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Biomedical subjects

J S Wilson

Publications and source records attributed to J S Wilson.

At least 55 records · Page 3Linked to original sources

Chronic ethanol administration decreases rat pancreatic GP2 content.

Postulated mechanisms of alcoholic pancreatitis include (i) zymogen granule fragility facilitating intracellular activation of digestive enzymes and (ii) ductular obstruction by protein plugs. GP2, a pancreatic glycoprotein, stabilizes zymogen granule membranes and is an important constituent of pancreatic protein plugs. Therefore, this study examined the pancreatic content and messenger RNA levels of GP2 after chronic ethanol administration. Rats were fed liquid diets with or without ethanol, for four weeks. GP2 levels in pancreatic homogenates, crude zymogen granules and zymogen granule membrane fractions were assessed by immunoblotting. Messenger RNA levels for GP2 were measured by Northern and dot blotting of pancreatic RNA. Pancreatic GP2 levels were lower in ethanol-fed rats than in controls (GP2 levels expressed as % of control: 38.75 +/- 5.8, p < 0.001 in homogenate; 31.28 +/- 3.5, p < 0.0005 in crude zymogen granules and 22.89 +/- 5.4, p < 0.0005 in zymogen granule membranes). Messenger RNA levels for GP2 were unchanged after ethanol feeding. Chronic ethanol consumption decreases GP2 content of pancreatic homogenate and zymogen granules. This decrease could (i) result from an increased release into pancreatic juice thereby favouring protein plug formation and (ii) impair zymogen granule stability. Both these mechanisms could potentiate pancreatic damage.

Animals↗

Clinical update: management of acute pancreatitis.

The management of acute pancreatitis commences with confirming the diagnosis and establishing the aetiology. Improved methods of assessing the biliary tree may reduce the number of patients regarded as having idiopathic pancreatitis. Detailed clinical and laboratory protocols, designed to assess severity, have no major advantage over clinical assessment. The contrast-enhanced computed tomography scan is important to assess the degree of pancreatic necrosis and to detect local complications. The treatment of pancreatitis continues to be largely supportive. However, controlled studies support the use of antibiotics in severe acute pancreatitis and indicate a possible role for the use of octreotide and antioxidants. The place of endoscopic and surgical intervention is becoming better defined. Once an attack has passed, further investigation is often required in a bid to prevent further episodes of inflammation.

Acute Disease↗

Quantification of idiopathic pulmonary fibrosis using computed tomography and histology.

We used computed tomography (CT) and histologic analysis to quantify lung structure in idiopathic pulmonary fibrosis (IPF). CT scans were obtained from IPF and control patients and lung volumes were estimated from measurements of voxel size, and X-ray attenuation values of each voxel. Quantitative estimates of lung structure were obtained from biopsies obtained from diseased and normal CT regions using stereologic methods. CT density was used to calculate the proportion of tissue and air, and this value was used to correct the biopsy specimens to the level of inflation during the CT scan. The data show that IPF is associated with a reduction in airspace volume with no change in tissue volume or weight compared with control lungs. Lung surface area decreased two-thirds (p < 0.001) and mean parenchymal thickness increased tenfold (p < 0.001). An exudate of fluid and cells was present in the airspace of the diseased lung regions and the number of inflammatory cells, collagen, and proteoglycans was increased per 100 g of tissue in IPF. We conclude that IPF reorganized lung tissue content causing a loss of airspace and surface area without increasing the total lung tissue.

Aged↗

Alcohol-related pancreatic damage: mechanisms and treatment.

Pancreatitis is a potentially fatal inflammation of the pancreas often associated with long-term alcohol consumption. Symptoms may result from blockage of small pancreatic ducts as well as from destruction of pancreatic tissue by digestive enzymes. In addition, by-products of alcohol metabolism within the pancreas may damage cell membranes. Research on the causes of pancreatitis may support more effective disease management and provide hope for a potential cure.

Alcohol Drinking↗

Effect of mood and food cues on body image in women with bulimia and controls.

