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Replication of hepatitis C virus in ascitic mononuclear cells with development of distinct viral quasispecies.

To investigate whether distinct compositions of viral quasispecies developed in the ascitic fluid of patients with late-stage chronic hepatitis C virus (HCV) infection, samples of various origins, including ascitic fluid and ascitic mononuclear cells (AMCs), were analyzed by the method of single-strand conformation polymorphism (SSCP). Subsequently, the major species were isolated, sequenced, and subjected to phylogenetic analysis. Of 42 patients analyzed, HCV-RNA was detectable in the AMCs of 25 patients. SSCP analysis indicated that the compositions of viral quasispecies among samples of different origins were markedly different in this group of patients. Phylogenetic analysis revealed that the ascitic-fluid-derived clones were most closely related to the AMC-derived clones. Minus-strand HCV-RNA was detectable in 5 of them. Our data suggest that HCV can replicate in the AMCs of patients with late-stage chronic HCV, which results in the development of distinct viral quasispecies.

Adult↗

Whole-body and segmental bioelectrical-impedance analysis in patients with cirrhosis of the liver: changes after treatment of ascites.

Bioelectrical impedance analysis (BIA) is a simple technique for determining body water and calculating body composition. It has been validated in healthy control subjects but not in patients with liver disease. We examined the ability of BIA to detect changes in total body water (TBW) due to removal of ascites. In 12 cirrhotic patients, BIA of the whole body and of body segments was performed before and after treatment of ascites with paracentesis (n = 12) and diuretics (n = 2). TBW changes predicted by BIA, by using two prediction equations, were significantly less than body weight changes (51% and 45% of the weight loss). BIA of body segments showed highly significant changes in both the trunk and the leg and small changes in the arm. These data indicate that BIA of the whole body is not a suitable technique for monitoring fluid changes in cirrhotic patients with ascites. Changes in BIA of body segments may be due to mobilization of edema after the removal of ascites.

Adult↗

Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells.

Autophagy, measured as the sequestration of an endogenous cytosolic enzyme (LDH), showed a progressive rate reduction during diethylnitrosamine-induced rat liver carcinogenesis. In primary hepatocellular carcinomas the autophagic activity was only one-fourth of that seen in normal hepatocytes. Reduced autophagy was also observed in peritumorous hepatocytes and in cells from preneoplastic liver, and a complete suppression of autophagic protein degradation was seen in normal hepatocytes treated with ascitic fluid from an ascites hepatoma, suggesting that tumour cells and their precursors may produce autophagy-suppressive factors with an autocrine and paracrine action. In cells from the transplantable rat ascites hepatoma, Yoshida AH-130, autophagic activity was negligible during active (logarithmic) growth, but increased to approximately 0.4%/h at high cell density, i.e. in stationary phase. In contrast to normal hepatocytes, autophagy in the AH-130 cells was not inhibited by ascitic fluid. The hepatoma cells would thus appear to have lost some aspects of autophagy regulation while retaining others. However, even the highest rate of hepatoma cell autophagy was only one-tenth of the maximal activity seen in normal hepatocytes, confirming the hypothesis that reduced autophagy may be an important aspect of growth deregulation in liver cancer.

Animals↗

Massive ascites due to abdominal pregnancy.

We describe a case of an abdominal pregnancy which presented in the first trimester with rapid accumulation of blood stained ascites. The ascites resolved completely following surgical removal of a gestational sac from the peritoneal cavity. The pathophysiology of ascites in this case may be similar to that in cases of ascites in other non-malignant gynaecological conditions.

Adult↗

Phase II study of sequential methotrexate and 5-fluorouracil chemotherapy against peritoneally disseminated gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial.

BACKGROUND: The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting. METHODS: The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration. RESULTS: Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%). CONCLUSIONS: Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.

Adult↗

Conversion of a poorly differentiated human adenocarcinoma to ascites form with invasion and metastasis in nude mice.

