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Distribution of ceftazidime in ascitic fluid.

The pharmacokinetics of ceftazidime were investigated in eight normal subjects and eight patients with ascites after intravenous administration of 1 g of the drug. Samples of blood and ascitic fluid were collected for 6 h after dosage, and urine samples were collected for 24 h. Pharmacokinetic data were calculated by using a one-compartment model. The apparent volume of distribution and half-life of elimination (t1/2 beta) in patients with ascites were approximately three times those in normal subjects. In contrast, renal clearance was greater in the normal subjects. With respect to ascites, the mean area under the concentration-time curve was 95.3 +/- 38.3 micrograms X h/ml. The mean ratio of the area under the concentration-time curve for ascitic fluid to that for plasma was 69.9% (+/- 38.2). These data show that ceftazidime rapidly diffuses into the peritoneal space, in which concentrations greater than 10 micrograms/ml were present for at least 6 h.

Adult↗

Morbidity and mortality after peritoneovenous shunt surgery for refractory ascites.

A prospective analysis of the morbidity and mortality after peritoneovenous shunting was carried out in 25 patients who had a total of 27 shunts for refractory ascites. Major complications were limited to the patients in whom ascites was secondary to hepatic rather than peritoneal disease. Immediate postoperative complications followed 17 out of the 23 shunts carried out in patients with liver disease and included septicaemia (two), profound hypotension (two), pulmonary oedema (one), and clinically evident disseminated intravascular coagulation (14). Long term morbidity was again limited to the patients with liver disease and included chronic shunt infection (two) and major venous thrombosis (two). Shunt associated mortality was only seen in the patients with liver disease. Despite late shunt blockage in five long term survivors with alcoholic liver disease fluid retention was easily controlled by simple medical means probably because of improved liver function associated with abstinence from alcohol. It is concluded that: (1) patients with hepatic and malignant ascites respond differently to the insertion of a peritoneovenous shunt; (2) Shunt patency should be monitored regularly in patients with liver disease and, because of the potential for septic and thrombotic complications, if blocked the shunt should be removed and; (3) because of the morbidity and mortality of peritoneovenous shunt surgery in patients with liver disease and refractory ascites, an alternative mode of therapy, such as repeated ultrafiltration and reinfusion of ascitic fluid, may be a more effective initial therapeutic approach especially in patients in whom there is a reversible element to their underlying liver disease.

Ascites↗

Abdominal decompression plays a major role in early postparacentesis haemodynamic changes in cirrhotic patients with tense ascites.

BACKGROUND: Some cirrhotic patients with tense ascites who undergo paracentesis develop a circulatory dysfunction syndrome, manifested by an increase in plasma renin activity. Recently, a significant inverse correlation between postparacentesis changes in plasma renin activity and systemic vascular resistance has been demonstrated in these patients, suggesting that peripheral arterial vasodilatation could be responsible for this circulatory dysfunction, but the mechanisms by which tense ascites removal induces such changes are unknown AIM: To investigate the role of a decrease in intra-abdominal pressure (IAP) in the development of early postparacentesis haemodynamic changes METHODS: Eleven cirrhotic patients with tense ascites received a large volume paracentesis. A specially designed pneumatic girdle was used to compress the abdomen to avoid a decrease in IAP during ascites removal. Haemodynamic studies were performed before paracentesis, one hour after ascites flow stopped, and 30 minutes after pneumatic girdle deflation RESULTS: When IAP was maintained at its original level, no haemodynamic changes were observed, despite large volume paracentesis. However, a significant decrease in systemic vascular resistance was seen immediately after pneumatic girdle deflation CONCLUSIONS: Early haemodynamic changes after paracentesis are avoided if IAP is maintained at its original level. The abrupt decrease in IAP could be the trigger for the development of the initial haemodynamic changes that eventually produce postparacentesis circulatory dysfunction.

Abdomen↗

Increased tumour necrosis factor alpha production in mesenteric lymph nodes of cirrhotic patients with ascites.

