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Biomedical subjects

V S Lim

Publications and source records attributed to V S Lim.

At least 19 recordsLinked to original sources

Ventilatory and metabolic changes during high efficiency hemodialysis.

Ventilatory and metabolic changes were measured in seven patients undergoing high efficiency hemodialysis using a cuprophane dialyzer and bicarbonate-containing dialysate. At an HCO3 concentration of 35 mEq/liter and a mean in vivo urea clearance of 3.6 ml/kg/min, hypoxemia was not detected during dialysis (PaO2 was 14.00 and 13.60 kPa before and during dialysis). The new findings, related to high efficiency bicarbonate dialysis, include a sustained rise in minute ventilation (VE, 6.1 to 6.8 liter/min, P less than 0.01), an increase in CO2 excretion (VCO2, 194 to 214 ml/min, P less than 0.05), and O2 consumption (VO2, 215 to 246 ml/min, P less than 0.05). The increment in VE and VCO2 was attributed to the high flux rate of bicarbonate while the rise in VO2 is likely the result of metabolic alkalosis. Arterial pH rose from 7.40 to 7.49 mm Hg and serum HCO3 increased from 23.8 to 29.2 mEq/liter, while pCO2 remained normal at 5.07 kPa throughout the study. The acid-base status of the blood changed from that of a metabolic acidosis to that of a respiratory acidosis across the dialyzer where the pH decreased from 7.47 to 7.41 and pCO2 rose from 5.31 to 7.72 kPa. These data indicate that a healthy ventilatory response is needed to excrete the excess CO2 generated during high efficiency bicarbonate hemodialysis. The significance and etiology of the elevated O2 consumption is undetermined.

Acid-Base Equilibrium

Tidal peritoneal dialysis: preliminary experience.

OBJECTIVES: To determine the feasibility of home tidal peritoneal dialysis (TPD) and to assess whether eight hours of TPD can achieve uremia control and urea removal equal to that of continuous cycling peritoneal dialysis (CCPD). DESIGN: An open enrollment pilot study. SETTING: The Home Dialysis Training Center of the University of Iowa Hospitals and Clinics, a tertiary care teaching hospital. PATIENTS: Nine patients experienced with CCPD and living 80 km to 280 km from the dialysis center began TPD, because they wished to decrease their dialysis time. INTERVENTIONS: Following baseline measurements, each patient was taught to perform TPD. TPD consisted of an initial fill volume of 40 mL/kg, a residual volume approximately 20 mL/kg, and tidal exchanges of 10 to 20 mL/kg to achieve the desired hourly flow rate. Clinic assessments took place every four to six weeks, and prescriptions were subsequently altered to attain urea removal equal to that of CCPD. MEASUREMENTS: Patient interviews were used to determine TPD acceptance. Prior to each clinic visit, dialysate effluent volume and dialysis duration were recorded, and a sterile sample of the effluent was obtained for urea, creatinine, and total nitrogen measurement. RESULTS: Urea and creatinine clearances increased with dialysate flow. Dialysate nonurea nitrogen was 3.0 +/- 0.2 mmol/kg/D and changed minimally with increasing dialysate volumes. Eight hours of TPD (initial fill: 40 mL/kg; residual volume: 20 mL/kg; tidal inflow: 20 mL/kg) with hourly tidal flow exceeding 40 mL/kg/hr and no daytime volume achieved urea removal equal to that of the patient's prior CCPD prescription. CONCLUSION: TPD can provide dialysis equal to that of CCPD within a shorter amount of time (eight vs ten hours), but uses a greater volume of dialysate (16.0 L for TPD vs 9.5 L for CCPD).

Adolescent

Quantitating hemodialysis: a comparison of three kinetic models.

