Intermittent outpatient ultrafiltration for the treatment of severe refractory congestive heart failure

BACKGROUND: Patients with severe congestive heart failure (CHF) become refractory to conventional medical therapy, leading to recurrent rehospitalizations. We examined the impact of intermittent outpatient ultrafiltration (UF), using either peritoneal dialysis or hemofiltration, on long-term clinical outcomes in patients with refractory CHF. METHODS AND RESULTS: We analyzed clinical and hemodynamic data in 19 consecutive patients with refractory CHF who received intermittent outpatient UF for at least 1 year between July 1998 and November 2002. The mean left ventricular ejection fraction of all 19 patients was 30.2 +/- 19.0%. All patients (100.0%) were New York Heart Association (NYHA) class IV. Only 5 patients (26.3%) received peritoneal dialysis; the remaining 14 (73.7%) received hemofiltration. There were 6 patients with a normal left ventricular ejection fraction (45%). After UF was started, the number of patients that were considered inotrope-dependent was reduced from 86.4% to 36.8% (P < .005). Compared with the year before UF was initiated, the number of CHF hospitalizations during follow-up was reduced from 2.6 to 0.3 (P < .005), and the NYHA class was improved from 4 to 3.1 (P < .005). Among all patients, 2 deaths were related to complications of UF, and cumulative 1-year survival was 63.2%. CONCLUSION: Our study suggests that UF is a safe, feasible therapy, but it needs further evaluation in carefully designed, prospective, randomized clinical trials. UF has the potential for offering another important therapeutic option for patients with severe and refractory CHF.     

Prognosis for the newborn with transposition of the great arteries

To determine the prognosis for the newborn with transposition of the great arteries, the clinical course of 112 consecutive neonates with dextro-transposition was reviewed. Patients were managed with balloon atrial septostomy at initial cardiac catheterization, palliative operation if needed in the 1st year of life and Mustard's intraatrial baffle repair.The 1st month of life was the period of greatest risk (8 percent mortality rate). Between balloon septostomy and baffle repair, 14 of 103 patients at risk (14 percent) either died or had a cerebrovascular accident. The mortality rate at baffle repair was 14 percent (10 deaths in 71 patients), and there were 3 late postoperative deaths. Actuarial analysis of the data indicates that with this plan of management, approximately 50 percent of newborns with transposition of the great arteries will survive 5 years with excellent function and an additional 15 to 20 percent will survive with one or more medical handicaps.     

Helicobacter pylori and gastric cancer

Gastric cancer despite a declining incidence remains a significant cause of morbidity and mortality world wide. There is strong epidemiological and histological evidence to associate Helicobacter pylori infection with the subsequent development of gastric cancer. The exact pathophysiological mechanisms involved remain to be elucidated. There is evidence to relate Helicobacter pylori infection and subsequent inflammation with an increase in gastric epithelial cell proliferation and with the induction of apoptosis. Such alterations in cellular dynamics may promote the development of mitogenic cell lines by inducing DNA damage. Studies have shown that following successful treatment, proliferation rates return to normal. At what histological stage, eradication is of benefit is less clear. It is likely that following the development of atrophy or intestinal metaplasia eradication will only slow progression. It would, therefore, seem logical, that to establish any benefit for a population, treatment should be employed at an earlier stage. As yet, an at risk group has not been identified, and as such population screening cannot be advised, mainly as a result of financial implications and the risk of promoting the development of resistant strains. Recent studies have explored the rules of bacterial factors, CagA and VacA status, host factors, HLA type, and environmental factors as determinants of outcome. Results have been variable. The establishment of an at risk group would enable selective screening and treatment, and thus prevent the development of gastric carcinoma as a result of Helicobacter pylori infection in the long-term.     

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: Transgenic rescue and interactions with gene background

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an ≈50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKC expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKC expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes.     

Dicarbonyl Electrophiles Mediate Inflammation-Induced Gastrointestinal Carcinogenesis

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Exercise assessment of sinoatrial node function following the Mustard operation

To screen for sinoatrial node dysfunction following the Mustard procedure for transposition of the great arteries, we studied the chronotropic response to graded maximal treadmill exercise in 29 patients at mean 6.7 years after operation. Although 93% of patients had normal resting heart rate (HR), 83% demonstrated significant depression of maximum HR and/or recovery HR after termination of exercise. These findings were similarly present among a subset of 13 patients with normal exercise tolerance. Resting and exercise-induced HR in 10 patients receiving chronic digoxin therapy were no different than in the 19 patients without medication. Sixteen patients with abnormal chronotropic responses to exercise had intracardiac electrophysiologic evaluation which confirmed sinoatrial node dysfunction in nine. Abnormal HR responses did not correlate with clinical symptoms, cardiac arrhythmias, or postoperative hemodynamics. Maximal exercise testing may be a sensitive noninvasive method to identify sinoatrial node dysfunction in postoperative children.     

Anomalous origin of left coronary artery from the pulmonary artery with ventricular septal defect

Only two cases have been reported previously of the association of ventricular septal defect (VSD) with anomalous origin of the left coronary artery (ALCA) arising from the pulmonary artery. The purpose of this paper is to present two additional cases, to describe the pathophysiology, and to emphasize how the clinical course of this combination of defects differs from that of isolated ALCA. Patients with both of these anomalies present in infancy with manifestations only of a large left-right ventricular shunt and pulmonary hypertension. Initially the ALCA is well perfused from the high pressure in the pulmonary artery. In these instances in which the pulmonary artery pressure subsequently decreased because of spontaneous reduction in size of the VSD, the left coronary arterial system became less well perfused. Because of this decreased perfusion in association with the left ventricular myocardial stress initially caused by volume overload, myocardial ischemia and ultimately infarction occurred. Early identification and repair of the anatomic abnormality could prevent irreversible myocardial damage.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.