tbuckley/cabot-search huggingface dataset:
The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study
Authors: Richard S Finn, John P Crown, Istvan Lang, Katalin Boer, Igor M Bondarenko, Sergey O Kulyk, Johannes Ettl, Ravindranath Patel, Tamas Pinter, Marcus Schmidt, Yaroslav Shparyk, Anu R Thummala, Nataliya L Voytko, Camilla Fowst, Xin Huang, Sindy T Kim, Sophia Randolph, Dennis J Slamon
Journal: The Lancet Oncology (2014)
Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study
Authors: Wai-Kay Seto, Aric Josun Hui, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Kevin Sze-Hang Liu, Ching-Lung Lai, Man-Fung Yuen, Henry Lik-Yuen Chan
Journal: Gut (2014)

<h3>Background and objective</h3> The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated. <h3>Methods</h3> Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥2 years with undetectable HBV DNA levels on ≥3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6–12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA &gt;2000 IU/mL). <h3>Result</h3> 184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11 000 (range 2115 to &gt;1.98×10<sup>8</sup>) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37–1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (±0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=−0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p&gt;0.05). <h3>Conclusions</h3> Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.
Cardiac Arrest
Authors: Kaustubha D. Patil, Henry R. Halperin, Lance B. Becker
Journal: Circulation Research (2015)

The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The 2 primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation remain of paramount importance for saving lives. They have undergone significant improvements in technology and dissemination into the community subsequent to their establishment 60 years ago. The evolution of artificial circulation includes efforts to optimize manual cardiopulmonary resuscitation, external mechanical cardiopulmonary resuscitation devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the-counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a 3-phase model of treatment, newer approaches targeting patients who have had a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electric activity, which is the presenting rhythm in at least one third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level about ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a cocktail of multiple agents targeted at restoration of normal metabolism and prevention of reperfusion injury, as this holds the promise of restoring life to many patients for whom our current therapies fail.
Nuclear Factor-κB Is Selectively and Markedly Activated in Humans With Unstable Angina Pectoris
Authors: Michael E. Ritchie
Journal: Circulation (1998)

Nuclear factor-kappaB (NF-kappaB) resides inactive in the cytoplasm of lymphocytes, monocytes, endothelial cells, and smooth muscle cells, where, after stimulation, it transcriptionally activates interleukins, interferon, tumor necrosis factor-alpha, and adhesion molecules. Because acute inflammation may play a role in coronary artery plaque rupture, it was hypothesized that NF-kappaB activation correlated with coronary artery disease (CAD) activity.Evidence of NF-kappaB activation in the circulation of 102 consecutive patients without an acute myocardial infarction who were undergoing cardiac catheterization was determined. Of these, 19 had unstable angina (USA) and were within 24 hours of the last episode of chest pain. The remaining 83 were being evaluated for stable angina (53), valvular heart disease (8), atypical chest pain (12), or congestive heart failure (10). Evidence of NF-kappaB activation was determined by electromobility shift assays (EMSAs) with the NF-kappaB binding-site-specific probe and nuclear proteins isolated from the buffy coat of blood obtained at the beginning of the procedure. Specificity of this DNA-protein interaction was confirmed by competition and supershift EMSAs. Analyses showed that 17 of 19 patients with USA had marked activation of NF-kappaB. Despite a significant number of patients with severe CAD (69%), only 2 of the 83 without USA showed marked NF-kappaB activation. A lack of NF-kappaB activation was not due to a lack of functional cell/protein because NF-kappaB was appropriately activated by lipopolysaccharide ex vivo in all patients. NF-kappaB activation was not a nonspecific response of all transcription factors because neither Sp1 or Oct1 was activated in patients with activated NF-kappaB. There was no relationship between drugs used, hemodynamic status, or other clinical characteristics and state of NF-kappaB activation.These data show that NF-kappaB is specifically and significantly activated in unstable angina pectoris and is not affected by severity of CAD or medical therapy. Furthermore, because NF-kappaB is activated before a clinical event, it may be mechanistically involved in the plaque disruption that produces acute coronary artery syndromes.
Pulmonary perfusion defects in postoperative chest infections
Authors: M. H. Irving, R. A. Payne, E. N. O'Brien, R. Wilks
Journal: Thorax (1973)

The repeated demonstration by many workers that there is a high incidence of asymptomatic postoperative lower limb venous thrombosis suggests that pulmonary embolism is likely to be a more frequent occurrence than is commonly accepted. If this assumption is correct then many emboli must be asymptomatic or producing atypical symptoms. The incidence of pulmonary artery perfusion defects in 50 general surgical patients who developed postoperative chest complications has been investigated by radioisotope scanning of the lungs. Nine of 10 patients considered on clinical grounds to have had a pulmonary embolus were shown on pulmonary scanning to have perfusion defects which would support such a diagnosis. Of the 40 patients diagnosed as having postoperative chest infections, perfusion defects in the lung scan were present in 33. In 19 of these 33 the perfusion defect was associated with an inflammatory lesion or an abnormal position of the diaphragm, visible on the chest radiograph. However, in 7 of the 19 patients the size of the perfusion defect seemed disproportionately large when compared with the extent of the lesion visible on the chest radiograph. In the remaining 14 patients the perfusion defects were not associated with any abnormality visible on the chest radiograph. It is considered that the perfusion defects in these 14 cases together with those in the seven cases in which the defect was disproportionately large represent `silent9 pulmonary emboli. It is suggested that pulmonary scanning carried out in cases of persistent postoperative chest infection will reveal, in many instances, a perfusion defect indicative of the presence of an underlying pulmonary embolus. In some cases this will be the precursor of a more major embolus.
Outcomes of In-Hospital Cardiopulmonary Resuscitation in Maintenance Dialysis Patients
Authors: Fahad Saeed, Malik M Adil, Ahmed A. Malik, Jesse D. Schold, Jean L. Holley
Journal: Journal of the American Society of Nephrology (2015)

Outcomes of cardiopulmonary resuscitation (CPR) in hospitalized patients with ESRD requiring maintenance dialysis are unknown. Outcomes of in-hospital CPR in these patients were compared with outcomes in the general population using data from the Nationwide Inpatient Sample (NIS; 2005-2011). The study population included all adults (≥ 18 years old) from the general population and those with a history of ESRD. Baseline characteristics, in-hospital complications, and discharge outcomes were compared between the two groups. The effects of in-hospital CPR on mortality, length of stay, hospitalization charges, and discharge destination were analyzed. Yearly national trends in survival, discharge to home, and length of stay were also examined using the Cochran-Armitage trend test. During the study period, 56,069 patients with ESRD underwent in-hospital CPR compared with 323,620 patients from the general population. Unadjusted in-hospital mortality rates were higher in patients with ESRD (73.9% versus 71.8%, P<0.001) on univariate analysis. After adjusting for age, gender, and potential confounders, patients with ESRD had higher odds of mortality (odds ratio, 1.24; 95% confidence interval, 1.11 to 1.3; P<0.001). Survival after CPR improved in the year 2011 compared with 2005 (31% versus 21%, P<0.001). Multivariate analysis also revealed that a greater proportion of patients with ESRD who survived were discharged to skilled nursing facilities. In conclusion, outcomes after in-hospital CPR are improving in patients with ESRD but remain worse than outcomes in the general population. Patients with ESRD who survive are more likely to be discharged to nursing homes.
An Evaluation of Total Correction of Tetralogy of Fallot
Authors: JAMES R. MALM, FREDERICK O. BOWMAN, A. GREGORY JAMESON, KENT ELLIS, SYLVIA P. GRIFFITHS, SIDNEY BLUMENTHAL
Journal: Circulation (1963)

Forty-one consecutive patients, ranging in age from 41/2 to 27 years, were operated upon for complete repair of tetralogy of Fallot without an operative mortality. Postoperative catheterization of 25 patients permitted objective evaluation of the results which were, by the criteria adopted, excellent in 16 patients, good in 5, and poor in 4, including the 2 late deaths. Surgical experience has shown the necessity for extensive resection of the right ventricular outflow tract. Prosthetic patches are considered necessary for closure of most of the ventricular septal defects encountered, but are infrequently needed for reconstruction of the right ventricular outflow tract. Its use is indicated in certain patients with hypoplasia of the pulmonary annulus or artery. Age has been an important factor in patient selection. It is suggested that symptomatic patients under five years of age may benefit from a systemic-to-pulmonary arterial anastomosis before definitive correction is undertaken later in childhood.
Guillain-Barré Syndrome
Authors: James J. Gilbert
Journal: JAMA (1973)

To the Editor.—  Idiopathic polyneuritis (Guillain-Barre syndrome) is an interesting and relatively common neurological problem. The following case illustrates an almost unique example.  Report of a Case.—  A 59-year-old man was in excellent health until he developed a 48-hour illness characterized by diarrhea, low-grade fever, and generalized malaise. Three days after recovery he noted a change in his voice and a slight difficulty in swallowing, without any sore throat. When these symptoms persisted, he was admitted to the hospital the following day. Neurological examination 24 hours later revealed an alert and well-developed man with mild, bilateral impairment of masseter function, a severe bilateral seventh nerve palsy, a diminished gag reflex, and marked impairment of tongue movements. He was extremely dysarthric and was having some difficulty swallowing. Eye movements were full and there was no ptosis nor diplopia with red glass testing. Deep tendon reflexes were brisk and motor strength was
Transgenic rat hearts overexpressing SERCA2a show improved contractility under baseline conditions and pressure overload
Authors: O MULLER, M LANGE, H RATTUNDE, H LORENZEN, M MULLER, N FREY, C BITTNER, W SIMONIDES, H KATUS, W FRANZ
Journal: Cardiovascular Research (2003)

The activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is reduced in the failing myocardium. Therefore, transfer of SERCA2a cDNA is considered as a therapeutical approach. The aim of this study was analysis of the long-term effect of SERCA2a overexpression in normal as well as pressure overload challenged myocardium of transgenic rats.Independent transgenic rat lines were established expressing the rat SERCA2a cDNA specifically in the myocardium resulting in increased SERCA2a protein levels by 30-70%. Simultaneous measurements of isometric contraction and calcium transients were carried out in right ventricular papillary muscle preparations. Hemodynamic parameters were measured in hearts of unchallenged rats as well as 10 weeks after pressure overload induced by abdominal aortic banding.Analysis of calcium handling and contractile parameters in isolated right ventricular papillary muscles revealed significant shortening of intracellular calcium transients and half maximal relaxation times (RT(50)). Assessing myocardial contractility in working heart preparations, both transgenic rat lines revealed elevated left ventricular pressure, improved systolic and diastolic parameters, attenuated negative force-frequency relation, and a dose-dependent beta-adrenergic effect. Aortic banding resulted in reduction of left ventricular pressure and worsening of contraction and relaxation parameters with no differences in mortality in both transgenic (+dP/dt 3084+/-96 vs. 3938+/-250 mmHg/s; RT(50) 47.0+/-1.2 vs. 36.7+/-1.4 ms) and wild-type rats (+dP/dt 2695+/-86 vs. 3297+/-122 mmHg/s; RT(50) 53.0+/-1.6 vs. 44.1+/-1.4). SERCA2a overexpressing hearts revealed improved hemodynamic parameters compared to wild-type controls. Acceleration of isovolumetric relaxation characterized by the index Tau was directly correlated to SERCA2a protein concentrations.Overexpression of SERCA2a protein results in a positive inotropic effect under baseline conditions remaining preserved under pressure overload without affecting mortality. Therefore therapeutic transfer of SERCA2a may become a potential approach for gene therapy of congestive heart failure. Moreover, transgenic SERCA2a rats will be useful for studies of long-term SERCA2a overexpression in further cardiovascular disease models.
Transforming a Targeted Porphyrin Theranostic Agent into a PET Imaging Probe for Cancer
Authors: Jiyun Shi, Tracy W.B. Liu, Juan Chen, David Green, David Jaffray, Brian C. Wilson, Fan Wang, Gang Zheng
Journal: Theranostics (2011)

Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT) and fluorescence imaging of cancer. Porphyrins are also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles for radioisotopes. Here we investigated the possibility of incorporating (64)Cu into a porphyrin-peptide-folate (PPF) probe developed previously as folate receptor (FR) targeted fluorescent/PDT agent, and evaluated the potential of turning the resulting (64)Cu-PPF into a positron emission tomography (PET) probe for cancer imaging. Noninvasive PET imaging followed by radioassay evaluated the tumor accumulation, pharmacokinetics and biodistribution of (64)Cu-PPF. (64)Cu-PPF uptake in FR-positive tumors was visible on small-animal PET images with high tumor-to-muscle ratio (8.88 ± 3.60) observed after 24 h. Competitive blocking studies confirmed the FR-mediated tracer uptake by the tumor. The ease of efficient (64)Cu-radiolabeling of PPF while retaining its favorable biodistribution, pharmacokinetics and selective tumor uptake, provides a robust strategy to transform tumor-targeted porphyrin-based photosensitizers into PET imaging probes.
Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.
Authors: C Lacombe, J L Da Silva, P Bruneval, J G Fournier, F Wendling, N Casadevall, J P Camilleri, J Bariety, B Varet, P Tambourin
Journal: Journal of Clinical Investigation (1988)

