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Biomedical subjects

H L Moore

Publications and source records attributed to H L Moore.

At least 55 records · Page 3Linked to original sources

Total creatine kinase and isoenzyme fractions in chronic dialysis patients.

We measured total serum creatine kinase (CK) and serum creatine kinase MB fraction (CK-MB) in 53 patients on continuous ambulatory peritoneal dialysis (CAPD) and 52 patients on maintenance hemodialysis (HD), using Scalva UV methodology for CK and electrophoresis for CK-MB. Seven of the 53 CAPD patients (13%) had an elevated total CK, and only one of these 7 patients had an elevated CK-MB greater than 5%. In contrast 22 HD patients (42%) had increased total CK values, and 6 of these 22 HD patients (27%) showed elevated CK-MB isoenzyme greater than 5%. For each sex, blacks had higher mean CK values than whites. Twenty-one out of the 43 HD patients who received intramuscular injections had elevated total CK values and 6 of these 21 patients had elevated CK-MB isoenzyme independent of the timing of injection. The increased frequency of higher total CK values in HD patients appears to be related to race and androgen administration. The modest elevations in CK-MB fraction (5 to 8%) in these patients require careful interpretation.

Adult↗

Acute changes in peritoneal morphology and transport properties with infectious peritonitis and mechanical injury.

Peritoneal clearance studies were performed in rats undergoing acute peritoneal dialysis. Some of these animals were then exposed to laparotomy and mechanical drying of the peritoneum. Peritoneal clearance studies were repeated at intervals up to 11 days. Another group of rats was placed on daily peritoneal dialysis and allowed to spontaneously develop peritonitis which was not treated. These rats underwent peritoneal transport studies at differing durations of infection. In all groups, animals were sacrificed at the time of the last transport studies for morphological assessment of the peritoneum by light microscopy, scanning electron microscopy, and transmission electron microscopy. The results showed similar decreases in drainage volume and increases in glucose absorption and protein losses with both infection and drying. Both types of injury resulted in extensive mesothelial structural changes. While drying caused mainly denudation of the mesothelial surface, infectious peritonitis was associated with separation of mesothelial cells, and the appearance of numerous white blood cells between and on mesothelial cells. Exposure to peritoneal dialysis alone had no obvious effects on anatomy. Although changes in the peritoneal microcirculation and deeper structures cannot be excluded as contributing to peritoneal transport alterations, the findings suggest that alterations of mesothelium might explain some of the changes in peritoneal transport properties under the conditions of these studies.

Acute Disease↗

Polyanions and glucose as osmotic agents in simulated peritoneal dialysis.

Peritoneal dialysis solutions contain glucose as an osmotic agent to obtain ultrafiltration. Due to rapid absorption, glucose does not sustain high ultrafiltration during long exchanges. Nonabsorbable polyanions might be effective as osmotic agents when suspended in electrolyte solution. Concentrations of freely diffusible ions should be in Gibbs-Donnan equilibrium with plasma electrolytes. The ideal proportion of diffusable to polymerbound cation concentrations is unknown. To obtain concentrations of free ions in equilibrium with plasma, it is assumed that the polymer solution dialyzed against a polyelectrolyte solution of the desired composition (with hydraulic pressure higher on the polymer side) will approach the same thermodynamic activity as the electrolyte solution. Subsequently, if transmembrane pressure is released, osmotic ultrafiltration will occur in proportion to the hydrostatic pressure applied during polymer solution preparation. Polyacrylate solution so prepared was compared with a commercial dextrose dialysis solution in an in vitro simulation of peritoneal dialysis. With dwell times up to 24 h, sustained ultrafiltration with polymer was observed, whereas, with dextrose, ultrafiltration ceased after 8 h. Concentrations of diffusible bivalent cations in polyacrylate were lower than intended due to avid polymer complexing; however, dextran sulfate solutions were developed to contain desired concentrations of diffusible electrolytes. The conclusion is that some polymer solutions might be useful in clinical settings when high sustained ultrafiltration is needed.

