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Biomedical subjects

J S Wilson

Publications and source records attributed to J S Wilson.

At least 19 recordsLinked to original sources
PubMed1995

Balloon aortic valvuloplasty in adults: failure of procedure to improve long-term survival.

OBJECTIVES: This study sought to determine the long-term outcome of adult patients undergoing percutaneous balloon aortic valvuloplasty. BACKGROUND: Percutaneous balloon aortic valvuloplasty has been offered as an alternative to aortic valve replacement for selected patients with valvular aortic stenosis. Although balloon aortic valvuloplasty produces an immediate reduction in the transvalvular aortic gradient, a high incidence of restenosis frequently leads to recurrent symptoms. Therefore, it is unclear whether balloon aortic valvuloplasty impacts on the long-term outcome of these patients. METHODS: Clinical, hemodynamic and echocardiographic data were collected at baseline in 165 patients undergoing balloon aortic valvuloplasty and examined for their ability to predict long-term outcome. RESULTS: The median duration follow-up was 3.9 years (range 1 to 6). Ninety-nine percent follow-up was achieved. During this 6-year period, 152 patients (93%) died or underwent aortic valve replacement, and 99 (60%) died of cardiac-related causes. The probability of event-free survival (freedom from death, aortic valve replacement or repeat balloon aortic valvuloplasty) 1, 2 and 3 years after valvuloplasty was 40%, 19% and 6%, respectively. In contrast, the probability of survival 3 years after balloon aortic valvuloplasty in a subset of 42 patients who underwent subsequent aortic valve replacement was 84%. Survival after aortic valvuloplasty was poor regardless of the presenting symptom, but patients with New York Heart Association functional class IV congestive heart failure had events earliest. Univariable predictors of decreased event-free survival were younger age, advanced congestive heart failure symptoms, lower ejection fraction, elevated left ventricular end-diastolic pressure, presence of coronary artery disease and increased left ventricular internal diastolic diameter. Stepwise multivariable logistic regression analysis found that only younger age and a lower left ventricular ejection fraction contributed independent adverse prognostic information (chi-square 14.89, p = 0.0006). CONCLUSIONS: Long-term event-free and actuarial survival after balloon aortic valvuloplasty is dismal and resembles the natural history of untreated aortic stenosis. Aortic valve replacement may be performed in selected subjects with good results. However, the prognosis for the remainder of patients who are not candidates for aortic valve replacement is particularly poor.

Aged↗
PubMed1995

Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography.

BACKGROUND: Although serotonin has been postulated as an etiologic agent in the development of carcinoid heart disease, no direct evidence for different ambient serotonin levels in cardiac and noncardiac patients has been reported to date. METHODS AND RESULTS: The present study reviews our experience with 604 patients in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart disease (by cardiac catheterization and/or echocardiogram) were compared with the remaining 585 noncardiac patients in the database with regard to circulating serotonin and its principal metabolite, 5-hydroxyindole acetic acid (5-HIAA). No significant demographic differences existed between the cardiac and noncardiac groups; however, typical carcinoid syndrome symptoms (ie, flushing and diarrhea) were almost threefold more common in the cardiac group (P < .001). Compared with the noncardiac group, heart disease patients demonstrated strikingly higher (P < .0001) mean serum serotonin (9750 versus 4350 pmol/mL), plasma serotonin (1130 versus 426 pmol/mL), platelet serotonin (6240 versus 2700 pmol/mg protein), and urine 5-HIAA (219 versus 55.3 mg/24 h) levels. The spectrum of heart disease among the 19 patients showed a strong right-sided valvular predominance, with tricuspid regurgitation being the most common valvular dysfunction (92% by cardiac catheterization; 100% by echocardiogram). CONCLUSIONS: These data suggest that serotonin plays a major role in the pathogenesis of the cardiac plaque formation observed in carcinoid patients.

Carcinoid Heart Disease↗
PubMed1995

Transesophageal echocardiographic assessment of reversal of systolic pulmonary venous flow in mitral stenosis.