OBJECTIVE: The present study evaluated body image assessment and cue reactivity in women with bulimia and controls in response to neutral, mood, and food cues in isolation, and mood and food cues in combination. METHOD: Subjects were 7 women with bulimia nervosa and 8 control women. Food cues were individualized high-risk/favorite foods. Low mood was elicited using the Musical Mood Induction Procedure. Order of cue presentation was random across subjects. Body image and cue reactivity were assessed using a computer version of the silhouette method and self-report ratings, respectively. RESULTS: Women with bulimia consistently rated their current body as being larger and their body image satisfaction as being lower than control women. In addition, women with bulimia differentially rated their current body and a picture of a healthy weight woman as being larger following exposure to food and/or mood cues. Ratings of ideal body were differentially affected by mood cues for control women. Ratings of body satisfaction were not affected by cue presentation. Mere presentation of high-risk foods in the absence of eating was sufficient to elicit urges to binge in women with bulimia. DISCUSSION: Body size estimation is not only affected by enduring characteristics (i.e., bulimia nervosa), but also more transient factors such as short-term exposure to salient food and mood cues.

Adolescent↗

Selective inhibition of the reverse transcription of duck hepatitis B virus by binding of 2',3'-dideoxyguanosine 5'-triphosphate to the viral polymerase.

Hepatitis B virus (HBV) replication is mediated by the viral polymerase that possesses three functional domains: primer, DNA polymerase/reverse transcriptase, and RNase H. Using the Pekin duck as an animal model, we demonstrate a novel mechanism of inhibition of duck hepatitis B virus (DHBV) by 2,6-diaminopurine 2',3'-dideoxyriboside (ddDAPR), a prodrug of 2',3'-dideoxyguanosine (ddG). A selective and irreversible inhibition of DHBV DNA replication is found in ducklings treated with high doses of ddDAPR (20 to 50 mg/kg), but not with similar doses of 2',3'-dideoxycytidine (ddC). The inhibition mediated by ddDAPR occurs at a very early stage of the reverse transcription. Despite the inhibition of DHBV DNA replication by ddDAPR, the DNA polymerase and reverse transcriptase activities of the polymerase are found to remain active when tested on exogenous templates in activity gels. We have demonstrated direct binding of [alpha-32P]ddGTP to the DHBV polymerase expressed in an in vitro transcription and translation system. These results suggest that the binding of ddGTP to the polymerase blocks the initial DNA replication.

Animals↗

Both ethanol and protein deficiency increase messenger RNA levels for pancreatic lithostathine.

Both ethanol abuse and protein deficiency are well known associations of chronic pancreatitis. An early event in chronic pancreatitis is the deposition of protein plugs in small pancreatic ducts, leading to ductular obstruction and acinar cell damage. Lithostathine, a pancreatic secretory protein, is a major organic component of protein plugs. The aim of this study was to determine the effect of chronic ethanol administration and dietary protein deficiency, separately and in combination, on messenger RNA (mRNA) levels for pancreatic lithostathine. Male Sprague-Dawley rats were fed in groups of four, for four weeks, protein sufficient and protein deficient diets with or without ethanol. Messenger RNA levels for pancreatic lithostathine were assessed in all four groups. Both ethanol and protein deficiency, separately and in combination, increased mRNA levels for lithostathine. Thus, both chronic ethanol consumption and dietary protein deficiency increase the capacity of the pancreatic acinar cell to synthesize lithostathine.

Alcoholism↗

National certification for home care nurses: bird by bird.

The opportunity to be certified as a generalist in home care nursing has been available since 1993, with the new certification as specialist available in 1996. Home Healthcare Nurse asked Janet Wilson, a nurse educator and member of our editorial board, to answer the questions: What is certification? Why should I think of becoming certified? and How do I go about it?

Certification↗

Pediatric exercise-induced laryngomalacia.

Laryngomalacia is a well-recognized cause of airway obstruction and inspiratory stridor in infants. As children grow and become more active, laryngomalacia may manifest in different, unexpected ways. Otherwise healthy athletes may generate enough inspiratory force to draw the aryepiglottic folds into the endolarynx, causing a subtotal glottic obstruction. This problem may be overlooked or attributed to asthma, lack of fitness, or functional abnormalities. The purpose of this report is to review the prevalence, diagnosis, and treatment of exercise-induced laryngomalacia (EIL) in children and young adults. To study the incidence and diagnosis of this disorder, we examined 10 healthy volunteers. Fiberoptic laryngoscopy was used to videotape each subject's larynx during active exercise on a stationary bicycle. All volunteers demonstrated altered laryngeal dynamics with exercise, and 1 of the 10 volunteers developed laryngomalacia. Anatomically, it appears that the aryepiglottic fold serves as the critical point of obstruction. When symptomatic, laryngomalacia may be treated with supraglottoplasty. We have had experience with 2 EIL patients in the last 12 months who have undergone carbon dioxide laser microlaryngoscopy. Both patients benefited significantly from surgery. We conclude that EIL is underdiagnosed but responds well to treatment.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