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Biomedical subjects

A K Cheung

Publications and source records attributed to A K Cheung.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of hemodialyzer reuse on clearances of urea and beta2-microglobulin. The Hemodialysis (HEMO) Study Group.

Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, performance of reused dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and beta2-microglobulin (beta2M) clearance by low-flux and high-flux dialyzers reprocessed with various germicides. The dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen peroxide combination (Renalin), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of beta2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodialysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the prescription of hemodialysis in centers practicing reuse.

Acetic Acid↗
PubMed1998

Herpes simplex virus type 1 ICP-0 induces reactivation of pseudorabies virus from latently infected trigeminal ganglia explant cultures.

Pseudorabies virus (PrV), like other alphaherpesviruses, is a neurotropic virus that can establish a latent infection in swine. Reactivation of PrV from latency may occur spontaneously or after induction with corticosteroids. The mechanisms involved in the establishment of latency and reactivation are currently unknown. Here, we examined gene-specific reactivation of PrV by herpes simplex virus type 1 (HSV-1) immediate early protein, ICP-0. Primary neuronal cell cultures established from the trigeminal ganglia of latently infected swine were superinfected with recombinant adenoviruses expressing ICP-0. Reactivation of PrV occurred in cultures that were superinfected with two different ICP-0-expressing adenovirus recombinants, but not in cultures that were either mock-infected, or superinfected with wild-type adenovirus, or recombinant adenoviruses not expressing ICP-0. Infectious PrV was detected between 4 and 7 days postinfection, regardless of the promoter driving expression of ICP-0. Results from these experiments show that HSV-1 ICP-0, a homologue of PrV EP0, can induce PrV reactivation from explanted trigeminal ganglia of latently infected swine.

Animals↗
PubMed1998

Evaluating volume status in hemodialysis patients.

Accurate determination of the volume and distribution of body fluids in end stage renal disease patients will permit improved assessment of dry weight and strategies for optimal fluid removal. Certain biochemical markers and anatomical measures have been proposed as markers of dry weight, but these markers primarily reflect the volume of the intravascular compartment and may not reflect total body volume status. Noninvasive determination of total body water and extracellular fluid volumes using bioimpedance analyses has also been proposed for assessment of dry weight, but such determinations do not yet have sufficient accuracy for routine use. Several devices have been recently developed for continuously monitoring changes in blood volume on-line during routine hemodialysis. Such blood volume monitors cannot be used to determine dry weight directly; however, continuous monitoring of blood volume can be used to detect fluid overload because intradialytic changes in blood volume are small in hemodialysis patients who are overhydrated. Furthermore, continuous monitoring of blood volume can be used to predict symptoms resulting from intradialytic hypovolemia. The combined use of blood volume monitoring and time-dependent ultrafiltration and dialysate sodium profiles will be used increasingly in the future to assist in the prevention of hypotension and symptoms that result from intradialytic hypovolemia, especially when automated systems for controlling intradialytic blood volume are individualized and shown to be safe and effective.

Blood Volume↗
PubMed1998

Enhanced fluid removal guided by blood volume monitoring during chronic hemodialysis.

Fluid overload predisposes chronic hemodialysis patients to cardiovascular disease, a significant cause of morbidity and mortality in these patients. We evaluated the efficacy of monitoring changes in blood volume during routine hemodialysis to detect fluid overload. Intradialytic changes in blood volume were monitored by continuously measuring hematocrit in all 56 patients in a single dialysis unit over 7 weeks. After Week 1, patients were categorized into 2 separate groups depending on their maximum intradialytic decreases in blood volume. In Group 1, 46 of 56 or 82% had greater than a 5% decrease in blood volume while in Group 2, 10 of 56 or 18% had less than a 5% decrease in blood volume. During Weeks 2-7, dialytic fluid removal was intentionally increased in Group 2 patients by 0.80 +/- 0.62 L (mean +/- SD) or 47 +/- 43%. This intervention resulted in a larger (p < 0.02) intradialytic decrease in body weight (2.7 +/- 0.9 kg versus 2.0 +/- 0.8 kg) and a larger (p < 0.02) intradialytic decrease in blood volume (15 +/- 5% versus 4 +/- 1%) than experienced during Week 1 with a low incidence of symptoms. We conclude that there is a significant percentage of chronic hemodialysis patients who can tolerate additional fluid removal without hypovolemic symptoms even though they are considered to be at dry weight by routine physical examination and that the identification of these patients can be facilitated by intradialytic blood volume monitoring.

