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Determination of the serum protein binding of oxycodone and morphine using ultrafiltration.

Protein binding of oxycodone and morphine in human serum was determined in vitro using ultrafiltration. Binding studies were also performed using both purified human serum albumin and human alpha 1-acid glycoprotein (AAG). Albumin was found to be the major binding protein for both oxycodone and morphine. The serum protein binding of both oxycodone and morphine was independent of drug concentration in the therapeutic range (5-100 ng/ml), but was dependent on protein concentration. In addition, bound fractions of oxycodone and morphine increased with increasing concentrations of both albumin and AAG. At physiological pH and temperature, the mean (+/- SD) serum protein binding of oxycodone was 45.1% (+/- 0.4%) and that of morphine was 35.3% (+/- 0.2%) A decrease in temperature from 37 to 23 degrees C significantly increased the serum protein binding of oxycodone and morphine by 8-9% (p < 0.0001) and 7-10% (p < 0.0001), respectively, indicating the importance of maintaining the temperature at 37 degrees C during protein binding experiments. A reduction in pH from 7.75-8.85 to 7.4 significantly reduced serum protein binding of both oxycodone and morphine by 4-5% (p < 0.0001) and 4-7% (p < 0.0001), respectively. Serum samples, to which known concentrations of oxycodone had been added and which were stored at -20 degrees C, showing a gradual but significant decline (p < 0.0001) in serum protein binding of oxycodone from approximately 45 to 39% during the 4-week storage period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Coronary bypass grafting for patients dependent on dialysis: modified ultrafiltration for perioperative management.

Coronary bypass grafting for patients on chronic dialysis has increased the risk of operative mortality, and long-term survival is considered poor. Thirty-three patients dependent on dialysis undergoing coronary bypass grafting were analyzed. The 33 patients were divided into two groups according to the strategy for renal support. In group A, 12 patients underwent continuous hemofiltration (CHF) during and after cardiopulmonary bypass and CHF in an intensive care unit (ICU) and then returned to regular dialysis. In group B, 21 patients underwent modified ultrafiltration (UF) immediately after cardiopulmonary bypass and continuous hemodialysis and filtration in an ICU with early reinstitution of regular dialysis. Two patients died in group A, and there were no operative deaths in group B (17% vs. 0%, p < 0.05). Three patients in group A and one patient in group B had bleeding complications requiring reoperation (25% vs. 5%, p < 0.05). Three patients in group A and one patient in group B needed intraaortic balloon pump (IABP) support postoperatively (25% vs. 5%, p < 0.05). Four patients in group A and one in group B required long-term ventilation of more than 3 days (33% vs. 5%, p < 0.05). There were five patients in group A and two patients in group B requiring long-term ICU stay of more than 4 days (41% vs. 10%, p < 0.05). Postoperative blood loss within 24 hours was 1310 ml in group A and 623 ml in group B (p < 0.05). Transfusion requirements were 9.3 units in group A and 3.0 units in group B (p < 0.05). During follow-up, the long-term survival, New York Heart Association (NYHA) functional class, and incidence of recurrent angina were considered favorable in both groups. Cardiac event-free rates after surgery at 1, 3, and 5 years were 88%, 73%, and 67%, respectively. The operative mortality, morbidity, and long-term survival for dialysis dependent patients were reasonably acceptable. As renal support, modified UF can play an important role in reducing bleeding complications, shortening the ICU stay, and decreasing blood loss and transfusion requirements.

Aged↗

Treatment of diuretic-resistant fluid retention with ultrafiltration.

Nine patients with diuretic-resistant edema, secondary to congestive heart failure, liver cirrhosis, or nephrotic syndrome, were treated with ultrafiltration using high water flux dialyzers. Access to the blood stream was obtained by femoral vein catheterization. As much as 8.3 kg of fluid were removed in 3--4 hours with only transient decline in blood pressure. The procedure was well tolerated and yielded immediate symptomatic relief. The potential for restoration of an edema-free state in patients with diuretic-resistant edema suggests that further experience with this technique is justified.

Diuretics↗

Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation.

The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30,000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/challenge procedures. The children were aged 1 month-14.5 years, median 1 11/12 years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Studies on ultrafiltration of antihemophilic factor.

Ultrafiltration as an alternative approach to reprecipitation was studied in the production of an intermediate-purity antihemophilic factor concentrate suitable for clinical use. Almost complete recoveries of factor-VIII-related activities have been demonstrated across the processing step resulting in increased net yield of the product. Several important processing parameters are discussed. The product thus prepared is stable and has improved VIII:C/mg fibrinogen ratio.

Electrophoresis, Cellulose Acetate↗

Preparation of lipid-free human hemoglobin by dialysis and ultrafiltration.