Three urea kinetic analyses were applied to hemodialysis and their conformity assessed. Sixteen patients underwent 50 measurements of dialyzer clearance (K), protein catabolic rate (PCR), and dialysis quantification (Kt/V) using the urea kinetic model (UKM) of Gotch and Sargent, Malchesky's direct dialysis quantification (DDQ), and the graphic technique of urea reduction analysis (URA) devised by Keshaviah. Additionally, the equations proposed by Jindal (percent urea reduction), and Daugirdas were used to calculate Kt/V values for each study. Dialyzer performance determined by whole blood urea clearance consistently exceeded simultaneous dialysate urea removal and was 55% greater than the clearance calculated by DDQ. Despite these variations, dialysis adequacy (Kt/V) and normalized protein catabolic rate (nPCR) were remarkably constant when derived by fixed-volume single-pool analyses (ie, UKM, DDQ, and URA). Application of variable-volume corrections increased Kt/V and nPCR, but caused DDQ values to diverge from those of UKM and URA. During rapid high-efficiency dialysis (RHED), the UKM predicted urea removal in excess of that documented by DDQ. During this trial (low-level RHED with K = 2.98 mL.kg-1 per min), urea dysequilibrium across blood-cell interfaces was sufficient to cause UKM to overestimate protein catabolism by 5%. The basic assumption of single-pool kinetics may be inappropriate during RHED, and further increases in dialyzer clearance will increase the discrepancy between projected and actual urea removal. Future comparisons of RHED prescriptions should employ mass balance data, or redesigned kinetic analyses.

Blood Urea Nitrogen

Recombinant human erythropoietin in predialysis patients.

This report reviews the author's experience and the results of a multicenter study with regard to the use of recombinant human erythropoietin (Epo) in predialysis patients. The data demonstrate that Epo corrects anemia and improves quality-of-life assessment and exercise capacity in patients who are not dialyzed, but who have renal insufficiency. The incidence of hypertension was 22% in the Epo-treated subjects and 19% in the placebo group. Within the Epo-treated group, there appears to be a greater frequency of hypertensive events in those subjects receiving the higher dosages. The concern that Epo might accelerate the deterioration of renal function is not substantiated by several clinical studies.

Anemia

Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin.

OBJECTIVE: To determine if intraperitoneal administration of vancomycin (a slowly absorbed antibiotic) improves the management of dialysis-associated peritonitis over that obtained by using cefazolin, an equally potent, rapidly absorbed antibiotic. SETTING: A university operated teaching hospital, with patient treatment initiated at home. PATIENTS: One hundred thirty-one patients trained to perform peritoneal dialysis (CAPD and CCPD) and followed at the University of Iowa Hospitals and Clinics Home Dialysis Treatment Center. DESIGN: Patients were prospectively allocated into groups adding either vancomycin 25 mgm/L, or cefazolin 50 mgm/L to their dialysate when signs or symptoms of peritonitis developed. Treatment results were analysed using chi-square testing. FINDINGS: Compared to cefazolin, initial peritonitis therapy with vancomycin improved the peritonitis resolution rate [67% vs 81%; p = 0.008], reduced the incidence of hospital admissions [68% vs 48%; p = 0.001], and decreased the risk of superinfection [4% vs 0%; p = 0.039]. CONCLUSION: Vancomycin appeared to be superior to cefazolin in the treatment of peritoneal dialysis associated peritonitis.

Adult

Effect of hematocrit on solute removal during high efficiency hemodialysis.

The effect of changing hematocrit (Hct) on solute removal during high efficiency hemodialysis was evaluated in 12 patients. In five subjects, Hct was raised by recombinant human erythropoietin (rHuEPO) treatment, and in the other seven by blood transfusion. Solute removal was assessed by measuring: (1) whole blood (kb), blood water (kbw) and dialysate (kd) clearances; (2) the amount of solute in the spent dialysate; (3) the fractional decrement of serum solute concentration achieved by hemodialysis; and (4) urea kinetics, including kt/V and protein catabolic rate (PCR). The results showed that increasing the Hct did result in a slight reduction in some solute clearances. The decrement, however, was minor (5 to 8%), whereas the rise in Hct was marked (55 and 65%) in the transfused and EPO-treated groups, respectively. More importantly, linear regression analysis of kd/kb ratios versus Hct indicated that a rise of Hct from 20 to 40% would reduce creatinine and phosphate clearance by 8 and 13%, respectively. By contrast, assessment of the absolute amount of solute removed in the spent dialysate failed to detect differences between the two study periods. Additionally, a rise in Hct also did not affect urea kinetic parameters including kt/V and PCR. Based on these data, it appears prudent to increase hemodialysis prescription by 10 to 15% when Hct is raised to near 40% to avoid excessive retention of molecules with slow transcellular movement.