Erythropoietin (Epo)-producing cells were identified in the murine hypoxic kidney by in situ hybridization. Profound anemia was induced in order to greatly increase Epo production. This resulted in high levels of Epo mRNA in the kidney. 35S-labeled DNA fragments of the murine Epo gene were used as probes for in situ hybridization. Control experiments conducted in parallel included kidneys of nonanemic mice, RNase-treated hypoxic kidney sections, and 35S-labeled non-Epo-related DNA. The Epo probe gave a specific hybridization signal in the hypoxic kidney in the cortex and to a lesser extent in the outer medulla. Glomerular and tubular cells were not labeled. All positive cells were identified as peritubular cells. Using immunofluorescence, we showed that cells with the same topography contained Factor VIII-related antigen. These data demonstrated that peritubular cells, most likely endothelial cells, constitute the major site of Epo production in the murine hypoxic kidney.
Nuclear factor-kappa B activity in T cells from patients with rheumatic diseases: A preliminary report
Authors: E. Collantes, M V. Blazquez, V. Mazorra, A. Macho, E. Aranda, E. Munoz
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> The NF-κB/Rel family of transcription factors regulates the expression of many genes involved in the immune or inflammatory response at the transcriptional level. The aim of this study was to determine whether distinctive patterns of NF-kB activation are seen in different forms of joint disease. <h3>METHODS</h3> The DNA binding activity of these nucleoproteins was examined in purified synovial and peripheral T cells from patients with various chronic rheumatic diseases (12: four with rheumatoid arthritis; five with spondyloarthropathies; and three with osteoarthritis). <h3>RESULTS</h3> Electrophoretic mobility shift assays disclosed two specific complexes bound to a NF-κB specific<sup>32</sup>P-labelled oligonucleotide in nucleoproteins extracted from purified T cells isolated from synovial fluid and peripheral blood of patients with rheumatoid arthritis. The complexes consisted of p50/p50 homodimers and p50/p65 heterodimers. Increased NF-kB binding to DNA in synovial T cells was observed relative to peripheral T cells. In non-rheumatoid arthritis, binding of NF-κB in synovial T cells was exclusively mediated by p50/p50 homodimers. <h3>CONCLUSION</h3> Overall, the results suggest that NF-κB may play a central part in the activation of infiltrating T cells in chronic rheumatoid arthritis. The activation of this nuclear factor is qualitatively different in rheumatoid synovial T cells to that in other forms of non-rheumatoid arthritis (for example, osteoarthritis, spondyloarthropathies).
Response assessment after an inductive CHOP or CHOP-like regimen with or without rituximab in 103 patients with diffuse large B-cell lymphoma: integrating 18fluorodeoxyglucose positron emission tomography to the International Workshop Criteria
Authors: J. Dupuis, E. Itti, A. Rahmouni, F. Hemery, C. Gisselbrecht, C. Lin, C. Copie-Bergman, K. Belhadj, T. El Gnaoui, I. Gaillard, F. Kuhnowski, M. Meignan, C. Haioun
Journal: Annals of Oncology (2008)
Estradiol Therapy Combined With Progesterone and Endothelium-Dependent Vasodilation in Postmenopausal Women
Authors: Marie Gerhard, Brian W. Walsh, Ahmed Tawakol, Elizabeth A. Haley, Shelly J. Creager, Ellen W. Seely, Peter Ganz, Mark A. Creager
Journal: Circulation (1998)

Background —Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function. Methods and Results —Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent vasodilation, brachial artery diameter was measured after administration of sublingual nitroglycerin. During estradiol therapy, reactive hyperemia caused an 11.1±1.0% change in brachial artery diameter compared with 4.7±0.6% during placebo therapy ( P &lt;0.001). Progesterone did not significantly attenuate this improvement. During combined estrogen and progesterone therapy, flow-mediated vasodilation of the brachial artery was 9.6±0.8% ( P =NS versus estradiol alone). Endothelium-independent vasodilation was not altered by estradiol therapy, either with or without progesterone, compared with placebo. There was a modest decrease in total and LDL cholesterol during treatment both with estradiol alone and when estradiol was combined with progesterone (all P &lt;0.001 versus placebo). In a multivariate analysis that included serum estradiol, progesterone, total and LDL cholesterol concentrations, blood pressure, and heart rate, only the estradiol level was a significant predictor of endothelium-dependent vasodilation. Conclusions —The addition of micronized progesterone does not attenuate the favorable effect of estradiol on endothelium-dependent vasodilation. The vasoprotective effect of hormone replacement therapy may extend beyond its beneficial actions on lipids.