Biomedical subjects

M E Brier

Publications and source records attributed to M E Brier.

At least 19 recordsLinked to original sources

PubMed1997

Pharmacokinetics of oral glyburide in subjects with non-insulin-dependent diabetes mellitus and renal failure.

To test the hypothesis that renal failure has no effect on the pharmacokinetics of glyburide, five subjects with non-insulin-dependent diabetes mellitus (NIDDM) and end-stage renal disease requiring hemodialysis, and four NIDDM subjects with normal renal function were studied. On days 0, 1, and 15, subjects consumed 33 carbohydrate grams, and glucose, insulin, and C-peptide were measured for 4 hours. On day 1, subjects received 3 mg glyburide and measured plasma concentrations for 48 hours. On day 3, multiple dosing on 3 mg glyburide daily began. On day 15, plasma concentrations were measured for 48 hours. The pharmacokinetics and pharmacodynamics of glyburide, glucose, insulin, and C-peptide were determined as well as daily fasting blood glucose. Glucose area under the curve (AUC) and daily fasting glucose levels did not change in either controls or hemodialysis subjects. The mean serum glyburide blood levels and pharmacokinetics did not differ after initial or chronic glyburide administration in NIDDM subjects with end-stage renal disease treated with hemodialysis compared with controls. Glyburide half-life averaged 3.3 hours in control subjects and 5.0 hours in hemodialysis subjects. Hemodialysis subjects had increased C-peptide and insulin AUC with chronic dosing. Renal failure does not affect the pharmacokinetics of 3.0 mg oral glyburide.

Administration, Oral↗

PubMed1997

Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study.

The use of the "peritonitis rate" in the management of patients undergoing peritoneal dialysis is assuming importance in comparing the prowess of facilities, care givers and new innovations. For this to be a meaningful outcome measure, the type of infection (causative pathogen) must have less clinical significance than the number of infections during a time interval. The natural history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not support that the outcome of an episode of peritonitis is independent of the causative pathogen. Could this concern be extended to other more frequently occurring pathogens? To address this, the Network 9 Peritonitis Study identified 530 episodes of single organism peritonitis caused by a gram positive organism and 136 episodes caused by a single non-pseudomonal gram negative (NPGN) pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred equally in both groups. Outcomes of peritonitis were analyzed by organism classification and by presence or absence of a soft tissue infection. NPGN peritonitis was associated with significantly more frequent catheter loss, hospitalization, and technique failure and was less likely to resolve regardless of the presence or absence of a soft tissue infection. Hospitalization and death tended to occur more frequently with enterococcal peritonitis than with other gram positive peritonitis. The outcomes in the NPGN peritonitis group were significantly worse (resolution, catheter loss, hospitalization, technique failure) compared to coagulase negative staphylococcal or S. aureus peritonitis, regardless of the presence or absence of a coincidental soft tissue infection. Furthermore, for the first time, the poor outcomes of gram negative peritonitis are shown to be independent of pseudomonas or polymicrobial involvement or soft tissue infections. The gram negative organism appears to be the important factor. In addition, the outcome of peritonitis caused by S. aureus is worse than that of other staphylococci. Thus, it is clear that all peritonitis episodes cannot be considered equivalent in terms of outcome. The concept of peritonitis rate is only meaningful when specific organisms are considered.

Aged↗

PubMed1996

Hemodynamic, renal, and hormonal responses to lower body positive pressure in human subjects.

