Perioperative and postoperative predictors of outcome in patients with low ejection fraction early after coronary artery bypass grafting: the additional value of left ventricular remodeling

BACKGROUND: Scant data exist on factors that may identify outcome in patients with severe left ventricular (LV) dysfunction early after coronary artery bypass graft surgery (CABG). DESIGN: This study was designed to determine the prognostic value of clinical, operative, and postoperative factors in patients with LV dysfunction early after CABG. METHODS: In 333 consecutive patients with ejection fraction < or =35% on admission to residential cardiac rehabilitation after isolated CABG, potential preoperative, perioperative, and postoperative predictors of outcome, including 6-month LV remodeling, were recorded and patients followed up for a median of 3 years. The study end points were cardiovascular (CV) mortality and the combination of CV mortality and nonfatal CV events requiring hospitalization. RESULTS: The 3-year CV mortality-free survival and survival free of nonfatal CV event rates were 87 and 73%, respectively. Independent predictors of CV mortality were history of congestive heart failure [hazard ratio, HR: 2.8; 95% Confidence Interval (CI): 1.51-5.21], low ejection fraction on admission to cardiac rehabilitation (HR: 0.9; 95% CI: 0.87-0.96), and early complications after CABG (HR: 2.5; 95% CI: 1.23-5.15). When the combined end points were considered, postoperative left atrial size (HR: 1.07; 95% CI: 1.01-1.11), New York Heart Association class III or IV (HR: 1.69; 95% CI: 1.04-2.74), and 6-month remodeling (HR: 2.12; 95% CI: 1.33-3.36) were independent predictors. CONCLUSION: Simple preoperative and postoperative variables may help identify patients with LV dysfunction early after CABG who are still at risk of major CV events. In this setting, 6-month LV remodeling is a strong predictor of a poor prognosis.     

Responses of the rabbit epicardial coronary artery to acetylcholine and adrenoceptor agonists.

STUDY OBJECTIVE--The aim was to identify the role of the endothelium in mediating the responses to acetylcholine in the rabbit coronary artery, and to determine whether alpha or beta adrenergic stimulation may cause relaxation via endothelial receptors in the coronary arteries of this species. DESIGN--Responses to acetylcholine and adrenoceptor agonists were compared in isolated ring preparations with and without endothelium. The adrenoceptor agonists were examined in the presence of phentolamine or propranolol to block alpha and beta adrenoceptors, respectively. EXPERIMENTAL MATERIAL--30 New Zealand white rabbits (2.3-3.4 kg) were killed by an overdose of barbiturate and exsanguination, and the left epicardial coronary artery was dissected free. Ring preparations were suspended in organ baths under isometric tension and, where required, the tone of the preparations was raised by KC1. MEASUREMENTS AND MAIN RESULTS--Concentrations of acetylcholine up to 10(-6) mol.litre-1 produced dose dependent relaxation of the preparations with endothelium intact, but no relaxation in preparations denuded of endothelium. At higher concentrations, a marked vasoconstrictor response was seen in all preparations regardless of the presence of endothelium. At basal tone, acetylcholine produced vasoconstriction which reached a maximum of 1.0 (SEM 0.14)g tension in preparations with endothelium and 1.74(0.27) g tension in those without endothelium (p less than 0.05). In coronary arteries pretreated with 50 mumol.litre-1 phenoxybenzamine to block alpha adrenoceptors, noradrenaline, isoprenaline, and salbutamol produced dose dependent relaxation of the preparations; this was unaffected by the absence of endothelium. In vessels not pretreated with phenoxybenzamine, propranolol inhibited the relaxation to noradrenaline and isoprenaline but again there was no difference between vessels with and without endothelium. CONCLUSIONS--In the rabbit isolated epicardial coronary artery, acetylcholine produces an endothelium dependent relaxant response over a limited concentration range; a vasoconstrictor response via smooth muscle dominates at higher concentrations. beta Adrenoceptors mediating relaxation are present on the smooth muscle, but there was no evidence for either alpha or beta adrenoceptor mediated responses via the endothelium. Important differences with coronary arteries from other species are discussed.     

