tbuckley/cabot-search huggingface dataset:
Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)
Authors: Maria Gonzalez-Cao, Teresa Puertolas, Mar Riveiro, Eva Muñoz-Couselo, Carolina Ortiz, Roger Paredes, Daniel Podzamczer, Jose Luis Manzano, Jose Molto, Boris Revollo, Cristina Carrera, Lourdes Mateu, Sara Fancelli, Enrique Espinosa, Bonaventura Clotet, Javier Martinez-Picado, Pablo Cerezuela, Ainara Soria, Ivan Marquez-Rodas, Mario Mandala, Alfonso Berrocal
Journal: Journal for ImmunoTherapy of Cancer (2021)

Cancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities.
Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect.
Authors: HIida, IKanno, ATakahashi, SMiura, MMurakami, KTakahashi, YOno, FShishido, AInugami, NTomura
Journal: Circulation (1988)

An in vivo technique was developed for measuring the absolute myocardial blood flow with H215O and dynamic positron-emission tomography. This technique was based on a new model involving the concept of the tissue fraction, which was defined as the fraction of the tissue mass in the volume of the region of interest. The myocardium was imaged dynamically by positron-emission tomography, starting at the time of intravenous bolus injection of H215O. The arterial input function was measured continuously with a beta-ray detector. A separate image after C15O inhalation was also obtained for correction of the H215O radioactivity in the blood. The absolute myocardial blood flow and the tissue fraction were calculated for 15 subjects with a kinetic technique under region-of-interest analysis. These results seem consistent with their coronary angiographic findings. The mean value of the measured absolute myocardial blood flows in normal subjects was 0.95 +/- 0.09 ml/min/g. This technique detected a diffuse decrease ...
Cellular thin filament protein contents and force generation in porcine arteries and veins.
Authors: D MCohen, R AMurphy
Journal: Circulation Research (1979)

We estimated the cellular myosin, actin, and tropomyosin contents of vascular smooth muscle from (1) seven major arteries, (2) seven large veins, and (3) the first through third order branches of the uterine vasculature to determine whether variations in the contractile apparatus contribute to the functional diversity of vascular smooth muscle. We obtained the estimates by quantitative densitometry of stained polyacrylamide gels after electrophoresis of sodium dodecyl sulfate-treated tissue homogenates. No differences in cellular myosin content were found (18.7 +/- 1.0 mg/g cell wet weight in arteries vs. 17.2 +/- 0.7 in veins). However, the actin and tropomyosin contents were higher in arteries (49.7 +/- 2.9 and 13.1 +/- 0.8 mg/g cell, respectively) than in veins (25.5 +/- 1.4 and 7.0 +/- 0.3 mg/g cell). These differences persisted in the smaller uterine vessels. The higher contents of thin filament proteins in arteries, compared with veins and several other smooth muscle tissues previously studied, may ...
Engineering multi-tissue units for regenerative Medicine: Bone-tendon-muscle units of the rotator cuff
Authors: Dan Wang, Xu Zhang, Shuting Huang, Yang Liu, Bruma Sai-chuen Fu, Kingston King-lun Mak, Anna Maria Blocki, Patrick Shu-hang Yung, Rocky S. Tuan, Dai Fei Elmer Ker
Journal: Biomaterials (2021)

Our body systems are comprised of numerous multi-tissue units. For the musculoskeletal system, one of the predominant functional units is comprised of bone, tendon/ligament, and muscle tissues working in tandem to facilitate locomotion. To successfully treat musculoskeletal injuries and diseases, critical consideration and thoughtful integration of clinical, biological, and engineering aspects are necessary to achieve translational bench-to-bedside research. In particular, identifying ideal biomaterial design specifications, understanding prior and recent tissue engineering advances, and judicious application of biomaterial and fabrication technologies will be crucial for addressing current clinical challenges in engineering multi-tissue units. Using rotator cuff tears as an example, insights relevant for engineering a bone-tendon-muscle multi-tissue unit are presented. This review highlights the tissue engineering strategies for musculoskeletal repair and regeneration with implications for other bone-tendon-muscle units, their derivatives, and analogous non-musculoskeletal tissue structures.
Relation of parental history of early myocardial infarction to the level of apoprotein B in men.
Authors: FCambien, J MWarnet, AJacqueson, PDucimetiere, J LRichard, J RClaude
Journal: Circulation (1987)

