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Altered kinetics of etozolin and its active metabolite ozolinone in hepatitis and hepatic cirrhosis with ascites.

The single dose kinetics of (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin) and its active metabolite ozolinone were determined in 6 healthy volunteers, in 12 patients with acute hepatitis and in 15 patients with hepatic cirrhosis with ascites. In hepatitis, the elimination half-life of etozolin was 4 times longer resulting in a 2 fold rise in the AUC. At the same time, plasma levels of ozolinone were lower and consequently the AUC of his metabolite was reduced. In cirrhosis, the plasma level time curves of etozolin and ozolinone differed significantly from the controls and also from those of the patients with acute hepatitis. For etozolin Cmax was reduced to about 1/2, the elimination half-life being increased by a factor of 5. This resulted in a 3 fold higher AUC. As for ozolinone the reduction of plasma levels was more pronounced--Cmax fell to 1/6 of the control value--so that in spite of a longer elimination half-life, the AUC fell to 1/2. Ascites concentrations of etozolin and ozolinone were almost identical to the plasma concentration. The results suggest that acute hepatitis and hepatic cirrhosis lead to a reduced formation of ozolinone. As a result, etozolin accumulates and plasma levels of oxolinone drop. Moreover, both substances enter the ascites to a significant degree. It is concluded that these changes in the kinetics of this lipophilic diuretic do not allow a reliable dosage regimen in patients with hepatic cirrhosis and ascites.

Acute Disease↗

[Hemopexin and immunoglobulins in benign and malignant ascites. Experience in 66 patients].

Sixty six patients with ascites of different etiologies were studied. Both serum and peritoneal fluids were examined through proteic electrophoresis, being the haemopexin determined in the peritoneal fluids. Immunoglobulins usually show high values in neoplastic effusions, especially igG (x +/- ES = 928.57 +/- 86.87 mg/dl) and IgA (x +/- ES = 157 +/- 17.84 mg/dl). However, the highest determinations were found in those of the congestive heart failures. The quotients obtained from the ascites immunoglobulin/serum immunoglobulin ratio are useful from a statistics point of view, though their practical value is limited. No plasma/ascites correlation was observed either in cirrhotic or in neoplastic patients. Quantification of haemope in proved to be conclusive in differential diagnosis. The 100% of benign ascites (cirrhosis, congestive heart failure and kidney failure) showed lower values than 170 mg/dl while 90.5% of neoplastic patients showed higher figures than said value. The average was 30.79 +/- 5.31 mg/dl for cirrhotic patients and 205.19 +/- 9.62 mg/dl for neoplastic patients with a statistically significative different for both groups (p less than 0.001). There is a high probability that its determination could show the etiology of the process. It was useful not only in cases of both neoplastic and cirrhotic ascites but also in those which had a cardiac origin, in which it showed intermediate values (mean +/- ES = 83.75 +/- 15.77 mg/dl). We feel that its incorporation to the routine followed when studying peritoneal effusions will afford a quick etiologic orientation.

Adult↗

Chylous ascites after abdominal aortic surgery.

Chylous ascites is an unusual postoperative complication that can lead to significant mechanical, nutritional, and immunologic consequences. We present the report of a patient with chylous ascites after abdominal aortic aneurysm repair. Paracentesis is essential for diagnosis and is often useful in the initial management of the patient with mechanical respiratory distress. Nonoperative management is appropriate, but careful attention must be given to the patient's nutritional status. Elemental diet supplementation or total parenteral nutrition may be necessary to minimize lymph flow. The sequestration of lymphocytes into the ascitic fluid may result in a profound decrease in absolute lymphocyte count. With appropriate nutritional support the prognosis of postoperative chylous ascites is excellent and reoperation rarely necessary.

Aged↗

[Pancreatogenic ascites].

Pancreatic ascites is a rare disease which is often misinterpreted as ascites secondary to alcoholic cirrhosis or to intraabdominal cancer. It can be diagnosed by a high protein and amylase/lipase content of the ascitic fluid. If diagnosis and subsequent surgery occur at an early stage, the prognosis is good. The natural course, therapy, prognosis, and pathogenesis of pancreatic ascites are discussed on the basis of experience with 7 patients.

Adolescent↗

The clinical value of ascitic fluid culture and leukocyte count studies in alcoholic cirrhosis.

