tbuckley/cabot-search huggingface dataset:
Abstract 16947: Initial Brain Natriuretic Peptide Levels, but not Hemodynamics, Predict 5-Year Survival in Patients with Pulmonary Arterial Hypertension
Authors: Vikram Gurtu, Laura Morrison, Linda Webster, Ian Paterson, Evangelos Michelakis
Journal: Circulation (2012)

Brain natriuretic peptide (BNP) correlates with prognosis in patients with LV dysfunction but its role in Pulmonary Arterial Hypertension (PAH) is unknown outside of short-term data. The strongest predictor of morbidity and mortality in PAH is right ventricular (RV) function. We hypothesized that BNP at the time of referral would predict long-term survival better than hemodynamic parameters or subsequent PAH therapies. We followed a cohort of 72 consecutive patients at our PAH program between 2002 and 2011, that had BNP levels on referral, as well as echocardiography and right heart catheterization, all performed within 24 hours. A subset of these patients (n=27) also had cardiac MRI at the same time. Survival was followed up to five years. We followed a goal-oriented therapy protocol with the 3 classes of approved PAH therapies, adding a class to reach at least 350m in the 6min walk (6MW). The initial BNP levels were not a part of the medical record and were not included in therapeutic decisions. Pearson correlations assessed relationships between parameters and Kaplan Meier Curves compared survival depending on BNP range. BNP correlated with RV mass index, right atrial pressure (RAP) and 6MW (R2=0.588; 0.215, 0.224, p 400pg/mL, cumulative survival at 60 months was 93.1% vs 22.7% respectively, while the 2 groups did not differ in terms of PAP, PVR or type of PAH-therapy. The data suggest that RV fails independently of afterload. The predictive power of initial BNP levels on long-term survival in PAH and its correlation with RV remodeling suggests that RV function upon referral may determine prognosis regardless of PVR and subsequent interventions. BNP could potentially be used to alter clinical care, identifying patients that need earlier referral for transplantation and intensified/accelerated treatment protocols.
Abstract 2873: Association of Endothelial Precursor Colony Counts with Cardiovascular Risk Burden
Authors: Ibhar Al Mheid, Muhiddin Ozkor, Kreton Mavromatis, Salman Sher, Konstantinos Aznaouridis, Farheen Shirazi, Tanuj K Kamineni, Muhammad Ali, Sarfraz Ali, Diane Sutcliffe, Muhammed Amer, Wayne R Alexander, Robert Taylor, Arshed A Quyyumi
Journal: Circulation (2007)

Studies investigating endothelial progenitor cell levels and cardiovascular (CVD) risk and outcomes have yielded contradictory information based on the assays employed. Culture assays of early ``angiogenic” endothelial cells differ from the late outgrowth ``proliferative” ones. We hypothesized that the number of colonies, representing the circulating pool of endothelial precursors, will be significantly stimulated by the presence of CVD and risk factors (RF). Methods We performed an ``intermediate” duration assay where peripheral blood mononuclear cells were cultured on fibronectin plates for 7 days and the number of colonies with endothelial-type cells at their periphery were counted by the same technician in all subjects. We sampled 420 subjects who either: were healthy and free of RF (n = 36, age = 47 ± 10), had metabolic syndrome, overt diabetes, or increased carotid thickness (n = 131, age = 59 ± 10), had coronary artery disease (n = 206, age = 61 ± 10), or peripheral vascular disease (n = 45, age = 64 ± 8). Results Endothelial precursor colony counts were lowest in the healthy subjects, higher in patients with RF, and highest in those with CVD (Figure ). These differences persisted after correcting for age. Conclusion Our data unequivocally demonstrates that the numbers of cultured endothelial colonies, utilizing an intermediate duration assay, are stimulated by the presence of risk factors, sub-clinical disease and overt CVD. This illustrates the presence of a reparative or compensatory regenerative response by endothelial progenitors to vascular injury. Whether an inadequate repair response is associated with increased risk needs to be further studied.
Delayed Puberty
Authors: Mark R. Palmert, Leo Dunkel
Journal: New England Journal of Medicine (2012)

