tbuckley/cabot-search huggingface dataset:
Differences in the determinants of overdrive suppression between sinus rhythm and slow atrioventricular junctional rhythm.
Authors: B H Neely, F Urthaler, G R Hageman
Journal: Circulation Research (1985)

Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle lengths. Data relating recovery times and return to control conditions to prepacing cycle length, pacing cycle length, duration of pacing, site of pacing, and origin of rhythms were analyzed by covariance analysis. From the analyses, the relative contribution of the determinants are: the prepacing cycle length 73%, the site of pacing 3.5%, the pacing cycle length 2%, and the interaction of the site of pacing and pacing cycle length 1% for sinus node recovery time; and for slow atrioventricular junctional rhythm recovery time, the duration of pacing 40%, the interactions between the duration of pacing and the pacing cycle length 27%, and the prepacing cycle length 9%. A modified exponential decay model predicted 8 beats for return to prepacing conditions during sinus rhythm and 66-100 beats during atrioventricular junctional rhythm. We conclude that the single most important determinant of sinus node recovery time is the prepacing cycle length. Pacing cycle length and site of pacing have a significant but small influence on sinus node recovery time and duration of pacing, beyond 20 seconds, has no significant influence. In contrast, duration of pacing is the most important determinant of slow atrioventricular junctional recovery time. Another major determinant of slow atrioventricular junctional recovery time is the interactions between pacing cycle length and duration of pacing. Prepacing cycle length has a minor influence, and site of pacing has no influence, on slow atrioventricular junctional recovery time.
Assessing airway inflammation
Authors: D. R. Taylor, D. C. Cowan
Journal: Thorax (2010)

In the first paragraph of most reviews we are reminded that ‘asthma is an inflammatory disease characterised by … ’. This perspective has been influenced by—and, in turn, has driven—a great deal of respiratory research over the last 20 years. In the clinical sphere, studies based on factor analysis inform us that airway inflammation is an independent domain of the asthma syndrome, distinct from airways hyper-responsiveness, abnormal lung function and symptoms.1 2 Established treatments (notably inhaled corticosteroids and antileukotrienes) as well as potential new therapies are directed towards modifying the underlying inflammatory process rather than just providing symptom relief. For all of these reasons, actually measuring airway inflammation ought to be a regular feature in the management of asthma. In that regard, the renowned passion of Professor Freddie Hargreave and colleagues for using induced sputum analysis in the routine assessment of airways disease is entirely logical and is to be applauded.3 The strength of induced sputum analysis is that inflammatory cell characteristics (eosinophil predominance or not) may be used to interpret the aetiology of a patient's symptoms, anticipate the short to medium-term prognosis and, most importantly, the likelihood of response to treatment with corticosteroid.4–6 Unfortunately, 15 years on, for pragmatic reasons, the approach he encouraged is not routine except in a few centres.

Against this background, the measurement of nitric oxide as the fraction in exhaled air (FeNO) came on the scene and interest in its clinical applications has grown.7 Chief among these, for reasons we have referred to, has been its role as a surrogate measurement of eosinophilic airway inflammation. This appeared to be very convenient, given the desirability of measuring airway inflammation by a less time-consuming and …
Lysis of oncornaviruses by human serum. Isolation of the viral complement (C1) receptor and identification as p15E.
Authors: R M Bartholomew, A F Esser, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1978)

Moloney leukemia virus activated both the classical and alternative pathways of human complement. About 500,000 virions were required to detect activation of the classical pathway whereas 5,000 times as many virions were necessary to initiate the alternative pathway, indicating that in this system only the former is of biological significance. Disruption of the virus with Triton X-100 destroyed its ability to initiate the alternative pathway without affecting its ability to activate the classical pathway. After ultracentrifugation of disrupted virus the active component could be recovered in the supernate and was isolated by isoelectric focusing in granulated gels. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic and analysis and cyanogen bromide digestion studies revealed that the activity resided in a methionine-containing protein having a pI of 7.5 and a molecular weight of approximately equal to 15,000 daltons. The purified protein interacts strongly with Clq and efficiently activates Cl. RNase and lipolytic enzymes had no effect on the isolated protein but incubation with trypsin resulted in loss of activity. Enzymatic digestion studies of surface-labeled virus indicate that the active protein is a viral membrane protein. On the basis of these results it is concluded that the complement receptor of Moloney leukemia virus is the surface protein p15E.
Impact of Statin Therapy on Central Aortic Pressures and Hemodynamics
Authors: Bryan Williams, Peter S. Lacy, J. Kennedy Cruickshank, David Collier, Alun D. Hughes, Alice Stanton, Simon Thom, Herbert Thurston
Journal: Circulation (2008)

