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Biomedical subjects

B A Runyon

Publications and source records attributed to B A Runyon.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites.

OBJECTIVE: To compare the serum-ascites albumin gradient to the exudate-transudate concept in the classification of ascites. DESIGN: Prospective collection of ascitic fluid data from patients with well-characterized causes of ascites. SETTING: Hepatology inpatient and outpatient ward and consult service of a large, urban hospital. PATIENTS: A total of 901 paired serum and ascitic fluid samples were collected from consecutive patients with all forms of ascites. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The utility of the serum-ascites albumin gradient and the old exudate-transudate concept (as defined by ascitic fluid total protein concentration [AFTP]) were compared for their ability in discriminating the cause for ascites formation. RESULTS: The albumin gradient correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. The AFTP, when used as defined in the old exudate-transudate concept, classified the causes of ascites correctly only 55.6% of the time. This resulted in part because the AFTP of most spontaneously infected samples (traditionally expected to be exudates) was low, and the AFTP of most cardiac ascites samples (traditionally expected to be transudates) was high. CONCLUSIONS: The exudate-transudate concept should be discarded in the classification of ascites. The serum-ascites albumin gradient is far more useful than the AFTP as a marker for portal hypertension, but the latter remains a useful adjunct in the differential diagnosis of ascites.

Albumins↗
PubMed1992

Diuresis increases ascitic fluid opsonic activity in patients who survive spontaneous bacterial peritonitis.

Patients with low protein ascites and deficient ascitic fluid opsonic activity have been shown to be unusually predisposed to development of spontaneous bacterial peritonitis. Survivors of spontaneous peritonitis frequently develop recurrent infection. Diuresis has been shown to increase the ascitic fluid opsonic activity of patients who have never had spontaneous bacterial peritonitis. Patients with adequate opsonic activity are protected from ascitic fluid infection. Theoretically, the subset of patients who develop spontaneous peritonitis may have such severe liver disease that (i) their ascites is refractory to diuretic therapy or (ii) their ascitic fluid opsonic activity does not increase in response to diuresis. In this study, opsonic activity and concentrations of total protein and complement components were measured in the ascitic fluid of 11 patients who were hospitalized with spontaneous bacterial peritonitis and who responded to oral diuretics. The mean values of all of these parameters were found to increase significantly comparing the end-of-diuresis samples to the specimens that were diagnostic of ascitic fluid infection. Patients who survive spontaneous bacterial peritonitis are able to increase their ascitic fluid total protein and opsonic activity in response to diuresis. This increase in endogenous antimicrobial activity may help prevent recurrence of ascitic fluid infection.

Amiloride↗
PubMed1991

Effect of marked peripheral leukocytosis on the leukocyte count in ascites.

Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x 10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid.

Ascites↗
PubMed1991

Ascitic fluid and serum cefotaxime and desacetyl cefotaxime levels in patients treated for bacterial peritonitis.

Forty-one episodes of ascitic fluid infection were treated with cefotaxime 2 g intravenously every 8 hr, and ascitic fluid and serum were sampled 6, 12, 24, 48, and 96 hr after the first dose of antibiotic. Concentrations of cefotaxime and desacetyl cefotaxime were measured in ascitic fluid and serum by high-performance liquid chromatography. There was essentially 100% penetration of cefotaxime and metabolite from serum into ascitic fluid at all time points. Ascitic fluid was sterilized in 94% of episodes after the first dose of antibiotic. The ascitic fluid concentration of cefotaxime 6 hr after the first dose of antibiotic was greater than 20 times the minimal inhibitory concentration of the drug for 90% of the isolated flora. This rapid ascitic fluid penetration of cefotaxime in high concentration explains the rapid sterilization of ascitic fluid by the drug in the setting of bacterial peritonitis and obviates the need to give a loading dose or intraperitoneal injection.

Adult↗
PubMed1991

A rodent model of cirrhosis, ascites, and bacterial peritonitis.

We sought to develop a rodent model of spontaneous bacterial peritonitis and report here the preliminary results of carbon tetrachloride-induced cirrhosis in which ascites and bacterial peritonitis predictably develop. Of 41 rats that survived the initial carbon tetrachloride toxicity, 38 (92.7%) developed cirrhosis with ascites. Of these 38, 21 (55.3%) developed 24 episodes of ascitic fluid infection without iatrogenic colonization. No surgically treatable source of infection was identified at autopsy in any rat; therefore, the infections were presumed to be "spontaneous." Eight (50%) of the 16 rats with culture-positive ascitic fluid at postmortem examination also had spontaneous pleural fluid infection with the same organism. Escherichia coli and Proteus sp. were the organisms most commonly isolated. This rodent model of cirrhosis with ascites appears to be the first high-yield animal model of spontaneous bacterial peritonitis. Ascitic fluid infection in these rats resembles ascitic fluid infection in humans. This model will allow further investigation of the mechanisms of pathogenesis of ascitic fluid infection and provide insight into the prevention and treatment of spontaneous bacterial peritonitis and pleural fluid infection in patients with cirrhosis.

Animals↗
PubMed1991

Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis. A randomized controlled study of 100 patients.

