PubMed HealthSearch

Biomedical subjects

B A Runyon

Publications and source records attributed to B A Runyon.

At least 19 recordsLinked to original sources

Management of adult patients with ascites caused by cirrhosis.

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of abstinence from alcohol, sodium restricted diet, and diuretics. This regimen is effective in approximately 90% of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracenteses, liver transplantation, and peritoneovenous shunting.

Ascites

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites.

BACKGROUND/AIMS: Translocation of indigenous bacteria from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats. METHODS: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria. RESULTS: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice. CONCLUSIONS: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.

Animals

Historical aspects of treatment of patients with cirrhosis and ascites.

The most striking feature of the history of treatment of patients with cirrhosis and ascites is the recurring cycle of initial enthusiasm for a new modality based on uncontrolled observations, followed by reports of complications and failures and/or negative randomized control trials (RCTs). The RCTs tend to be performed rather late, after it is realized that there are problems with the new treatment. In 1975 Tom Chalmers made a plea for randomization of the first patient treated with a new modality. The appropriateness of performing RCTs very early in the evaluation of a new treatment cannot be overemphasized today. Carefully designed RCTs that focus on appropriate subsets of patients and evaluate clinically important endpoints (rather than easier-to-measure, but unimportant indirect endpoints) are the keys to "evidence-based medicine" that will lead to the best outcomes for our patients. If we do not remember that uncontrolled studies regularly lead us into years or even decades of "blind alleys" of investigation, we are destined to repeat the mistakes of the past.

Ascites

Treatment of patients with cirrhosis and ascites.

The treatment of patients with cirrhosis and fluid overload has undergone substantial change in recent years, because of new information regarding old treatments, as well as new treatments. The goals of treatment are to maximize life expectancy and quality of life. Development of ascites is a landmark in the natural history of cirrhosis signaling poor life expectancy, in general. Patients who are appropriate candidates for liver transplantation should undergo evaluation for this procedure after development of ascites. Patients awaiting transplantation as well as non-candidates for this procedure should be managed by restriction of dietary sodium and prescription of diuretics. This approach is effective in controlling fluid overload in > 90% of patients. Only the 10% who fail this simple medical treatment should be considered for second-line therapy.

Ascites

Ascitic fluid adenosine deaminase insensitivity in detecting tuberculous peritonitis in the United States.

Tuberculous peritonitis, although common in Third World countries, remains an uncommon cause of ascites in the United States. Ascitic fluid adenosine deaminase (ADA) activity has been proposed as a useful diagnostic test. The aim of this retrospective study was to determine the clinical utility of ascitic fluid ADA activity in diagnosing tuberculous peritonitis in a U.S. patient population. A total of 368 ascitic fluid specimens from a well-characterized ascitic fluid bank, including tuberculous peritonitis (n = 7), tuberculous peritonitis in the setting of cirrhosis (n = 10), and consecutive specimens of widely varied etiologies (n = 351) were analyzed for ADA activity by ultraviolet spectrophotometry at 265 nm. The overall sensitivity of the ADA determination in diagnosing tuberculous peritonitis was only 58.8%, and the specificity was 95.4%. The accuracy of ADA determination (93.8%) compared favorably with that of the common ascitic fluid tests of white blood cell (WBC) count (>500/mm3), total protein (>2.5 g/dL), and combined WBC count and total protein (45.8%, 74.4%, and 81.3%, respectively). However, ADA was only 30% sensitive in detecting tuberculous peritonitis in the setting of cirrhosis, and cirrhosis was present in 59% of the tuberculous peritonitis patients in our population. In addition, malignancy-related ascites (13%) and bacterial peritonitis specimens (5.8%) occasionally yielded false-positive results. In conclusion, our results indicate that the ascitic fluid ADA activity has good accuracy but poor sensitivity and imperfect specificity in a U.S. patient population in which the prevalence of tuberculosis is low and underlying cirrhosis is common.

Adenosine Deaminase

Antimicrobial activity of 11 newer and investigational drugs tested against aerobic isolates from spontaneous bacterial peritonitis.