Background— Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation–Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension. Methods and Results— CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, −0.1 mm Hg [95% CI, −1.8 to 1.6], P =0.9; change in brachial pulse pressure, −0.02 mm Hg [95% CI, −1.6 to 1.6], P =0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, −0.5 mm Hg [95% CI, −2.3 to 1.2], P =0.5; change in aortic pulse pressure, −0.4 mm Hg [95% CI, −1.9 to 1.0], P =0.6) and had no influence on augmentation index (change in augmentation index, −0.4%; 95% CI, −1.7 to 0.8; P =0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, −1.3 to 1.8; P =0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure–lowering treatment strategy in the factorial design. Conclusions— Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.
“RAS”ling β cells to proliferate for diabetes: why do we need MEN?
Authors: Adolfo García-Ocaña, Andrew F. Stewart
Journal: Journal of Clinical Investigation (2014)

Adult human pancreatic β cells are refractory to current therapeutic approaches to enhance proliferation. This reluctance to expand is problematic, especially for people with diabetes who lack sufficient numbers of functional insulin-producing β cells and could therefore benefit from therapies for β cell expansion. In this issue of the JCI, Chamberlain et al. describe a surprising series of observations that involve two downstream arms of the RAS signaling pathway, MAPK and RASSF proteins, which also involve the tumor suppressor menin. The findings of this study may help explain the difficulty of inducing β cell proliferation and may provide leads for therapeutic expansion of human β cells.
<i>In situ</i> photoimmunotherapy: a tumour-directed treatment for melanoma
Authors: M.F. Naylor, W.R. Chen, T.K. Teague, L.A. Perry, R.E. Nordquist
Journal: British Journal of Dermatology (2006)

We report a new immunological treatment for advanced cutaneous melanoma which combines laser stimulation with topical application of a toll-like receptor agonist. This treatment, in situ photoimmunotherapy (ISPI), provides an alternative to traditional therapies for melanoma patients with cutaneous metastases. A 6-week cycle of ISPI is carried out on cutaneous metastases located in a designated 20 x 20 cm treatment area: 2 weeks of pretreatment with twice-daily topical applications of imiquimod (5% cream under plastic occlusion), with a laser treatment session at week 2 and again at week 4. Topical imiquimod is continued for the entire 6-week cycle. Two patients with late-stage melanoma were treated with ISPI. Patient 1 had the primary tumour and local metastases on the left arm, as well as metastatic tumours in the lungs [American Joint Committee on Cancer (AJCC) stage IV]. Patient 2 had a head and neck melanoma with multiple local metastases (AJCC stage IIIC), which had failed repeated attempts at surgical resection and high-dose radiation therapy. Patient 1 is now free of all clinically detectable tumours (including the lung metastases) >20 months after the first treatment cycle. Patient 2 has been free of any clinical evidence of the tumour for over 6 months. These two cases demonstrate that ISPI can clear local tumour and trigger beneficial systemic responses, with a side-effect profile that compares favourably with other treatments for advanced melanoma.
Outcome and follow-up of children born after IVF-surrogacy
Authors: P. Serafini
Journal: Human Reproduction Update (2001)