Blood Volume↗
PubMed1998

Effect of hemodialyzer reuse: dissociation between clearances of small and large solutes.

Dialyzers are reused in approximately three quarters of the dialysis units in the United States, but the effect of reprocessing on dialyzer performance has not been extensively evaluated. In a crossover study of six chronic hemodialysis patients, we determined urea, creatinine, phosphate, and beta2-microglobulin clearances and dialysate protein loss for two types of low-flux and two types of high-flux dialyzers during use numbers 1, 2, 5, and 15. Dialyzers were reprocessed by an automated machine using Renalin (Renal Systems, Plymouth, MN) as the germicide. Dialyzer arterial and venous blood and dialysate outflow samples were obtained at 5 and 180 minutes of each dialysis session to evaluate solute clearances. Urea, creatinine, and phosphate clearances were calculated using dialysate concentrations, whereas beta2-microglobulin clearance was calculated using plasma concentrations to include its removal by adsorption to the dialysis membrane. There was a trend for urea, creatinine, and phosphate clearances to decrease with reuse for both low-flux and high-flux dialyzers, but these differences were not statistically significant. The clearance of beta2-microglobulin and dialysate total protein concentration was small for low-flux dialyzers; these values were not dependent on reuse. There was a trend for beta2-microglobulin clearance and dialysate total protein concentration to decrease during a dialysis treatment using high-flux dialyzers. More significantly, beta2-microglobulin clearance and dialysate total protein concentration decreased substantially with the reuse of high-flux dialyzers. These observations show that the maintenance of small solute clearances during reuse of high-flux dialyzers does not ensure the maintenance of large solute clearances.

Acetic Acid↗
PubMed1997

Spurious hypophosphatemia in a patient with multiple myeloma.

We report a patient with multiple myeloma and a prolonged history of hypophosphatemia who had remained asymptomatic. Extensive evaluation for a cause, including the search for a renal tubular disorder, oncogenous osteomalacia, or a parathyroid hormone (PTH)-related protein was unproductive. Renal biopsy showed no evidence of myeloma kidney. Subsequent mixing of the immunoglobulin G (IgG) fraction from the patient's serum with normal human serum, confirmed that the observed hypophosphatemia was spurious, resulting from interference of large amounts of an abnormal IgG with a standard automated laboratory assay for phosphate.

Autoanalysis↗
PubMed1997

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The Hemodialysis (HEMO) Study.

The dialyzer mass transfer-area coefficient (KoA) for area is an important determinant of urea removal during hemodialysis and is considered to be constant for a given dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber dialyzers (N = approximately 5/model, total N = 107) in vitro at 37 degrees C for three countercurrent blood (Qb) and dialysate (Qd) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and output flows on both the blood and dialysate sides. Urea KoA values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230 ml/min depending on the dialyzer model, but the effect of blood and dialysate flow rate on urea KoA was similar for each. Urea KoA did not change (690 +/- 160 vs. 680 +/- 140 ml/min, P = NS) when Qh increased from 306 +/- 7 to 459 +/- 10 ml/min at a nominal Qd of 500 ml/min. When Qd increased from 504 +/- 6 to 819 +/- 8 ml/min at a nominal Qh of 450 ml/min, however, urea KoA increased (P < 0.001) by 14 +/- 7% (range 3 to 33%, depending on the dialyzer model) to 780 +/- 150 ml/min. These data demonstrate that increasing nominal Qd from 500 to 800 ml/min alters the mass transfer characteristics of hollow fiber hemodialyzers and results in a larger increase in area clearance than predicted assuming a constant KoA.

Blood Flow Velocity↗
PubMed1997

ACE inhibitor effects on platelet function in stages I-II hypertension.