Because of the paucity of studies establishing the accepted leukocyte count is sterile ascites, less than 300 WBC per mm3 with 25% polymorphonuclear (PMN) leukocytes, peritoneal fluid WBC counts and bacterial cultures were studied in 63 consecutive hospitalized patients with alcoholic cirrhosis and ascities. In 58 culture-negative patients the ascitic fluid WBC count range was 28 to 1800 and 50% of counts were greater than 300 WBC per mm3. The percentage of PMN leukocytes ranged from 2 to 98%. Five patients with spontaneous bacterial peritonitis (SBP), proven by positive cultures, had an ascitic WBC count range of 300 to 6320 WBC per mm3 and a PMN leukocyte range of 20 to 76%. Physical findings did not allow clear separation of the two groups. Anaerobic organisms were not found. It is concluded: (1) differentiation of SBP from sterile ascities relies on prompt ascitic fluid bacteriology; (2) the improved survival of 40% of SBP patients in this study may be related to an increased awareness of the entity and early treatment.

Adult↗

Identification of transforming growth factor-beta and interleukin-6 in chicken ascites fluid.

Ascites fluids from chickens were analyzed for the occurrence of transforming growth factor-beta (TGF-beta) and interleukin-6 (Il-6) using the mink lung epithelial cell inhibition and B9 hybridoma proliferation assays, respectively. Both of these cytokines were significantly elevated in ascites fluids (TGF-beta, 0.129 +/- 0.017 ng/mg protein; Il-6, 0.054 +/- 0.011 ng/mg protein) relative to serum (TGF-beta, 0.005 +/- 0.003 ng/mg protein; Il-6, < 0.002 ng/mg protein) derived from the same individual birds. TGF-beta occurred in a latent form and required activation by heat or acid (heat, 100%; non-activated, 5.2 +/- 1.1%; acid-activated, 89.5 +/- 12.3%). Heat treatment destroyed Il-6 activity. Both TGF-beta and Il-6 activities could be neutralized by antibodies directed against the recombinant human counterpart of these cytokines. Increasing dilutions of ascites fluid caused proportionate decreases in cytokine activities. Il-6 activity was further characterized by gel filtration using high-pressure liquid chromatography, which yielded a peak of biological activity corresponding to an approximate molecular weight of 35,000. These data suggest that ascites fluid may be an interesting biological model and source for studying avian cytokines and their physiological relevance.

Animals↗

[Pancreatico-peritoneal fistula in the newborn infant revealed by a hemorrhagic ascites].

Chronic haemorrhagic ascites in an infant is reported. After much hesitation without a definite diagnosis the first laparotomy was carried out and the estimation of amylase, lipase and proteolytic enzyme activities in the ascitic fluid suggested a pancreatic origin for the ascites. This was conformed at a second laparotomy when the condition was correted. This emphasises the importance of the estimation of pancreatic enzymes in unexplained ascites in children.

Ascites↗

[A case of ascites in the course of acute pancreatitis].

The case of acute alcoholic pancreatitis, complicated by internal pancreatic fistula is being reported. The general patients symptom in initial illness period was ascites in peritoneal cavity. Biochemical investigation of ascites has shown elevated activity of amylase and protein which is typical for pancreatic ascites. The late diagnosis of ascites cause (in 3rd week of the illness) and complications decreased efficacy of the treatment used (parenteral nutrition and somatostatin). Thus worse the course of the illness.

Acute Disease↗

Cerebrospinal fluid ascites.

Cerebrospinal fluid (CSF) ascites can be a refractory problem in the management of patients with hydrocephalus developing as a result of tuberculous meningitis. A young 17-year-old patient developed CSF ascites due to the drainage of CSF into the peritoneal cavity via a ventriculoperitoneal shunt. The ascites failed to resolve despite repeated courses of antituberculous chemotherapy. Eventually diversion of CSF away from the peritoneal cavity through a ventriculoatrial shunt relieved the ascites

Adolescent↗

Intractable ascites treated with peritoneovenous shunts (LeVeen). A 24- to 64-month follow-up of results in 52 alcoholic cirrhotics.

Peritoneovenous shunts (LeVeen) were placed in 52 patients with intractable ascites due to alcoholic cirrhosis between March 1975 and June 1978. The ascites was defined as intractable if it persisted despite at least six weeks of in-hospital medical management. Only 4.5% of such patients seen during this interval met this criterion by failing to respond to intensive drug and diet therapy. Eight (15%) died five to 60 days postoperatively; six of these did not undergo diuresis. Hepatic encephalopathy and sepsis were important contributing factors. There were 21 late deaths (mean survival, 16 months), primarily related to complications characteristic of this group of cirrhotics: upper gastrointestinal hemorrhage and infection. Twenty-three patients were alive by June 25, 1980, with mean survival of 46 months. Four patients operated on five or more years ago survive without ascites. An accurately placed LeVeen shunt dramatically relieves intractable ascites with improvement in renal function, nutrition, and general health. The operation enables at least partial rehabilitation so that ambulatory care becomes feasible for many of these chronically and seriously disabled patients.