Transesophageal echocardiography and diagnostic cardiac catheterization were performed in 36 patients with symptomatic mitral stenosis to assess the incidence and significance of systolic flow reversal in the pulmonary veins. Mitral regurgitation was graded by contrast ventriculography, and left atrial pressure was directly measured after transseptal puncture. Pulmonary venous flow was recorded with transesophageal Doppler imaging from the left upper pulmonary vein. Early systolic flow reversal was identified in 11 patients (31%) and began an average of 58 +/- 13 ms after QRS onset. This pattern correlated strongly with the presence of atrial fibrillation or flutter. Late systolic flow reversal was identified in 8 patients (22%), beginning an average of 245 +/- 46 ms after the QRS complex. These patients had higher left atrial V-wave pressure (36 +/- 10 vs 29 +/- 8 mm Hg; p < 0.05) and V-wave peak-X-descent trough (18 +/- 7 vs 11 +/- 5 mm Hg; p < 0.01) than patients without systolic flow reversal. Neither pattern of pulmonary venous flow reversal was related to the severity of angiographic mitral regurgitation. Systolic reversal of pulmonary venous flow is not specific for angiographically severe mitral regurgitation in patients with mitral stenosis. Similar limitations to pulmonary venous flow analysis likely apply to other patient groups with elevated left atrial pressure and poor left atrial compliance.

Adult↗
PubMed1995

The forgotten chamber: the importance of the right ventricle.

Historically, the right heart was viewed as less important than the left heart in the maintenance of normal overall hemodynamic performance. However, there is now considerable evidence that emphasizes the significance of intact right ventricular (RV) function. The RV's anatomy and physiology are reviewed in order to provide insight into how changes in volume can be accommodated within a low-pressure environment and how this contributes to hemodynamic stability. The interdependent relationship between the right and left ventricles is also explored. The contribution of RV performance to overall hemodynamics is best exemplified when the RV becomes diseased. RV infarction, atrial septal defect, and cor pulmonale are used as examples to illustrate the dramatic sequelae associated with RV dysfunction, as well as to identify the RV's specific adaptive mechanisms.

Heart Septal Defects, Atrial↗
PubMed1995

The effect of chronic alcohol administration on cerulein-induced pancreatitis.

Alcohol consumption i associated with pancreatitis, but the mechanism underlying this injury remains unclear. Alcohol consumption has recently been shown to increase the fragility of both rat pancreatic lysosomes and zymogen granules in vitro, which may predispose to autodigestion via the intracellular activation of digestive enzymes by lysosomal enzymes. Cerulein-induced pancreatitis is also associated with lysosomal fragility. To determine the effect of alcohol consumption on this form of pancreatic injury, the severity of pancreatitis was compared in three groups of rats following i.v. cerulein infusion: rats fed alcohol in a liquid diet, pair-fed dextrose controls, and chow-fed controls. The histological severity of pancreatitis induced by supramaximal cerulein infusion was not found to be increased by prior alcohol consumption. Since alcohol did not appear to increase the severity of pancreatic injury induced by cerulein, we sought to define biochemical parameters that might precede obvious injury. The subcellular distribution of cathepsin B activity and markers of lysosomal fragility were compared in the same groups of experimental animals. Cerulein infusion led to a marked redistribution of cathepsin B activity from the lysosomal to the zymogen-granule-enriched fractions.For animals killed in the fed state, a redistribution of cathepsin B activity toward the zymogen-granule-enriched fraction was also demonstrated in alcohol-fed animals compared to their pair-fed controls. However, chronic alcohol administration did not influence the effect of cerulein on subcellular cathepsin B distribution or lysosomal fragility. In this rat study, administration of alcohol did not increase the effects of supramaximal doses of cerulein on the pancreas.

Amylases↗
PubMed1995

Mechanism of inhibition of duck hepatitis B virus polymerase by (-)-beta-L-2',3'-dideoxy-3'-thiacytidine.