Acrylic Resins↗

Insulin binding to plastic bags: a methodologic study.

A radiotracer method to assess insulin binding to commercially available plastic peritoneal dialysis solution containers was developed. A peritoneal dialysis bag (bag 2) was emptied and attached to another full bag (bag 1) of the same kind. In the syringe-to-bag method, bag 1 was symmetrically injected through the bag wall with four syringes containing dialysis solution and radioactive insulin, with or without regular insulin. The radioactivity in each syringe was measured with a gamma counter before injection, and all of the samples were counted afterwards directly in the syringes. Using a bag-to-bag transfer method, bag 1 was agitated, eight samples were taken from different parts through the wall, and then the contents were transferred to bag 2. Bag 2 was then agitated and eight samples were taken and counted. In the bag-pieces method, pieces of bag wall were cut and the radioactivity on the walls was measured to determine the amount of binding. The syringe-to-bag method gave negative results, severely underestimating the amount of insulin binding. The bag-to-bag transfer method yielded positive results in all instances. Increasing the amounts of regular insulin had no demonstrable impact on percent of binding. When the bag-to-bag method was compared with the bag-pieces method, it gave only slightly higher values; however, the bag-to-bag method was considered more reliable because the counting can be controlled more effectively. A 15-minute delay in sampling was not found to influence insulin binding. A reliable method of assessing insulin binding must be based on the following two principles: (1) The transfer of samples to intermediate containers should be avoided, and (2) radiotracer concentrations in the samples should be similar.

Dialysis↗

Nature of insulin binding to plastic bags.

The nature of insulin binding to plastic bags was evaluated to determine if it followed the physical laws of adsorption. To determine whether insulin is adsorbed on a liquid/air interface, the influence of foam in vials of radiolabeled insulin was evaluated. Using a bag-to-bag transfer method, the influence of regular insulin and detergent on radiotracer insulin binding was assessed. To evaluate the reversibility of the binding, bag pieces with bound radioactive insulin were washed with distilled water, detergent, and left to soak in detergent before measuring radioactivity. The radiolabeled insulin was adsorbed in the foam and then released into the bulk of the solution when the foam disappeared; hence, insulin can be entrapped in a liquid/air interface. The addition of regular insulin decreased the binding of the radiotracer insulin to the bag walls. The bound insulin could be removed by washing with water and detergent, but soaking in detergent did not remove a small residual quantity of the bound insulin, suggesting that minimal chemical binding or diffusion of the insulin into the plastic may occur. Insulin binding to plastic bags primarily follows the physical laws of adsorption.

Adsorption↗

Influence of temperature and time on insulin adsorption to plastic bags.

The influence of temperature and time on insulin adsorption to plastic peritoneal dialysis bags was evaluated. A dialysis bag (1.5% dextrose, 2 liters) was injected with 25-microCi insulin I 125 and gently mixed. This bag was then attached to another empty bag of the same type. Following a bag-to-bag transfer method, the amount of insulin adsorbed on the plastic bags was measured at 24 degrees C and 37 degrees C, and after a 12-hour warming period at 37 degrees C. Regular insulin was added to the system in 40-unit increments up to 280 units. Radioactivity in all of the samples was measured in a gamma counter. As the amount of regular insulin increased, the percentage of insulin adsorbed decreased at both temperatures. More insulin was bound at 37 degrees C than at 24 degrees C for all levels of insulin. Data calculated according to the Langmuir isotherm equation showed that the maximum possible values of adsorption to the system at 24 degrees C and 37 degrees C were 17.8 and 18.4 units, respectively. The affinity constants at 24 degrees C and 37 degrees C were 0.0039 and 0.0065, respectively. The influence of prolonged warming at 37 degrees C was minimal. At the usual dosage of insulin (below 40 units) prescribed to the majority of dialysis patients, less than 9% (3.5 units) is adsorbed onto the dialysis bags.