Studies in healthy human subjects subjected to lower body positive pressure (LBPP) have failed to elucidate many of the physiologic effects of this maneuver. In 7 healthy, well-hydrated men we studied the following responses to LBPP (35 mm Hg, 1 hour, supine position): systemic and renal hemodynamics; urine volume (UV), urine osmolality (Uosm), and urine sodium level (UNaV); free water (CH20) and osmolar (Cosm) clearances; plasma renin activity (PRA); levels of aldosterone (PA), cortisol (CORT), norepinephrine (NE), atrial natriuretic peptide (ANP), and vasopressin (AVP); osmolality (Posm); and serum sodium level. Subjects were restudied on a control day with zero trouser pressure. The recorded changes (p < 0.05) when comparing the LBPP day with the control day were as follows: fractional Na+ reabsorption increased (98.7% +/- 0.2% to 99.3% +/- 0.1%) and UNaV decreased (0.19 +/- 0.03 mEq/min to 0.10 +/- 0.01 mEq/min), with concomitant increases in PRA (1.7 +/- 0.2 ng/ml/90 min to 4.5 +/- 1.8 ng/ml/90 min), PA (7.7 +/- 0.7 ng/dl to 9.3 +/- 1.5 ng/dl), and CORT (13.0 +/- 2.6 mg/dl to 19.2 +/- 3 mg/dl); the increase in blood pressure with LBPP (96 +/- 3 mm Hg to 112 +/- 4 mm Hg) was greater than that during control conditions. Renal plasma flow tended to display an interactive pattern across days, with a slight decline during LBPP (5%) and a slight elevation under control conditions (9%). On the LBPP day only, filtered Na+ declined (15 +/- I mEq/min to 12 +/- 1 mEq/min) as a function of reduced glomerular filtration rate (112 +/- 5 ml/min to 91 +/- 7 ml/min), blood volume decreased (by 2.7% +/- 0.7%), CO decreased (5.5 +/- 0.3 L/min to 4.7 +/- 0.3 L/min), and stroke volume declined (101 +/- 6 ml to 84 +/- 3 ml). On both days, NE increased (control, 221 +/- 23 pg/ml to 340 +/- 33 pg/ml; LBPP, 236 +/- 17 pg/ml to 369 +/- 31 pg/ml) and ANP increased (control, 47 +/- 7 pg/ml to 97 +/- 21 pg/ml; LBPP, 49 +/- 10 pg/ml to 104 +/- 30 pg/ml). We concluded that LBPP reduces renal sodium excretion. The mechanism for this reduction is not known, although it did occur in association with an increase in plasma renin activity, which in turn results from mechanical reduction of renal perfusion, stress-related CORT stimulation, a reflex-based elevation in peripheral vascular resistance leading to a reflex increase in plasma renin activity, or a combination of these.

Adult↗

PubMed1996

Risk factors for peritonitis in long-term peritoneal dialysis: the Network 9 peritonitis and catheter survival studies. Academic Subcommittee of the Steering Committee of the Network 9 Peritonitis and Catheter Survival Studies.

To determine factors involved in peritoneal dialysis-associated peritonitis and catheter loss, all point prevalent peritoneal dialysis patients in Health Care Finance Administration (HCFA) end-stage renal disease (ESRD) Network 9 were followed throughout 1991 for peritonitis events and throughout 1991 to 1992 for catheter survival. Data were collected by questionnaires compiled by the dialysis facility and validated by network staff. Peritonitis was reported 1,168 times in 729 of the 1,930 patients. By gamma-Poisson regression, a significantly increased risk for peritonitis was observed for patients with previous peritonitis, black race, and those dialyzing with standard connectors or cyclers compared with disconnect systems. Decreased risks were observed for patients with longer ESRD experience and when prophylactic antibiotics were administered before catheter insertion. Postinsertion leakage, diabetes, visual problems, previous or current immunosuppression, and physical activity were not risk factors. Infection of any kind caused the removal of 68% of the 414 catheters lost. Patients with downward-directed tunnels were less likely to experience concomitant exit site/tunnel infections associated with peritonitis. Peritonitis episodes with Staphylococcus epidermidis-like organisms were more likely to resolve with a single course of antibiotics. Perhaps because of their higher infection rate, blacks were more likely than whites to use a disconnect system. In general, the outcome of peritonitis in blacks was similar to that in whites, except that blacks were less likely to be hospitalized and were less likely to die.

