more second PTC...
Immediate hemodynamic effects of a dopamine-receptor agonist (fenoldopam) in patients with essential hypertension.
Authors: H OVentura, F HMesserli, E DFrohlich, IKobrin, WOigman, F GDunn, R MCarey
Journal: Circulation (1984)

Systemic, splanchnic, and renal hemodynamics, intravascular volume, and reflexive and endocrine changes were measured before and after a single dose of fenoldopam, a novel antihypertensive agent that acts through stimulation of specific dopamine receptors. A 13% reduction in mean arterial pressure was mediated by a fall in total peripheral resistance association with an increase in cardiac index, heart rate, stroke volume, left ventricular ejection rate, and circumferential fiber shortening. Renal blood flow increased, thereby reducing the renal vascular resistance by more than 40%. In contrast, splanchnic hemodynamics failed to change. Likewise, there were no changes in intravascular volume, plasma renin activity, or norepinephrine, serum aldosterone, or prolactin levels.
An Fc-free EGFR-specific 4-1BB-agonistic Trimerbody Displays Broad Antitumor Activity in Humanized Murine Cancer Models without Toxicity
Authors: Marta Compte, Seandean L. Harwood, Ainhoa Erce-Llamazares, Antonio Tapia-Galisteo, Eduardo Romero, Irene Ferrer, Eva M. Garrido-Martin, Ana B. Enguita, Maria C. Ochoa, Belén Blanco, Marta Oteo, Nekane Merino, Daniel Nehme-Álvarez, Oana Hangiu, Carmen Domínguez-Alonso, Manuela Zonca, Angel Ramírez-Fernández, Francisco J. Blanco, Miguel A. Morcillo, Ines G. Muñoz, Ignacio Melero, José L. Rodriguez-Peralto, Luis Paz-Ares, Laura Sanz, Luis Alvarez-Vallina
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The induction of 4-1BB signaling by agonistic antibodies can drive the activation and proliferation of effector T cells and thereby enhance a T-cell–mediated antitumor response. Systemic administration of anti-4-1BB–agonistic IgGs, although effective preclinically, has not advanced in clinical development due to their severe hepatotoxicity. Experimental Design: Here, we generated a humanized EGFR-specific 4-1BB-agonistic trimerbody, which replaces the IgG Fc region with a human collagen homotrimerization domain. It was characterized by structural analysis and in vitro functional studies. We also assessed pharmacokinetics, antitumor efficacy, and toxicity in vivo. Results: In the presence of a T-cell receptor signal, the trimerbody provided potent T-cell costimulation that was strictly dependent on 4-1BB hyperclustering at the point of contact with a tumor antigen-displaying cell surface. It exhibits significant antitumor activity in vivo, without hepatotoxicity, in a wide range of human tumors including colorectal and breast cancer cell-derived xenografts, and non–small cell lung cancer patient-derived xenografts associated with increased tumor-infiltrating CD8+ T cells. The combination of the trimerbody with a PD-L1 blocker led to increased IFNγ secretion in vitro and resulted in tumor regression in humanized mice bearing aggressive triple-negative breast cancer. Conclusions: These results demonstrate the nontoxic broad antitumor activity of humanized Fc-free tumor-specific 4-1BB-agonistic trimerbodies and their synergy with checkpoint blockers, which may provide a way to elicit responses in most patients with cancer while avoiding Fc-mediated adverse reactions.
Indomethacin-induced scar thinning after experimental myocardial infarction.
Authors: HHammerman, R AKloner, F JSchoen, E JBrown, EBraunwald
Journal: Circulation (1983)

We investigated the effect of indomethacin, a widely used nonsteroidal antiinflammatory drug, on the healing of myocardial infarction (MI). Experimental MI was produced in anesthetized, open-chest dogs by occluding the left anterior descending coronary artery. Ten dogs received indomethacin, 10 mg/kg i.v., and 11 received saline, 15 minutes and 3 hours after occlusion. After 6 weeks, the dogs were killed and their hearts were subjected to morphologic and biochemical analysis. The average thickness of the transmural scar and the noninfarcted left ventricular wall was measured at multiple sites in formalin-fixed left ventricular slices and the ratio of the thickness of the transmural scar to the noninfarcted wall determined. The average thickness of the noninfarcted wall was 8.80 +/- 0.19 mm (mean +/- SEM) in the control group and 8.44 +/- 0.26 mm in the indomethacin group (NS). The scar thickness was 7.24 +/- 0.64 mm in the control group and 3.56 +/- 0.40 mm in the indomethacin group (p less than 0.001). T...
Community-acquired Haemophilus influenzae meningitis in adults
Authors: Nora Chekrouni, Diederik L.H. Koelman, Matthijs C. Brouwer, Arie van der Ende, Diederik van de Beek
Journal: Journal of Infection (2021)

BackgroundHaemophilus influenzae is an uncommon cause of meningitis in adults.MethodsWe analyzed episodes of community-acquired H. influenzae meningitis in adults included in a prospective nationwide cohort study in the Netherlands.ResultsFrom 2006 to July 2018, 82 of 2272 (4%) bacterial meningitis episodes were caused by H. influenzae (mean annual incidence 0.5 patients per 1,000,000). Median age was 61 years (IQR 46–68), and 48 episodes (59%) occurred in woman. Predisposing factors were otitis and/or sinusitis in 33 of 76 patients (49%), immunocompromising conditions in 19 of 75 patients (25%) and cerebrospinal fluid leak in 13 of 79 patients (17%). Serotyping showed 63 of 80 isolates (79%) were non-typeable (NTHi). Three patients (4%) died and 14 patients (17%) had an unfavorable outcome (Glasgow Outcome Scale score < 5 at discharge). Pneumonia (odds ratio [OR] 5.8, 95% confidence interval [95%CI] 1.1–30.8), presence of immunocompromising conditions (OR 6.0, 95%CI 1.5–24.4), and seizures on admission (OR 10.7, 95%CI 1.6–72.8) were associated with an unfavorable outcome, while NTHi was associated with a favorable outcome (OR 5.6, 95%CI 1.6–19.5).ConclusionH. influenzae is an uncommon cause of adult bacterial meningitis patients mainly causing disease in those with predisposing factors, such as CSF leakage, ENT infections, and immunocompromised state. In adult patients the majority of H. influenzae meningitis is caused by non-typeable strains.
Zoledronic Acid Dosing Interval for Metastatic Cancer
Authors: Marcello Tucci, Consuelo Buttigliero, Massimo Di Maio
Journal: JAMA (2017)

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