Adsorption↗

The role of complement, immunoglobulin and bacterial antigen in coagulase-negative staphylococcal shunt nephritis.

We describe three patients with arrested hydrocephalus in whom glomerulonephritis developed secondary to Staphylococcus epidermidis bacteremia from an infected ventriculoatrial shunt. Investigation of the immune-mediated renal disease associated with this chronic infection showed that (1) complement depletion during the acute phase of bacteremia and nephritis was predominantly via the classic pathway; (2) rheumatoid factor was associated with bacteremia, fever, proteinuria and low complement levels; (3) early complement components (C1q, C4, C3), immunoglobulin (predominantly immunoglobulin M [IgM], Staph. epidermidis antigen(s) and electron denxe subendothelial deposits were localized within the renal glomerulus; (4) C1q, and IgM derived from patient serums, were the most prominent in vitro immunoreactants to Staph. epidermidis cell walls; and (5) the causative organisms, Staph. epidermidis, shared common antigens with Staph. aureus, and antibody from patient serums cross reacted with extracts from both of these organisms.

Antigens, Bacterial↗

Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis.

In 55 patients on continuous ambulatory peritoneal dialysis, the authors determined daily renal and dialysate clearances of urea nitrogen (CUN) and creatinine (CCr). Results are expressed as weekly CUN in liters (Kt) divided by liters of total body water determined from a nomogram (V). The authors calculated weekly CCr as the weekly dialysis clearance plus the average of renal CUN and CCr (to correct for creatinine secretion); they normalized total weekly CCr to 1.73 m2 body surface area. Mean weekly Kt/V and CCr were 2.1 and 65.2, respectively. Mean dietary protein intake by dietary survey was 0.85 g/kg body weight. Protein catabolic rate (PCR) calculated from urea kinetics was 0.94 g/kg standardized weight (V/0.58); PCR was significantly (p < 0.01) correlated with Kt/V (r = 0.53). The authors used linear regression to determine PCR, as follows: PCR = 0.80 [weekly Kt/V]/3 + 0.39. This slope is nearly 1.5 times that reported for the relationship of PCR to [weekly Kt/V]/3 in hemodialysis patients. Eighty-two percent of patients on continuous ambulatory peritoneal dialysis had more than the targeted minimum weekly Kt/V of 1.7, 71% had a weekly CCr more than the targeted minimum of 50, and 75% had a PCR > 0.8 g/kg/day. In support of the hypothesis that Kt/V requirements are related to peak concentration control rather than to time averaged blood urea nitrogen, patients on continuous ambulatory peritoneal dialysis have a higher PCR at given Kt/V values compared to hemodialysis patients. These patients are more likely to have a PCR > 0.8 if weekly Kt/V > 1.7.

Blood Urea Nitrogen↗

A new approach to optimizing urea clearances in hemodialysis and continuous ambulatory peritoneal dialysis.

Recent studies suggest that the relationship of the net normalized protein catabolic rate (which is the normalized protein equivalent of nitrogen appearance [nPNA]) to the weekly clearance of urea normalized to total body water (Kt/V urea) in patients on continuous ambulatory peritoneal dialysis (CAPD) is curvilinear, rather than linear, as has been thought. The authors have reexamined the relationship of nPNA to weekly Kt/V urea in a CAPD population by cross-sectional analysis to see if the curvilinear definition of the relationship is as good as or better than the usual linear description. They also examined this relationship in the hemodialysis populations at the Dialysis Clinics Inc. in Columbia, Missouri, and in the Renal Kidney Disease Program in Minneapolis, Minnesota. It seems obvious that there should be a plateau of nPNA in each therapy because extension of linear regressions would predict protein intakes of normal individuals exceeding 8 g/kg/body weight/day. The authors compared their findings to other published results. Intuitively and analytically, the curvilinear relationships seem likely. The authors observed that the nPNA plateau is achieved at lower Kt/V in patients on CAPD than in those on hemodialysis, which is compatible with the peak concentration hypothesis. Asymptotes for CAPD and hemodialysis are similar. Weekly Kt/V urea requirements to achieve nPNA values at 95% of the asymptote are greater than those usually delivered. However, such nearly complete elimination of uremic appetite suppression may not be practical or necessary for achieving acceptable nutritional status and long-term survival in most patients. Optimum therapy may be well above adequate therapy relative to minimizing appetite suppression by uremia.