The relations between parental history of early myocardial infarction and plasma lipids and apoproteins have been examined in a population of 4045 middle-aged (20 to 60 years old) working men at the initial examination of the Paris Prospective Study 2. Subjects with a history of myocardial infarction, angina pectoris, or peripheral arterial disease or those treated with hypolipidemic drugs were excluded from the analysis. The numbers of subjects with a paternal or maternal history of early myocardial infarction were 123 and 30, respectively. After adjustment for age, cigarette consumption, alcohol consumption, and body mass index, subjects with parental history of myocardial infarction had higher levels of total cholesterol (p less than .01), low-density lipoprotein (LDL) cholesterol (p less than .01), and apoprotein B (APOB) (p less than .0001) and a lower level of high-density lipoprotein (HDL) cholesterol (p less than .05) than subjects with no parental history of myocardial infarction. On the other ha...
Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function.
Authors: G VMartin, F HSheehan, MStadius, CMaynard, K BDavis, J LRitchie, J WKennedy
Journal: Circulation (1988)

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had ...
India plans to audit clinical trials
Authors: Biju Basil, Maju Mathews, Jamal Mahmud, Babatunde Adetunji, Kumar Budur
Journal: BMJ (2005)

Adjuvant trastuzumab for breast cancer Assessing HER2/neu status incurs more costs for treatmentEditor-The results of recent trials are likely to continue to fuel the demand for trastuzumab in the adjuvant setting of early breast cancer, 1 as well as a possible neoadjuvant treatment in the near future.However, Dent and Clemons did not discuss the difficulty in obtaining accurate and reproducible assessment of HER2/neu gene overexpression.Immunohistochemical testing measures HER2/neu protein expression whereas in situ hybridisation measures gene amplification.Patients with equivocal immunohistochemical results require in situ hybridisation to determine definitive status because interobserver variability using immunohistochemical testing is appreciable.At least 20% of patients with positive immunohistochemical results will be truly negative for HER2/neu gene amplification; these patients would not benefit from trastuzumab. 2 These difficulties in assessing HER2/ neu status have been encountered in studies testing trastuzumab, and in situ hybridisation testing has been used as the gold standard. 3 As the clinical utility of trastuzumab widens guidelines on HER2/neu testing must be clear to ensure appropriate use of trastuzumab.Clearly this testing will incur additional costs to trastuzumab treatment.
Negative inotropic effects of amrinone in the neonatal piglet heart.
Authors: NRoss-Ascuitto, RAscuitto, VChen, S EDowning
Journal: Circulation Research (1987)

Cardiac mechanical function and coronary flow (CF) were measured in isovolumically beating hearts from neonatal piglets 0.5 to 12 days of age. The hearts were perfused retrogradely at 70 cm H2O with a recirculating modified Krebs-Henseleit solution containing washed adult pig red cells (hematocrit, 25%). They were electrically paced (180 beats/min), and left ventricular developed pressure (delta P), maximum rate of rise of pressure (dP/dt), CF, and myocardial oxygen consumption were measured. These parameters were found to remain stable for at least 60 minutes. In one group, a single dose of amrinone was added to the perfusate to yield a concentration of 50 micrograms/ml. Within 5 minutes delta P decreased from 104.0 +/- 7.1 to 65.3 +/- 8.6 mm Hg (p less than 0.001), and dP/dt fell from 1,160 +/- 96 to 658 +/- 78 mm Hg/sec (p less than 0.001). In a second group, successive doses of amrinone were added to yield concentrations ranging from 5 to 50 micrograms/ml. There was a progressive decrease in delta P a...
Increased protein kinase C and isozyme redistribution in pressure-overload cardiac hypertrophy in the rat.
Authors: XGu, S PBishop
Journal: Circulation Research (1994)