Dialysis of human red blood cells using a hypotonic solution and a commercial kidney dialysis unit followed by ultrafiltration through 0.1 micron pore hollow fibers provides an easily managed method for isolation of lipid-free hemoglobin. High pressure liquid chromatography analysis of lipid-free hemoglobin (LFHB) indicates 99-100% protein purity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that LFHB migrates as a single band. The process requires hypoosmotic dialysis of human RBC to a final 119-139 (av 132) mosmol/kg osmotic pressure. Additional reduction in osmotic pressure results in irreversible cell lysis which results in lipid contamination of the hemoglobin. Processing one-half liter of packed red blood cells requires 10 h, resulting in an average of 90% hemoglobin recovery.

Dialysis↗

The delipidation of brain proteolipid protein by ultrafiltration.

It has been very difficult to prepare the apoprotein moiety of brain white matter proteolipid so that it is completely devoid of complex lipids, without suffering aggregation and protein denaturation. The reason is that complex lipids are tightly bound to the proteolipid apoprotein. Using a new ultrafiltration method, we obtained, in a gradual way and in a relatively short time, more than 99% delipidation in water-saturated n-butanol, with and without 0.1 M acetic acid, and recovered up to 86% of the protein with no detectable reducing sugars remaining. The delipidated protein remained in solution and in a relatively nondenatured state for several days. In 2% sodium dodecyl sulfate (SDS)-aqueous media, 90% of the lipids were removed and the yield of recovered protein in solution was near 90%; nearly 6% of the reducing sugars remained in the apoprotein. A higher delipidation was obtained by washing with 0.1 M NaOH. The content of reducing sugars was greater but the protein was less stable. When 10% SDS was employed to dissociate lipid-protein interaction, an almost complete delipidation was obtained and reducing sugars disappeared.

Animals↗

Comparison of the "zero crossing" method in derivative spectroscopy and ultrafiltration for the determination of free and bound fractions of mitoxantrone.

In vitro mitoxantrone binding to human serum, human serum albumin (HSA, 600 microM) and alpha-1-acid glycoprotein (AAG, 15 microM) was investigated by ultrafiltration and the first-derivative spectrophotometry based on the "zero crossing" method. The binding of mitoxantrone to isolated proteins was studied at eight concentrations whose range depended on the protein used. The results showed that mitoxantrone binding to human plasma and HSA involved a saturable binding. The AAG binding involved a saturable binding followed by a non saturable process. Within the concentration range studied, the percent and binding parameters which characterize the drug-protein interaction were comparable in both methods.

Humans↗

Sorbent regeneration of ultrafiltrate as a long-term treatment of end-stage renal failure.

A sorbent system (Redy D 11 cartridge) capable of on-line regeneration of ultrafiltrate during hemofiltration (Amicon 0.5 m2) has been developed and applied on a 3 X 4 hr/week schedule to three patients with end-stage renal failure previously treated for up to six months with hemodialysis. Total experience, to date, is sixteen patient months (three to seven months). Tolerance to fluid removal improved with the new system. Patient well-being and rehabilitation have been maintained. The system offers the potential of hemofiltration without sterile replacement fluid or expensive fluid-balancing machines.

Aluminum↗

Isolated ultrafiltration in the treatment of dialysis ascites.

Three patients with dialysis ascites improved markedly after treatment with isolated ultrafiltrations. This simple, noninvasive technique should be applied first to patients with dialysis ascites before resorting to more drastic therapeutic measures.

Ascites↗

Evaluation of the impact of ultrafiltration on dialyzer clearance.

The influence of ultrafiltration on dialyzer clearance is analyzed. As the starting point for the analysis, the known theoretical and experimental expressions for clearance are utilized. The results obtained theoretically are verified with experimental data.

Blood Flow Velocity↗

A model of ultrafiltration and glucose mass transfer kinetics in peritoneal dialysis.

We have investigated the variation with dwell time of dialysate volume and glucose concentration during continuous ambulatory peritoneal dialysis using a one-pool model. No assumption was made regarding the ultrafiltration rate that was calculated by the model. Results show that the volume ultrafiltered during dwell time is an increasing function of peritoneal membrane hydraulic permeability and a decreasing function of glucose mass transfer coefficient (MTC). For large MTC and low initial glucose concentration there is reabsorption of dialysate into the blood at large dwell times. For a 6 h dwell time, glycerol (92 daltons) is a more effective osmotic agent than glucose (198 daltons) at the same weight concentration. These results are in quantitative agreement with published clinical studies.

Biological Transport, Active↗

Theoretical basis and experimental verification of the impact of ultrafiltration on dialyzer clearance.