Puberty is considered delayed when it has not yet occurred at an age that is 2 to 2.5 SD later than average (traditionally, 14 years in boys and 13 years in girls). Constitutional delay of growth and puberty (CDGP) is the most common cause. Management of CDGP is discussed.
Abstract 63: Early Predictors of Good Neurologic Outcome From Out of Hospital Cardiac Arrest Treated With Therapeutic Hypothermia.
Authors: Brian Oneil, Mary Ann Peberdy, Michael Sayre, Arthur Sanders, Romergryko Geocadin, Norman Paradis, Kennon Heard
Journal: Circulation (2010)

Objective: To evaluate early predictors of neurological outcome in patients (pts) resuscitated from OOHCA from any initial rhythm treated with TH. Methods: This is a sub-analysis of a multi-center ...
Imported dengue virus serotype 1 from Madeira to Finland 2012
Authors: E Huhtamo, E M Korhonen, O Vapalahti
Journal: Eurosurveillance (2013)

Imported dengue cases originating from the Madeiran outbreak are increasingly reported. In 2012 five Finnish travellers returning from Madeira were diagnosed with dengue fever. Viral sequence data was obtained from two patients. The partial C-preM sequences (399 and 396 bp respectively) were found similar to that of an autochthonous case from Madeira. The partial E-gene sequence (933 bp) which was identical among the two patients grouped phylogenetically with South American strains of dengue virus serotype 1.
Placebo response in panic disorder
Authors: W Coryell, R Noyes
Journal: American Journal of Psychiatry (1988)

Of 43 patients with panic disorder or agoraphobia with panic attacks who took placebo for 8 weeks in two double-blind studies, one in four markedly improved. Those with consistently normal dexamethasone suppression test results were significantly more likely to show a placebo response as were those with lower anxiety ratings at the outset of treatment.
Abstract 2937: Association Of Low Body Mass Index And Weight Loss With Increased Mortality In 14,065 Transplant-wait-listed Hemodialysis Patients
Authors: Kamyar Kalantar-Zadeh, Elani Streja, Jennie Jing, Csaba P Kovesdy, David Van Wyck, Gabriel M Danovitch, Gabriel M Danovitch, Suphamai Bunnapradis
Journal: Circulation (2008)

Obese individuals with terminal heart failure (HF) or end-stage renal disease (ESRD) are often asked to lose weight prior to heart or kidney transplantation despite recent findings of “obesity paradox” or “reverse epidemiology” indicating survival advantages of obesity in HF and ESRD. We hypothesized that lower BMI and weight loss over time in transplant-waitlisted hemodialysis (HD) patients (pts) is associated with increased death risk during the waiting period. By linking the 5-yr (7/2001– 6/2006) national database of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients , we identified 14,065 HD pts, who were transplant-waitlisted but who did not receive any kidney transplantation over the 5-yr period. Time-dependent survival models examined associations of calendar-quarterly measured BMI (using 13-wk averaged post-HD dry weight) and the percentage of change in weight over 6 mo with survival adjusted for case-mix and time-varying surrogates of malnutrition-inflammation complex syndrome (MICS). The 14,065 HD pts were 59.7±15.4 yrs old and included 47% women and 39% diabetics. The 13-wk averaged BMI was 26.4±6.7 kg/m 2 . Unadjusted and adjusted survival analyses showed progressively greater survival with higher BMI&gt;23 kg/m 2 and higher death risk across weight loss increments: Obese transplant-waitlisted HD pts appear to have greater survival that is incrementally associated with higher height-adjusted-weight, whereas weight loss over time appears associated with increased death risk. These findings may question the benefit of recommending weight reduction during the pre-transplant waiting period in obese MHD pts. This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada &amp; Utah).
Metabolic Requirement for Inorganic Phosphate by the Rabbit Proximal Tubule
Authors: Peter C. Brazy, Steven R. Gullans, Lazaro J. Mandel, Vincent W. Dennis
Journal: Journal of Clinical Investigation (1982)

These studies examine the effects of acute changes in the availability of inorganic phosphate on the function of isolated proximal renal tubules from rabbit kidney. We removed phosphate from the extracellular fluids and measured fluid absorption rates in isolated perfused tubules and oxygen consumption rates in suspensions of cortical tubules. In proximal convoluted tubules, the selective removal of phosphate from the luminal fluid reduced fluid absorption rates from 1.11±0.12 to −0.01±0.08 nl/mm · min. This effect on fluid absorption was dependent on the presence of glucose transport and metabolism. The addition of phlorizin to the phosphate-free luminal fluid preserved fluid absorption rates (1.12±0.12 nl/mm · min) as did the substitution of nonmetabolized α-methyl d-glucopyranoside for glucose (1.05±0.21 nl/mm · min) or the addition of 2-deoxyglucose, an inhibitor of glycolysis, to the bathing medium (1.01±0.15 nl/mm · min). There was no effect on fluid absorption if phosphate was removed from the bath only. Additionally, removal of phosphate from the luminal fluid of proximal straight rather than convoluted tubules had no effect on fluid absorption rates. Oxygen consumption rates in suspensions of cortical tubules were reduced from 18.9±0.6 to 10.6±0.6 nmol O2/mg tubular protein · min by the removal of phosphate from the medium. This inhibition was prevented by the substitution of α-methyl d-glucopyranoside for glucose in the phosphate-free medium. The data indicate that under certain conditions, proximal convoluted tubules require the presence of phosphate in the luminal fluid to preserve tubular function. In the absence of intraluminal phosphate, glucose metabolism causes a reduction in both oxidative metabolism and fluid absorption. This response is analogous to the Crabtree effect and suggests limitations on the intracellular availability of inorganic phosphate.
Abstract 2305: Pulmonary Vascular Reactivity And Prognosis In Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Nika Skoro-Sajer, Nicklas Hack, Roela Sadushi, Johannes Jakowitsch, Diana Bonderman, Meinhard Kneussl, Walter Klepetko, Irene Lang
Journal: Circulation (2007)

Hemodynamic responder status defined as an acute decrease of mean pulmonary arterial pressure (mPAP)&gt;10mmHg and below 40mmHg is associated with improved outcome in patients (pts) with pulmonary arterial hypertension (PAH). Pulmonary vascular reactivity to nitric oxide (NO) is controversial in chronic thromboembolic pulmonary hypertension (CTEPH). We speculated that the magnitude of the acute decrease in mean pulmonary artery pressure (mPAP) after exposure to NO might reflect the degree of small vessel disease in CTEPH and thus, affect long-term outcome. Methods: Right heart catheterization was performed in 62 (55 Â ± 15 years, 32 female) pts with major-vessel CTEPH, at baseline and during inhalation of 40ppm NO. Within 25Â±15 days patients underwent pulmonary endarterectomy (PEA). Pts were followed for 11.3Â±26 months. Predictors of survival were analyzed by Cox regression analysis, and survival was described by Kaplan-Meier curves. Results: Significant reductions in mean pulmonary arterial pressure (mPAP; p&lt;0.001), pulmonary vascular resistance (PVR; p&lt;0.001) and an increase in mixed venous oxygen saturation following NO inhalation were demonstrated (p&lt;0.001) by a paired t-test. Stepwise multivariate analysis revealed the relative change of PVR after NO inhalation as a predictor of survival. Patients whose PVR during NO inhalation declined below 789.8 dynes.s.cm-5 had significantly better outcome than patients with above median PVR. There was a strong negative correlation between the relative change of PVR under NO and recurrent pulmonary hypertension after PEA (p=0.02). Conclusions: Patients with operable CTEPH demonstrated acute pulmonary vascular reactivity, mostly not corresponding to a complete responder status, but accounting for a wide range of decreases of mPAP [change of mPAP (%) (−10.9Â±14)] and PVR [change of PVR (%) (−17 Â±15)]. Reduction of PVR under 800 dynes.s.cm-5 after inhalation of NO was associated with better outcome. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with CTEPH undergoing PEA.
Abstract 16038: Bone Marrow SSEA1+ Cells Contribute in the Response to Cardiac Pressure Overload
Authors: Amanda Finan, Nikolai A Sopko, Feng Dong, Matthew Kiedrowski, Marc S Penn
Journal: Circulation (2011)