Angiotensin II enhances platelet aggregation through activation of the G protein-linked pathway present in platelets. Studies of several angiotensin-converting enzyme (ACE) inhibitors have demonstrated marked differences on platelets. Therefore this prospective, randomized, double-blind, crossover study compared the ex vivo effects of equivalent antihypertensive doses of captopril, enalapril, and fosinopril on platelet aggregation and thromboxane B2 (TxB2) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a baseline mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enrolled. The decline in mean arterial pressure after 4 weeks of stable dosing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapril, and fosinopril, respectively (p = NS). There was no significant change in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimulated platelet aggregation from baseline or between ACE inhibitors. Compared with baseline, fosinopril decreased TxB2 concentrations 27.5-67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB2 formation, but this effect was stimulus and time dependent. Enalapril consistently increased TxB2 concentrations, independent of stimuli or time. We conclude that different ACE inhibitors have distinct effects on platelet TxB2 formation without significant effects on platelet aggregation. Fosinopril may be a direct antagonist ofTxA2 synthase, suggesting benefit in syndromes of platelet activation or vascular occlusion.

Adult↗
PubMed1997

The hemodialysis membranes: a historical perspective, current state and future prospect.

Transport and biocompatibility characteristics are two important considerations when choosing hemodialysis membranes. Dialyzer performance depends on clearances of small solutes, middle molecules, and oncotically active proteins. Although complement and neutrophil activation have become the gold standards for biocompatibility testing of dialysis membranes, alterations of other cellular and noncellular blood elements as a result of blood-membrane interactions are also important. Because of concerns about middle molecule transport and biocompatibility, the original cellophane membrane has been gradually replaced by modified cellulosic membranes and synthetic membranes for clinical use. Recent studies suggest that the choice of dialysis membrane influences the clinical outcome of patients in several areas, including intradialytic acute anaphylactoid reactions, beta 2-microglobulin associated amyloidosis, recovery from acute renal failure, and mortality of chronic hemodialysis patients. However, the relative contributions of middle molecule transport, biocompatibility, and other factors in determining these differences in outcome are unclear. Future development of hemodialysis membranes should focus on improving biocompatibility and enhancing clearances of small solutes and middle molecules, while minimizing the loss of larger plasma proteins.

Biocompatible Materials↗
PubMed1997

Determination of glomerular filtration rate using technetium-99m-DTPA with differing degrees of renal function.

UNLABELLED: Glomerular filtration rate (GFR) is an important index of renal function. Twenty-four-hour creatinine clearance overestimates GFR in patients with poor renal function. Inulin and iothalamate clearances are accepted reference standards for determining GFR but are expensive and laborious. We have previously reported that GFRs obtained by measuring the disappearance of 99mTc-DTPA from ultrafiltered (protein-free) samples of plasma were virtually identical to those obtained by the iothalamate method. However, the subjects used in that study had normal to only moderately decreased renal function. METHODS: The accuracy of measuring GFR by plasma clearance of 99mTc-DTPA was determined in subjects where renal function varied from normal to severely impaired. In all subjects, GFR was established by clearance of 125I-iothalamate from urine and serum and was used as the standard of reference. RESULTS: For subjects with normal to moderately diminished renal function (GFR > 20 ml/min), the correlation between values of GFR obtained by the DTPA and iothalamate methods was high (n = 18, r = 0.966). The difference between the pairs of GFR values obtained by the two methods was not statistically significant (p > 0.1). In patients with severe renal insufficiency (GFR < 20 ml/min), the correlation between the DTPA and iothalamate methods was poor (n = 11, r = 0.236), and the GFR values obtained by the two methods were statistically different (p < 0.01). CONCLUSION: These results suggest that GFR can be determined accurately by plasma clearance of 99mTc-DTPA in all patients except those with severe renal insufficiency.

Adult↗
PubMed1996

Replication and pathogenicity after intranasal and intracranial inoculation of swine with a recombinant pseudorabies virus containing a deletion at the UL/IR junction.