p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells

OBJECTIVE: Thyrotropin activates the cAMP pathway in thyroid cells, and stimulates cell cycle progression in cooperation with insulin or insulin-like growth factor-I. Because p38 mitogen-activated protein kinases (p38 MAPKs) were stimulated by cAMP in the FRTL-5 rat thyroid cell line, we investigated (i) the effect of the specific inhibition of p38 MAPKs on FRTL-5 cell proliferation and (ii) the mechanism of action of p38 MAPKs on cell cycle control, by studying the expression and/or the activity of several cell cycle regulatory proteins in FRTL-5 cells. METHODS: DNA synthesis was monitored by incorporation of [(3)H]thymidine into DNA and the cell cycle distribution was assessed by fluorescence-activated cell sorter analysis. Expression of cell cycle regulatory proteins was determined by Western blot analysis. Cyclin-dependent kinase 2 (Cdk2) activity associated to cyclin E was immunoprecipitated and was measured by an in vitro kinase assay. RESULTS: SB203580, an inhibitor of alpha and beta isoforms of p38 MAPKs, but not its inactive analog SB202474, inhibited DNA synthesis and the G1-S transition induced by forskolin plus insulin. SB203580 inhibited specifically p38 MAPK activity but not other kinase activities such as Akt and p70-S6 kinase. Treatment of FRTL-5 cells with SB203580 decreased total and cyclin E-associated Cdk2 kinase activity stimulated with forskolin and insulin. However, inhibition of p38 MAPKs by SB203580 was without effect on total cyclin E and Cdk2 levels. The decrease in Cdk2 kinase activity caused by SB203580 treatment was not due to an increased expression of p21(Cip1) or p27(Kip1) inhibitory proteins. In addition, SB203580 affected neither Cdc25A phosphatase expression nor Cdk2 Tyr-15 phosphorylation. Inhibition of p38 MAPKs decreased Cdk2-cyclin E activation by regulating the subcellular localization of Cdk2 and its phosphorylation on Thr-160. CONCLUSIONS: These results indicate that p38 MAPK activity is involved in the regulation of cell cycle progression in FRTL-5 thyroid cells, at least in part by increasing nuclear Cdk2 activity.     

Spontaneous rupture of the spleen in chronic calcifying pancreatitis: report of three cases

Spontaneous rupture of the spleen is a rare complication of chronic calcifying pancreatitis. Anemia and hemorrhagic shock may not occur, making diagnosis more difficult. Favourable response to conservative treatment does not prevent the need for splenectomy, as calcifiying chronic pancreatitis may progress locally. We report three cases of spontaneous rupture of the spleen. In two cases, splenic rupture revealed calcifying chronic pancreatitis and both patients underwent urgent splenectomy. In the third case, the patient was known to have calcifying chronic pancreatitis, and splenectomy was performed because of unsuccessful conservative treatment. We discuss the role of distal pancreatectomy during splenectomy to reduce the rate of postoperative complications and additional surgery. We also discuss the role of arterial embolisation and laparoscopy in the management of this rare condition.     

Chronic Chagas' heart disease in children and adolescents: a clinicopathologic study

A retrospective study of the medical records filed at the University Hospital from 1965 to 1983 and of 18456 autopsies carried out in the Department of Pathology of this Institution from 1953 to 1983, referring to patients aged less than 18 years was performed in an attempt to fully characterize chronic Chagas' heart disease in children and adolescents. Only 19 of these patients fulfilled the criteria for inclusion in the present study (12 cases with only clinical information and 7 cases with clinical and pathological information). We noted that the clinical manifestations of chronic Chagas' heart disease are congestive heart failure, thromboembolism and sudden death. Radiologic, electrocardiographic and anatomo-pathological findings demonstrated serious myocardial involvement. This set of alterations is also detected in adults with chronic Chagas' heart disease. Among adolescents, however, the disease exhibits relevant peculiarities such as rapid evolution to death within a short period of time (128 days), diagnostic difficulty related to the presence of significant mitral regurgitation (61% erroneous initial diagnosis), and low frequency of right bundle branch block (11% of cases). These findings suggest that among children and adolescents, chronic Chagas' heart disease may be of a peculiar type and therefore may be useful to clarify the pathogenetic mechanism of the disease.     

Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure.

Cardiopulmonary exercise testing (CPET) provides a global assessment of the integrated response to exercise involving the pulmonary, cardiovascular, haematopoietic, neuropsychological, and skeletal muscle systems. This information cannot be obtained through investigation of the individual organ systems in isolation. The non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the physician with relevant information for clinical decision making. The use of CPET in management of the chronic heart failure patient is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that, furthermore, overall health status and prognosis are predicted better by indices of exercise tolerance than by resting measurements. Our aim is to produce a statement which provides recommendations on the interpretation and clinical application of CPET in heart failure, based on contemporary scientific knowledge and technical advances: the focus is on clinical indications, issues of standardization, and interpretative strategies for CPET.     

The anaerobic index: uses and limitations in the assessment of heart failure

Limitation of exercise tolerance is a hallmark of heart failure. Anaerobic threshold is a quantitative, reproducible, nonmotivational, submaximal index of exercise tolerance. The pathophysiological significance and methods of determination of anaerobic threshold are matters of debate. The principal aspects of such problems are discussed in this paper.     

Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta‐analysis

Aims

To conduct a systematic review and meta‐analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past‐month marijuana use prevalence among adolescents.

Methods

A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta‐analyzed. Estimates of MML effects on any past‐month marijuana use prevalence from included studies were obtained from comparisons of pre–post MML changes in MML states to changes in non‐MML states over comparable time‐periods. These estimates were standardized and entered into a meta‐analysis model with fixed‐effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F‐test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed.

Results

None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. The meta‐analysis yielded a non‐significant pooled estimate (standardized mean difference) of ?0.003 (95% confidence interval = ?0.012, +0.007). Four studies compared MML with non‐MML states on pre‐MML differences and all found higher rates of past‐month marijuana use in MML states pre‐MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non‐significant results, although limited heterogeneity may warrant further study.

Conclusions

Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.

     

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.