The in vitro susceptibility of 124 aerobic bacterial pathogens isolated from patients with spontaneous bacterial peritonitis (SBP) were tested against 11 antimicrobial agents, including parenteral or oral cephalosporins and fluoroquinolones. Most SBP isolates were Gram-negative organisms, and Escherichia coli and Klebsiella pneumoniae were responsible for 63% of the episodes evaluated. The fluoroquinolones (ciprofloxacin and ofloxacin) and the "fourth-generation" cephalosporin cefpirome were the most active agents against the Gram-negative bacteria. Commonly used cefotaxime and cefotaxime-desacetylcefotaxime (DES-CTX) combinations were also very active against Gram-negative bacteria with only few Enterobacter cloacae isolates being resistant (minimum inhibitory concentrations > 32 micrograms/ml). All streptococci were susceptible to cefotaxime, cefpirome, and cefdaloxime and to the cefotaxime-DES-CTX combinations, whereas only ofloxacin demonstrated acceptable activity against the enterococci. The widest spectrum of activity versus SBP isolates was found for ofloxacin (98% susceptibility) among the fluoroquinolones. For the beta-lactams, the widest spectrum of activity was demonstrated by cefpirome and the 2:1 cefotaxime-DES-CTX combination (93% susceptibility). These results indicate that the role of ofloxacin and newer parenteral or orally administered cephalosporins in the treatment of prophylaxis of SBP should be further evaluated.

Anti-Bacterial Agents

In vitro activity of levofloxacin and FK-037 against aerobic isolates from spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is a potentially fatal complication of ascites, most often caused by the Enterobacteriaceae or streptococci. We have evaluated the in vitro activity of FK-037, a new cephalosporin, cefotaxime, cefpirome, ceftazidime, levofloxacin, and ofloxacin against a collection of 124 isolates from patients with spontaneous bacterial peritonitis. Levofloxacin (< or = 2 mg/L) was active against all isolates and ofloxacin (< or = 2 mg/L) against 98.4% of isolates. The cephalosporins (< or = 8 mg/L) were less active against cefpirome = 95.4%, FK-037 = 94.4%, and cefotaxime and ceftazidime = 91.1%. Given the high mortality associated with spontaneous bacterial peritonitis, clinical studies of the quinolones (specifically of levofloxacin) and the alternative cephalosporins presented for treatment of spontaneous bacterial peritonitis appears warranted.

Anti-Bacterial Agents

Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis.

Selective bowel decontamination with the orally administered quinolone antibiotic, norfloxacin, has been shown to suppress gut gram-negative bacteria and help prevent gram-negative infections in cirrhotic patients who are at high risk of bacterial infection. Because this drug does not eradicate gram-positive organisms, it is conceivable that gram-positives could replace the suppressed gram-negatives in the gut and lead to subsequent infection. Also the effect of norfloxacin on translocation (as defined by culture positivity of mesenteric lymph nodes) has received little attention. In this study, the effect of oral norfloxacin on translocation, bacterial peritonitis, and survival was investigated in an animal model of carbon tetrachloride-induced cirrhosis and ascites. Treated rats received daily doses of orally administered norfloxacin from the onset of cirrhosis until they died or were killed. Controls received no antibiotic. Norfloxacin led to a reduction in bacterial peritonitis from 70% in untreated cirrhotic controls to 28% in treated cirrhotic rats; these data were statistically significant (P = .012). There was no effect on overall translocation rate (28% with norfloxacin vs. 50% without norfloxacin) (P > .1). Gram-positives were isolated in 100% of the bacterial peritonitis episodes and in 71.4% of culture-positive mesenteric lymph nodes in treated animals compared with only 25% of peritonitis episodes and 10% of culture-positive mesenteric lymph nodes of untreated cirrhotic controls (P < .01 for peritonitis and P < .05 for translocation). The survival rate was not different between groups (P > .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Spontaneous bacterial peritonitis: pathogenesis, diagnosis, and management.

Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of cirrhosis. Multiple variants of this infection have been described during the past decade; each has a slightly different clinical setting and outcome. The pathogenesis of spontaneous ascitic fluid infection appears to involve translocation of bacteria from the gut to the mesenteric lymph nodes, depressed reticuloendothelial phagocytic activity, and deficient ascitic fluid antibacterial activity. A high index of suspicion of this infection and a low threshold for performing an abdominal paracentesis are required to detect infection early, when survival is most likely. The diagnosis of SBP is based on ascitic fluid analysis, specifically polymorphonuclear cell count and culture (in blood culture bottles). Treatment with a third-generation cephalosporin achieves a cure rate in more than 80% of patients. Despite the improvement in short-term survival during the last decade, the long-term prognosis of cirrhotic patients who survive an episode of SBP remains poor because of the severity of the underlying liver disease and the high rate of recurrence of infection. Selective intestinal decontamination to prevent SBP should be considered in patients at high risk for development of this infection, including hospitalized cirrhotic patients with gastrointestinal hemorrhage or with low ascitic fluid total protein concentration. Because SBP is a marker for poor prognosis in patients with cirrhosis, survivors of an episode of this infection should also be considered for liver transplantation.