Introduction:  SSEA1+ cells have been described as the most primitive mesenchymal progenitor cell in the bone marrow (BM). We have observed a significant proliferative response of SSEA1+ in response to pressure overload (PO) but their role in response to cardiac injury remains to be defined.   Methods and Results:  Lethally irradiated mice were transplanted with normal bone marrow in which the wild-type SSEA1+ were replaced with GFP+ SSEA1+. PO was induced by trans-aortic constriction (TAC). The fate of GFP+ cells was determined in the BM, spleen, and heart by flow cytometry 1 w post-TAC. Mice were also transplanted with either total GFP BM or GFP BM depleted of SSEA1+ cells. TAC and Sham operations were performed and cardiac function was assessed by echocardiography. Consistent with the proliferative response of SSEA1+ following PO, we observed a 66.8% increase of GFP+ cells in the BM 1 w after TAC. However, this increase did not correlate with an increase in SSEA1+ cells. GFP+ hematopoietic stem cell (HSC) and endothelial progenitor cell (EPC) were observed in Sham (7 weeks post-transplant) in the BM and spleen, with GFP contribution increasing after TAC (BM - HSC 1.9% vs 10.92 %, EPC 9.3% vs 32.3%; spleen - HSC 1.5% vs 6.8%, EPC 2.4% vs 10.5%). Similarly, in the heart, there was an increase in the percentage of GFP+ EPC after TAC (Sham 1.6% vs TAC 9%). Interestingly, we observed minimal contribution of GFP+ cells to the cardiac stem cell population (Sham 0% vs TAC 0.5%). Mice with SSEA1 depleted BM had normal cardiac function and normal blood cell counts at baseline compared to total BM transplanted mice. However, in response to TAC, mice with SSEA1+ depleted BM had a reduced cardiac function in response to TAC resulting in decreased ejection fraction (SSEA1 depleted -19.4±2.1%, total GFP BM -6.1±0.7% percent change in EF compared to sham, p=0.04) 2 weeks post TAC.   Conclusions:  Our results demonstrate for the first time, in vivo, the natural fate of BM SSEA1+ cells to become cells of hematopoietic and endothelial origin. We also have determined that BM SSEA1+ deficiency results in a reduced compensatory capacity in response to pressure overload. Further studies are in progress understand the mechanism in which SSEA1+ cells support the myocardium in response to TAC
Quantitative estimates of the effects of concomitant chemotherapy on acute dysphagia in patients receiving radical treatment for head and neck cancer
Authors: S. Bhide, S. Gulliford, R. A'Hern, E. Hall, K. Newbold, K. Harrington, C. Nutting
Journal: Journal of Clinical Oncology (2009)

