tbuckley/cabot-search huggingface dataset:
Arrhythmias and Conduction Defects as Presenting Symptoms of Fatty Acid Oxidation Disorders in Children
Authors: Damien Bonnet, Delphine Martin, None Pascale de Lonlay, Elizabeth Villain, Philippe Jouvet, Daniel Rabier, Michèle Brivet, Jean-Marie Saudubray
Journal: Circulation (1999)

The clinical manifestations of inherited disorders of fatty acid oxidation vary according to the enzymatic defect. They may present as isolated cardiomyopathy, sudden death, progressive skeletal myopathy, or hepatic failure. Arrhythmia is an unusual presenting symptom of fatty acid oxidation deficiencies.Over a period of 25 years, 107 patients were diagnosed with an inherited fatty acid oxidation disorder. Arrhythmia was the predominant presenting symptom in 24 cases. These 24 cases included 15 ventricular tachycardias, 4 atrial tachycardias, 4 sinus node dysfunctions with episodes of atrial tachycardia, 6 atrioventricular blocks, and 4 left bundle-branch blocks in newborn infants. Conduction disorders and atrial tachycardias were observed in patients with defects of long-chain fatty acid transport across the inner mitochondrial membrane (carnitine palmitoyl transferase type II deficiency and carnitine acylcarnitine translocase deficiency) and in patients with trifunctional protein deficiency. Ventricular tachycardias were observed in patients with any type of fatty acid oxidation deficiency. Arrhythmias were absent in patients with primary carnitine carrier, carnitine palmitoyl transferase I, and medium chain acyl coenzyme A dehydrogenase deficiencies.The accumulation of arrhythmogenic intermediary metabolites of fatty acids, such as long-chain acylcarnitines, may be responsible for arrhythmias. Inborn errors of fatty acid oxidation should be considered in unexplained sudden death or near-miss in infants and in infants with conduction defects or ventricular tachycardia. Diagnosis can be easily ascertained by an acylcarnitine profile from blood spots on filter paper.
EULAR recommendations for the management of large vessel vasculitis
Authors: C Mukhtyar, L Guillevin, M C Cid, B Dasgupta, K de Groot, W Gross, T Hauser, B Hellmich, D Jayne, C G M Kallenberg, P A Merkel, H Raspe, C Salvarani, D G I Scott, C Stegeman, R Watts, K Westman, J Witter, H Yazici, R Luqmani
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.
Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States
Authors: Fang Fang, Nancy L. Keating, Lorelei A. Mucci, Hans-Olov Adami, Meir J. Stampfer, Unnur Valdimarsdóttir, Katja Fall
Journal: JNCI Journal of the National Cancer Institute (2010)