Ascitic Fluid

Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is a common infection of ascitic fluid that develops in cirrhosis. The offending organisms are predominantly of enteric origin. However, the mechanism and route by which bacteria exit from the gut and enter the fluid remain unclear. "Translocation" of bacteria from the gut to extraintestinal sites has been postulated in the pathogenesis of gram-negative sepsis in intensive care unit patients, burn-wound sepsis, and sepsis associated with chemotherapy. Translocation is defined by culture-positivity (with enteric flora) of mesenteric lymph nodes. In this study we assessed the frequency of translocation in a carbon tetrachloride-induced rat model of cirrhosis, ascites, and spontaneous bacterial peritonitis. We determined that translocation was more common in rats with cirrhosis (78.1%) than in normal controls (4.3%) (p < 0.001). Escherichia coli and other gram-negative enteric organisms were cultured. Translocation of enteric bacteria in rats with cirrhosis to extraintestinal sites may be an important early step in the pathogenesis of spontaneous bacterial peritonitis.

Animals

Malignancy-related ascites and ascitic fluid "humoral tests of malignancy".

A large number of ascitic fluid tests, e.g., fibronectin and cholesterol, have been proposed as helpful in detecting malignancy as the cause of ascites. Unfortunately, these "humoral tests of malignancy" are nonspecific. Although the ascitic fluid concentrations of these proteins or protein-bound substances tend to be quite high in patients with peritoneal carcinomatosis and low in the setting of cirrhotic ascites, the problem is that patients with tuberculous peritonitis, cardiac ascites, pancreatitis ascites, etc. usually have values in the malignancy range, i.e., false-positive results. This can lead to an extensive search for a nonexistent tumor, with confusion and anxiety for patient and physician. The cytology is the single best test to order when peritoneal carcinomatosis is suspected; its sensitivity approaches 100%. However, peritoneal carcinomatosis is only one of several mechanisms by which tumors can cause ascites. No one test can be expected to detect tumors as the cause of these diverse mechanisms of ascites formation. The serum-ascites albumin gradient is a helpful test in classifying ascitic fluid specimens into portal-hypertension-related and non-portal-hypertension-related categories. An elevated serum alpha-fetoprotein test can be useful in raising suspicion of hepatocellular carcinoma. Careful analysis of ascitic fluid, without measurement of "humoral tests of malignancy," combined with information obtained from the history and physical examination, usually lead to an accurate diagnosis of the cause of ascites.

Ascites

Refractory ascites.

The first step in the approach to the ascites patient, after the history and physical examination, is to perform a diagnostic abdominal paracentesis for SAAG to determine whether portal hypertension is present (SAAG 1.1 g/dl or higher) or not (SAAG less than 1.1 gm/dl) (Table 1). Patients without portal hypertension probably do not have liver disease as the cause of their ascites formation and probably should not be treated with dietary sodium restriction and diuretics. Patients with portal hypertension-related ascites usually have chronic parenchymal liver disease and usually require hospitalization for diet education, diuretic treatment, and evaluation of the underlying liver disease. Approximately 90% of patients with ascites due to chronic parenchymal liver disease respond to dietary sodium restriction and diuretics. Because of the poor prognosis associated with ascites, patients who are good candidates for transplantation should be considered for listing when they develop this complication of their underlying liver disease. The 10% of patients with cirrhosis whose ascites is refractory to routine medical treatment must be offered alternative therapy. Transplant candidates should be listed, in my opinion, once they are documented to have diuretic-resistant ascites. Fortunately, alcoholics (who are usually not good candidates for transplantation) who abstain from alcohol may revert from diuretic-resistant to diuretic-sensitive ascites over a period of months. Chronic outpatient therapeutic paracentesis is the most popular short-term treatment for patients with diuretic-resistant ascites. Paracentesis can be used as a "bridge" to alternative therapies or can be continued indefinitely.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal