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A rapid procedure for purifying IgM monoclonal antibodies from murine ascites using a DEAE-disk.

A method for purifying IgM monoclonal antibodies (mAbs) from murine ascites using a DEAE-disk is described. After ammonium sulfate precipitation, ascites proteins are redissolved and loaded onto a DEAE-disk. MAb then is eluted from the disk using a stepwise NaCl gradient. IgM mAb produced by this procedure was > 95% pure as assessed by reducing SDS-PAGE analysis and was free of significant IgG contamination as determined by double radial immunodiffusion analysis. Yield of IgM mAb was approximately 2% of total ascites protein and approximately 10% of the amount of IgM contained in crude ascites. MAb retained immunoreactivity as assessed by ELISA, and the affinity index was evaluated by thiocyanate elution and remained unchanged. This two step technique for purifying IgM mAb from murine ascites is rapid, simple, and yields mAb of sufficient purity and immunoreactivity for the majority of mAb applications.

Animals↗

Ovarian cancer and ascites: A questionnaire on current management in the United kingdom.

A questionnaire on ovarian cancer ascites management was sent to members of the British Gynaecological Cancer Society (BGCS), the National Gynaecological Oncology Nurses, and the Assoication of Palliative Medicine. Questions were asked on diuretics, hematologic investigations, paracentesis, and duration of stay. Nine hundred ninety-five questionnaires were distributed, of which 492 replies were received (49% response rate). Fifty-five percent of responders used paracentesis as first-line management of ovarian cancer ascites (15% diuretics). Seventy-five percent performed some blood tests in relation to paracentesis. Ultrasound was used by 43.6% during paracentesis (15.7% for direct visualization, 27.9% to mark an entry site). Seventy-seven percent used a Bonanno catheter. Eighty-three percent used no intravenous fluids during paracentesis, and there was a wide variation in the amount and rate of drainage of ascites (1 L maximum up to free drainage of all ascites, median 5 L; 0.5 L per hour to free drainage). Gynecologists tended to use more interventions (paracentesis, ultrasound, and intravenous fluids) than palliative care physicians or medical oncologists, while palliative care physicians used fewer interventions but admitted patients for longer periods of time. This identified several areas for future study: the value of hematologic investigations, the use of outpatient management for paracentesis, and the use of ultrasound and the rate of drainage of ascites.

Ascites↗

Pharmacokinetics of amoxycillin/clavulanic acid in serum and ascitic fluid in cirrhotic patients.

A combination of amoxycillin and clavulanic acid (Augmentin) might be useful for first-line treatment of spontaneous bacterial peritonitis in patients with cirrhosis. We have studied the pharmacokinetics of amoxycillin/clavulanic acid in serum and ascitic fluid of six cirrhotic patients. A total of 66 simultaneous serum and ascitic samples were analysed. Following iv injection of 1 g amoxycillin plus 0.2 g clavulanic acid, the ascites to serum AUC ratio was 1.38 for amoxycillin and 1.01 for clavulanic acid, indicating a good distribution of these drugs into the ascitic fluid. In this study, experimental data were fitted to a three compartment body model which revealed that the prolonged serum half-lives of amoxycillin (274 min) and clavulanic acid (200 min) were probably due to the slow return from the ascitic compartment.

Adult↗

Pathogenesis of ascites in mice with peritoneal carcinomatosis.

For clarification of the mechanisms underlying formation of malignant ascites, alterations in lymphatic transport from the peritoneal cavity and in peritoneal capillary permeability to protein were studied sequentially in mice inoculated ip with Ehrlich-Lettre ascites tumor cells. All animals developed detectable ascites within 5-7 days of the injection. Diaphragmatic and retrosternal lymph vessels became radiopaque within 30 hours of the ip injection of radiopaque contrast material in control animals without ascites and in 12 experimental mice receiving contrast material 1-3 days after injection of tumor cells. No lymph vessels were opacified in 3 of 4 animals when contrast material was injected on day 5 or in any animal receiving contrast material on or after day 7 following the tumor cell injection. We determined alterations in peritoneal capillary permeability in the second group by measuring the concentration of iv injected Evans blue dye in eluates of sections of peritoneum and contiguous underlying tissue removed 3 hours after injection of dye. Permeability averaged 1.5 times normal (P = 0.02) by day 3 after tumor cell injection, 2 times normal by day 5, and 3 times normal by day 7; it remained at the final level. Although lymph drainage became impaired within 24 hours of the detection of ascites, a progressive increase in capillary permeability began 2 days earlier and was probably the predominant alteration in pathogenesis of the effusion.

Animals↗

Ascites syndrome and related pathologies in feed restricted broilers raised in a hypobaric chamber.

It has been demonstrated that the incidence of ascites can be significantly reduced through feed restriction. This method is thought to have an effect by slowing the growth rate of the birds. Interestingly, when birds are grown in a hypobaric chamber, ascites incidence increases while the overall growth rate of the birds is decreased. Unfortunately, the restriction programs practiced also have a detrimental effect on growth characteristics. An experiment was conducted to determine if the timing and duration of feed restriction can be used to reduce the incidence of ascites for broilers reared under high altitude and local elevation without having a negative impact on growth. A total of 600 commercial broiler males were used. Birds were divided, placing 360 birds in the hypobaric chamber at a simulated 2900 m (9,500 ft) above sea level, and 240 birds were placed at local elevation [390 m (1,300 ft) above sea level]. At each altitude there were four treatments: 1) fully fed controls; 2) feed available for 8 h/d for 6 wk (the duration of the study); 3) feed available for 8 h/d during the first 3 wk, then full feed for the remaining 3 wk; and 4) full feed for the first wk, then 3 wk of 8 h of feed availability, then 2 wk of full feed. Birds and feed were weighed weekly, and mortalities were necropsied to determine the cause of death. At the end of 6 wk, blood samples were taken, and the birds were weighed, necropsied, and scored for ascites, and organ weights were recorded. All feed restriction treatments significantly reduced ascites incidence, when compared with the fully fed controls. Treatment 2 birds were significantly lighter than any other group at both altitudes. The fully fed controls at local elevation were heavier than the fully fed controls at simulated high altitude, as seen in past experiments.

Animals↗

Evaluation of between-line variation for within-line selection against ascites in broilers.

Within-line opportunities for selection against ascites were studied in a data set comprising a 10-line comparison. The study attempted to reveal whether contrasts between lines provide reliable candidate traits for within-line selection. Mortality was chosen as the reference trait. As no pedigree information was available, a trait was required that related mortality to the nonmortality data. By principal component analysis, such a trait (ASC_INDIC = ascites indicator) was developed from pathology data. The composite trait ASC_INDIC ranked lines well for their mortality figures (r = 0.96), from which it was concluded that ASC_INDIC represents an underlying continuous ascites trait. Between lines, blood gas traits seemed to be the most promising traits. Within lines, performance traits appeared to be highly correlated to ascites. Comparison of within-line variation to between-line contrasts revealed considerable differences. The high correlation of the blood gas traits with mortality was not present within lines. However, although the magnitude was considerably reduced, the nature of the blood gas traits in their relationship to ascites was similar within and between lines. The study primarily demonstrates that contrasts between lines carry systematic but limited information for within-line coherence. Therefore, line contrasts must be interpreted with care when aiming to study genetic variation and coherence within lines.

Animal Husbandry↗

Reduction of ascites mortality in broilers by coenzyme Q10.

Effects of coenzyme Q10 (CoQ10) supplementation on growth performance and ascites were studied in broilers. One hundred eighty 1-d-old Arbor Acre male broiler chicks were randomly allocated into 3 groups with 6 replicates each. From d 8, the diets were supplemented with CoQ10 at levels of 0, 20, and 40 mg/kg, respectively. From d 15 to 21, all the chicks were exposed to low ambient temperature (15 to 18 degrees C) to induce ascites. Average feed intake, BW gain, and feed conversion ratio of the broilers during 0 to 3 wk, 3 to 6 wk, and 0 to 6 wk were measured. The results showed that there were no influences observed on broilers' growth performance, but the mortality due to ascites was reduced by CoQ10 supplementation (P < or = 0.05). Erythrocyte osmotic fragility (EOF) was significantly decreased by 40 mg/kg CoQ10 compared with the control, but no significant changes were observed on blood packed cell volume (PCV) among the treatments. Pulmonary arterial diastolic pressure was significantly decreased on d 36, but no significant changes were observed on right ventricular pressure (RVP), pulmonary arterial systolic pressure, and the maximum change ratio of right intraventricular pressure (+/- dp/ dtmax). Ascites heart index (AHI) was significantly decreased by 40 mg/kg CoQ10 supplementation (P < or = 0.05). The results of this study suggested that CoQ10 has a beneficial effect in reducing ascites mortality in broilers, and 40 mg/kg CoQ10 seems to be more effective than 20 mg/ kg CoQ10.

Animal Feed↗

CT differentiation of pleural effusion from ascites. An evaluation of four signs using blinded analysis of 52 cases.

Four criteria have been described to differentiate ascites from pleural effusion by computed tomography (CT). These four signs (the diaphragm sign, the displaced crus sign, the interface sign, and the bare area sign) were compared in a retrospective blinded analysis in 52 patients with ascites, right pleural effusion, or both ascites and right pleural effusion. There were limitations with each of the four criteria. Each of the individual criteria was reliable when only one abnormal fluid collection, either pleural effusion or ascites, was present. When both a right pleural effusion and ascites were present, none of the four criteria reliably identified both fluid collections. The combined use of the four criteria, however, led to a correct identification of all the abnormal fluid collections.

Ascites↗

Flow cytometry. A new technique in the diagnosis of malignant ascites.

The diagnosis of peritoneal carcinomatosis is often dependent on the finding of malignant cells in ascitic fluid analysis by a trained cytologist. Other methods are needed to increase the current diagnostic yield of 60-90%. Abnormal DNA content is characteristic of most malignancies. In an attempt to detect aneuploidy, we used high-resolution DNA histogram analysis with fluorescent DNA-specific stains and flow cytometry to evaluate 33 ascitic fluid samples. Of 13 patients with malignant ascites, aneuploidy was demonstrated in 10. Six patients with proven peritoneal carcinomatosis and normal cytologic examination had abnormal DNA histograms. DNA quantitation and cytologic examination agreed in 24 of 33 cases. These findings suggest that flow cytometry is a rapid and useful technique in the diagnosis of malignant ascites. The presence of aneuploidy in cells from ascitic fluid is highly suspicious for peritoneal carcinomatosis and suggests the need for further evaluation for malignancy.

Aneuploidy↗

Large volume paracentesis and intravenous dextran to treat tense ascites.

Forty patients with cirrhosis of the liver and tense ascites were randomized to receive either aldactone 400 mg/day and furosemide 80 mg/day (n = 20) or repeated large volume paracentesis (LVP) and infusion of low molecular weight dextran (n = 20). Both treatment groups were similar in clinical and laboratory parameters. Complete mobilization of the ascitic fluid was achieved in all receiving LVP and dextran therapy within 1 week of the treatment, in contrast to the minimal mobilization of the ascitic fluid in patients receiving diuretics even after 2 weeks of therapy. Renal function, the clinical parameters of systemic hemodynamics, serum electrolytes, and hepatic function remained stable in patients receiving LVP and dextran and were similar to those in the diuretic-treated patients. We found no deterioration of these functions in the nonedematous patients treated by LVP and dextran even though the protective effect of edema against LVP was lacking in them. Plasma volume estimation in six nonedematous cirrhotic patients treated by LVP and dextran did not reveal any hypovolemia after complete mobilization of ascites. The frequency of complications and death were similar in the two groups. Dextran infusion is a safe, effective, and low-cost replacement therapy in patients with cirrhotic ascites treated by LVP.

Adult↗

The effect of mannitol infusion on the response to diuretic therapy in cirrhotic patients with ascites.

GOALS: A good response to diuretics is obtained initially in the treatment of cirrhotic ascites. However, unresponsiveness to therapy and various complications may develop with disease progression. This makes obligatory the search for new treatment methods that may be alternative to standard diuretics. In our study, we investigated the effect of mannitol infusion on current therapies in patients with cirrhotic ascites who were using diuretic treatment. BACKGROUND: Thirty cirrhotic patients with ascites who were using diuretic treatment were included in the study. The patients were randomly divided into two groups; a dose of 100-mL 20% mannitol was administered to the first group, and 100-mL 5% dextrose solution was administered to the second group. The patients' urinary volumes and serum and urine electrolyte levels (sodium, potassium) were determined before and after the test. RESULTS: In the mannitol group, a significant increase in urinary volume was observed (p < 0.05). However, in the control group no significant differences in urinary sodium excretion were observed after the test (p > 0.05). In the mannitol group, a concomitant increase in urinary volume and sodium excretion was observed in eight cases (53%). The urinary sodium excretions and serum sodium levels before the test were significantly lower in patients who responded to mannitol than in patients who did not respond (p = 0.001 and p = 0.04, respectively). CONCLUSIONS: As a result, short-term mannitol therapy makes a significant contribution to diuretic therapy in approximately half of cases with cirrhotic ascites. The results we obtained suggest that mannitol may be a useful alternative in the treatment of ascites.

Ascites↗

Large-volume paracentesis in the management of ascites in children.

BACKGROUND: Large-volume paracentesis has been evaluated for both therapeutic and diagnostic purposes in the management of ascites in cirrhotic adults. There are no published data relating to the safety, efficacy, or methods of this procedure in children. The objective of this study was to characterize the authors' initial experience with large-volume paracentesis (> 50 ml/kg of ascites) for removal of tense abdominal ascites in the pediatric population. METHODS: Retrospective chart review was performed of 21 large-volume paracentesis sessions in seven children (ages 6 months-18 years) with tense ascites that did not respond to other measures. RESULTS: Mean volume removed was 3,129 +/- 2,966 ml (mean +/- standard deviation) or 118 +/- 56 ml/kg over 2.9 +/- 3.7 hours by a 16-gauge intravascular catheter in 6 sessions, by an 18-gauge intravascular catheter in three sessions, and by a 15-gauge fenestrated, stainless-steel paracentesis needle in 12 sessions. Large-volume paracenteses performed with the paracentesis needle had significantly shorter duration of drainage and faster flow rates than those performed with the intravascular catheter. The only complication encountered was decreased urine output in one session. CONCLUSIONS: Large-volume paracentesis is a safe and effective therapeutic method for managing tense abdominal ascites in children. The use of the paracentesis needle significantly improved the speed and efficiency of large-volume paracentesis compared with the intravascular catheter.

Adolescent↗

Loop diuretic therapy in liver cirrhosis with ascites.

Medical treatment of ascites is aimed at reverting sodium retention, that is, at creating a negative sodium balance to relieve ascites. Bed rest and low-sodium diet induce the disappearance of ascites in about 10% of patients. Loop diuretics and aldosterone antagonists must be administered to the patients not responding to the previous regimen. Available evidence indicates that aldosterone antagonists are the first-choice drugs, as these substances are more effective than furosemide. Nevertheless, loop diuretics potentiate the effects of aldosterone antagonists. The reduced efficacy of furosemide in these patients, when compared with that of spironolactone, may be related to an impairment of both pharmacodynamics and pharmacokinetics. In fact, most sodium not reabsorbed in Henle's loop, due to the action of furosemide, is subsequently taken up in the distal nephron because of hyperaldosteronism. A further mechanism of resistance may be related to an impaired excretion of furosemide into the tubular lumen. The use of diuretics in the treatment of ascites is associated with several side effects, including prerenal azotemia, hepatic encephalopathy, and electrolyte and acid-base disorders. A stepped-care approach, together with careful monitoring of patients, is the best way to reduce the incidence of these complications. Ethacrynic acid has been shown to be highly effective in the treatment of ascites, even in patients refractory to other diuretics, but its use is associated with a high incidence of hypokalemia and hypochloremic alkalosis. Bumetanide and piretanide are comparable to furosemide, in terms of both efficacy and side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗

Development of renal function after neonatal urinary ascites due to obstructive uropathy.

PURPOSE: Neonatal urinary ascites is a rare complication of obstructive uropathy with possible lethal outcome if not treated adequately. We demonstrate that with adequate therapy the survival rate can be high and long-term survival, kidney function and lower urinary tract function of patients with urinary ascites can be good. MATERIALS AND METHODS: The study included 4 females and 8 males born with urinary ascites. Followup ranged from 3 to 14 years. Blood analysis for renal function, electrolytes and blood gas was performed at hospitalization and during followup. Ultrasound, cystourethrograms or cystoscopy showed the site of obstruction and leakage of urine. All patients were initially treated with drainage of the ascites and decompression of the obstructed urinary tract. All patients underwent surgery to remove the obstruction and reconstruct the urinary tract. Bladder and kidney function was evaluated at long-term followup. RESULTS: All patients had severe abdominal distention at presentation. Severe metabolic acidosis was present in cases that had not been detected prenatally or immediately after birth. Two patients died of causes related to pulmonary hypoplasia. Surprisingly urinary continence and renal function were good in 9 of 10 survivors. CONCLUSIONS: Long-term outcome of bladder and kidney function is surprisingly good in cases of severe obstructive uropathy with ascites. Intrauterine pressure relief of the bladder through urinary extravasation protects renal function and this decompression of the urinary tract prevents severe secondary changes to bladder function. Although not proven we believe that high intrauterine pressures in the abdominal cavity are prevented by peritoneal absorption of the extravasated urine and consequent dialysis through the placenta.

Adolescent↗

Ascites due to endometriosis.

Ascites is a rare but important complication of endometriosis because it mimics ovarian cancer. Most cases occur in nulliparous young black women and present with massive ascites. Treatment is effected by ablation of ovarian function by surgery, radiotherapy, or suppression of endometriosis by endocrine therapy. The pathogenesis is unknown. In this paper, we present a case report and review of the other 19 cases in the literature. Because of the age of most of these women, endocrine therapy is preferred rather than castration. The majority of symptoms and signs of endometriosis are well known, including pelvic pain, dysmenorrhea, dyspareunia, infertility, and pelvic tenderness with or without masses. However, it is seldom appreciated that the disease can be a cause of, and can present with ascites, often massive and recurrent. It is important for gynecologists and oncologists to be aware of this entity because the presence of ascites with abdominal and/or pelvic masses and weight loss immediately suggests the diagnosis of malignancy, and the possibility of endometriosis is rarely considered. We are reporting a case of endometriosis causing massive and recurrent ascites, along with a review of the literature and a discussion of the epidemiology, pathogenesis, and management of this disorder.

Adult↗

Transjugular intrahepatic portosystemic shunt: a limited role in refractory ascites.

OBJECTIVE: To evaluate the role of the transjugular intrahepatic portosystemic shunt (TIPS) in the management of patients with refractory ascites. DESIGN: A retrospective study of 25 consecutive patients for whom refractory ascites was the primary indication for TIPS insertion. SETTING: Regional liver unit at Freeman Hospital, Newcastle upon Tyne, UK. PARTICIPANTS AND INTERVENTIONS: Twelve male and 13 female patients with a mean age of 58 years and mean Child-Pugh score of 10, treated with TIPS for refractory ascites between July 1992 and September 1995. MAIN OUTCOME MEASURES: Effect of TIPS on mortality, ascites and hospital admission rate. RESULTS: TIPS was successfully placed in all patients with a 59% mean reduction in portosystemic pressure gradient. Response rate was 68%, 48% and 33% at 1, 3 and 12 months, respectively. Mortality was 48% at 3 months and 67% at 12 months, being higher in those patients older than 60, those with renal impairment and those with higher Child-Pugh score. Amongst nine patients surviving long term (> 12 months) the mean time spent in hospital in the 3 months before TIPS was 35 days and in the year following TIPS 30 days. Patients who died (16 in total) spent a mean of 19 days in hospital before TIPS, 10 never leaving hospital, and 6 who were discharged spent a mean of 19 days post procedure in hospital (mean survival 84 days). CONCLUSION: TIPS has a limited role in the management of patients with refractory ascites. It is not an appropriate treatment where patients are older than 60, have renal impairment (creatinine > 200 mumol/l) or have a Child-Pugh score greater than 10.

Ascites↗

Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis.

OBJECTIVE: Large-volume paracentesis associated with plasma volume expansion with albumin is an effective, safe, but costly therapy for ascites in patients with cirrhosis. The aim of this study was to compare the use of a synthetic plasma expander, hydroxyethyl starch (HES), with that of albumin. DESIGN: Sixty cirrhotic patients with ascites were studied. Patients were randomly assigned to be infused with either albumin (8 g/l of ascites removed, n = 33) or HES (200 ml/l of ascites removed, n = 27). None of the patients was treated with diuretics or had renal impairment or hyponatremia at entry. Clinical and laboratory data were obtained before and 1, 3 and 15 days after treatment. RESULTS: There were no significant differences in clinical and laboratory parameters between the two groups at entry into the study. None of the patients developed renal impairment during the trial. One patient (HES group) presented with hyponatremia. Plasma atrial natriuretic factor and aldosterone levels did not differ between the two groups at baseline or at 1 and 3 days after paracentesis. The volume of ascites removed did not differ between the albumin (7.9 +/- 4.4 l) and HES (6.9 +/- 5.3 l) groups. However, there was a significant difference in weight loss between the albumin and HES groups (7.9 +/- 5.2 kg vs 4.7 +/- 3.4 kg; p = 0.01). Clinical and laboratory parameters indicated that HES was well tolerated except for hypoalbuminemia. CONCLUSION: HES is well tolerated in patients with cirrhosis. There is no difference between HES and albumin in the prevention of complications related to large-volume paracentesis. The lesser degree of weight loss observed with HES needs further study.

Aged↗

Correlation between portal/hepatic vein gradient and response to transjugular intrahepatic portosystemic shunt creation in refractory ascites.

PURPOSE: Transjugular portosystemic shunt (TIPS) creation is widely used in the treatment of patients with refractory ascites caused by portal hypertension. Although it is well-established that an optimal portosystemic gradient (PSG) to prevent recurrent variceal bleeding should be lower than 12 mm Hg, there are no clear data on the correlation between the post-TIPS portal/hepatic vein gradient (PHG) and control of ascites. The purpose of the present study was to determine whether there was any correlation between PHG and control of ascites after TIPS creation. MATERIALS AND METHODS: Portal/hepatic vein gradients before and after TIPS creation were studied in 28 patients who underwent TIPS creation. A multivariate analysis was performed to determine whether the portal/hepatic vein gradient independently predicted response to TIPS. Patients were considered responders if ascites disappeared or there was no further need for paracentesis. Patients were considered nonresponders if they required repeat paracentesis one or more months after TIPS creation. RESULTS: Among patients who experienced a response, the mean pre-TIPS PHG was significantly higher than that in those who did not respond (20.9 mm Hg +/- 5.1 vs 15 mm Hg +/- 3.4; P = .002). A higher pre-TIPS PHG was predictive of better response independent of severity of liver disease and serum creatinine level (odds ratio, 2.45; 95% CI, 1.23-4.9; P = 0.011). CONCLUSION: If the findings established in this study are confirmed in prospective long-term studies, a pre-TIPS PHG measurement can be a useful tool in helping clinicians assess the potential benefit of TIPS in refractory ascites.

Ascites↗