BACKGROUND: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with bacterial translocation may participate in circulatory alterations of cirrhosis. AIM: To investigate whether cirrhotic patients present an increased local generation of cytokines in mesenteric lymph nodes. METHODS: Mesenteric lymph nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis factor alpha (TNF) and interleukin 6 mRNA and protein expression by competitive reverse transcription-polymerase chain reaction, and by enzyme immunoassay and immunohistochemistry, respectively. RESULTS: Interleukin 6 levels were not different between cirrhotics and controls. Protein and mRNA TNF levels in mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05). Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics. Ascitic patients showed higher TNF levels (47 (34-54) pg/mg protein) than patients without ascites (18 (17-25) pg/mg protein) (p<0.001). Elevated TNF levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin and blood TNF levels. The strongest association, confirmed by multivariate analysis, was with the presence of ascites (p<0.001). Bacterial infections after transplantation, mainly by enteric bacteria, were only detected in patients with high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). CONCLUSION: Patients with advanced liver cirrhosis, and especially with ascites, have increased local production of TNF in mesenteric lymph nodes that, in common with experimental cirrhosis, may also be induced by bacterial translocation.

Ascites↗

Heterogeneity of alkaline ribonuclease in the mouse and Ehrlich ascites cells.

The specific activity of alkaline RNase II was l00 to 1800 times higher in mouse pancreas than in mouse liver, serum, ascites fluid, and Ehrlich ascites cell grown intraperitoneally. Ehrlich ascites cells grown in cell culture medium had a much lower alkaline RNase II activity than cells grown intraperitoneally. Chromatography on CM-52 cellulose of acid- and heat-treated preparations showned a considerable heterogeneity of the mouse enzymes. Depending on the source of the extract, two to six forms fo alkaline RNase were eluted. Pancreatic extract contained two RNase forms. These also seemed to be present as minor components in preparations from other sources except Ehrlich ascites cells grown in vitro. Ehrlich ascites cells grown in vivo contained forms of the RNase which were not present in other extracts. Possible reasons for this heterogeneity were investigated. In addition to their stability to acid and heat the different RNase forms were similar in that they were much more active at alkaline pH than at acidic pH, they did not require divalent metal ions for activity, and they degraded RNA 'endonucleolytically.' Also, native DNA, denatured DNA, and poly A were poor substrates compared with RNA. Some differences seemed to exist, however, with respect to their abilities to degrade poly U and poly C and their sensitivities to the endogenous RNase inhibitor.

Animals↗

Neonatal ascites due to lysosomal storage disease.

The clinical and radiographic features of four newborns with lysosomal storage disease (LSD) in whom the dominant presenting clinical feature was ascites are presented. The diseases included infantile Gaucher disease, GM I gangliosidosis, infantile sialidosis, and Salla disease. Abdominal distention due to ascites and hepatosplenomegaly, and hypoplastic lungs were seen in all four infants. In the infant with Gaucher disease, the ribs and long bones were markedly thinned. Varying degrees of coarsening of the trabecular pattern of the bones and thinning of the cortex, and a lack of modeling were seen in all patients. Metaphyseal irregularity was noted in the patients with sialidosis and Salla disease. These skeletal radiographic findings may alert the radiologist to the cause for ascites in these patients, which is obscure. In all four patients, there was a history of perinatal death due to the same disease in a sibling; ascites was present in three of the siblings. The diagnosis was missed at autopsy in each of these siblings, underlining the lack of awareness of LSD as a cause for neonatal ascites.

Ascites↗

A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian cancer.

PURPOSE: To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses of the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and cytomorphometric biomarkers in cancer cells collected from ascitic fluid before and after treatment. METHODS: Twenty-two naive patients with ascitic ovarian cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area, DNA index, and chromatin texture) were determined in ascitic cells. Drug levels were measured by high-performance liquid chromatography. RESULTS: Doses up to 800 mg/d were well tolerated, and no adverse reactions occurred. There was no effect of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75% of subjects, and cytomorphometric variables, which were assessed in 80% of subjects. Plasma retinol levels were significantly lower in affected women than healthy donors. 4-HPR plasma concentrations increased slightly with increasing doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in malignant ascitic cells and tumor tissue were higher than in plasma but were 50 and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1 micromol/L 4-HPR. CONCLUSIONS: Cell biomarkers can be measured in ascitic cells to assess drug activity. Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention.

Adult↗

Vascular endothelial growth factor trap combined with paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model.

Ovarian cancer is characterized by i.p. carcinomatosis and massive ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis and vascular leakage leading to ascites. We assessed the efficacy of a soluble decoy receptor (VEGF Trap) combined with paclitaxel, in a mouse model of human ovarian cancer. Tumor burden after VEGF Trap plus paclitaxel was reduced by approximately 98% versus controls. No measurable ascites developed in the treated group. Morphologic studies showed that most residual tumor had degenerative changes. Diaphragmatic and hepatic tumors were not found in the VEGF Trap plus paclitaxel group in contrast to controls, indicating lack of metastasis. In vivo FITC-lectin tumor vessel imaging showed sparse, short, straight vessels in treated mice as compared to controls, in which vessels were numerous, irregular, tortuous, and leaky. In a survival study, all controls underwent euthanasia between 29 and 58 days after tumor cell inoculation (cachexia, extensive ascites, and tumor masses). In the VEGF Trap plus paclitaxel group, mice were ambulating and eating normally with no signs of disease for at least 81 days after tumor cell inoculation, and survival occurred for 129.9 +/- 38.88 days with no further treatment. We conclude that combination therapy with VEGF Trap plus paclitaxel may provide a novel, long-lasting therapeutic strategy for treatment of patients with ovarian cancer associated with ascites.

Analysis of Variance↗

A new chemosensitivity assay for ascites tumor cells using a thermoreversible gelation polymer as a culture medium and the observed clinical responses.

BACKGROUND/AIM: Ascites tumor cells from patients with peritonitis carcinomatosa were tested for cis-diamminedichloroplatinum (CDDP) sensitivity. The patients were divided into CDDP-sensitive and resistant groups. Survival and time to progression (TTP) rates were compared. MATERIALS AND METHODS: 18 peritonitis carcinomatosa patients with class V ascites based on cytologic diagnosis were enrolled in this study. Chemosensitivity testing of the ascites tumor cells was done to determine their sensitivity to CDDP using a three-dimensional culture matrix of thermoreversible gelation polymer (TGP). CDDP at a dose calculated to achieve ascitic fluid drug levels equivalent to the IC(50) was given intraperitoneally to 12 CDDP-sensitive patients and 6 CDDP-resistant patients. RESULTS: Both the median survival time and the median TTP were significantly longer in CDDP-sensitive patients than in CDDP-resistant patients (survival time 105 vs. 13 days, p = 0.019; TTP 90 vs. 5 days, p = 0.029). CONCLUSION: The results indicate the potential feasibility of controlling ascites in cancer patients in whom a maximal dose effect can be achieved with a minimal dose of chemotherapy.

Aged↗

Toxic products in hemorrhagic ascitic fluid generated during experimental acute hemorrhagic pancreatitis in dogs and a treatment which reduces their effect.

Toxic substances produced in hemorrhagic ascitic fluid during experimental hemorrhagic pancreatitis in dogs were investigated. An average of 394 ml of ascitic fluid was produced within 5 h after the induction of acute pancreatitis by intraductal injection of a mixture of autologous bile and trypsin. Hemorrhagic ascitic fluid was collected under sterile conditions, which was confirmed by aerobic and anaerobic culture and a Limulus test. The sterile fluid was injected intraperitoneally into mice in doses of 2 and 3 ml, and the mortality rate 72 h after injection was 66.0 and 88.4%, respectively. It contained high concentrations of pancreatic enzymes, including trypsin and esterase activity, as well as bradykinin, histamine and prostaglandin. Autopsy and histological examination of mice revealed shock with lung damage. The results suggest that hemorrhagic ascitic fluid produced in pancreatitis may be an important factor for early deaths in acute pancreatitis. When a new synthetic antiprotease (nafamstat mesilate) in a dosage of 0.2 mg was mixed with 1 ml of ascitic fluid, trypsin was not detectable, and bradykinin was reduced 1.0 ng/ml from 8.0 ng/ml, while esterase activity decreased to one tenth of its previous activity. The mortality following injection of the solution decreased to 26.7 and 80.6%, respectively. These results indicate that peritoneal lavage with a solution containing antiprotease may be an effective treatment for hemorrhagic acute pancreatitis.

Acute Disease↗

Immunosuppression related to ascitic fluid in patients with ovarian carcinoma.

The immune response to SRBC (PFC assay) was suppressed in mice injected with cell-free ascitic fluid from patients with ovarian carcinoma. The immunosuppressive effect of ascitic fluid obtained from stage IV patients was stronger than that of stage III patients. These data were correlated with the patient's immune status (number of E and EAC rosettes, PHA reactivity of lymphocytes, skin reactivity in recall antigens) and with changes in protein fractions in the serum and ascitic fluid. A good correlation was found between the immunosuppressive effect in the mouse PEC assay and the increased quantity of alpha-1-globulins in ascites. Skin nonreactivity to PPD also correlated with the immunosuppressive effect of ascitic fluid. However, the lymphocyte response to PHA and the numbers of E and EAC rosettes did not correlate either with skin reactivity or recall antigens or with the suppression of PFC response in mice.

Adult↗

Gastrointestinal stromal tumor in ascitic fluid. A case report.

BACKGROUND: There are few published data on the cytologic features of gastrointestinal stromal tumors (GISTs) in ascitic fluid and whether these features may mimic those of other malignancies. CASE: An 80-year-old woman presented with ascitics associated with multiple intraperitoneal masses. Cytologic examination of the ascitic fluid showed numerous three-dimensional clusters of epithelioid cells. These features and the presence of large, intracytoplasmic vacuoles raised a possible diagnosis of adenocarcinoma. However, mucin could not be demonstrated in the vacuoles, and the cells showed immunoreactivity for vimentin and c-kit but not for cytokeratins. Eighteen months earlier the patient had undergone a partial gastrectomy for a GIST, which predominantly comprised vacuolated, epithelioid cells. The immunoprofile of the primary tumor was identical to that of the ascitic fluid cells. CONCLUSION: GIST cells may closely mimic adenocarcinoma cells in ascitic fluid. Distinguishing between the two neoplasms has important clinical repercussions and is aided by histochemical and immunocytochemical studies--in particular, c-kit immunostaining.

Adenocarcinoma↗

Glutathione S-transferase pi immunostaining of cisplatin-resistant ovarian cancer cells in ascites.

OBJECTIVE: To clarify immunohistochemically the correlation between glutathione S-transferase pi (GST pi) expression of surgically resected specimens and clinical response in ovarian cancer and to evaluate ascites cytology using GST pi staining. STUDY DESIGN: Eighty-seven patients with ovarian cancer underwent initial debulking surgery and received cisplatin-based chemotherapy after surgery. Immunostaining for GST pi was performed on formalin-fixed sections of the patients' tumors. The cytologic slides of 24 cases were acquired for evaluation of GST pi staining. RESULTS: Of 87 surgically resected specimens, 55 (63.2%) were GST pi positive. Twenty-five of 28 patients (89.3%) who showed no response to chemotherapy had GST pi-positive tumor cells. The predictive value of positive GST pi staining for drug resistance was 75.8% (25/33). Of 18 cases that were GST pi positive in surgically resected specimens, 17 were positive in ascites cytology. Five cases were negative in both resected specimens and ascites cytology. There was a significant correlation in the GST pi labelling index between resected specimen and ascites cytology from the same case; the correlation coefficient was .701 and P value < .001. CONCLUSION: Overexpression of GST pi is related to resistance to cisplatin, and GST pi staining of ascites cytology can be used in pretherapeutic assessment of patients with ovarian cancer.

Adult↗

Primary malignant lymphoma of the central nervous system presenting with ascites and pleural effusion.

A 70-year-old woman was admitted to our hospital owing to ascites and pleural effusion. Though malignant cells (B-cell type lymphoma) were detected in both the ascites and pleural effusion, neither lymph node swelling nor a tumor was detected upon chest, abdominal and pelvic computed tomography (CT). After weekly THP-COP therapy for 8 weeks, the ascites and pleural effusion completely disappeared. Two years after the first admission, she was re-admitted because of a disturbance of consciousness, and a brain tumor was detected on CT scan. The immunohistological and genetic data for the brain tumor were identical to those of the malignant cells in the pleural effusion and ascites detected 2 years previously. Whereas the symptoms at onset of a primary lymphoma of the central nervous system (CNS) are usually neurological ones, in this rare case of primary CNS lymphoma, the symptoms at onset were the ascites and pleural effusion without neurological symptoms.

Aged↗

The value of emergency CT studies in spontaneous rupture of hepatocellular carcinoma. Analysis for tumor protrusion and hemorrhagic ascites.

CT characteristics of spontaneous rupture of HCC (n = 13) were reviewed retrospectively, and the value of emergency CT studies in this disease was evaluated. Especially, tumor protrusion ratio (TPR) and ascitic CT numbers were measured to for comparison with the data for unruptured HCCs and ordinary (e.g. non hemorrhagic) ascites (n = 13). As a result, except for diffuse type HCCs, the TPR was significantly higher than for the unruptured HCCs. Nine cases had intraperitoneal HDAs, and the laterality of the HDAs corresponded with that of the ruptured tumors in 8 cases. Also, the ascitic CT numbers apart from the HDA were still higher than the ordinary ascites. Therefore, a high TPR, HDAs adjacent to the tumor, and elevated ascitic CT numbers are important CT manifestations indicating HCC rupture. Diffuse HCCs, however, require careful clinical evaluation.

Adult↗

Rapid induction of lymphoid leukosis and ascites by avian leukosis virus from a lymphoid leukosis cell line.

To examine whether a lymphoid leukosis (LL) cell line releases an LL-specific avian leukosis virus (ALV) or not, two viral materials, culture fluid and a concentrated viral material from an LL-cell line, were inoculated into a total of 74 day-old chicks of line 15I in 5 experiments. Spectrum of diseases induced, their incidence and incubation periods to onset were examined. Fifteen chicks were inoculated with the culture fluid and 9 (60%) developed ascites [59-119 days post inoculation (dpi); geometric mean (GM) of dpi, GM: 89.6)], but LL was not induced in any chicks inoculated. Fifty-nine chicks were inoculated with the concentrated viral material and LL was recognized in 13 (22.0%) (27-74 dpi; GM: 48.4), ascites with LL in 11 (18.6%) (34-75 dpi; GM: 41.3), ascites alone in 21 (35.6%) (32-83 dpi; GM: 48.2), erythroblastosis in 2 (3.4%) (70-102 dpi; GM: 84.5), and other diseases in 12 (20.3%) (43-102 dpi; GM: 61.8). LL lesions were frequently observed in the liver, spleen, kidneys, bursa of Fabricius (bursa), bone marrow and gonads. Mild lymphocytic foci in some visceral organs and perivascular cuffing in the central nervous system were observed mainly in several chicks diagnosed as having complication of ascites with LL or other diseases. In addition to these lesions, atrophy of bursa and thymuses was recognized in them. No antibodies against Marek's disease virus (MDV) and reticuloendotheliosis virus were detected in 36 sera taken from the chicks inoculated with the concentrated viral material. Serotype 2 MDV was isolated from the buffy coat of some inoculated chicks. These results suggest that the properties of ALV inoculated and immunosuppression caused by inoculation with high doses of ALV are involved in rapid induction of LL and expression of pathogenicity of serotype 2 MDV released from the LL cell line and included in the viral inoculum. This is the first report describing the rapid induction of LL and ascites in chicks.

Animals↗

An angiotensin converting enzyme inhibitor, benazepril can be transformed to an active metabolite, benazeprilat, by the liver of dogs with ascitic pulmonary heartworm disease.

To examine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, can be transformed to the active metabolite, benazeprilat, by severely injured liver of dogs with ascitic heartworm disease, benazepril hydrochloride was administered orally to dogs once daily for 7 consecutive days at a dose rate of 0.29 mg/kg to 0.63 mg/kg of body weight, and plasma benazepril and benazeprilat concentrations were determined on the 1st and 7th administration days. In 7 dogs with ascitic pulmonary heartworm disease, plasma benazeprilat concentrations tended to be higher than in 7 control dogs both on the 1st and 7th administration days. The peak concentration and area under the concentration-time curve tended to be greater in dogs of the ascites group than in control dogs, but the statistics could not detect significant differences in the time to peak concentration and t(1/2) between the control and ascites groups. Plasma ACE activities decreased after administration of benazepril. In dogs with ascitic heartworm disease, benazepril was readily transformed to benazeprilat by the liver, and was effective for suppression of plasma ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗

Severe infantile sialidosis--the characteristics of oligosaccharides isolated from the urine and the abdominal ascites.

A female infant presenting congenital ascites, hepatosplenomegaly, coarse face, and delayed mental and physical development is described. Oligosaccharides in the urine and the abdominal ascites of this patient were investigated by Bio-Gel column chromatography. The level of urinary oligosaccharides excreted (nmol/mg creatinine) by the patient was 25.8 times the levels of the controls. The oligosaccharides in the urine and the ascites were composed almost entirely of sialyl oligosaccharides. The structures of urinary oligosaccharides were the same as those of oligosaccharides in the ascites. The ratio of high molecular weight sialyl oligosaccharides with repeating structures to low molecular weight sialyl oligosaccharides was higher in the ascites than in the urine.

Ascites↗