Pseudorabies virus (PRV) is a neurotropic herpesvirus of swine. Previously, we described construction of a recombinant strain of PRV (LLT beta delta 2) which contains a 3.0-kb deletion spanning the junction of the unique long and internal repeat sequences. Compared to the parental strain, Indiana-Funkhauser, and a virus rescued for the deleted sequences (LLT beta res), LLT beta delta 2 replicated efficiently at the site of inoculation, yet exhibited significantly reduced virulence when inoculated intranasally in pigs. In this report, we investigated the effect of the deletion on PRV replication and virulence after intracranial inoculation of swine, in comparison to replication and virulence after intranasal inoculation, in order to more precisely locate the defect in LLT beta delta 2. Four-day-old pigs were infected intranasally with LLT beta delta 2 or LLT beta res and necropsied at various times postinfection. Compared to LLT beta res-infected pigs, tissue distribution of virus, PRV antigen, and lesions of LLT beta delta 2-infected pigs were comparable in all peripheral tissues examined, including trigeminal ganglia, but were reduced in tissues from the central nervous system (CNS). LLT beta delta 2 was able to replicate in the CNS after intracranial inoculation into the cerebral cortex of 2-day-old piglets and to spread from CNS to peripheral tissues. Neurovirulence of LLT beta delta 2 was somewhat reduced, as demonstrated by delayed onset of neurological signs and death in intracranially inoculated pigs. These results indicate that decreased neurovirulence after intranasal inoculation is not due to inability of LLT beta delta 2 to replicate in CNS tissues. The difference in the amount of antigen detected in CNS tissues after intracranial inoculation compared to intranasal inoculation suggests that one defect in LLT beta delta 2 is reduced ability to spread from peripheral neurons to the CNS after intranasal inoculation.

Animals↗
PubMed1996

Reducing symptoms during hemodialysis by continuously monitoring the hematocrit.

Previous studies have demonstrated that patients on hemodialysis develop intradialytic symptoms when the blood volume decreases to a critical level. Using a continuous monitor (CRIT-LINE; In-Line Diagnostics, Riverdale, UT) to determine the instantaneous hematocrit and blood volume, we observed that certain intradialytic symptoms occurred at a patient-specific hematocrit. In the present study, we exploited this hematocrit threshold concept to decrease the occurrence of lightheadedness, cramping, and nausea, regardless of blood pressure changes. In the first phase of the study, hematocrit threshold was established in six hypotension-prone patients. Five patients entered into the second phase in which ultrafiltration rates were increased 25 percent above prescribed values at the beginning of the experimental sessions. Subsequently during the experimental sessions, ultrafiltration rates were manipulated to maintain the instantaneous hematocrit value 2 units below the established hematocrit threshold. Sessions without ultrafiltration rate adjustments based on hematocrit served as controls. There were no differences between experimental (n = 27) and control (n = 28) sessions with respect to treatment time (230 minutes v 229 minutes), fluid volume removed (3,351 mL v 3,383 mL), and maximum percentage change in systemic blood pressure (-26 percent v -24 percent). However, there were less symptoms during the experimental sessions (26 percent v 57 percent; P = 0.038). These data suggest that a twofold reduction in intradialytic symptoms can be achieved using continuous hematocrit monitoring without altering treatment times or volume removed in hypotension-prone patients.

Blood Volume↗
PubMed1996

Increased lipase inhibition in uremia: identification of pre-beta-HDL as a major inhibitor in normal and uremic plasma.

The hypertriglyceridemia commonly observed in uremia has been attributed to an abnormally high inhibitor activity in plasma for lipoprotein lipase (LPL) and hepatic lipase (HL), both of which have a key role in lipoprotein metabolism. The purpose of this investigation was to establish a relationship between plasma lipase inhibitor activity and hypertriglyceridemia, identify the main plasma lipase inhibitor, and determine the basis for the greater inhibitor activity in uremia. In a mixed population of normal (N = 8) and uremic subjects (N = 12), log-transformed plasma triglycerides correlated with both inhibitor activity and uremic status. However, inhibitor activity was the only retained predictor variable for triglycerides in a multiple linear regression model (r = 0.91; P < 0.0001). An inhibitor isolated from normal plasma was identified as a particle containing apolipoprotein A-I (apo A-I) and 3% phospholipid. This particle, which has pre-beta electrophoretic mobility and a Stokes' radius of 54 A, therefore corresponds to a form of the previously described pre-beta-HDL (free apo A-I) in the non-lipoprotein fraction of plasma. Comparison of normal and uremic plasma indicated that the greater lipase inhibitor activity in the latter could be attributed to an increased concentration of apo A-I in the non-lipoprotein fraction of plasma (pre-beta-HDL), as well as to increased inhibition by the uremic lipoproteins. The increased plasma lipase inhibitor activity may be important in the pathogenesis of hypertriglyceridemia in chronic renal failure.