This study addresses various outcomes and follow-up of children born after IVF–surrogacy. Recent reports on perinatal outcome after IVF–surrogacy and on data generated by the Society of Assisted Reproductive Technology (SART) Registry between 1991 and 1995 were examined. A review of recently published perinatal outcomes of children born after IVF–surrogacy, including the developmental information of 110 children after the first 2 years of life, was undertaken. The birth weights for singleton pregnancies following IVF–surrogacy and IVF were similar, whereas the birth weights of twins and triplets born from the IVF–surrogates were significantly heavier than those delivered from conventional IVF patients. Preterm delivery was increased in twin and triplet gestations in all segments analysed. The incidence of low birth weight was significantly lower in children born after IVF surrogacy than in those born after IVF, for all births recorded. The incidence of congenital abnormalities following IVF and IVF–surrogacy was within the expected range for spontaneous conceptions. Speech delays were predominant in the multiple births, but neither speech nor motor delays persisted at 2 years of age in children born after IVF–surrogacy. These findings would imply that a gestational carrier would provide potential environmental benefits for the infant.
Effects of Volume Expansion, Purified Parathyroid Extract, and Calcium on Renal Bicarbonate Absorption in the Dog
Authors: Charles K. Crumb, Manuel Martinez-Maldonado, Garabed Eknoyan, Wadi N. Suki
Journal: Journal of Clinical Investigation (1974)

The role of parathyroid hormone (PTH) and of Ca(++) in the regulation of bicarbonate absorption (RHCO(3)) and its response to extracellular volume expansion (VE) was studied in HCO(3) (-)-loaded dogs.VE lowered RHCO(3) in both intact (from 24.8 to 22.0 mmol/liter GFR, P < 0.01) and thyroparathyroid-ectomized (TPTX) (from 24.5 to 18.0 mmol/liter GFR, P < 0.001) dogs; glomerular filtration rate (GFR) and filtered HCO(3) (-) did not change. Both groups showed a significant increase in the fractional excretion of sodium (C(Na) x 100/GFR), calcium (C(Ca) x 100/GFR), and chloride (C(Cl) x 100/GFR) and a decrease in phosphorus reabsorption. Fractional clearance of phosphate (C(P) x 100/GFR) rose in both groups but did not achieve significance. Infusion of purified parathyroid extract (PTE) decreased RHCO(3) in intact dogs (from 24.6 to 22.5 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.9 to 22.6 mmol/liter GFR, P < 0.05). No change was noted in GFR, renal blood flow (RBF), filtered HCO(3) (-), or fractional excretion of sodium, calcium, or chloride in either group. There was a significant increase in fractional phosphorus clearance and a decrease in phosphorus reabsorption in each group. Infusion of Ca(++) raised ultrafilterable Ca(++) from 5.7 to 7.9 mg/100 ml in intact and from 4.9 to 7.2 mg/100 ml in TPTX dogs; RHCO(3) increased in intact (from 22.9 to 26.9 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.6 to 28.6 mmol/liter GFR, P < 0.05). The GFR, RBF, and the fractional excretion of sodium, chloride, and calcium did not change in either group. The reabsorbed phosphate increased in both groups, and fractional phosphorus clearance fell in the intact group but did not change significantly in the TPTX group. Superimposition of PTE on hypercalcemia in TPTX dogs resulted in a decrease in RHCO(3) (from 27.3 to 23.9 mmol/liter GFR, P < 0.001), which was accompanied by an increase in the fractional excretion of phosphate and a decrease in the reabsorbed phosphate. In this group of TPTX dogs hypercalcemia caused a drop in RBF from 135.6 to 105.8 ml/min with no change in GFR. The RBF returned to control value with PTE infusion. IT IS CONCLUDED THAT: (a) the lowering of RHCO(3) by VE is not dependent solely on stimulation of PTH by the lowered Ca(++), (b) PTE acts directly on the renal tubules to lower RHCO(3), (c) Ca(++) enhances RHCO(3) and this effect is exerted in the absence of PTH and calcitonin, (d) neither the effects of Ca(++) nor of PTH appear to be mediated by altered hemodynamics, although this cannot be excluded in Ca(++)-infused TPTX dogs, (e) Ca(++) enhanced phosphate reabsorption in the absence of PTH; this may be a specific effect of hypercalcemia on phosphate reabsorption or the nonspecific consequence of the rise in serum phosphorus.
Early Prediction of Gestational Diabetes Mellitus in Vietnam
Authors: Thach S. Tran, Jane E. Hirst, My An T. Do, Jonathan M. Morris, Heather E. Jeffery
Journal: Diabetes Care (2012)