Adult

Effect of recombinant human erythropoietin on renal function in humans.

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.7 to 24 months. Ten patients received r-HuEPO and the anemia was corrected (Group I). Sixteen patients did not receive r-HuEPO. Ten of them were anemic (Group II) and six had normal hematocrits (Group III). All study groups were matched for age, diagnosis and degree of renal insufficiency. All cohorts were followed prospectively (Period B, from the first day of the study to the time of data analysis or dialysis and transplantation); renal function was also examined retrospectively (Period A, from the first day of the study to the time of first renal function measurement). Hematocrit was lowest in Group II control patients, 27%, highest in the Group III control subjects, 43%, and intermediate in Group I EPO-treated patients, 36%. Serum creatinine uniformly increased in all three groups of patients. The rate of progression, as measured by the slopes of the reciprocal of serum creatinine versus time, however, was similar in all three groups of subjects and during both periods. The mean slopes for Group I patients before and after r-HuEPO were, respectively, -0.0058 and -0.0054, that of the control cohorts with low and normal hematocrit during period B were -0.0063 and -0.0010, respectively. Thus, it appeared that neither r-HuEPO administration nor a normal hematocrit accelerated the deterioration of renal function in these patients with renal insufficiency.

Aged

Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial.

STUDY OBJECTIVE: To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients. DESIGN: Randomized, double-blind, placebo-controlled trial for 8 weeks. SETTING: Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital. PATIENTS: Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01). INTERVENTIONS: Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week. MEASUREMENTS AND MAIN RESULTS: Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9. CONCLUSIONS: Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients.

Adult

Augmentation of protein degradation by L-triiodothyronine in uremia.

To ascertain if excessive protein catabolism is a feature of uremia, we determined leucine flux and nitrogen balance in 11 stable chronic dialysis patients and in 7 normal subjects. Leucine flux was determined during primed constant infusion of 2H3 and 15N leucine. Nitrogen balance was determined by measurement of nitrogen in the food, dialysate, and urine, and in the dialysis patients by correcting for the changing urea nitrogen pool. To assess if thyroid hormone adversely affects protein metabolism, the above-mentioned studies were done once in the basal state and once after a 7-day course of L-triiodothyronine (T3) treatment. Leucine carbon flux (mumol/kg/min) was 1.22 +/- 0.05 in the controls and 1.40 +/- 0.09 in the renal patients in the basal state (P = NS). Following T3 treatment, leucine carbon flux was increased to 1.40 +/- 0.05 and 1.72 +/- 0.09, respectively, in the controls and the renal patients (P less than .05). Fractional increment of the leucine carbon flux was 14% +/- 3% in the controls and 23% +/- 9% in the renal patients (P less than .05). The leucine nitrogen flux (mumol/kg/min) was 2.10 +/- 0.15 in the controls and 2.54 +/- 0.23 in the renal patients in the basal state (P = NS), and increased to 2.48 +/- 0.14 and 3.44 +/- 0.22, respectively, in controls and renal patients after T3 administration (P less than .05). Fractional increment of leucine nitrogen flux was 19.5% +/- 4.3% in the controls and 36.4% +/- 5.0% in the renal patients (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The safety and the efficacy of maintenance therapy of recombinant human erythropoietin in patients with renal insufficiency.