Appetite↗

A prospective study of the effect of noncompliance on small solute removal in continuous ambulatory peritoneal dialysis. Preliminary report.

In nine patients on continuous ambulatory peritoneal dialysis (CAPD) who were in stable condition, the authors measured the effects of an extra daily exchange on small solute removals and clearances and the measured/predicted creatinine production (M/P). The goal was to evaluate the sensitivity of M/P to single exchange noncompliance. Daily collections of urine and dialysate were performed on the usual prescribed program and on the next day with an extra exchange of usual exchange volume. The average increase in drain volume of 26% was associated with an average increase in M/P of 6%. The maximum M/P increase was 15%; the percentage increase in M/P correlated inversely with renal creatinine clearance. Daily total urea clearance normalized to total body water by dialysis and renal function increased 12%. Extrapolating these findings suggests that an average patient with a baseline M/P near 1.0 and renal creatinine clearance of 5 ml/min would require more than 50% drain volume noncompliance to yield a M/P of 1.24 on the complaint day. A 50% noncompliance may not yield a M/P greater than 1.0 on the first compliant day if baseline M/P is less than 0.94. The authors suggest monitoring daily urine and dialysis creatinine output because M/P creatinine is relatively insensitive to noncompliance (particularly in patients with residual renal function) and because there are questions about the accuracy of predictions in patients with renal failure using formulae established in different populations. The authors recommend simply monitoring total daily creatinine output and establishing patients as their own controls. The authors provide a table for the interpretation of changes in creatinine output in conjunction with changes in other routinely monitored parameters.

Blood Urea Nitrogen↗

Polycation as an alternative osmotic agent and phosphate binder in peritoneal dialysis.

We have previously shown that polyanions can be utilized to achieve balanced removal of sodium and water during peritoneal dialysis. The excessive binding of potassium, calcium, and magnesium to anionic polymers proves undesirable. The present study was designed to demonstrate the reversibility of cation binding by using a polycation (polyethylenimine) as the osmotic agent, thus favoring the removal of undesirable excess phosphate anions via peritoneal dialysis. Polyethylenimine shows a measurable affinity for phosphorus when present as dialysate in an in vitro system simulating peritoneal dialysis. The polycation also stimulates ultrafiltration across the rat peritoneum when present in dialysate. The polymer is toxic to the rat and light microscopy reveals gross morphological tissue alterations of the visceral mesothelium and associated organs. We have demonstrated that a polycation can give ultrafiltration with enhanced removal of phosphate. Although the polymer we chose as a prototype is toxic to the rat, other polycations should be studied.

Animals↗

Advanced glycosylation end-products in diabetic rats on peritoneal dialysis using various solutions.