Dialyzer clearance K is usually presented as K = K0 + Tr Qu, were Qu is ultrafiltration rate, K0 is clearance for Qu = 0, and Tr is transmittance coefficient. Although a simple and accurate mathematical description of K0 is widely used, only a somewhat inaccurate formula for Tr that predicts a linear relationship between Tr and K0 has been proposed before. In this study the detailed investigation of Tr using a one-dimensional theory of a dialyzer is presented. In general, the application of a one-dimensional theory requires sophisticated numerical methods, but for small and middle molecular weight solutes an analytical formula for K can be derived. Tr predicted by the developed theory in comparison to Tr predicted by the previous linear formula is higher for small molecular weight solutes and lower for middle and large molecular weight solutes. These theoretical results were confirmed in experiments carried out in vitro for hollow-fiber dialyzers and small molecular weight solutes (urea, creatinine, sodium, TcO4) as well as middle molecular weight solutes (vitamin B12).

Hemofiltration↗

Use of a rate-limited ultrafiltration circuit with centrifugal ventricular assist.

Renal insufficiency and pulmonary edema are frequently observed in patients who require centrifugal ventricular assist for postcardiotomy ventricular failure. We describe a technique of using a rate-limited ultrafiltration device in parallel with the assist device circuit to remove excess intravascular volume.

Cardiac Output, Low↗

Effect of modified ultrafiltration on inflammatory mediators, coagulation factors, and other proteins in blood after an extracorporeal circuit.

Modified ultrafiltration (MUF) is a technique able to remove the excess body fluid and inflammatory mediators associated with the use of a cardiopulmonary bypass (CPB). It has been shown to reduce morbidity after cardiac operations in children. Application of MUF after adult cardiac operations has also been suggested being associated with a lower prevalence of early morbidity. However, the relationship between the concentration of mediators in the blood and postoperative morbidity remains yet to be proved. In this study, changes of various chemical mediators in the filtrate and blood before and after MUF have been evaluated in adult patients. Significant reductions of blood levels of inflammatory cytokines were not observed after MUF. On the other hand, MUF significantly elevated hematocrit, number of red cells, concentrations of albumine, coagulation Factor VII and X, platelet factor (PF)-4, and antithrombin (AT-) III.

Blood Cells↗

Can a decreasing ultrafiltration profile affect the dialytic dose administered?

During hemodialysis, ultrafiltration (UF) seems to affect the dialytic dose because of convective removal of urea and contraction of its distribution volume. We aimed to assess whether the adoption of a decreasing UF profile could yield a different dialytic dose from that obtained with a constant UF mode. Ten patients were randomly assigned to undergo 12 sessions with a constant UF mode (phase A) followed by 12 sessions with a decreasing UF rate (phase B), or the reverse. Kt/V and urea reduction ratio (URR) were 1.77 +/- 0.26 and 70.02 +/- 8.26% in phase A vs. 1.81 +/- 0.36 and 71.02 +/- 6.48% in phase B, respectively, showing no significant difference. Measurement of the differences in volemic variations between the two phases showed a statistically significant difference at the second hour (P < 0.001, the volemic reduction being greater in phase B than A) and at the fourth hour (P < 0.001, being greater in phase A than B). In standard bicarbonate dialysis, the adoption of a decreasing UF profile rather than a constant one does not alter the efficiency of the dialytic treatment.

Aged↗

The separation of unbound prednisolone in plasma by centrifugal ultrafiltration.

To study variable plasma protein binding of prednisolone in children with nephrotic syndrome we have devised a simple rapid method for measuring unbound prednisolone. The plasma was initially ultrafiltered at 37 degrees C fixed angle head at 1500 g for 30 min then the filtrate was analysed by high pressure liquid chromatography. The effects of variable ultrafiltration conditions were studied. The method was used to compare the AUC unbound prednisolone in a nephrotic child (plasma albumin concentration 18 g L-1) with a control (plasma albumin concentration 43 g L-1); their respective AUC unbound prednisolone values were 4.02 mg h L-1 and 1.07 mg h L-1.

Adult↗

A one-dimensional model of simultaneous hemodialysis and ultrafiltration with highly permeable membranes.

A one-dimensional model of combined convective and diffusive mass transfer in a hemodialyser is presented. Solutions and results are given for two regimes of ultrafiltration (UF): at low transmembrane pressures when UF flow is proportional to transmembrane pressure and in the limit of large transmembrane pressures when UF is limited by protein concentration polarization. It is found that the overall clearance is always less than the sum of dialytic and UF clearances due to interaction between convective and diffusive transfers. For a given UF flow the clearance is not sensitive to UF flux distribution along the membrane. Model predictions of urea clearance are in good agreement with measurements obtained in vitro with saline on hemodialysers equipped with a polyacrylonitrile membrane.

Blood↗