Pulmonary vein total occlusion following catheter ablation for atrial fibrillation: clinical implications after long-term follow-up.

OBJECTIVES: We present the clinical course and management outcomes of patients with total pulmonary vein occlusion (PVO). BACKGROUND: Pulmonary vein occlusion is a rare complication that can develop after radiofrequency catheter ablation (RFA) of atrial fibrillation (AF). The long term follow-up data of patients diagnosed with PVO are minimal. METHODS: Data from 18 patients with complete occlusion of at least one pulmonary vein (PV) were prospectively collected. All patients underwent RFA for AF using different strategies between September 1999 and May 2004. Pulmonary vein occlusion was diagnosed using computed tomography (CT) and later confirmed by angiography when intervention was warranted. Lung perfusion scans were performed on all patients before and after intervention. The percent stenoses of the veins draining each independent lung were added together to yield an average cumulative stenosis of the vascular cross-sectional area draining the affected lung (cumulative stenosis index [CSI]). RESULTS: The patients' symptoms had a positive correlation with the CSI (r = 0.843, p < 0.05) and a negative one with the lung perfusion (r = -0.667, p < 0.05). A CSI > or =75% correlated well with low lung perfusion (<25%; r = -0.854, p < 0.01). Patients with a CSI > or =75% appeared to improve mostly when early (r = -0.497) and repeat dilation/stenting (r = 0.0765) were performed. CONCLUSIONS: Patients with single PVO are mostly asymptomatic and should undergo routine imaging. On the other hand, patients with concomitant ipsilateral PV stenosis/PVO and a CSI > or =75% require early and, when necessary, repeated pulmonary interventions for restoration of pulmonary flow and prevention of associated lung disease.     

Association of extent and infection of pancreatic necrosis with organ failure and death in acute necrotizing pancreatitis.

BACKGROUND & AIMS: Organ failure is the usual cause of death in acute necrotizing pancreatitis. Our objective was to study whether the extent and infection of pancreatic necrosis correlate with organ failure and mortality. METHODS: All consecutive patients with acute pancreatitis were prospectively studied. They underwent a detailed clinical and investigative evaluation. Pancreatic necrosis, diagnosed on a computed tomography scan, was graded as <30%, 30%-50%, and >50% necrosis and characterized as either sterile or infected. Logistic regression analysis was done to find out the association of the extent and infection of pancreatic necrosis with organ failure and mortality. RESULTS: Of 276 patients (mean age, 41.25 years; 172 men), 104 had pancreatic necrosis: 30 had <30% necrosis, 37 had 30%-50% necrosis, and 37 had >50% necrosis; 74 had sterile necrosis, and 30 had infected necrosis. Of them, 37 (35%) patients developed organ failure. Two significant factors were associated with the development of organ failure, the extent of necrosis (<30% necrosis vs 30%-50% necrosis: P = .03; odds ratio [OR], 5.82; 95% confidence interval [CI], 1.15-29.45; <30% necrosis vs >50% necrosis: P = .0004; OR, 18.86; 95% CI, 3.75-94.92) and infected pancreatic necrosis (P = .02; OR, 3.29; 95% CI, 1.17-9.24). The overall mortality was 22%. Infected pancreatic necrosis (P = .006; OR, 4.99; 95% CI, 1.56-16.02) and Acute Physiology, Age, and Chronic Healthy Evaluation II score (P = .004; OR, 1.28; 95% CI, 1.08-1.52) were 2 independent predictors of mortality. CONCLUSIONS: Extent of necrosis and infected pancreatic necrosis were associated with the development of organ failure in patients with acute necrotizing pancreatitis. Infected pancreatic necrosis was the most significant predictor of mortality.     

Age- and sex-related analysis of methylation of 5′-upstream sequences of <Emphasis Type="Italic">Fmr-1</Emphasis> gene in mouse brain and modulation by sex steroid hormones