Receiving a cancer diagnosis is a stressful event that may increase risks of suicide and cardiovascular death, especially soon after diagnosis.We conducted a cohort study of 342,497 patients diagnosed with prostate cancer from January 1, 1979, through December 31, 2004, in the Surveillance, Epidemiology, and End Results Program. Follow-up started from the date of prostate cancer diagnosis to the end of first 12 calendar months after diagnosis. The relative risks of suicide and cardiovascular death were calculated as standardized mortality ratios (SMRs) comparing corresponding incidences among prostate cancer patients with those of the general US male population, with adjustment for age, calendar period, and state of residence. We compared risks in the first year and months after a prostate cancer diagnosis. The analyses were further stratified by calendar period at diagnosis, tumor characteristics, and other variables.During follow-up, 148 men died of suicide (mortality rate = 0.5 per 1000 person-years) and 6845 died of cardiovascular diseases (mortality rate = 21.8 per 1000 person-years). Patients with prostate cancer were at increased risk of suicide during the first year (SMR = 1.4, 95% confidence interval [CI] = 1.2 to 1.6), especially during the first 3 months (SMR = 1.9, 95% CI = 1.4 to 2.6), after diagnosis. The elevated risk was apparent in pre-prostate-specific antigen (PSA) (1979-1986) and peri-PSA (1987-1992) eras but not since PSA testing has been widespread (1993-2004). The risk of cardiovascular death was slightly elevated during the first year (SMR = 1.09, 95% CI = 1.06 to 1.12), with the highest risk in the first month (SMR = 2.05, 95% CI = 1.89 to 2.22), after diagnosis. The first-month risk was statistically significantly elevated during the entire study period, and the risk was higher for patients with metastatic tumors (SMR = 3.22, 95% CI = 2.68 to 3.84) than for those with local or regional tumors (SMR = 1.57, 95% CI = 1.42 to 1.74).A diagnosis of prostate cancer may increase the immediate risks of suicide and cardiovascular death.
A Phase I Clinical Trial of the Sequential Combination of Irinotecan Followed by Flavopiridol
Authors: Manish A. Shah, Jeremy Kortmansky, Monica Motwani, Marija Drobnjak, Mithat Gonen, Sandy Yi, Amanda Weyerbacher, Carlos Cordon-Cardo, Robert Lefkowitz, Baruch Brenner, Eileen O'Reilly, Leonard Saltz, William Tong, David P. Kelsen, Gary K. Schwartz
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Flavopiridol potently enhances the effect of irinotecan with cures in colorectal cancer xenografts, and is associated with modulation of several molecular targets, including p21, Differentiation-related gene 1 (Drg1), and p53. We initiated a phase I trial of the sequential combination of irinotecan followed by flavopiridol to determine the maximal tolerated dose of this combination therapy. Patients and Methods: Forty-five patients with advanced solid tumors were enrolled. Irinotecan was administered first (100 or 125 mg/m2) followed 7 hours later by escalating flavopiridol (10-70 mg/m2) given weekly over 1 hour for 4 of 6 weeks. At the maximal tolerated dose, the pharmacokinetic analysis was expanded and pre- and posttreatment tumor biopsies were done. Results: At irinotecan 100 mg/m2, dose-limiting diarrhea and myelosuppression were observed with flavopiridol 70 mg/m2. At irinotecan 125 mg/m2, we observed dose-limiting hyperbilirubinemia, fatigue, and myelosuppression at flavopiridol 60 mg/m2. Peak flavopiridol concentrations of ≥2 μmol/L were achieved above flavopiridol 50 mg/m2. No significant pharmacokinetic interactions with irinotecan were noted. Baseline serum bilirubin significantly predicted cycle 1 dose-limiting toxicity and neutropenia. We observed partial responses in three patients and prolonged stable disease (i.e., &amp;gt;6 months) in 36% of patients including adrenocortical cancer and hepatocellular cancer. Patients with wild-type p53 and either no change or low posttreatment biopsy p21 and a decrease in Drg1 expression showed stable or responsive disease to the combination therapy. Conclusions: The recommended phase II dose with irinotecan 100 mg/m2 is flavopiridol 60 mg/m2 and with irinotecan 125 mg/m2 is flavopiridol 50 mg/m2. Toxicity can be predicted by baseline bilirubin. Clinical activity is encouraging and may correlate to changes in p21 and Drg1 levels in patients with wild type p53 tumors following therapy.
Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses
Authors: Hideo Negishi, Hideyuki Yanai, Akira Nakajima, Ryuji Koshiba, Koji Atarashi, Atsushi Matsuda, Kosuke Matsuki, Shoji Miki, Takahiro Doi, Alan Aderem, Junko Nishio, Stephen T Smale, Kenya Honda, Tadatsugu Taniguchi
Journal: Nature Immunology (2012)
Epigenetic regulation of adult neural stem cells: implications for Alzheimer’s disease
Authors: Carlos P Fitzsimons, Emma van Bodegraven, Marijn Schouten, Roy Lardenoije, Konstantinos Kompotis, Gunter Kenis, Mark van den Hurk, Marco P Boks, Caroline Biojone, Samia Joca, Harry WM Steinbusch, Katie Lunnon, Diego F Mastroeni, Jonathan Mill, Paul J Lucassen, Paul D Coleman, Daniel LA van den Hove, Bart PF Rutten
Journal: Molecular Neurodegeneration (2014)

Experimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those encoding for small non-coding RNAs, indicating a complex interplay between various epigenetic factors and cellular functions. Previous studies had indicated that in addition to the neuropathology in Alzheimer's disease (AD), plasticity-related changes are observed in brain areas with ongoing neurogenesis, like the hippocampus and subventricular zone. Given the role of stem cells e.g. in hippocampal functions like cognition, and given their potential for brain repair, we here review the epigenetic mechanisms relevant for NSCs and AD etiology. Understanding the molecular mechanisms involved in the epigenetic regulation of adult NSCs will advance our knowledge on the role of adult neurogenesis in degeneration and possibly regeneration in the AD brain.
Alternative method of positioning the pH probe for oesophageal pH monitoring.
Authors: A Anggiansah, N Bright, M McCullagh, K Sumboonnanonda, W J Owen
Journal: Gut (1992)