Protein kinase C (PKC) activity and isozyme distribution were evaluated during development of pressure-overload-induced cardiac hypertrophy. Three-week-old rats were loosely banded on the ascending aorta (left ventricular hypertrophy [LVH] group). Two weeks later, when left ventricular mass was 50% greater than in the sham-operated control group and cardiac mass was still rapidly increasing beyond that of normal growth, PKC activity and [3H]phorbol 12,13-dibutyrate (PDBu) binding capacity were determined. In LVH, PKC activity was 119 +/- 14%, 158 +/- 17%, and 152 +/- 9% of the control value in cytosol, membrane, and nuclear-cytoskeletal fractions, respectively (n = 9 or 10). [3H]PDBu binding assay revealed increased PKC concentration in LVH cytosolic (control, 0.51 +/- 0.06 pmol/L per milligram; LVH, 0.78 +/- 0.09 pmol/L per milligram; n = 5; P < .05) and membrane fractions (control, 1.33 +/- 0.15; LVH, 2.32 +/- 0.39; n = 5; P < .05). Scatchard analysis indicated no difference in Kd values between control...
From the authors
Authors: G. L. Biscione, J. Corne, A. J. Chauhan, S. L. Johnston
Journal: European Respiratory Journal (2005)

Chlamydophila pneumoniae in asthmaTo the Editors: BISCIONE et al. [1] reported a significant association of upper airway Chlamydophila pneumoniae RT-PCR positivity in atopic asthmatics (cumulative rate 22%) compared with nonatopic nonasthmatic spouses (9%).In the discussion, BISCIONE et al. [1] argued in favour of acute, rather than chronic, infection as the explanation for their observation that detection was mostly intermittent rather than persistent.I would like to address three issues raised by this interesting study. From the authors:We thank D.L. Hahn for his interest in our study [1] and for commenting upon the interesting issues he raised relating to the study and its interpretation, particularly regarding the presence of acute infection, reactivation, colonisation or chronic infection.These are important issues and informed debate about them is to be welcomed.D.L. Hahn comments that, in the introduction, we stated that Chlamydophila pneumoniae serology could not differentiate acute from other infections.In fact, we stated that serology cannot reliably differentiate between past and present infection, or acute and chronic infection.We acknowledge that there are published proposed serological criteria for acute primary infection using the microimmunofluorescence (MIF) test [2].However, these authors stated that ''standardized definitions
Enhanced hypoxic pulmonary vasoconstriction in hypertension.
Authors: M DGuazzi, MAlimento, MBerti, CFiorentini, CGalli, GTamborini
Journal: Circulation (1989)

In this study, we tested the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension. The hypothesis took origin from the following two considerations: alveolar hypoxia constricts the pulmonary vessels by enhancing the Ca2+ penetration across sarcolemma of the smooth muscle cells and systemic high blood pressure is associated with an elevation of tone and reactivity of the lung vessels, which seems to depend on an excessive cytosol free Ca2+ concentration due to alterations in sodium handling and in the Na+-Ca2+ exchange system. These considerations suggest the possibility that the disorders in the biochemistry of smooth muscle contraction in hypertension facilitate the rise of cytosol Ca2+ concentration during alveolar hypoxia, thus resulting in a potentiation of the vasoconstrictor properties of this stimulus. In 43 hypertensive and 17 normotensive men, pulmonary arteriolar resistance has been evaluated during air respiration and after 15 minutes of breathing 17%, 15%...
Abstract #3952: Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach
Authors: Eunjung Lee, Chris Hsu, Christopher Haiman, Pamela Horn-Ross, David Van Den Berg, Leslie Bernstein, Loic Le Marchand, Brian Henderson, Wendy Setiawan, Giske Ursin
Journal: Cancer Research (2009)

Background: It is well known that estrogen increases endometrial cancer risk, while progesterone opposes the effect of estrogen. The PROGINS allele of the progesterone receptor gene (PGR) has been shown to reduce the stability of the PGR transcript and transactivation activity of PGR in selected cell lines. Further, the PROGINS allele and the associated haplotypes have been shown to be associated with increased risk of ovarian cancer. In this study, we investigated whether genetic variation in PGR, including the PROGINS allele, is associated with endometrial cancer risk using a haplotype-based approach. Methods: We pooled data from two endometrial cancer case-control studies nested in two prospective cohorts, the Multiethnic Cohort Study and the California Teachers Study. We genotyped 17 haplotype-tagging SNPs across 4 linkage-disequilibrium (LD) blocks spanning the PGR locus in 627 incident cases and 2074 control women. Unconditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence interval (95% CI) associated with each haplotype, adjusting for age and ethnicity. Results: We observed significant evidence of heterogeneity across ethnic groups (p  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3952.
A Comparison of Budesonide and Mesalamine for Active Crohn's Disease
Journal: New England Journal of Medicine (2001)