Adult↗

Peritoneovenous shunt for refractory ascites: operative complications and long-term results.

We studied the clinical course of 35 patients with refractory ascites who underwent 51 peritoneovenous shunts. Nine of them had hepatorenal syndrome (HRS). Operative complications included shunt malfunction, shunt infection, ascitic leak, fluid overload, and disseminated intravascular coagulation. Two of the patients without HRS died postoperatively. The survival rate in this group was 67% at one year and 43% at two years. Ascites was completely controlled in 83% of the survivors at two months and 50% at two years. Neither survival nor shunt patency were predictable. The shunt reversed HRS in three patients, but failed to do so in the other six. Late complications included shunt malfunction and infection. During the first two years of follow-up, five patients bled from esophageal varices. Liver failure was the sole cause of late death. Peritoneovenous shunt should be reserved for patients with truly refractory ascites, for whom it provides excellent palliation.

Adolescent↗

The vasoactive properties of ascitic fluid in acute pancreatitis in a porcine model.

The hemodynamic effect of pancreatic ascitic fluid was studied in a porcine model. Pancreatitis was induced by a low-pressure infusion of trypsin and taurocholate sodium into the pancreatic duct. The ascitic fluid that accumulated was then injected into the inferior vena cava of five pigs, with each pig receiving five infusions at 40-minute intervals. Mean arterial blood pressure and peripheral vascular resistance fell with each infusion, while pulmonary artery pressure increased. The magnitude of the drop in arterial blood pressure decreased with subsequent infusions, suggesting tachyphylaxis. The rise in pulmonary artery pressure increased with successive infusions. Anesthesia artifact and decay of the pancreatic ascitic fluid were ruled out as causes of the tachyphylaxis. Filtration separated the substances producing pulmonary effects and systemic blood pressure effects (0.2 to 11 microns vs 10,000 daltons to 0.2 micron). These data suggest that two mediators may produce the hemodynamic effects of pancreatic ascitic fluid.

Animals↗

The cause of coagulopathy after peritoneovenous shunt for malignant ascites.

Thirty-five patients with malignant ascites who received a peritoneovenous shunt were studied to determine the type and duration of postoperative coagulopathy. Coagulation factors were measured before and on the first and third day after the placement of a Denver peritoneovenous shunt; 1 to 10 L of ascites was removed at operation. Levels of platelets, antithrombin III, plasminogen, antiplasmin, fibrinogen, and factors V and VIII decreased by the first postoperative day but did not change further through the third day. The levels of fibrinolytic split products increased on day 1 but were lower by day 3. The platelet count reduction by the third day correlated with the hematocrit change (-0.031). The prothrombin and activated partial thromboplastin times remained normal postoperatively. The patterns of change were similar for patients with positive (n = 18) and negative (n = 17) ascites cytologic findings, with elevated (n = 24) and normal (n = 11) preoperative fibrinolytic split product levels, and elevated bilirubin value (greater than 25 mumol/L; n = 9), and no jaundice (n = 26). Bleeding did not occur. The data indicated that plasminogen-rather than thromboplastin-activated fibrinolysis occurred and that platelet reduction was largely dilutional. The reactions were not progressive when ascites was removed operatively.

Adult↗

Pancreatic ascites and effusion. Risk factors for failure of conservative therapy and the role of octreotide.

The possible risk factors for failure of medical therapy were examined in 23 patients with pancreatic ascites or effusion. The ascites or effusion resolved completely in 10 patients after a mean (+/- SEM) of 30 +/- 2 days of conventional medical treatment. In five patients in whom conventional medical therapy failed, the addition of an octreotide (SMS 201-995) analogue to the medical therapy led to a resolution of the ascites (three patients) or effusion (two patients). Six patients underwent surgery after failed medical therapy, one patient died while receiving conservative therapy, and one patient refused hospital treatment. Serum sodium and albumin levels were significantly lower, and the ratio of total fluid protein to total serum protein was significantly higher in the group that failed to heal in response to conventional medical therapy. Nine of 11 patients with mild to moderately severe chronic pancreatitis healed in response to conservative therapy. Only one of 10 patients with advanced pancreatitis healed in response to conventional medical therapy. Our results suggest that a selective surgical approach is warranted to treat pancreatic ascites and effusion. In patients with mild or moderately severe pancreatitis, medical therapy is recommended. Patients with advanced pancreatic disease should be selected for early surgery. Octreotide may be useful in the patient in whom surgery may be associated with a prohibitive morbidity or mortality.