In an attempt to determine the optimal duration of therapy of spontaneous bacterial peritonitis, 100 patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis were randomized to short-course vs. long-course treatment groups. Empiric therapy was initiated before the results of ascitic fluid culture were available. Of the 90 patients who met strict criteria for spontaneous bacterial peritonitis or culture-negative neutrocytic ascites, 43 were randomized to a group receiving 5 days and 47 to a group receiving 10 days of single-agent cefotaxime, 2 g IV every 8 hours. Infection-related mortality (0% vs. 4.3%), hospitalization mortality (32.6% vs. 42.5%), bacteriologic cure (93.1% vs. 91.2%), and recurrence of ascitic fluid infection (11.6% vs. 12.8%) were not significantly different between the 5- and 10-day treatment groups, respectively. Recurrence rates were comparable to the values reported in the literature. The cost of antibiotic and antibiotic administration were significantly lower in the short-course group. Short-course treatment of spontaneous bacterial peritonitis is as efficacious as long-course therapy and significantly less expensive.

Bacterial Infections↗
PubMed1991

The opacity of portal hypertension-related ascites correlates with the fluid's triglyceride concentration.

To determine if an elevated triglyceride concentration can explain the opacity of some cirrhotic ascites specimens, the authors measured triglyceride concentration by Coulter DACOS (Hialeah, FL) on 133 paired serum and ascitic fluid specimens. The specimens were categorized as clear or cloudy by coded visual inspection. In addition, the ascitic fluid specimens were inspected for a lipid supernatant after 48 hours of refrigeration at 4 degrees C. The ascitic fluid triglyceride concentration of the 87 clear specimens was 1.9 +/- 1.0 mmol/L compared with 7.0 +/- 4.6 mmol/L for the opalescent specimens (P less than 0.001). Only 17% of the clear specimens demonstrated any lipid layer after refrigeration, compared with 94% of opalescent specimens (P less than 0.001). The triglyceride concentrations were not significantly different between the serum samples obtained from patients with clear compared with opalescent ascites. The opacity of portal hypertension-related ascites appears to be related to the triglyceride concentration of the fluid.

Ascites↗
PubMed1991

Ascitic fluid pH and lactate: insensitive and nonspecific tests in detecting ascitic fluid infection.

Ascitic fluid pH and lactate concentration have been proposed as useful tests for the detection of ascitic fluid infection. However, past studies involved small numbers of infected patients, and all did not use optimal culture techniques. This large study was performed using highly sensitive culture methods and sought (a) to compare the sensitivity, specificity and accuracy of pH and lactate to that of the ascitic fluid neutrophil count and (b) to determine whether evaluation of ascitic fluid pH or lactate (or arterial-ascitic fluid pH or lactate gradient) would result in improved decision-making regarding empirical treatment of suspected ascitic fluid infection. Analysis of 206 ascitic fluid specimens obtained in 175 patients, including 101 infected specimens, revealed that ascitic fluid (or arterial-ascitic fluid) pH and lactate were less than 50% sensitive in detecting bacterial peritonitis and that these tests did not improve clinical decision-making about empirical treatment of suspected ascitic fluid infection. Although statistically significant differences in ascitic fluid pH were detected between infected samples and control samples, these differences did not appear to be clinically helpful. The ascitic fluid pH was 0% sensitive in detecting the presence of bacteria in the absence of neutrophils (i.e., no such specimens had a pH lower than 7.35). Ascitic fluid pH correlated well with neutrophil count and appears to be, at least in part, an indirect measure of the presence of neutrophils in ascitic fluid. Measurement of pH or lactate (or arterial-ascitic fluid gradients) is not helpful in the clinical management of infected ascitic fluid.

Ascites↗
PubMed1990

Monomicrobial nonneutrocytic bacterascites: a variant of spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is diagnosed when (a) the ascitic fluid culture is positive, (b) the ascitic fluid neutrophil count is greater than or equal to 250 cells/mm3 and (c) there is no evident intraabdominal surgically treatable source for infection. Few details are available regarding the variant of ascitic fluid infection in which the culture grows bacteria (pure growth of a single type of organism), but the neutrophil count is less than 250 cells/mm3. In this prospective study of 138 episodes of culture-positive spontaneously infected ascites detected in 105 patients, 44 (31.9%) were episodes of "monomicrobial nonneutrocytic bacterascites" compared with 94 (68.1%) episodes of spontaneous bacterial peritonitis. Seventeen patients had both types of infection. The infection-related mortality and hospitalization mortality were similar between the two groups. Patients with bacterascites appeared to have less severe liver disease. In 62% of bacterascites episodes in which a second paracentesis was performed before any treatment the fluid spontaneously became sterile without development of ascitic fluid neutrocytosis. Thirty-eight percent of patients with bacterascites (who underwent a second paracentesis before treatment was started) progressed to spontaneous bacterial peritonitis--sometimes within a few hours. The concentration of the chemoattractant C5a was not decreased in the ascitic fluid of the bacterascites patients; this excludes ascitic fluid C5a deficiency as the explanation of the lack of neutrocytosis. Monomicrobial nonneutrocytic bacterascites is a common variant of ascitic fluid infection that may resolve without treatment or may progress to spontaneous bacterial peritonitis.

Anti-Bacterial Agents↗