OBJECTIVE: To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and advanced glycosylation end-product (AGE) formation in the peritoneal membrane in a diabetic rat model of peritoneal dialysis (PD). DESIGN: Thirty-three male Sprague-Dawley rats weighing between 275-300 g were divided into five groups: group C (n = 6), control rats implanted with a catheter but not dialyzed; group D (n = 5), diabetic rats implanted with a catheter but not dialyzed; group G (n = 7), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for overnight exchanges; group H (n = 8), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats implanted with a catheter and dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges (25 mL per exchange) were performed three times daily for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. RESULTS: The level of immunostaining was lowest in group C and highest in group G. Significant differences in immunostaining were seen between group C and group G (p < 0.001), group C and group H (p = 0.001), and group C and group I (p < 0.05). Significant differences were also found between group G and group D (p < 0.05), and between group G and group I (p < 0.05). Over time, the ratio of glucose concentration after 1 hour to glucose concentration at instillation (D/D0) decreased and the dialysate-to-plasma ratio (D/P) of urea increased. Significant differences in D/D0 glucose and D/P urea were found between group C and group H (D/D0: 0.40 +/- 0.01 vs 0.35 +/- 0.01, p < 0.05; D/P urea: 0.87 +/- 0.03 vs 0.97 +/- 0.02, p < 0.05). CONCLUSIONS: These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solution. We conclude that use of icodextrin may help to slow the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Animals↗

Peritoneal transfer of carbon dioxide in the rat.

In the authors' previous rat studies (Kidney Int 39: 608-617, 1991), peritoneal clearances (Cp) representing near exclusively diffusive CO2 transfer were evaluated: for isosmotic (0.37% dextrose) and hyperosmotic (15% dextrose) solutions with pH 7.2-7.3, Cp CO2 were 1.20 +/- 0.08 and 1.84 +/- 0.04 ml/min, respectively. In the present studies peritoneal transfer parameters (D/B, Cp) of CO2 gas, HCO3-, and total CO2 (tCO2) in anesthetized rats have been compared (n = 22) using solutions with dextrose contents as mentioned above but with a pH of 6.5 or 7.6; how much Cp CO2 measurements obtained with solutions at these pH values differ from Cp shown earlier with solutions of pH 7.2-7.3 has also been evaluated. When the pH was the same, transfer parameters of CO2 gas, HCO3-, and tCO2 were significantly higher under hyperosmotic conditions. The use of solutions with a pH different from 7.2-7.3 resulted in higher Cp of CO2 gas: with isosmotic solutions at pH 6.5 and 7.6, mean increases were 25 and 75%, respectively; with hyperosmotic solutions respective increases were 45 and 134%. The authors conclude that dialysis solution pH, especially under hyperosmotic conditions, significantly changes parameters of diffusive CO2 transfer in the rat. For evaluation of peritoneal blood flow from diffusive transfer parameters of CO2 gas, smaller overestimation can be expected when dialysis solution pH is slightly under than overadjusted compared to blood pH.

Animals↗

Preclinical toxicology studies with acyclovir: teratologic, reproductive and neonatal tests.

Five studies were done to define the potential of Acyclovir (ACV), a new nucleoside analog for antiviral chemotherapy, to produce adverse effects on reproduction and development in laboratory animals. ACV produced no adverse effects when given by gavage to F0 generation mice at 50, 150 and 450 mg/kg/day in a two generation reproduction/fertility study. Some mice were evaluated for teratologic effects and others for postnatal development, including behavior, with negative results. ACV was not embryotoxic and did not increase the incidence of fetal malformations when given by subcutaneous injection to pregnant rats and rabbits at dose levels of 12, 25 and 50 mg/kg/day during the periods of major organogenesis. A comparative LD50 study revealed that 3-day-old rats were not more sensitive to acute toxic effects of ACV than more mature rats. Finally, in a comprehensive multidose toxicity study ACV was given subcutaneously to neonatal rats at 5, 20 and 80 mg/kg/day for 19 consecutive days. There was minimal effect on body weight gain in neonates treated at 20 mg/kg/day and a significant decrease in body weight gain at 80 mg/kg/day. Minimal renal lesions occurred at 80 mg/kg/day but no other signs of adverse effects on developing organ systems were observed. Except for decreased body weight gain in neonatal rats treated at 80 mg/kg/day, ACV did not produce adverse effects on mammalian development when tested in a variety of preclinical toxicology studies.

Abnormalities, Drug-Induced↗