Ten anemic predialysis renal patients participated in a study to examine the long-term effects of recombinant human erythropoietin (r-HuEPO) treatment. The drug was initially given intravenously three times a week for 1 to 5 months, then by subcutaneous injections three times each week for 4 to 8 months, and finally by subcutaneous injection once weekly for 3 to 18 months. The duration of follow-up ranged from 11 to 29 months. Anemia was ameliorated in all participants. Mean hematocrit increased from a basal value of 26.8% to 35.1% during the intravenous phase and to 36.7% and 34.6% during the two subcutaneous periods. Mean weekly doses of erythropoietin (EPO) were 276 units/kg during intravenous therapy and 134 and 108 units/kg in the two subcutaneous periods. The differences in the doses were significant only between the intravenous and the two subcutaneous periods. Mean erythrocyte mass increased from a baseline value of 13.6 mL/kg to 20.4 mL/kg 8 months after initiation of treatment. Mean erythrocyte survival half-time was increased from 23 days before to 26 days, 8 months after r-HuEPO treatment, P less than 0.002. Mean blood pressure (mm Hg) was 105 before and 95 after treatment. Mean serum creatinine was 513 mumol/L (5.8 mg/dL) at the beginning of the study. At the time of this writing (11 to 29 months after treatment), seven patients have required dialysis treatment. There were three episodes of transient refractoriness to r-HuEPO documented during periods of infection and surgical procedures. All subjects tolerated the medication well, and no serious side effects attributable to the medication were noted. Furthermore, circulating antibodies against r-HuEPO were consistently negative.

Aged

The effect of interdialytic interval on protein metabolism: evidence suggesting dialysis-induced catabolism.

While examining protein metabolism in hemodialysis patients, we noted that lengthening the interdialytic intervals from two to three days reduced the dialysate nitrogen waste excretion (D-N2; mg/min) and lowered the patient's protein catabolic rate (PCR; g/kg/d). D-N2 was measured in the spent dialysate and PCR derived from urea kinetics while patients maintained a constant dietary intake. In the basal state (B), D-N2 decreased from 5.43 to 4.32 mg/min when the interdialytic interval was increased from two to three days (P less than 0.001). Similarly, PCR was reduced from 0.96 to 0.82 g/kg/d when the interdialytic period was extended. The same phenomenon was observed when subjects were taking either thyroid hormone (T3) or ipodate (lp) to increase or decrease body metabolism. In the T3 period, D-N2 was 6.12 and 5.06 mg/min and PCR was 1.08 and 0.92 g/kg/d, respectively, when the interdialytic intervals were two and three days (P less than 0.001). During the lp period, N-D2 was 4.78 and 4.03 mg/min and PCR was 0.88 and 0.76 g/kg/d, respectively, for the two- and three-day intervals (P less than 0.05). These data are consistent with dialysis-related protein catabolism. It appears that the longer interdialytic interval allowed the body to shift to a more anabolic state.

Adult

L-triiodothyronine at a slightly over physiologic dose increases leucine flux, which suggests an increase in protein degradation in normal subjects.

The present study was undertaken to determine whether minor alterations of serum thyroid hormone concentration have an effect on plasma amino acid kinetics. Flux rates of 2H3-labeled leucine, 15N-labeled leucine, and 2H3-labeled alanine were determined in the basal state and after a 7-day course of L-triiodothyronine (T3) supplementation in seven normal adult subjects. A small dose of T3 was given (0.8 microgram/kg/day) that resulted in only slightly higher than physiologic serum T3 concentration. After T3 treatment, leucine carbon flux increased from 1.22 +/- 0.05 to 1.40 +/- 0.05 mumol/kg/minute (p less than 0.001) and leucine nitrogen flux increased from 2.10 +/- 0.15 to 2.48 +/- 0.14 mumol/kg/minute (p less than 0.005), but alanine carbon flux did not change significantly, going from 6.26 +/- 0.67 to 6.58 +/- 0.58 (p = not significant). Because the experiment was performed in the postabsorptive state, increased leucine flux after T3 treatment suggests accelerated protein degradation.