Ascites↗

Cure of malignant ascites and generation of protective immunity by monoclonal antibody-targeted activation of a glucuronide prodrug in rats.

We examined the in vivo efficacy of targeting beta-glucuronidase (betaG) to activate a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at hepatoma ascites in Sprague-Dawley rats. Injection i.p. of 500 microg RH1-betaG, a conjugate formed between recombinant betaG and monoclonal antibody RH1 with specificity for an antigen expressed on AS-30D rat hepatoma cells, into rats bearing AS-30D ascites resulted in the accumulation of 54 microg conjugate per 10(9) tumor cells after 2 hr. Ascites fluid and serum contained 0.53 and 0 microg/ml, respectively, RH1-betaG 2 hr after injection of the conjugate. Conjugate binding to AS-30D cells was heterogeneous and non-saturated, as determined by flow cytometry. BHAMG was less toxic than pHAM to SD rats based on measures of animal mortality, weight loss and hematological toxicity. Treatment of rats bearing established hepatoma ascites with 500 microg RH1-betaG followed 2 hr later with a single i.p. injection of 30 mg/kg BHAMG or 3 i.p. injections of 10 mg/kg BHAMG 2, 3 and 4 hr later resulted in the cure of 6/8 and 8/8 animals, respectively. Treatment with BHAMG or pHAM alone did not produce cures, whereas treatment with a control antibody-betaG conjugate and BHAMG produced significantly greater hematological toxicity compared to treatment with RH1-betaG and BHAMG. All cured rats were completely protected from rechallenge with 2 x 10(7) AS-30D cells, indicating that successful treatment of animals induced protective immunity.

Aniline Mustard↗

Coagulative and fibrinolytic properties of ascitic fluid associated with ovarian tumors.

Ascitic fluid samples from 19 patients with ovarian carcinoma, 3 with a benign ovarian tumor, and 5 with cirrhosis of the liver were examined for their content of coagulation factors and components of the fibrinolytic system. The concentration of trypsin inhibitors in the ascitic fluid was significantly higher in the presence of carcinoma. Large amounts of FDP were found in the ascitic fluid in all patients with malignant tumors, but not in the other two groups. Determination of FDP may therefore make it possible to differentiate between malignant and nonmalignant ascitic fluid.

Alpha-Globulins↗

Peritoneovenous shunt for palliation of malignant ascites.

Forty patients with malignant ascites refractory to conventional medical management had peritoneovenous shunt for palliation. The shunt provided effective palliation in 28 with decrease in weight, abdominal girth, number of paracenteses required and increase in urine output. These patients also had improvement in strength, appetite and ambulation. Complications such as hemodilution, volume overload, and sepsis do not contraindicate surgery. In 12 patients with high ascitic fluid protein content (4.5 g/liter) and a large number of malignant cells, loculated ascites and prior severe renal and cardiac disease, the shunt did not provide palliation. Peritoneovenous shunt appears to provide effective palliation in carefully selected patients with refractory malignant ascites.

Aged↗

Selection of patients with malignant ascites for a peritoneovenous shunt.

Twenty-two patients with intractable malignant ascites who received a peritoneovenous shunt were studied. We found that the peritoneovenous shunt functioned longer in patients whose ascitic fluid was negative for malignant cells. The median shunt survival in alive patients in the negative cytologic group was 140 days compared to 26 days in the positive cytologic group (P = 0.01). The overall survival of these patients was poor, with a median of 32 days. Median survival of patients with positive cytologic results (26 days) was significantly worse than for the cytologically negative group (80 days; P = 0.05). The incidence of tumor emboli, confirmed at autopsy, was estimated to be about 5%. Seventy-five percent of all complications occurred in the group of patients with a positive cytologic result. We conclude that a positive ascites fluid cytologic finding is a relative contraindication to placement of a peritoneovenous shunt since this is associated with early shunt failure, postoperative coagulopathy, infection, and tumor emboli. However, since the serious complication rate is only 4% and tumor emboli rate 5%, peritoneovenous shunting in symptomatic patients with cytologically negative malignant ascites is a useful palliative procedure.

Adult↗