Catheters, Indwelling↗

PubMed1996

Statistical approach to neural network model building for gentamicin peak predictions.

Feed forward neural networks are flexible, nonlinear modeling tools that are an extension of traditional statistical techniques. The hypothesis that feed forward neural network models can be built in a similar fashion as a statistical model was tested. Feed forward neural network models were built using forward and backward variable selection, and zero to five hidden nodes, and tanh and linear transfer functions were used. Gentamicin serum concentrations were predicted as a model drug for testing these methods. Peak observations from 392 patients were used to train, test, and validate the feed forward neural network. Inputs were demographic and drug dosing information. Model selection was performed using the Akaike information criteria (AIC), Bayesian information criteria (BIC), and a method of stopped training. The models with lowest root mean square (rms) error were those with all 10 inputs and five hidden nodes. Average rms error in the validation set was lowest for stopped training (1.46), then AIC (1.51), and finally BIC (1.56). Larger models tended to result in the best predictions. Overfitting can occur in models that are too large, either by using too many nodes in the hidden layer (rms = 1.49) or by using too many inputs with little information associated with them (rms = 1.70). We conclude that neural networks can be built using a large number of parameters that have good predictive performance. Care must be used during training to avoid overfitting the data. A stopped training method resulted in the network with the lowest rms error.

Adult↗

PubMed1996

Application of artificial neural networks to clinical pharmacology.

Drug dosages and drug choices are determined by a knowledge of the drug's pharmacokinetics and pharmacodynamics. Often, insufficient information is available to determine the pharmacokinetics of a drug or which drug will have a desired effect for an individual patient. We propose that a form of nonlinear regression, an artificial neural network, can be used. We have demonstrated this use with 2 examples. In the first example we use a neural network to predict gentamicin peak and trough concentrations from routine therapeutic drug monitoring. In the second example we predict delayed renal allograft function as a guide for induction of immunosuppression therapy. Predictions were made using a multilayer feedforward perceptron and compared to nonlinear mixed effect modeling (NONMEM) and logistic regression. Neural network peak and trough gentamicin predictions were more precise and less biased than control predictions made using NONMEM. Prediction error for peak serum concentrations averaged 16.5% for the neural networks and 18.6% for NONMEM. Prediction error for trough concentrations were 48.3% for neural networks and 59.0% for NONMEM. When used for the prediction of delayed graft function, the neural network correctly predicted immediate graft function 73% of the time and delayed graft function 65% of the time. For those patients predicted to develop delayed graft function, alternate induction using anti-lymphocyte globulin may be indicated. These 2 examples demonstrate how an artificial neural network may be applied to predictions in clinical pharmacology.

Anti-Bacterial Agents↗

PubMed1995

Population pharmacokinetics of the active metabolite of nabumetone in renal dysfunction.

We determined the pharmacokinetics of 6-methoxy-2-naphythylacetic acid (6-MNA), the active metabolite of nabumetone, in normal subjects and in subjects with impaired renal function, including subjects requiring hemodialysis. Subjects received a 1000 mg oral dose of nabumetone either as a single dose or daily for 15 days. We used a noncompartmental pharmacokinetic analysis and compared those results to a population pharmacokinetic analysis performed with nonlinear mixed-effects modeling (NONMEM). The results of the two different analyses were similar. The elimination half-life increased with decreased renal function and ranged from 22 to 44 hours. The area under the curve decreased significantly at steady state, regardless of renal function. The apparent clearance determined by NONMEM analysis increased from 0.68 L/hr after a single dose to 1.13 L/hr at steady state. The apparent volume of distribution was directly proportional to the nonalbumin protein concentration and ranged from 23 to 60 L. We conclude that the pharmacokinetics of 6-MNA in this population are complicated by possible protein binding changes. However, the increased half-life in patients with renal failure is offset by changes in the apparent volume of distribution that prevent the accumulation of 6-MNA in the serum of patients with impaired renal function. Therefore dosage adjustments may not be necessary in patients with decreased renal function.