We have used the endogenous reverse transcriptase reaction of viral core particles from duck liver to elucidate the mechanism of inhibition of duck hepatitis B virus (DHBV) replication by the nucleoside analog (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC). As is the case in human immunodeficiency virus replication, 3TC-5'-triphosphate (3TC-TP) acts as a chain terminator for the DNA polymerase activities. The results of several different experiments support this conclusion, which explains the potent activity of 3TC against the hepadnaviruses. In isolated DHBV core particles, 3TC-TP inhibited the reverse transcriptase in a manner that resembled competitive inhibition with respect to dCTP. However, the kinetics of inhibition was not linear on a double-reciprocal plot for the highest concentrations of 3TC-TP and the lowest concentration of dCTP. This anomaly would be expected if binding to the nucleotide site was followed by DNA chain termination. Calculations that used only the linear part of the curve yielded a Ki of 0.78 +/- 0.10 microM 3TC-TP. The inhibition of core particles incubated in vitro with 3TC-TP was not reversed by removal of the free inhibitor. 3TC-TP inactivated the reverse transcriptase activity in a concentration-dependent manner. The Km of the chain termination reaction was calculated at 0.71 +/- 0.05 microM. Similar competitive kinetics and irreversible inhibition were also obtained on the endogenous DNA polymerase from viral particles from serum, suggesting that 3TC-TP also acts as a chain terminator of the DNA-directed DNA polymerase of DHBV replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of ethanol and protein deficiency on pancreatic digestive and lysosomal enzymes.

The pathogenesis of alcoholic pancreatitis is not fully understood. An increase in pancreatic digestive and lysosomal enzyme synthesis because of ethanol consumption could contribute to the development of pancreatic injury in alcoholics. This study aimed, firstly, to determine the effect of ethanol on the content and messenger RNA levels of pancreatic digestive enzymes and on the messenger RNA level of the lysosomal enzyme cathepsin B, and secondly, to examine the influence of concomitant protein deficiency (a known association of alcoholism and pancreatic injury) on these effects. A rat model of chronic ethanol administration was used in which rats were fed in groups of four, and for four weeks, protein sufficient and protein deficient diets with or without ethanol. Ethanol increased the pancreatic content of lipase but did not influence chymotrypsinogen or trypsinogen values. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in rats fed ethanol. Protein deficiency resulted in reduced tissue levels of lipase, chymotrypsinogen, and amylase but did not influence trypsinogen values. mRNA levels for proteases were increased in protein deficient rats, while those for lipase remained unaltered. Both ethanol and protein deficiency increased mRNA levels for cathepsin B. It is concluded that chronic ethanol consumption, in both protein sufficient and protein deficient states, increases the capacity of the pancreatic acinar cell to synthesise digestive and lysosomal enzymes.

Amylases↗
PubMed1995

Ethanol-induced alterations in messenger RNA levels correlate with glandular content of pancreatic enzymes.

Ethanol abuse is a well-known association of pancreatitis. The effects of chronic ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an important role in the development of pancreatic injury. The aims of this study were to determine the effects of ethanol on gene expression and glandular content of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen). Pancreatic content and mRNA levels for lipase, trypsinogen, and chymotrypsinogen were determined in rats that were pair-fed a nutritionally adequate liquid diet with or without ethanol for 4 weeks. mRNA levels for the lysosomal enzyme cathepsin B were also assessed in this model. Ethanol significantly increased the content of lipase in the pancreas. There was a trend toward an increase in trypsinogen and chymotrypsinogen levels; however, these differences were not statistically significant. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in ethanol-fed rats. Ethanol feeding also increased mRNA levels for the lysosomal enzyme cathepsin B. Furthermore, there was a close, statistically significant correlation between changes in mRNA levels and tissue activities of pancreatic digestive and lysosomal enzymes after ethanol consumption. These results suggest that ethanol increases the capacity of the pancreatic acinar cell to synthesize digestive and lysosomal enzymes, thereby increasing the susceptibility of the gland to enzyme-related injury.

Acetaldehyde↗
PubMed1994

Intracellular response of neurons of the caudate nucleus and putamen to intrastriatal stimulation in cat.