Cells (1 X 10(7)/0.5 ml) from a Borrmann type III poorly differentiated adenocarcinoma of the human stomach were injected ip into nude mice. The injection resulted in ascites carcinoma with invasion (carcinomatous peritonitis) and liver metastasis. The inoculum was obtained from subcutaneous tumors at passage 9 in nude mice that had received serial transplants from the patient with Borrmann type III poorly differentiated adenocarcinoma of the stomach. Serial transfers of 1.5 X 10(6) dispersed cancer cells/0.5 ml into the peritoneal cavity of nude mice converted this adenocarcinoma to an ascites form. Hemorrhagic ascites accumulated within 3 weeks at the first passage and 4-6 weeks in serial passages. Carcinomas peritonitis occurred consistently and was observed in the diaphragm, mesenteries, omentum, and pancreas; metastases were seen in the liver and spleen. Subsequently, iv injection of ascites at passage 3 (6 X 10(5) cells/0.2 ml) into nude mice produced metastatic lesions in the lung and the heart. The histology of the invasive and metastatic lesions in the nude mice was similar to that of the original tumor in the patient with stomach carcinoma.

Adenocarcinoma↗

Hepatocyte growth factor in ascites from patients with cirrhosis.

Hepatocyte growth factor (HGF) stimulating DNA synthesis of adult rat hepatocytes in primary culture was found in the ascites and plasma from patients with liver cirrhosis, but not in those from patients without cirrhosis. HGF was purified about 400-fold in 10% yield from cirrhotic ascites by ultrafiltration, cation-exchange chromatography on a S-Sepharose column, and affinity chromatography on a heparin-Sepharose CL-6B column. The partially purified factor was a heat- and acid-labile cationic protein with a molecular weight of 100,000-150,000. Its effect was half-maximal at 3.8 micrograms/ml, and was additive with those of insulin and epidermal growth factor. HGF in ascites from patients with cirrhosis had the same properties as HGF purified and characterized from rat platelets. These findings suggest that HGF is secreted into the ascites from the plasma or liver of patients with cirrhosis and may increase in the plasma with the development of hepatic impairment and act in repair of the damaged liver of patients with chronic liver disease.

Adult↗

Intermittent lighting reduces the incidence of ascites in broilers: an interaction with protein content of feed on performance and the endocrine system.

An experiment with 840 day-old male broiler chicks (Ross) was initiated to investigate the effect of intermittent lighting schedules, combined with two isocaloric feeds differing in protein content, on ascites mortality. At 9 d of age, chicks were randomly distributed over two rooms: one room with a 23 h light(L):1 h dark (D) lighting schedule (CL), and another room with an intermittent lighting schedule (IL, 1L:3D). In each room, two isocaloric feeds differing in CP content, supplemented or not supplemented with 1.5 ppm triiodothyronine (T3), were provided. The experiment was repeated under identical conditions except that lighting schedules were changed between rooms. From Day 14 onwards, biweekly growth and feed intake were determined and feed conversion (FCR) was calculated. Daily mortality was recorded and necropsies were performed. Weekly blood samples were taken from 10 randomly chosen birds per experimental group for measurements of growth hormone (GH), thyroid hormones [thyroxine (T4) and triiodothyronine (T3)], and hematocrit values. Birds reared in IL manifested a more concave growth trajectory than those in CL, which was associated with a lower FCR and higher plasma GH levels during the finisher period. Mortality due to ascites was markedly increased by dietary T3 supplementation. In hyperthyroid chickens, ascites mortality was lower in IL than in CL and lower in birds fed normal protein than in those fed subnormal protein levels. Dietary T3 decreased plasma GH and T4 levels, whereas T3 levels were increased. It is concluded that IL or a higher protein content of the feed reduces the incidence of T3-induced ascites mortality. Possible causal mechanisms are discussed.

Animal Feed↗

Broiler breeder survivors of chronic unilateral pulmonary artery occlusion produce progeny resistant to pulmonary hypertension syndrome (ascites) induced by cool temperatures.