Administration, Oral↗

PubMed1995

Pseudomonas peritonitis in peritoneal dialysis patients: the Network #9 Peritonitis Study.

To determine risk factors for the development of Pseudomonas peritonitis (PsP) and outcomes of PsP, the authors compared peritoneal dialysis patients who developed PsP with peritoneal dialysis patients who developed non-Pseudomonas bacterial peritonitis (non-PsP). The authors also sought to determine if there were differences in patients who had resolution of PsP compared with those patients whose PsP did not resolve. The data were derived from the prospective Tristate Renal Network Peritonitis and Catheter Survival Study. Resolution in this study was defined as clearing of peritoneal dialysate on visual inspection, with up to three courses of antibiotic therapy allowed. Catheter removal, switch to hemodialysis, or death were outcomes that were considered separately from resolution because of the study design. There were 31 cases of PsP in 28 patients and 886 cases of non-PsP identified in 667 adult patients. There were no differences in race, gender, age, or incidence of diabetes between the groups. The PsP group had a 25% incidence of previous exposure to immunosuppressive agents, whereas it was 10.6% in the non-PsP group (P = 0.028). PsP infections were more frequently associated with concomitant exit and tunnel infections, higher hospitalization rates, increased incidence of catheter loss, switch to hemodialysis, and a worse rate of resolution when compared with non-PsP (all, P < 0.05). Logistic regression could not identify patients at increased risk of PsP. PsP resolved with antibiotic therapy only in 10 of 31 episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1995

Neural network predicted peak and trough gentamicin concentrations.

Predictions of steady state peak and trough serum gentamicin concentrations were compared between a traditional population kinetic method using the computer program NONMEM to an empirical approach using neural networks. Predictions were made in 111 patients with peak concentrations between 2.5 and 6.0 micrograms/ml using the patient factors age, height, weight, dose, dose interval, body surface area, serum creatinine, and creatinine clearance. Predictions were also made on 33 observations that were outside the 2.5 and 6.0 micrograms/ml range. Neural networks made peak serum concentration predictions within the 2.5-6.0 micrograms/ml range with statistically less bias and comparable precision with paired NONMEM predictions. Trough serum concentration predictions were similar using both neural networks and NONMEM. The prediction error for peak serum concentrations averaged 16.5% for the neural networks and 18.6% for NONMEM. Average prediction errors for serum trough concentrations were 48.3% for neural networks and 59.0% for NONMEM. NONMEM provided numerically more precise and less biased predictions when extrapolating outside the 2.5 and 6.0 micrograms/ml range. The observed peak serum concentration distribution was multimodal and the neural network reproduced this distribution with less difference between the actual distribution and the predicted distribution than NONMEM. It is concluded that neural networks can predict serum drug concentrations of gentamicin. Neural networks may be useful in predicting the clinical pharmacokinetics of drugs.

Adult↗

PubMed1995

Omeprazole therapy does not affect pharmacokinetics of orally administered ethanol in healthy male subjects.

The purpose of this study was to study the effect of high-dose omeprazole therapy (20 mg twice daily) on kinetics of moderate amounts of orally administered ethanol. Eight healthy men participated in the study. After an overnight fast, they drank 0.5 g/kg body weight ethanol over 20 min. Blood samples were drawn before and then every 20 min after ethanol ingestion for the next 3 h. Subjects then ingested omeprazole 20 mg twice daily for 6 days. On the seventh day, the same dose of oral ethanol was administered as before and blood samples drawn. Blood ethanol concentrations were determined. We fit a one-compartment model with first-order absorption and zero order elimination to the blood ethanol data with PCNONLIN (SCI Software, Lexington, KY, U.S.A.) separately for each subject before as well as after omeprazole therapy. Area under the curve was calculated using the trapezoidal rule. There were no differences in the peak concentration, time to peak concentration, area under the curve, or elimination rate constant for ethanol before and after omeprazole treatment. Omeprazole treatment (20 mg twice daily) does not affect the pharmacokinetics of orally ingested ethanol in healthy male subjects. Our results do not rule out a possible effect on psychomotor function as a result of a pharmacodynamic interaction.