The most reliable method of positioning a pH probe for oesophageal pH monitoring is to use manometry to determine the upper margin of the lower oesophageal sphincter and to place the probe 5 cm above this point. Manometry is expensive, however, requires special equipment and training, and is not widely available. An alternative cheaper way of determining the site of the lower oesophageal sphincter has been evaluated. A fine bore nasogastric tube with a latex balloon at its tip was inserted transnasally into the stomach. The balloon was inflated with 10 ml of water and the tube withdrawn until resistance was met. The distance from the nose (in cm) was noted and compared with the upper margin of the lower oesophageal sphincter as determined by oesophageal manometry. The manometric distance agreed closely with the balloon distance minus 1 cm (bias 0.29 cm; 95% CI of bias, 0.03 to 0.55 cm; 2 SD, limits of agreement, 1.58 cm). We conclude that where oesophageal manometry is not available, balloon localisation is a suitably accurate way of identifying the lower oesophageal sphincter.
Multicenter, Randomized, Controlled Trial of 150-J Biphasic Shocks Compared With 200- to 360-J Monophasic Shocks in the Resuscitation of Out-of-Hospital Cardiac Arrest Victims
Authors: Thomas Schneider, Patrick R. Martens, Hans Paschen, Markku Kuisma, Benno Wolcke, Bradford E. Gliner, James K. Russell, W. Douglas Weaver, Leo Bossaert, Douglas Chamberlain
Journal: Circulation (2000)

In the present study, we compared an automatic external defibrillator (AED) that delivers 150-J biphasic shocks with traditional high-energy (200- to 360-J) monophasic AEDs.AEDs were prospectively randomized according to defibrillation waveform on a daily basis in 4 emergency medical services systems. Defibrillation efficacy, survival to hospital admission and discharge, return of spontaneous circulation, and neurological status at discharge (cerebral performance category) were compared. Of 338 patients with out-of-hospital cardiac arrest, 115 had a cardiac etiology, presented with ventricular fibrillation, and were shocked with an AED. The time from the emergency call to the first shock was 8.9+/-3.0 (mean+/-SD) minutes.The 150-J biphasic waveform defibrillated at higher rates, resulting in more patients who achieved a return of spontaneous circulation. Although survival rates to hospital admission and discharge did not differ, discharged patients who had been resuscitated with biphasic shocks were more likely to have good cerebral performance.
Evaluation of the effectiveness of anterior cruciate ligament injury prevention programme training components: a systematic review and meta-analysis
Authors: Jeffrey B Taylor, Justin P Waxman, Scott J Richter, Sandra J Shultz
Journal: British Journal of Sports Medicine (2013)

Background Anterior cruciate ligament (ACL) injury prevention programmes have shown mixed results, which may be due to differing emphasis on training components. The purpose of this study was to (1) quantify the overall and relative duration of each training component encompassed within these programmes and (2) examine the effect of these durations on ACL injury rates. Methods A systematic review was completed and meta-analyses performed on eligible studies to produce a pooled OR estimate of the effectiveness of these programmes. Meta-regression was used to detect any relationship that programme duration and the duration of individual training components had on ACL injury rates. Results 13 studies were included for review. Results of the meta-analyses revealed a significant reduction of injuries after preventative training programmes for all ACL injuries (pooled OR estimate of 0.612, 95% CI 0.44 to 0.85; p=0.004) and for non-contact ACL injuries (OR 0.351, 95% CI 0.23 to 0.54; p&lt;0.001). Results of meta-regression analysis revealed that a greater duration of balance training was associated with a higher injury risk for ACL injury (p=0.04), while greater durations of static stretching was associated with a lower injury risk for non-contact ACL injuries (p=0.04). Conclusions While ACL prevention programmes are successful in reducing the risk of ACL injury, the ideal combination and emphasis of training components within these programmes remains unclear. Evidence indicates that greater emphases on balance training and static stretching may be associated with an increase and decrease in injury risk, respectively.
Spontaneous liver rupture in Ehlers-Danlos syndrome type IV
Authors: Siew Chien Ng, Paolo Muiesan
Journal: Journal of the Royal Society of Medicine (2005)

drain was in the liver.At operation on day 11 the liver and bowel contents were returned to the abdomen and a small defect in the centre of the right diaphragm was repaired.He recovered without incident. COMMENTWe suspect that both twins initially had group B streptococcal sepsis.In twin 2, herniation of liver and bowel through the diaphragmatic defect (perhaps intermittent 1,2 ) then caused the pleural effusion by obstructing hepatic venous outflow and causing transudative weeping from the liver surface.The rapid onset of respiratory distress at day 9 was presumably due to the combined effects of the hernia and the effusion.4][5] One lesson of this case, which fortunately ended happily, is that a previously normal chest radiograph does not preclude the diagnosis of a delayed presentation of congenital diaphragmatic hernia.Moreover, evidence of mediastinal shift, as seen here with the feeding tube, must be taken seriously.These observations are not new: indeed, more than 20 years ago Akierman and Maycock 2 proposed that congenital diaphragmatic hernia should be considered in exactly these circumstances-when early-onset group B streptococcal infection is followed by a period of improvement and then increased respiratory distress, right-sided pleural effusion and partial or complete opacification of the right side of the thorax associated with mediastinal shift to the left.
Effect of platelet-activating factor on microvascular permselectivity: dose-response relations and pathways of action in the hamster cheek pouch microcirculation.
Authors: P K Dillon, W N Durán
Journal: Circulation Research (1988)