Fmr-1 gene is implicated in synaptic plasticity and thereby learning, memory and cognition, and methylation of Fmr-1 gene is necessary for memory development that is an age-dependent phenomenon. Aging in general has been reported to affect methylation of gene, however, nothing is known on the age dependent variation in methylation of Fmr-1 gene. Using the brain tissues from male and female mice of various age groups and sex steroid hormones (testosterone or 17beta-estradiol) as modulators, restriction enzymes Hpa II and Msp I and Southern blotting technique, we studied methylation of 5'-upstream sequences of Fmr-1 gene. Our data reveal that the methylation of the 5'-upstream sequences that include CpG islands in promoter and 5'-untraslated region (5'-UTR) gradually increases due to advancing age in both the sexes. 17beta-estradiol lowers the methylation significantly in the brain of mouse of both male and female mouse in age-dependent manner where as testosterone does not affect it appreciably. The alteration in the methylation may be attributed to altered DNA methyl transferase (DNMT) activity as the age increases from young to old, and the 17beta-estradiol may down regulate the DNMT activity in both the age and sex groups whereas the testosterone may not have similar effect on DNMT. Down regulation of methylation of Fmr-1 CpG island and/or 5'-UTR by 17beta-estradiol might lead to derepression of Fmr-1 gene especially in old age. This finding on Fmr-1 methylation is novel and it might have implications in understanding fragile X related disorders and age-dependent alteration in LTP and LTD.     

Effects of chronic digoxin treatment on cardiac function, electrolytes, and sarcolemmal ATPase in the canine failing heart due to chronic mitral regurgitation

This study was designed to determine whether digoxin therapy in the canine heart failing because of mitral regurgitation (MR) provides only hemodynamic benefit and accompanying subjective improvement or if it also reverses the changes in intracellular Ca++ and sarcolemmal Na+-K+-ATPase. The dogs were divided into four groups: control, MR of 3 months' duration, MR of 6 months', and digoxin treatment for 3 months after 3 months of MR. Six months of MR produced a marked decrease in the index of myocardial contractility and function associated with a decrease in intracellular Ca++ and Na+, and an increase in intracellular K+, extracellular space, sarcolemmal Na+-K+-ATPase, and Mg++-ATPase. Digoxin treatment tended to return the changes in the index of myocardial contractility and cardiac function, intracellular Ca++, Na+, K+, extracellular space, and sarcolemmal Na+-K+-ATPase of the failing heart toward control levels. Digoxin treatment did not affect Mg++-ATPase. The right ventricle, which did not fail, also did not show any significant changes in the parameters measured. The results showed that digoxin treatment not only improved the index of myocardial contractility and cardiac function of the failing heart but also tended to return the electrolytes and sarcolemmal Na+-K+-ATPase toward control levels.     

Study of duodenal ulcer disease in 100 families using total serum pepsinogen as a genetic marker

Although various markers have been used in attempts to elucidate the mode of inheritance of duodenal ulcer, they have not significantly contributed to a clear understanding of the problem. In the present study total serum pepsinogen was used as a genetic marker and its concentrations were estimated in 100 ulcer patients and their family members up to three generations. Eighty three per cent of the ulcer patients had hyperpepsinogenaemia on a familial basis, and it followed an autosomal dominant mode of inheritance. Thus a large majority of ulcer patients have associated hyperpepsinogenaemia which forms a genetic basis of their disease. The remaining 17% ulcer patients did not have associated hyperpepsinogenaemia nor was the ulcer inherited by the family. Based on these observations we wish to suggest that duodenal ulcer associated with hyperpepsinogenaemia may be considered a genetic disease. This type may be termed 'primary duodenal ulcer'. In the remaining patients without hyperpepsinogenaemia or affected relatives the ulcer may be called 'secondary duodenal ulcer'. Thus total serum pepsinogen may be considered a reliable genetic marker in helping to delineate the genetic disorder from the non-genetic, thereby improving the predictive ability in duodenal ulcer.     

Past and current roles for cephalosporin antibiotics in treatment of meningitis: Emphasis on use in gram-negative bacillary meningitis

The therapy of gram-negative bacillary meningitis is less than adequate to date; the agents recommended do not achieve bactericidal levels in purulent cerebrospinal fluid. Because optimal antibiotic therapy of meningitis occurs when the cerebrospinal fluid level of an antibiotic is above the concentration needed to kill the offending pathogen, another group of agents needs to be considered. The newer cephalosporins or cehalosporin-type antibiotics (cefotaxime, moxalactam), by virtue of their marked activity against gram-negative bacilli and their ability to achieve significant CSF levels, merit serious consideration as therapy for gram-negative bacillary meningitis. Investigators in Europe and the United States have developed preliminary data demonstrating the efficacy of these agents in a growing number of cases. In the group presented herein, of the 35 cases in which gram-negative bacillary meningitis was treated with the newer cephalosporins, there were only four failures.