Administration, Oral↗

PubMed1995

Laser indirect ophthalmoscope photocoagulation and scleral depression for rhegmatogenous retinal detachment.

BACKGROUND: Transconjunctival cryotherapy or laser photocoagulation with simultaneous Eisner funnel scleral depression has been used to treat selected cases of rhegmatogenous retinal detachment. There are no studies to date reporting the use of the laser indirect ophthalmoscope coupled with scleral depression for treating retinal detachment. METHODS: 16 consecutive patients (18 retinal detachments in 17 eyes) were enrolled in a prospective, uncontrolled clinical trial using the laser indirect ophthalmoscope with scleral depression as the sole treatment for retinal detachment. The region immediately surrounding the break where subretinal fluid was present was directly treated rather than demarcated. All patients were treated with local anesthesia in an outpatient setting. RESULTS: Complete retinal reattachment was initially achieved in 14 (78%) of 18 eyes after scleral depression and laser alone. Significant postoperative complications of scleral depression with laser indirect ophthalmoscope photocoagulation included macular pucker (2 eyes), late recurrent rhegmatogenous retinal detachment without proliferative vitreoretinopathy (1 eye), and late recurrent rhegmatogenous retinal detachment with proliferative vitreoretinopathy (2 eyes). Failure of initial treatment to flatten the retina, late recurrent retinal detachment, macular pucker, or proliferative vitreoretinopathy led to scleral buckling and/or vitrectomy in 6 (86%) of the 7 eyes with clinical detachment and 3 (30%) of the 10 eyes with localized detachment. Final retinal reattachment at the last follow-up examination was achieved in all 17 eyes with subsequent surgical procedures. CONCLUSION: Although scleral depression with laser indirect ophthalmoscope photocoagulation is a noninvasive outpatient surgical procedure that is capable of flattening selected retinal detachments, its use cannot be recommended because of the relatively high rate of postoperative complications requiring further surgical procedures.

Adult↗

PubMed1995

Pharmacodynamics of atrial natriuretic peptide in isolated perfused Dahl rat kidneys.

Atrial natriuretic peptide (ANP) has been implicated in the development of hypertension in Dahl R and S rats. To test the responses of DR and DS kidneys in the absence of the influence of neural and humoral mechanisms, we investigated the pharmacokinetics and pharmacodynamics of ANP in isolated perfused DR and DS kidneys, obtained from rats given a high or low sodium diet, after a bolus injection of ANP (1 microgram) or after a bolus injection plus infusion of ANP to maintain the perfusate concentration at 1000 pg/ml. The elimination rate constant was not different between the groups (DR, 0.044 min-1 vs. DS, 0.050 min-1). Clearance of ANP was 4 times greater than the glomerular filtration rate, indicating that a receptor-mediated peritubular clearance is probably the primary route of elimination. DS kidneys excreted 50% less sodium than DR kidneys. However, ANP caused a 5-fold increase in fractional sodium excretion in both DR and DS. ANP also increased sodium excretion, creatinine clearance, and urine flow. No alteration in ANP kinetics occurred to account for the reportedly increased circulating concentrations of ANP seen in DS rats. We conclude that isolated DR and DS kidneys respond differently to ANP after bolus ANP administration to concentrations of 10,000 pg/ml. This difference in response is due to the sodium excretory defect inherent in the DS kidney and not to an alteration in the DS kidney's ANP responsiveness.

Animals↗

PubMed1994

Platelet calcium transport in hypertension.