Chronic occlusion of one pulmonary artery triggers a high incidence of pulmonary hypertension syndrome (PHS, ascites) in broilers. In the present study, the left pulmonary artery was chronically occluded in 295 male and 255 female chicks pedigreed from 18 sire families, leading to PHS in 74% of the males and 45% of the females. Survivors were reared to breeding age and served as parents for the resulting PHS-resistant chicks (Resistant), whereas control chicks were produced from the base population for this line (Base). In two experiments, male and female Resistant and Base chicks were reared separately by sex but mixed by group within environmental chambers, where they were exposed to cool (14 C) temperatures. In both experiments, the incidence of PHS was at least 50% lower in the Resistant males and females than in the Base males and females, respectively. When compared within a sex, the Base and Resistant broilers surviving to the end of both experiments did not differ in final body weight or body weight gain, nor did their right:total ventricular weight (RV:TV) ratios differ. These results demonstrate that broiler breeders capable of thriving after having their entire cardiac output forced to flow through one lung, subsequently produced male and female progeny with substantially improved resistance to the onset of PHS induced by fast growth and exposure to cool environmental temperatures. Fast growth and cool temperatures are primary triggers for PHS under most conditions of commercial broiler growout. In both experiments, final necropsies revealed higher RV:TV ratios in ascitic than in nonascitic broilers, whereas normalizing the left ventricle plus septum weight for differences in body weight generated similar values for ascitic and nonascitic males or females, respectively. These results support a primary role for pulmonary hypertension but not cardiomyopathy in the pathogenesis of ascites triggered by cool temperatures in both the Base and Resistant populations.

Animal Husbandry↗

Growth performance, carcass characteristics, and the incidence of ascites in broilers in response to feed restriction and litter oiling.

The effect of feed restriction and the application of canola oil to broiler straw litter to contain respirable dust on growth performance, carcass traits, and the incidence of ascites was evaluated with 800 male broilers studied in two 6-wk periods. Two pens of birds were feed restricted. Two pens of birds received feed ad libitum for the 6-wk trial. One restricted and one ad libitum pen received biweekly addition of canola oil to the litter. At 6 wk of age, 30 birds from each pen were killed for determination of breast muscle, fat pad, and heart weights. All birds were scored for the incidence of ascites at processing. A cross sectional image of each heart was digitally recorded and, using image analysis, the right ventricular area (RVA), left ventricular area (LVA), and total heart area (HA) were determined. The right ventricular wall was removed and its weight was expressed as a percentage of total heart weight (PRVW). The 40-d BW was significantly greater in the ad libitum birds (2.07 kg) than in the feed-restricted birds (1.86 kg). The right ventricular weight (RVW) (1.69 and 1.92 g) and the RVA (0.35 and 0.40 cm2) were also significantly different between the two feeding treatments. The ascites score was significantly correlated to the RVW (r = 0.50) and RVA (r = 0.52). The RVA was also correlated to the RVW (r = 0.63). Oiling the litter did not result in differences in carcass characteristics. Litter oiling significantly reduced the RVA of the ad libitum birds (0.36 cm2) compared to the ad libitum birds that did not have oiled litter (0.44 cm2). Feed restriction reduced the incidence of ascites, but also reduced gain. Litter oiling in the feed-restricted groups reduced the RVA, but did not reduce mortality.

Adipose Tissue↗

Direct and maternal genetic effects for ascites-related traits in broilers.

The objective of the present study was to estimate heritabilities for ascites-related traits in broilers and to assess the importance of maternal genetic effects for these traits. Several traits related to ascites were measured on more than 4,000 broilers kept under cold conditions. Heritabilities were estimated using an animal model with a direct genetic effect and a model with direct and maternal genetic effects. Estimated heritabilities from the direct genetic effects model were 0.46 for hematocrit value, 0.42 for BW, 0.47 for right ventricular weight, 0.46 for total ventricular weight, 0.45 for ratio of right ventricular weight to the total ventricular weight, 0.32 for total mortality, and 0.18 for fluid accumulation in the heart sac. Maternal effects significantly influenced the traits BW, total ventricular weight, and total mortality. Direct and maternal heritabilities, respectively, for BW were 0.21 and 0.04, for total ventricular weights were 0.29 and 0.03, and for total mortality were 0.16 and 0.05. The heritability estimates for ascites-related traits and the significance of maternal genetic effects for most of these traits indicate that direct and maternal genetic effects play an important role in the development of the ascites syndrome.