Adult

Reducing the hemorrhagic complications of hemodialysis: a controlled comparison of low-dose heparin and citrate anticoagulation.

We report a randomized prospective study comparing the results of anticoagulation using hypertonic trisodium citrate and low-dose controlled heparin during 45 hemodialysis treatments performed on patients determined to be at high or very high risk for bleeding. Dialysis-associated bleeding was more frequent following low-dose controlled heparin anticoagulation than during hypertonic citrate therapy (P less than .05). Dialysis effectiveness measured by postdialysis chemistries and weight loss was equivalent in the two groups.

Anticoagulants

Reproductive function in patients with renal insufficiency.

Hypogonadism is prevalent in patients with renal insufficiency and is manifested as sexual dysfunction and infertility in males and as anovulation and amenorrhea in females. Although many investigators believe that the defect represents primary gonadal damage by uremic toxins, we propose the coexistence of central neuroendocrine disorders in the regulation of gonadotropin secretion. Evidence supporting such a hypothesis is discussed.

Erectile Dysfunction

Blunted peripheral tissue responsiveness to thyroid hormone in uremic patients.

To understand the biologic significance of the low triiodothyronine (T3) syndrome in patients with chronic renal failure (CRF), we examined thyroid hormone profile, basal O2 uptake (VO2), and peripheral blood mononuclear leukocyte (PBL) ouabain binding in these patients and in the control subjects before and after L-triiodothyronine (T3) and sodium ipodate treatment. In the controls (N = 8), T3 administration increased serum total T3 from 136 +/- 15 to 232 +/- 11 ng/dl, and reduced total thyroxine (T4) from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, free T4 from 1.59 +/- 0.12 to 1.03 +/- 0.05 ng/dl and thyroid-stimulating hormone (TSH) from 1.74 +/- 0.24 to 0.41 +/- 0.09 microU/ml. VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg/min. Ipodate treatment, on the other hand, resulted in a reduction of serum total T3 to 102 +/- 21 ng/dl, an increase in total T4 to 9.59 +/- 0.50 micrograms/dl, free T4 to 1.91 +/- 0.13 ng/dl and TSH to 3.64 +/- 1.14 microU/ml. VO2 decreased to 2.43 +/- 0.06 ml/kg/min. P values ranged from less than 0.05 to less than 0.001. In the CRF patients (N = 14), T3 treatment also resulted in a rise in serum total T3 from 75 +/- 5 to 185 +/- 8 ng/dl. Total T4 declined from 6.68 +/- 0.34 to 5.18 +/- 0.48 micrograms/dl, free T4 from 0.85 +/- 0.1 to 0.67 +/- 0.08 ng/dl and TSH from 3.67 +/- 0.86 to 0.94 +/- 0.3 microU/ml. VO2, however, did not change (from 2.91 +/- 0.12 to 2.99 +/- 0.17 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Regional anticoagulation: hemodialysis with hypertonic trisodium citrate.

We have developed a simplified method for performing regional citrate anticoagulation during hemodialysis. High ultrafiltration rates and specialized equipment were obviated by the use of a 1.6-mol/L trisodium citrate solution and a standard calcium-containing dialysate. Thirty-six dialyses were performed with this technique on 14 stable and 22 high bleeding risk patients. There was no significant decline in plasma-ionized calcium during citrate dialysis, ie, 3.85 +/- 0.34 mg/dL (mean +/- SE) predialysis, to 3.31 +/- 0.26 postdialysis; furthermore, no patient developed neuromuscular symptoms or evidence of cardiovascular instability from hypocalcemia. Serum sodium rose with this procedure, but not to hypernatremic levels. This method of citrate dialysis is safe and effective during continuous blood flow (double-needle) hemodialysis, and is no more difficult to perform than conventional heparin dialysis. Single-needle (reciprocating blood flow) hemodialysis was successfully performed by the additional use of a calcium-free dialysate and separate calcium chloride infusion (10% calcium chloride), but risks the production of unexpected hypercalcemia.

Bicarbonates