Enzyme Inhibitors↗
PubMed1996

Stages of future technological developments in haemodialysis.

Understanding the needs of the patients, dialysis staff, and nephrologists is the first logical step in the technological development of better haemodialysis devices. This includes the understanding of large and small uraemic toxins and their removal by dialysis membranes, pathophysiology of intradialytic symptomatology, and problems associated with vascular access. Each of these areas can benefit from profiling techniques. Profiling of urea (urea kinetics), solute clearance profiles of dialysis membranes, and volume profiling are areas that are undergoing active investigations and incorporation into clinical practice. Volume profiling currently entails the monitoring of intravascular and total body fluids as well as the measurement of vascular access flow. Development of sophisticated software is necessary to integrate data from various profiling techniques into dialysis equipment in a meaningful manner in order to optimize the dialysis treatment. The ultimate benefits of these devices should take into account the medical, psychosocial, and financial aspects of various parties involved.

Algorithms↗
PubMed1996

Removal of high-molecular-weight solutes during high-efficiency and high-flux haemodialysis.

BACKGROUND: Although urea clearance is often increased during high-efficiency and high-flux haemodialysis to compensate for short treatment times, the impact of these treatment modalities on the removal of larger uraemic toxins has not been thoroughly investigated. METHODS: We compared solute removal rates for five haemodialysis treatment strategies in vitro using neutral dextrans (molecular radii between 15 and 50 A) as marker macromolecules. Removal rates were assessed by the decrease in dextran concentration within the reservoir of a model circuit using outdated human plasma as the test solution. Results for high-efficiency haemodialysis (CA110 dialyser at a blood flow rate of 400 ml/min and TAF175 dialyser at a blood flow rate of 300 ml/min) and high-flux haemodialysis (CT190G dialyser at a blood flow rate of 300 ml/min and F60 dialyser at a blood flow rate of 300 ml/min) were compared with those for conventional haemodialysis (CA110 dialyser at a blood flow rate of 200 ml/min). RESULTS: Dextran clearances were dependent on the dialyser employed, and they decreased with molecular size and time for each treatment strategy. Removal rates were greatest using the CT190G and F60 dialysers, intermediate for the TAF175 dialyser, and lowest for the CA110 dialyser at either blood flow rate. CONCLUSION: The results of this study demonstrate that increasing blood flow rates alone to increase urea clearance may not provide adequate removal of high-molecular-weight solutes. The use of high-flux or large surface area, high-efficiency dialysers are more effective in maintaining the removal of high-molecular-weight solutes when treatment time is shortened.

Dextrans↗
PubMed1996

Characterization of molecular transport in artificial kidneys.

Transport characterizations of artificial kidneys require the use of multiple marker molecules of various sizes, including small solutes, middle molecules, and albumin. Previous approaches for evaluating hemodialyzer transport performance are reviewed. New data obtained from in vitro experiments comparing 5 low molecular weight proteins of approximately the same molecular size as markers for middle molecule transport also are described. Sieving coefficients for marker low molecular weight proteins may vary substantially for a given artificial kidney membrane. Furthermore, sieving coefficients for marker proteins that do not absorb significantly to the membrane are comparable to those for polydisperse dextrans. These observations suggest that other protein properties besides molecular size are important determinants of protein sieving coefficients across artificial kidney membranes. We conclude that low molecular weight proteins can behave differently from one another and generalizations about artificial kidney membrane transport from data obtained on a single protein may be problematic, and that both low molecular weight proteins and polydisperse dextrans are useful markers of middle molecular transport across artificial kidney membranes.

Animals↗
PubMed1996

A pseudorabies virus mutant with deletions in the latency and early protein O genes: replication, virulence, and immunity in neonatal piglets.

The pathogenicity of a double mutant of pseudorabies virus (PRV) with deletions in the latency gene and the early protein O gene was examined. In comparison to the parent Indiana-Funkhauser virus, the ability of this mutant to replicate and to cause disease in piglets is greatly reduced. At an infection dose that caused no clinical signs in 5-day-old neonatal piglets, this mutant was capable of eliciting solid protective immunity against a lethal PRV challenge. Thus, the double-gene deletion attenuates PRV but does not affect its immunogenicity. These features may be desirable for inclusion into future PRV vaccines.

Animals↗