We aimed to compare the discriminative power of prognostic models for early prediction of women at risk for the development of gestational diabetes mellitus (GDM) using four currently recommended diagnostic criteria based on the 75-g oral glucose tolerance test (OGTT). We also described the potential effect of application of the models into clinical practice.A prospective cross-sectional study of 2,772 pregnant women was conducted at a referral maternity center in Vietnam. GDM was determined by the American Diabetes Association (ADA), International Association of the Diabetes and Pregnancy Study Groups (IADPSG), Australasian Diabetes in Pregnancy Society (ADIPS), and World Health Organization (WHO) criteria. Prognostic models were developed using the Bayesian model averaging approach, and discriminative power was assessed by area under the curve. Different thresholds of predicted risk of developing GDM were applied to describe the clinical impact of the diagnostic criteria.The magnitude of GDM varied substantially by the diagnostic criteria: 5.9% (ADA), 20.4% (IADPSG), 20.8% (ADIPS), and 24.3% (WHO). The ADA prognostic model, consisting of age and BMI at booking, had the best discriminative power (area under the curve of 0.71) and the most favorable cost-effective ratio if implemented in clinical practice. Selective screening of women for GDM using the ADA model with a risk threshold of 3% gave 93% sensitivity for identification of women with GDM with a 27% reduction in the number of OGTTs required.A simple prognostic model using age and BMI at booking could be used for selective screening of GDM in Vietnam and in other low- and middle-income settings.
Dietary Fat Supply to Failing Hearts Determines Dynamic Lipid Signaling for Nuclear Receptor Activation and Oxidation of Stored Triglyceride
Authors: Ryan Lahey, Xuerong Wang, Andrew N. Carley, E. Douglas Lewandowski
Journal: Circulation (2014)

Background— Intramyocardial triglyceride (TG) turnover is reduced in pressure-overloaded, failing hearts, limiting the availability of this rich source of long-chain fatty acids for mitochondrial β-oxidation and nuclear receptor activation. This study explored 2 major dietary fats, palmitate and oleate, in supporting endogenous TG dynamics and peroxisome proliferator–activated receptor-α activation in sham-operated (SHAM) and hypertrophied (transverse aortic constriction [TAC]) rat hearts. Methods and Results— Isolated SHAM and TAC hearts were provided media containing carbohydrate with either 13 C-palmitate or 13 C-oleate for dynamic 13 C nuclear magnetic resonance spectroscopy and end point liquid chromatography/mass spectrometry of TG dynamics. With palmitate, TAC hearts contained 48% less TG versus SHAM ( P =0.0003), whereas oleate maintained elevated TG in TAC, similar to SHAM. TG turnover in TAC was greatly reduced with palmitate (TAC, 46.7±12.2 nmol/g dry weight per min; SHAM, 84.3±4.9; P =0.0212), as was β-oxidation of TG. Oleate elevated TG turnover in both TAC (140.4±11.2) and SHAM (143.9±15.6), restoring TG oxidation in TAC. Peroxisome proliferator–activated receptor-α target gene transcripts were reduced by 70% in TAC with palmitate, whereas oleate induced normal transcript levels. Additionally, mRNA levels for peroxisome proliferator–activated receptor-γ-coactivator-1α and peroxisome proliferator–activated receptor-γ-coactivator-1β in TAC hearts were maintained by oleate. With these metabolic effects, oleate also supported a 25% improvement in contractility over palmitate with TAC ( P =0.0202). Conclusions— The findings link reduced intracellular lipid storage dynamics to impaired peroxisome proliferator–activated receptor-α signaling and contractility in diseased hearts, consistent with a rate-dependent lipolytic activation of peroxisome proliferator–activated receptor-α. In decompensated hearts, oleate may serve as a beneficial energy substrate versus palmitate by upregulating TG dynamics and nuclear receptor signaling.
The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue engineered cartilaginous constructs
Authors: J. Malda, T.B.F. Woodfield, F. van der Vloodt, F.K. Kooy, D.E Martens, J. Tramper, C.A.van Blitterswijk, J. Riesle
Journal: Biomaterials (2004)
TCTAP A-098 Outcomes Following Endovascular Therapy with a Drug-eluting Stent (Zilver PTX) in the Femoropopliteal Artery
Authors: Kiyonori Nanto, Osamu Iida, Shin Okamoto, Takuma Iida, Tatsuya Shiraki, Keisuke Okuno, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2014)
Noninducibility of Atrial Fibrillation as an End Point of Left Atrial Circumferential Ablation for Paroxysmal Atrial Fibrillation
Authors: Hakan Oral, Aman Chugh, Kristina Lemola, Peter Cheung, Burr Hall, Eric Good, Jihn Han, Kamala Tamirisa, Frank Bogun, Frank Pelosi, Fred Morady
Journal: Circulation (2004)