Background Crohn’s disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn’s disease affecting the ileum, the ascending colon, or both. Methods In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn’s Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn’s Disease Activity Index. Results In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02). Conclusions In patients with active Crohn’s disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine. (N Engl J Med 1998;339:370-4.)
Persistent reduction in left ventricular asynergy in patients with acute myocardial infarction by intravenous infusion of nitroglycerin.
Authors: B IJugdutt, B ASussex, J WWarnica, R ERossall
Journal: Circulation (1983)

Intravenous nitroglycerin (NG) infusion in patients with acute myocardial infarction (AMI) has been shown to improve left ventricular function and myocardial perfusion and to decrease ischemic injury and creatine kinase (CK) indexes of infarct size. To determine whether early NG infusions in patients with AMI decreases the extent of left ventricular asynergy, we used two-dimensional echocardiography to measure asynergic segments (akinesis and/or dyskinesis) at four serial short-axis levels from base to apex (mitral, M; chordal, C; midpapillary, MP; low papillary, LP) in 22 patients with a first anterior AMI. Patients were randomized between infusions of NG (n = 11) or 5% dextrose in water (controls, n = 11) within 5.6 hr after the onset of pain. NG infusion rates were titrated to lower mean arterial pressure to an average level of 7% below control (but not below 80 mm Hg) and were maintained at this level for the duration of the infusions (39 hr). After NG, left ventricular function improved as left ventr...
Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias
Authors: Rachel Thijssen, Sarah T. Diepstraten, Donia Moujalled, Edward Chew, Christoffer Flensburg, Melissa X. Shi, Michael A. Dengler, Veronique Litalien, Sarah MacRaild, Maoshan Chen, Natasha S. Anstee, Boris Reljić, Sarah S. Gabriel, Tirta M. Djajawi, Chris D. Riffkin, Brandon J. Aubrey, Catherine Chang, Lin Tai, Zhen Xu, Thomas Morley, Giovanna Pomilio, Claudia Bruedigam, Axel Kallies, David A. Stroud, Ashish Bajel, Ruth M. Kluck, Steven W. Lane, Marie Schoumacher, Sébastien Banquet, Ian J. Majewski, Andreas Strasser, Andrew W. Roberts, David C. S. Huang, Fiona C. Brown, Gemma L. Kelly, Andrew H. Wei
Journal: Blood (2021)
Percutaneous transluminal balloon valvuloplasty for pulmonary valve stenosis.
Authors: J SKan, R IWhite, S EMitchell, J HAnderson, T JGardner
Journal: Circulation (1984)

Transluminal balloon valvuloplasty was used to treat congenital pulmonary valve stenosis in 20 patients. Follow-up cardiac catheterization was performed in 11 patients at intervals of from 2 to 12 months after the procedure. Peak systolic pressure gradient across the pulmonic valve decreased from 68 +/- 27 to 23 +/- 5 mm Hg (p less than .001) after valvuloplasty. There were no complications. Follow-up catheterization demonstrated persistent relief of right ventricular hypertension in the patients with typical pulmonary valve stenosis.
Digital angiographic impulse response analysis of regional myocardial perfusion. Detection of autoregulatory changes in nonstenotic coronary arteries induced by collateral flow to adjacent stenotic arteries.
Authors: HSchühlen, N LEigler, J SWhiting
Journal: Circulation (1994)

BACKGROUNDOur study compares the effect of acute proximal stenosis of a coronary artery supplying a myocardial perfusion bed with that of stenosis of an adjacent artery resulting in collateral flow diversion supplied by the same perfusion bed. These alterations in coronary physiology were quantified by digital angiographic impulse response analysis of contrast material mean transit time for the coronary microcirculation, Tmicro, and by flowmeter and microsphere assessment of flow and regional flow distribution.METHODS AND RESULTSIn 25 open-chest, anesthetized dogs, progressive circumflex artery stenosis led to a concordant decrease of circumflex artery resting and hyperemic flow, coronary flow reserve, and inverse angiographic mean transit time Tmicro-1 (P < .01). Progressive left anterior descending artery stenosis led to no or only minor changes of circumflex artery resting or hyperemic flow or flow reserve; only occlusion induced a significant decrease of coronary flow reserve (from 4.0 +/- 0.7 to 3.2 ...
HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men.
Authors: J TSalonen, RSalonen, KSeppänen, RRauramaa, JTuomilehto
Journal: Circulation (1991)

BACKGROUNDWe investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old.METHODS AND RESULTSBaseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systo...