e22134 Purpose: To generate quantitative parameters describing the effect of concomitant chemotherapy on incidence of grade 3 dysphagia (CTCAE v3.0, assisted feeding) using dose response curves in patients receiving radical treatment for head and neck cancer. Methods: Patients treated at a single centre in prospective phase I and II trials of concomitant chemo-IMRT (CRT) (n=85) and the phase III trial of IMRT vs. conventional radiotherapy (PARSPORT) (n=82) formed the basis of this non-randomized comparison. Patients in the PARSPORT trial received radiation alone (RT). Radiation dose for all patients was radiobiologically equivalent to at least 70Gy in 35 fractions. Concomitant chemotherapy was cisplatin (100 mg/m 2 ) on days 1 and 29. G3 dysphagia was recorded prospectively. Dose volume histograms (DVH) were generated for the pharyngeal mucosa. The mean dose (converted to equivalent dose in 2Gy/fraction, MD 2 ) was used as a univariate descriptor of the DVH, for the generation of the dose response curves. A logistic function of the form p=1/[1+(MD 50 /D) k ] was fitted where, p is the probability of the incidence of toxicity, D is the mean dose, MD 50 is the mean dose at which 50% of patients experience toxicity and k describes the increase in incidence with increasing dose. The dose response curves were fitted using non-linear logistic regression. Results: The mean MD 2 to the pharyngeal mucosa were 56Gy and 55.8Gy respectively, in the CRT and RT groups. There was a statistically significant difference of 25% (95% CI: 10–38, p=0.002) in the incidence of G3 dysphagia between the CRT (68%) and RT (43%) groups. Fitting dose response curves to the clinical data yielded parameter values (95% CIs) of MD 50 =46 Gy (42–49), k=4.8 (2.3–7.2) for the CRT group and MD 50 = 58 Gy (55–61), k=3 (1.6-.45) for RT group. Dose response gradients for CRT and RT showed approximately 1.95% and 1.3% increase (respectively) in probability of G3 dysphagia resulting from an increase in mean dose of 1Gy between doses of 30Gy to 70Gy. Conclusions: Addition of concomitant chemotherapy increases the incidence of G3 dysphagia by 0.65% for every 1 Gy increase in radiation dose. The observed MD 50 for G3 dysphagia is lower for RT alone (46 Gy vs. 58 Gy). No significant financial relationships to disclose.
An Ethical Debate: Ethical issues
Authors: J. Davis
Journal: BMJ (1995)

Two sets of ethical principles have to be considered in this case: those which have come to be accepted criteria for genetic screening, and those underlying medical ethics. Since presence of the responsible gene is necessary, but not sufficient, for the development of hypertrophic cardiomyopathy; and since the condition is currently untreatable once it has developed, the screening criteria are not met. That does not, of course, preclude the …
Abstract 5142: Direct Monitoring of Mitochondrial Calcium Levels in Cultured Cardiomyocytes Using a Novel Fluorescent Indicator Protein, GCaMP2-mt
Authors: Moritake Iguchi, Masaharu Akao, Junichi Nakai, Masashi Kato, Toshihiro Takeda, Madoka Matsumoto-Ida, Takeshi Kimura, Toru Kita
Journal: Circulation (2009)