An anatomic approach of left atrial radiofrequency circumferential ablation (LACA) to encircle the pulmonary veins is often effective in eliminating paroxysmal atrial fibrillation (AF). However, no electrophysiological end points other than voltage abatement and/or conduction slowing or block across ablation lines have been used. It has been unclear whether noninducibility of AF is a clinically useful end point.In 100 patients with paroxysmal AF (mean age, 55+/-10 years), LACA to encircle the left- and right-sided pulmonary veins was performed during AF, with additional ablation lines in the posterior left atrium and mitral isthmus, with an 8-mm-tip catheter. After completion of this lesion set, sinus rhythm was present, and AF lasting >60 seconds was not inducible in 40 patients (40%; group 1). The 60 patients in whom AF was still present or who still had inducible AF were randomly assigned to no further ablation (group 2; 30 patients) or to additional ablation lines along the left atrial septum, roof, and/or anterior wall where there were fractionated electrograms (group 3; 30 patients). In group 3, AF was rendered noninducible in 27 of 30 patients (90%). At a 6-month follow-up, 67% of patients in group 2 were free of AF without drug therapy compared with 86% of patients in group 3. (P=0.05, log-rank test). Left atrial flutter occurred in 17% and 27% of patients in each group, respectively (P=0.3).After LACA in patients with paroxysmal AF, AF usually can be rendered noninducible by additional ablation at sites of fractionated electrograms. Noninducibility of AF attained by additional electrogram-guided left atrial ablation may be associated with a better midterm clinical outcome than when AF is still inducible after LACA alone.
Mottled chest radiograph and gas transfer defect in chronic liver disease
Authors: N. N. Stanley, D. J. Woodgate
Journal: Thorax (1972)

In a prospective study of 170 patients with various types of chronic liver disease, a pulmonary gas transfer defect was found in 20% and mottled shadowing in the chest radiograph in 6%. The presence of these abnormalities was not related to the cause of the liver disease. Reduction of transfer factor in liver disease was not accompanied by a restrictive ventilatory defect and was found in most cases with mottled radiographs. The incidence of finger clubbing and the levels of both venoarterial admixture and cardiac output were higher in patients with mottling than in those with normal radiographs. Mottling was also seen in the chest radiographs of five other patients with hepatic cirrhosis who had previously been investigated for cyanosis due to intrapulmonary shunting. Despite earlier reports of active chronic hepatitis and primary biliary cirrhosis occurring in patients with fibrosing alveolitis, we suggest that these radiographic changes in liver disease are usually caused by a pulmonary vascular disorder, rather than by coincidental lung disease, and are a local manifestation of a generalized vasodilated state. The low incidence of diffuse lung disease complicating chronic liver disease was confirmed by reviewing the hospital necropsy records. In one patient the radiographic mottling disappeared and the physiological evidence of a circulatory disorder became less marked during a period of improved hepatocellular function.