Platelet-activating factor (PAF) has recently been described as a mediator of inflammatory processes. In this study, we quantitated the dose-response effects of topically applied PAF on microvascular permselectivity and investigated the biochemical pathways of this compound. Permselectivity alterations were assessed by measuring the clearance of macromolecules with fluorescein isothiocyanate dextran 150 (FITC-dx 150) as a tracer. The microvascular bed of the hamster cheek pouch served as a model. PAF was found to induce leakage of macromolecules from postcapillary venules. Control FITC-dx 150 plasma clearance (+/- SEM) was 72 +/- 10 nl/90 min. Clearances of 61 +/- 10 474 +/- 145, 622 +/- 57, 301 +/- 86, and 142 +/- 3 nl/90 min were obtained at PAF concentrations of 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M, respectively. A one-way analysis of variance showed that the population means were not equal. Multiple comparison by the Student-Newman-Keuls test demonstrated that the clearances obtained with 10(-8), 10(-7), and 10(-6) M were significantly greater than controls. Significant differences existed between 10(-7) M PAF and 10(-9), 10(-6), and 10(-5) M PAF. In an effort to elucidate the biochemical pathways of PAF activity, several inhibitors of the arachidonic acid cascade and receptor blockers were used. Dexamethasone and kadsurenone attenuated the clearance response to PAF in a statistically significant manner, while indomethacin, OKY-046, and chlorpheniramine were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Letter by van Gelder and Bracke Regarding Article, “Left Ventricular Versus Simultaneous Biventricular Pacing in Patients With Heart Failure and a QRS Complex &gt;120 Milliseconds”
Authors: Berry M. van Gelder, Frank A. Bracke
Journal: Circulation (2012)

We read with interest the article by Thibault et al 1 comparing the effect of left ventricular (LV) pacing versus simultaneous biventricular pacing, a study with a crossover design between both pacing modes.Submaximal exercise was used as an elegant method of qualification of the clinical response.The optimal atrioventricular intervals (atrial sensed-ventricular paced and atrial paced-ventricular paced) were determined during LV pacing and defined as the longest atrioventricular interval that fully captured the ventricle (no fusion with intrinsic conduction).This atrioventricular delay was used for LV and biventricular pacing, along with the rate-adaptive atrioventricular delay feature, and was kept constant during the study.However, acute optimal hemodynamic effect of LV pacing is obtained with a longer atrioventricular interval, enabling fusion between LV pacing and intrinsic conduction over the right bundle, which is superior to optimized simultaneous biventricular pacing. 2,3his implies that LV pacing is performed under suboptimal conditions with a relative short atrioventricular interval, which also will be true for biventricular simultaneous pacing using the same atrioventricular interval.The aspect of fusion during LV pacing, which makes an important contribution to the effect of LV pacing, is not taken into consideration.The atrioventricular interval is determined only at the start of the study and kept constant for the duration of the study.This implies that the presence or absence of fusion during LV pacing is not checked at the time of crossover and that changes in intrinsic atrioventricular conduction may lead to fusion with LV pacing and an improved hemodynamic response.A second aspect is the activation of the rate-adaptive atrioventricular delay feature, which automatically shortens the atrioventricular interval at increasing heart rates.A study by Mokrani et al 4 demonstrated that optimization of the atrioventricular delay during exercise had a positive effect on echocardiographic indices of LV function.However, systematic shortening of the atrioventricular delay during exercise was not recommended because the optimal atrioventricular delay was longer during exercise than at rest in a high proportion of patients.According to these findings, activation of the rate-adaptive atrioventricular delay might have a negative effect on exercise capacity in a considerable number of patients.Ventriculo-ventricular optimization was not performed because randomized clinical trials have failed to demonstrate clinical benefit.
A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging
Authors: A.N. Cookson, J. Lee, C. Michler, R. Chabiniok, E. Hyde, D. Nordsletten, N.P. Smith
Journal: Medical Image Analysis (2014)

Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters, instead the contrast agents should be tailored to the specific imaging protocol and post-processing method to be used.