To determine platelet Ca2+ transport entities involved in increased cytosolic Ca2+ in the platelets of hypertensive individuals, we studied the relations between blood pressure and Ca2+ transporters in platelet membranes from 22 white male volunteers 32 to 68 years old. We used thapsigargin, a specific inhibitor of the internal membrane Ca(2+)-ATPase, to differentiate between plasma membrane and internal membrane Ca(2+)-ATPases. Inositol 1,4,5-trisphosphate-mediated and Ca2+ ionophore (A23187)-induced Ca2+ release was also assayed in membrane preparations using rhod-2, a fluorescent Ca2+ indicator. Levels of glycoprotein IIIa, a possible component of agonist-mediated Ca2+ influx, were measured by immunoblotting. The results show that plasma membrane Ca(2+)-ATPase is decreased as a function of diastolic blood pressure (P < .002), whereas the internal membrane Ca(2+)-ATPase is not (P < .148). Neither activity is correlated with age or systolic blood pressure. However, inositol trisphosphate-mediated Ca2+ release is negatively correlated with age (P < .024) but not blood pressure. Glycoprotein IIIa levels and A23187-induced Ca2+ release were not related to age or blood pressure, demonstrating that inhibition of the plasma membrane Ca(2+)-ATPase was not a result of differences in the proportion of plasma membrane in the preparation or differences in intravesicular Ca2+ concentration. Inhibition of the plasma membrane Ca(2+)-ATPase could directly cause elevation of cytoplasmic Ca2+ and enhancement of platelet sensitivity.

Adult↗

PubMed1994

Initial intraperitoneal therapy for CAPD peritonitis: the Network 9 Peritonitis Study.

The choice of initial antibiotic therapy for continuous ambulatory peritoneal dialysis (CAPD) peritonitis is complex. To test the hypothesis that the initial choice of intraperitoneal antibiotics does not influence the outcome of therapy for CAPD peritonitis, we studied 1930 patients on peritoneal dialysis as of 1 January 1991, and recorded all episodes of peritonitis for one year. There were 1168 episodes of peritonitis for which 64% of the patients received intraperitoneal antibiotics as the first course of treatment. We determined peritonitis resolution, technique failure, hospitalization, and catheter removal rates as measures of successful treatment for peritonitis. Cephalothin, cefazolin, vancomycin, and ceftazidime were used alone or in combination with the aminoglycosides, tobramycin and gentamicin. The mean resolution rate was 65% following the first course of antibiotics and 76% by the third course of antibiotics, if necessary. The antibiotic regimens were not different with respect to resolution rate except when aminoglycosides were used alone. Technique failure was also greater in patients treated with aminoglycosides without other antibiotics. Hospitalizations were increased in patients treated with single drug therapy. If initial intraperitoneal therapy includes treatment for both gram-positive and gram-negative bacteria, the initial choice of intraperitoneal antibiotics does not influence the outcome of therapy for CAPD peritonitis.

Anti-Bacterial Agents↗

PubMed1994

Culture-negative CAPD peritonitis: the Network 9 Study.

A portion of peritonitis episodes are reported as culture-negative or as initial no growth peritonitis (INGP). To determine if demographics, symptoms, signs, treatment, and outcome were different in INGP when compared to culture-positive peritonitis (Pos), we examined data from the Network 9 Peritonitis and Catheter Survival Study. Only peritonitis episodes occurring in adults with peritoneal dialysis (PD) fluid WBC counts greater than 100 were included in the analysis. INGP accounted for 14% of the episodes of peritonitis. Organisms grew out of 13 of the 37 patients in INGP that were recultured: 3 fungal, 5 gram-negative, and 5 gram-positive isolates. A difference in culture methodology for the two groups could not be detected. There was no difference in gender, race, incidence of diabetes, previous peritonitis, or exit-site infections between the two groups. INGP had a greater percentage of patients over age 70 (23.3% vs 14.7%, p < 0.05), and a larger percentage of INGP patients placed additives in their dialysate (55% vs 43.6%, p < 0.05). There was no difference in symptoms or signs between the two groups. The INGP group had half the catheter removal rate (9/103 vs 110/630 for Pos, p < 0.05), otherwise, there was no difference in the rate of hospitalization, death, or switch to hemodialysis. There was no difference in types of drugs used or method of drug administration between the two groups. A lower percentage of INGP patients were treated for 6 days or less and a higher percentage received 7-10 days of intraperitoneal (IP) therapy when compared to Pos.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

PubMed1994

Sodium kinetics in white and black normotensive subjects: possible relevance to salt-sensitive hypertension.

The hypothesis that sodium (Na) kinetics are not a first order process was tested. Twelve normotensive white and 12 normotensive black men were given 10, 200, and 400 mmol/d Na as the chloride salt for 7 days in random order. All urine made was collected. No effect of Na intake on blood pressure was identified in either whites or blacks. The half-life (T1/2) with decreasing Na intake to 10 mmol/d was 1.08 days in whites and 1.65 days in blacks (p = not significant [NS]). With increasing Na intake, T1/2 increased in both whites and blacks; at the 400 mmol/d intake, the T1/2 for whites was 2.88 days and for blacks was 5.81 days (p < 0.05). At that intake, whites accumulated 385 +/- 153 mmol compared with 909 +/- 153 mmol for blacks (p < 0.05). The data showed that T1/2 increases with increasing Na intake and is, therefore, dose-dependent or "zero" order. The effect of dose is more prominent in blacks than in whites; blacks accumulate more Na with increasing Na intake than whites. These data may have relevance for the pathogenesis of salt-sensitive hypertension in blacks.

Adult↗

PubMed1993

Erythropoietin-induced antinatriuresis mediated by angiotensin II in perfused kidneys.

Erythropoietin (EPO)-induced hypertension is a common complication of EPO usage. The hypothesis that erythropoietin is antinatriuretic and that the sodium retention is mediated by intrarenal angiotensin II production was tested. Experiments were performed in Wistar rat kidneys perfused for 60 min in an isolated system. A dose-response curve was performed for EPO at 0, 10, 100, 1,000, and 10,000 mU/mL. EPO administration resulted in a dose-dependent decrease in sodium excretion to a maximum of 50% at the 1,000 mU/mL dose. In a second experiment, kidneys from five groups were perfused: controls, EPO (100 mU/mL), captopril (50 ng/mL), captopril (50 ng/mL) plus EPO (100 mU/mL), and the angiotensin receptor antagonist losartan (1 nM) plus EPO (100 mU/mL). The administration of EPO resulted in an immediate decrease in average sodium excretion (30%) with no change in GFR or other renal function parameters. Pretreatment with captopril or losartan blocked the effect of EPO. Captopril alone had no effect on renal function. A final experiment demonstrated the ability of losartan (10 nM) to block the pressor effects of angiotensin II (0.01, 0.1, and 1 nM). It was concluded that EPO acts within the kidney to cause the production of angiotensin II, which mediates the increased reabsorption of sodium.

Angiotensin II↗

PubMed1993

Racial differences in the practice of peritoneal dialysis in Network 9.

In a 1991 prospective evaluation of infections and catheters in Network 9 (Indiana, Kentucky, Ohio), detailed demographic questionnaires on 1930 patients were examined, with special attention to practice management and comparisons between black and white patients. In Network 9, 18.2% of peritoneal dialysis (PD) patients were black compared to 22.6% in the USRDS, and 3.7% of PD patients were black and more than 65 years of age, compared to 3.7% in the USRDS. Statistically significant associations were found in the Network 9 data base. Blacks were less likely than whites to be under 16 years or over 65 years of age, to add insulin to bag, to have nasal cultures performed, to have received previous immunosuppression, to wear exit-site dressings, and to do their own tubing changes. Blacks are more likely than whites to be independent (not age-related), ambulatory (not age-related), to have had previous peritonitis, surgical catheter placement, and to do their own exchanges. There were no differences regarding the number of training days and the use of disconnect or other exchange systems or cyclers.

Adult↗