Acclimatization↗

Sequence analysis of bone morphogenetic protein receptor type II mRNA from ascitic and nonascitic commercial broilers.

Ascites syndrome, also known as pulmonary hypertension syndrome (PHS), is a common metabolic disorder in rapidly growing meat-type chickens. Environmental factors, such as cold, altitude, and diet, play significant roles in development of the disease, but there is also an important genetic component to PHS susceptibility. The human disease familial primary pulmonary hypertension (FPPH) is similar to PHS in broilers both genetically and physiologically. Several recent studies have shown that mutations in the bone morphogenetic protein receptor type II (BMPR2) gene are a cause of FPPH in humans. To determine whether mutations in the chicken BMPR2 gene play a similar role in PHS susceptibility, BMPR-II mRNA from ascitic and nonascitic commercial broilers were sequenced and compared with the published Leghorn chicken BMPR-II mRNA sequence. Fourteen single nucleotide polymorphisms (SNP) were identified in the commercial broiler BMPR-II mRNA. No mutations unique to ascites-susceptible broilers were present in the coding, 5' untranslated or 3' untranslated regions of BMPR-II mRNA. The twelve SNP present within the coding region of BMPR-II mRNA were synonymous substitutions and did not alter the BMPR-II protein sequence. In addition, analysis of BMPR2 gene expression by reverse transcriptase-PCR indicated that there were no differences in BMPR-II mRNA levels in ascitic and nonascitic birds. Therefore, it appears unlikely that mutations in the BMPR2 gene were responsible for susceptibility to PHS in these commercial broilers.

Animals↗

Graded atmospheric oxygen level effects on performance and ascites incidence in broilers.

The effects of graded atmospheric O2 concentration (12, 14, 16, 18, and 20.6%) on chick performance and propensity to develop ascites were investigated using commercial male broilers. Chicks were housed in calorimetry chambers for 2 wk with incoming air diluted with N to provide the desired O2 concentration at thermoneutral (TN) ambient temperature. Day 14 body weight, weight gain, feed consumption, and gain-to-feed ratio increased (P < 0.01) as O2 concentration incrementally rose from 12 to 20.6%. Body weight was 138 g for the lowest atmospheric O2 level compared to 371 g for 20.6% O2. The greatest treatment difference occurred between the 12 and 14% O2 concentrations. Growth depression appeared related to feed consumption. Ascites heart ratio (AHR), ascites score (AS), right ventricular mass (RVM), and hematocrit (HCT) all increased (P < 0.01) as O2 concentration decreased. Blood HCT appeared to be a more sensitive indicator of physiological change attributable to atmospheric O2 than AHR, AS, or RVM. The data reported herein suggests that 19.6% atmospheric O2 is the minimal allowable level for housing birds within a relatively stress-free, TN environment to avoid cardiac and HCT changes related to ascites.

Altitude↗

Effect of age of feed restriction and microelement supplementation to control ascites on production and carcass characteristics of broilers.

Three experiments were conducted, from January until September 2001, to estimate the optimized age to apply feed restriction to control mortality from ascites, with no negative effects on production and carcass characteristics of broilers. For each experiment, 1,200 1-d-old mixed Ross x Peterson chicks were reared in floor pens (50 chicks in each) and fed commercial feed. Feed restriction was applied for 8 h/d for 14 d at 21 or 28 d of age in experiment 1, 14 or 21 d in experiment 2, and 7 or 14 d in experiment 3. In experiments 2 and 3, a microelement supplement (without or with) was tested; the control groups received feed ad libitum and no supplement. Body weight gain, feed conversion, total mortality, and mortality from ascites, leg problems, and carcass characteristics were considered at the end of each experiment. The data were analyzed as a completely randomized design, or as a 2 x 2 factorial to estimate main and interaction effects (experiments 2 and 3). Additional analyses, including the control, were done; means comparisons were by orthogonal contrasts. The production and carcass characteristics of the restricted groups were lower than the control but were not statistically different in experiments 2 and 3, although the optimized age for feed restriction was at 7 d. Total mortality and mortality from ascites decreased by restriction, but leg problems increased without supplement. The results indicated that quantitative feed restriction and microelement supplementation at 7 d of age reduced mortality from ascites and leg problems and permitted compensatory growth sufficient to equal the production characteristics of the control group at 49 d of age. However, it is necessary to determine the specific microelements to be supplemented and to estimate the effects of season and genetic line.

