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Biomedical subjects

V S Lim

Publications and source records attributed to V S Lim.

At least 37 records · Page 2Linked to original sources

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↗

Basal oxygen uptake: a new technique for an old test.

To assess the metabolic effects of T4 and T3, we measured serum total T4 (TT4), free T4 (FT4), total T3 (TT3), TSH, and basal oxygen uptake (VO2) in eight normal subjects in the basal state and after treatment with L-T3 (T3) and sodium ipodate for 2 weeks. T3 treatment resulted in a rise of serum TT3 from a baseline of 137 +/- 16 (+/- SE) to a peak of 239 +/- 15 ng/dl. Serum TT4 declined from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, FT4 from 1.59 +/- 0.13 to 1.03 +/- 0.05 ng/dl, and TSH from 1.74 +/- 0.24 to 0.56 +/- 0.16 microU/ml. Basal VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg X min. Ipodate, on the other hand, led to a lower serum TT3 concentration (102 +/- 21 ng/dl), higher serum TT4 and FT4 (9.59 +/- 0.5 micrograms/dl and 1.91 +/- 0.13 ng/dl, respectively), and elevated TSH (3.64 +/- 0.14 microU/ml). Basal VO2 was reduced to 2.44 +/- 0.06 ml/kg X min. Linear regression analysis revealed an excellent positive correlation between serum TT3 and basal VO2 (n = 25; r = 0.747; P less than 0.001) and a significant negative correlation between serum TT3 and TSH (n = 26; r = -0.526; P less than 0.01). Serum TT4 and FT4 correlated negatively with VO2 and positively with serum TSH. The higher T4 level during ipodate treatment was associated with lower VO2 and higher TSH, and vice versa when T4 was suppressed while receiving T3. When ipodate was given concomitantly with T3 to five subjects, only the effects of T3, characterized by increased VO2 and decreased TSH, were evident. These data indicate that both basal VO2 and serum TSH are sensitive indices of thyroid hormone activities. The latter gives only the directional change (hyper- or hypothyroidism), while the former more accurately quantitates the magnitude of the derangement. Moreover, it appears that in man, T3, and not T4, is the primary hormone that regulates thermogenesis and TSH secretion.

Adult↗

Cellular response to peritonitis among peritoneal dialysis patients.

White blood cell counts and differential cell counts were performed on 249 peritoneal dialysis effluents from 48 patients using chronic peritoneal dialysis. The finding of more than 50% polymorphonuclear leukocytes in the dialysate was a more sensitive indicator of peritonitis than was an absolute cell count of 100 cells/microL. This finding was true for patients using intermittent peritoneal dialysis, continuous ambulatory peritoneal dialysis, and continuous cycling peritoneal dialysis.

Ascitic Fluid↗

Protective adaptation of low serum triiodothyronine in patients with chronic renal failure.

Low serum triiodothyronine (T3) concentration is frequently found in patients with chronic renal failure (CRF). To test the hypothesis that this may serve to minimize protein catabolism in these patients, we measured nitrogen balance (Nb) in seven CRF and four control subjects in the basal state and when serum T3 concentration was elevated by L-triiodothyronine (LT3) and suppressed by sodium ipodate administration. In the basal state, both the controls and the CRF patients were in positive Nb, 0.02 +/- 0.51 and 0.58 +/- 0.34 g/day, respectively. During LT3 administration, Nb decreased to -0.80 +/- 0.39 g/day in the CRF patients (P less than 0.01), but remained positive, 0.22 +/- 0.67 g/day, in the controls. There was a significant negative correlation between serum T3 concentration and Nb in the CRF patients (r = -0.63, P less than 0.005), but not in the controls. Furthermore, urea nitrogen generation rate, calculated from urea kinetics, increased from a baseline of 4.6 +/- 0.55 to 6.0 +/- 0.50 mg/min during LT3 administration in the CRF patients (P less than 0.01). Sodium ipodate, which significantly lowered serum T3 concentrations, had little effect on nitrogen metabolism in the controls and the CRF patients. These data support the concept that low serum T3 concentrations may confer a protective effect on CRF patients regarding protein-nitrogen conservation and provide a rationale for not correcting such deficiency.

Adaptation, Physiological↗