The purpose of this research was to determine if the different functional areas of the striatum, as defined by corticostriate connections, have excitatory and/or inhibitory interconnections. In cats anesthetized with barbiturates, an intracellular recording electrode was angled at 45 degrees such that it (1) crossed all functional areas of the striatum in a single pass and (2) traversed perpendicular to intrastriatal axonal bundles and their terminal fields. > 95% of the neurons recorded intracellularly in the head of the caudate (Cd) nucleus responded to stimulation of the rostromedial striatum (limbic area) producing an initial excitatory response in all cases. Membrane hyperpolarization and inhibition followed the initial excitatory response in approximately half of the responsive neurons. As the recording electrode approached the stimulating electrode, latencies to response onset decreased and amplitudes of the initial excitatory responses increased. Stimulation of a single site produced responses in neurons found in all functional areas of the Cd nucleus. Based on the known topography of afferents to the striatum, these results cannot be explained by stimulation of fibers en passant. Therefore, we conclude that the limbic striatum is connected to other functional areas of the Cd nucleus by intrinsic excitatory and inhibitory circuits. We speculate that intrinsic circuits are a hidden layer of organization providing connectional plasticity by which the influence of an input on striatal neurons may be expanded or contracted beyond the anatomical limits of the afferent terminal field.

Animals↗
PubMed1994

Lipid intolerance does not account for susceptibility to alcoholic and gallstone pancreatitis.

BACKGROUND/AIMS: Hypertriglyceridemia is an established cause of pancreatitis and has been suggested as a predisposing factor in alcohol and gallstone-induced pancreatitis. The aims of this study were to determine fasting and postprandial triglyceride levels of alcoholics with pancreatitis, alcoholics without pancreatitis, patients with previous gallstone pancreatitis, patients with choledocholithiasis, and healthy controls. METHODS: Oral lipid tolerance studies were performed in the above groups. RESULTS: No relationship was found between alcoholic pancreatitis and hypertriglyceridemia, regardless of whether subjects were studied in the fasting state, after ingestion of fat, or after ingestion of fat with ethanol. Plasma triglyceride levels of alcoholics with pancreatitis remained similar to those of alcoholics without pancreatitis, but levels in both groups varied in relation to recent alcohol intake. Plasma triglyceride levels from both groups of alcoholics were greater than those of nonalcoholic healthy subjects. In addition, the previously reported association between postprandial hypertriglyceridemia and gallstone pancreatitis was not observed. CONCLUSIONS: Plasma triglyceride levels do not account for individual susceptibility to either alcoholic or gallstone pancreatitis.

Alcoholism↗
PubMed1994

Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules.

Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases is thought to be an early event in the pathogenesis of pancreatic injury. As ethanol excess is an important association of pancreatitis, experimental work has been directed towards exploring possible mechanisms whereby ethanol may facilitate contact between inactive digestive enzyme precursors and lysosomal enzymes. The aim of this study was to find out if chronic ethanol administration increases the fragility of rat pancreatic zymogen granules. Sixteen male Sprague-Dawley rats were pair fed ethanol and control liquid diets for four weeks. Zymogen granule fragility was then assessed in pancreatic homogenate by determination of (a) latency and (b) per cent supernatant enzyme after sedimentation of zymogen granules. Amylase was used as a zymogen granule marker enzyme. Latency was significantly reduced in pancreatic homogenates of ethanol fed animals suggesting increased zymogen granule fragility. In support of this finding, there was a trend towards increased supernatant enzyme after ethanol feeding. In conclusion, administration of ethanol increases the fragility of pancreatic zymogen granules in the absence of morphological evidence of pancreatic injury. It is proposed that zymogen granule fragility may play an early part in the pathogenesis of alcoholic pancreatitis by permitting contact between digestive and lysosomal enzymes.

Amylases↗
PubMed1994

Relief of superior vena cava syndrome due to fibrosing mediastinitis using the Palmaz stent.