Animal Feed↗

Case report: hepatic hydrothorax without ascites.

Pleural effusion due to hepatic cirrhosis and ascites is well known. We describe three patients with right-sided hepatic hydrothorax in the absence of ascites. The formation of pleural fluid in these patients is probably a result of fluid movement from peritoneal to pleural space across diaphragmatic defects before ascites can form. The differential diagnosis of a right-sided transudative pleural effusion in a patient with chronic liver disease with or without ascites includes congestive left ventricular failure and nephrotic syndrome. These diseases are usually ruled out with standard clinical tests. Patients with hepatic hydrothorax should be treated with fluid restriction and diuretics. Patients with severe symptoms due to refractory hepatic hydrothorax might benefit from pleural sclerosis and surgical closure of diaphragmatic defects.

Adult↗

Myxedema ascites with elevated serum CA 125 concentration.

We report a case of myxedema ascites and markedly elevated serum CA 125 concentration. The cause of ascites and elevated tumor markers in hypothyroidism remains unknown. Diagnosis was characterized by no evidence of malignancy seen by transvaginal ultrasonography or abdominal computed tomography and ascites resolution with serum CA 125 normalization after adequate hormonal treatment. Our data suggest that hypothyroidism should be considered in patients with ascites and elevated serum CA 125.

Aged↗

Management of groin hernias in patients with ascites.

The records of 18 cirrhotic patients with ascites and groin hernias (20 inguinal and one femoral) were retrospectively reviewed. Eleven patients underwent repair of their groin hernias (total of 13 repairs). Ten herniorrhaphies were performed electively, two were performed urgently because of recent difficult reduction, and one was performed emergently for incarceration without strangulation. No major and four minor postoperative complications occurred. There were no perioperative deaths or ascites leaks. Of the 13 hernias in 11 patients undergoing repair, 12 (92%) were available for follow-up. In this group, the 12 groin hernia repairs were followed for a mean of 25 months. One recurrence (8%) occurred 11 months after repair. In this same group of patients, five umbilical hernias were repaired, with three recurrences (60%). From this retrospective study, it appears that serious complications from groin hernias in cirrhotics are not common, and elective repair can usually await control of ascites. Additionally, for appropriately selected patients with ascites, elective inguinal hernia repair can be performed safely, with an acceptable rate of recurrence.

Adult↗

Hepatic perfusion scintigraphy. Relationship of liver perfusion and ascites in patients with liver cirrhosis.

Radionuclide studies were performed on 38 patients with biopsy proven liver cirrhosis in an attempt to evaluate the interrelationship between liver perfusion and ascites in cirrhotic patients. Quantitative hepatic scintigraphy was used to evaluate the relative contribution of hepatic arterial and portal venous blood flow to the hepatic circulation. Using a gamma camera and on-line computer system, a bolus of 370 MBq Tc-99m pertechnetate was injected intravenously. Time activity curves of the abdominal aorta and right lobe of the liver were obtained using a region of interest analysis where arterial and portal components were calculated. Ascites was determined by clinical examination and by ultrasonography. Of 38 patients, 10 patients (26.3%) showed normal liver perfusion (group A), 22 patients (58%) showed reduced portal venous perfusion (group B), and 6 patients (15.7%) showed pure arterial hepatic perfusion (group C). The incidence, as well as the advancement, of ascites were significant (P < 0.05) and were most frequent in group C, frequent in group B, and less frequent in group A. The results of this study suggest that the development of ascites in patients with liver cirrhosis is closely correlated with the reduction in portal blood perfusion.

Adult↗