Background: An opening of the mitochondrial permeability transition pore (MPTP), which leads to loss of mitochondrial membrane potential (ΔΨ m ), is the earliest event that commits the cell to death. Mitochondrial matrix calcium ([Ca 2+ ] m ) is considered a critical regulator of MPTP, but direct monitoring of [Ca 2+ ] m has been difficult with previously reported sensors due to limited signal intensity or low targeting efficiency. We developed a novel fluorescent indicator for [Ca 2+ ] m , GCaMP2-mt, by adding the mitochondrial targeting sequence of cytochrome oxidase to a high signal-to-noise Ca 2+ sensor protein GCaMP2, and monitored the dynamic changes in oxidant-induced cardiomyocyte death. Methods and Results: GCaMP2-mt was transduced in neonatal rat cardiomyocytes using a recombinant adenovirus. We confirmed that GCaMP2-mt colocalized well with tetramethylrhodamine ethyl-ester, a fluorescent indicator of ΔΨ m . We monitored oxidant-induced response of [Ca 2+ ] m and ΔΨ m using time-lapse confocal microscopy. After H 2 O 2 exposure, [Ca 2+ ] m remained unchanged for about 20 min, followed by kinetically-distinct two-step increase; the first increase lasted for about 5 min, and the second increase was slower and persisted until cells underwent irreversible ΔΨ m loss. Importantly, there was a cellular heterogeneity in the second increase, and the level of [Ca 2+ ] m overload was variable. However, ΔΨ m loss occurred in an all-or-none manner depending on cellular [Ca 2+ ] m level, with a clear cut-off value. A Ca 2+ chelator BAPTA suppressed both the first and the second increase of [Ca 2+ ] m , and protected the cells against ΔΨ m loss. In contrast, ruthenium red, an inhibitor of mitochondrial Ca 2+ uniporter, suppressed only the second increase of [Ca 2+ ] m , but not the first increase. Despite the suppressed [Ca 2+ ] m overload, ruthenium red was unable to protect against ΔΨ m loss; it caused earlier increase in cytosolic Ca 2+ ([Ca 2+ ] c ) level which might have accelerated the MPTP opening, as measured by an indicator of [Ca 2+ ] c , Fluo-4. These findings support the central role of [Ca 2+ ] m as well as [Ca 2+ ] c overload in the MPTP opening. Conclusion: Direct monitoring of [Ca 2+ ] m using GCaMP2-mt provides deeper insight into the mechanism of cardiomyocyte death.
Abstract 2345: Radiofrequency Ablation of the Cavotricuspid Isthmus Independently Mitigates the Arrhythmogenicity of Remote Ectopic Atrial Beats
Authors: Alireza Nazeri, Ali Massumi, Abdi Rasekh, Mohammad Saeed, Christopher M Frank, Mehdi Razavi
Journal: Circulation (2009)

Background: Radiofrequency ablation (RFA) of isthmus-dependent atrial flutter (AFL) in patients with AFL and atrial fibrillation (AF) has been shown to decrease the future AF burden. The purpose of...
Screening For Hereditary Spherocytosis: EMA Binding Test and Flow Cytometric Osmotic Fragility Test Are Recommended, But Cryohemolysis Test Is Not Recommended
Authors: Sang Hyuk Park, Chan-Jeoung Park, Bo-Ra Lee, Young Jin Kim, Young-Uk Cho, Seongsoo Jang, Kyung Nam Koh, Ho-Joon Im, Jong Jin Seo, Hye-Lim Jung, Eun Sil Park, Ji Won Lee, Keon Hee Yoo, Hyun-Sook Chi
Journal: Blood (2013)
Abstract 21246: Non-Trivial Effects of Intercellular Coupling on Spatiotemporal Intracellular Ca2+ Dynamics in Cardiac Myocytes
Authors: Zhiheng Jia, Harold Bien, Emilia Entcheva
Journal: Circulation (2010)

Recent evidence from modeling and experiments casts intracellular Ca2+ dynamics as independent pro-arrhythmic factor. However, the detailed mechanism of instabilities progression to arrhythmias at ...
Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections
Authors: Dimpy P. Shah, Shashank S. Ghantoji, Ella J. Ariza-Heredia, Jharna N. Shah, Katia K. El Taoum, Pankil K. Shah, Lior Nesher, Chitra Hosing, Gabriela Rondon, Richard E. Champlin, Roy F. Chemaly
Journal: Blood (2014)
Abstract 13967: Role of PKC, PKG and Actin-Myosin Interaction in the Adaptive Diastolic Response to Acute Stretch
Authors: Ricardo Ladeiras-Lopes, Ricardo Castro-Ferreira, Joao Neves, Ricardo Fontes-Carvalho, Paulo Castro-Chaves, Adelino Leite-Moreira
Journal: Circulation (2011)

Objectives: Myocardial stretch elicits an adaptive diastolic response characterized by a progressive decrease in myocardial stiffness. We aimed to better understand the role of PKC, PKG and actin-m...