Relief of superior vena cava (SVC) syndrome due to non-neoplastic mediastinal disease presents a formidable challenge. Long-term patency of surgically created bypass grafts has been poor, and the morbidity associated with these procedures is substantial. We report a case of SVC syndrome, caused by fibrosing mediastinitis, treated with Palmaz balloon expandable intravascular stents. Intravascular stents are a promising alternative for relief of non-neoplastic SVC obstruction.

Adult↗
PubMed1994

Aortic valve replacement in adults after balloon aortic valvuloplasty.

BACKGROUND: Percutaneous balloon aortic valvuloplasty is limited by a high risk of procedural morbidity, transient clinical benefit, and a high restenosis rate. The management of patients with symptomatic aortic valve restenosis after percutaneous balloon aortic valvuloplasty is unclear. We hypothesized that aortic valve replacement would produce superior midterm survival compared with repeat balloon aortic valvuloplasty or medication alone in patients with symptomatic aortic valve restenosis after prior balloon aortic valvuloplasty. METHODS AND RESULTS: Baseline clinical, echocardiographic, and hemodynamic data were collected on 165 patients who underwent percutaneous balloon aortic valvuloplasty as treatment for symptomatic degenerative calcific aortic stenosis. In 144 of these patients (87%), aortic valve replacement was originally considered to carry excessive risk. The survival of three subgroups was calculated during a median follow-up period of 3.9 years (range, 1 to 6 years). Ninety-four patients (57%) had no further mechanical intervention (subgroup 1-BAV), 31 patients (19%) developed symptomatic aortic valve restenosis and underwent a repeat balloon aortic valvuloplasty (subgroup 2-BAV), and 40 patients (24%) subsequently underwent aortic valve replacement (subgroup BAV+AVR). Follow-up was 99% complete. Patients in subgroup BAV+AVR tended to be younger and have a lower prevalence of coronary artery disease or mitral regurgitation. Only 1 patient (2.5%) suffered a perioperative death during aortic valve replacement. The probability of survival 3 years from the date of the last mechanical intervention was 13% for subgroup 1-BAV, 20% for subgroup 2-BAV, and 75% for subgroup BAV+AVR. At the conclusion of follow-up, only 2 patients had symptoms of congestive heart failure or angina after aortic valve replacement. CONCLUSIONS: Aortic valve replacement may be performed with a low mortality rate, excellent palliation of symptoms, and prolongation of survival in selected high-risk patients with a history of previous balloon aortic valvuloplasty.

Actuarial Analysis↗
PubMed1994

Complications related to percutaneous transvenous mitral commissurotomy.

Recent randomized studies have demonstrated that percutaneous transvenous mitral commissurotomy (PTMC) has similar efficacy compared to surgical commissurotomy. Compared with surgery, PTMC is associated with shorter hospital stays, reduced patient discomfort, and significantly lower costs. The challenge of PTMC remains to provide increased safety. The most serious risks of balloon commissurotomy include cardiac perforation and embolic stroke. The creation of severe mitral regurgitation also limits the effectiveness of the procedure and occasionally leads to the requirement for emergency mitral valve replacement. Since 1986, procedure-related mortality has ranged from 0-2.7% with lower mortality rates reported recently. The most frequent cause of procedure-related death has been left ventricular (LV) perforation. This is almost exclusively a complication associated with the double balloon technique, which requires LV guidewires. Cardiac perforation due to inadvertent atrial perforation during transseptal catheterization may occur with the Inoue technique as well, but this tends to be less severe and has not resulted in death. Embolic stroke has occurred in 1.1-5.4% of cases. The incidence of embolic events has been favorably influenced by routine preprocedure transesophageal echocardiography (TEE), eliminating patients with left atrial thrombi. Significant mitral regurgitation occurs in 3.3-10.5% of patients undergoing balloon mitral commissurotomy. Fortunately, mitral regurgitation infrequently requires emergency surgery (0.3-3.3% of cases). Iatrogenic atrial septal defects are usually of no clinical consequence. Their frequency has been reduced with the use of the Inoue balloon catheter system and they rarely require surgical repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