PubMed Health⌕ Search

Biomedical subjects

D E Blake

Publications and source records attributed to D E Blake.

18 recordsLinked to original sources
PubMed1999

Cytokines and endotoxin removal by sorbents and its application in push-pull sorbent-based pheresis: the BioLogic-DTPF System.

The BioLogic-DTPF System (DTPF) combines the Biologic-DT hemodiabsorption system (DT) in series with the Biologic PF push-pull pheresis system (PF) in which PF membranes separate plasma for direct contact between plasma proteins and the sorbents. Preliminary studies conducted in bovine serum albumin (BSA) solution and in bovine plasma allowed charcoal and silica to be evaluated as adsorbents for the PF module. Equilibrium binding experiments in BSA showed a high capacity of cytokine (IL-1 beta, TNF alpha) binding by powdered charcoal, 70-90 ng/g. Kinetic binding studies in bovine plasma revealed relatively quick adsorption of IL-1 beta and IL-6 by charcoal with the capacity range of 1.2-2.0 ng/g for tested cytokines (IL-1 beta and TNF alpha). Further laboratory studies with plasma have shown that powdered silica has an even greater binding capacity, up to 13 ng/g for TNF alpha depending upon particle size, and more rapid binding for all tested cytokines than powdered charcoal. Cholestyramine is a more efficient sorbent for removal of endotoxin than either charcoal or silica. In vitro tests using whole blood have demonstrated that the DTPF, with powdered charcoal as the sorbent, clears cytokines (TNF alpha, IL-1 beta, and IL-6) at 12.6-23.4 ml/min, bilirubin at 17.8-34.7 ml/min, and creatinine at 53.6-82.6 ml/min. The removal of some cytokines during the first clinical trial is also discussed.

Adsorption↗
PubMed1999

Push-pull sorbent-based pheresis treatment in an experimental canine endotoxemia model: preliminary report.

The Biologic-DTPF System (DTPF), an extracorporeal blood treatment device with potential to treat sepsis, was tested in a preliminary study using a canine endotoxemia model. Six dogs were used and they formed four treatment groups, as control group (n=1) and three groups based on the type of sorbent present in the plasma filter (PF) system: sham treatment with no sorbent (n=1), charcoal as sorbent (n=2), and charcoal/silica as sorbent ("silica" group, n=2). Cardiodynamic data were recorded before treatment and every 30 minutes, and blood samples were collected to determine blood chemistry and to detect the levels of endotoxin and selected plasma cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). The dogs were given Escherichia coli endotoxin (2 mg/kg) as an intravenous drip (extended over a period of 30 minutes). Thirty minutes after the end of infusion all animals except the control were treated with the DTPF system for four hours. To determine the effect of treatment, data collected at one hour from the initiation of treatment until the end of treatment were compared between control and treated dogs. The endotoxin levels in the control dog were higher (P < 0.05) than other groups. The control dog had lower levels of TNF than other groups. The control dog had similar levels of IL-1 (P > 0.05) and higher levels (P < 0.05) at 4 hours into treatment compared to other groups. The control dog had similar levels of IL-6 as other groups (P > 0.05). In the control dog, the mean arterial pressure (MAP) fell and then remained low but stable at 1-4 hours. The charcoal group had lower MAP than the control dog at 1-4 hours (P < 0.05). The silica group had higher MAP levels similar to the control dog. After treatment, the control dog had higher (P < 0.05) values of hematocrit, hemoglobin, calcium, potassium, and albumin compared to the treated groups. As expected for a system removing plasma during sepsis, the DTPF System had some adverse effects on the physiologic status of the dogs, especially when loaded with charcoal sorbent only. The findings of the present study suggest that the filters are capable of eliminating endotoxin and there is some evidence of cytokine removal. Although the charcoal dogs did poorly, addition of silica to the sorbent offset any negative effects. Further work is underway to improve the efficiency of the system, primarily to enhance the capacity of the sorbents for cytokines. A more realistic canine sepsis model with mortality after several days (the Escherichia coli- infected intraperitoneal clot) will also be considered in future studies.

Analysis of Variance↗
PubMed1997

Wheat bread supplemented with depolymerized guar gum reduces the plasma cholesterol concentration in hypercholesterolemic human subjects.

Recent human studies have shown that the physiologic effects of guar gum are not diminished by partial depolymerization of its galactomannan fraction. We evaluated the effect of depolymerized guar galactomannan on fasting plasma cholesterol and triacylglycerol concentrations in healthy volunteers with moderately raised plasma cholesterol concentrations (range: 5.2-8.0 mmol/L). This study was designed as a randomized, double-blind crossover of two 3-wk feeding periods separated by a 4-wk washout period. Control and guar wheat breads were prepared by a commercial bread-making process. Subjects (n = 11) were asked to replace their normal bread with that provided, receiving control bread for one 3-wk period and guar bread for the other period, without altering their baseline diet. Subjects recorded their intake of foods for 6 consecutive days on three occasions during the study. Fasting venous blood samples (10 mL) were taken from subjects on two consecutive mornings at the start and end of each feeding period. No significant changes in body weight or dietary intake were recorded in the control and guar bread periods. There was a significant reduction (10%) in total plasma cholesterol concentration after the guar treatment (P < 0.001), mainly because of a reduction in the low-density-lipoprotein-cholesterol fraction. No changes in plasma high-density-lipoprotein-cholesterol or triacylglycerol concentrations were seen. The cholesterol-lowering effect of partially depolymerized guar gum appears to be of a magnitude similar to that of high-molecular-weight guar gum used in earlier studies.

Adult↗
PubMed1992

Clinical effects of a sorbent suspension dialysis system in treatment of hepatic coma (the BioLogic-DT).

Fifteen patients with acute deterioration of liver function, high serum ammonium, and an average coma level of 3.9 were identified. Eleven of the patients were on respirator support, and eleven had kidney failure pursuant to the liver failure. The patients were treated for 8-12 hours daily with the BioLogic-DT system, in which membranes of a cellulosic plate dialyzer actively pump blood through a single access at over 200 ml/min, and the dialysate contains a suspension of powdered activated charcoal (300,000 square meters surface area) and cation exchanger (160 meq capacity). No anticoagulant was used. In spite of the declining condition of the patients prior to treatment, there was a statistically significant improvement in neurologic status during individual treatments, and a positive trend over 1-12 (average four) daily treatments. Four patients recovered liver function and another four improved enough to receive a liver transplant operation. The BioLogic-DT system appears to be safe in treatment of patients with hepatic insufficiency and coma. The neurologic improvement of these patients indicates that many toxins of hepatic failure are dialyzable across cellulosic membranes and bound by charcoal.

Acute Disease↗
PubMed1982

A reciprocating, single-needle hemodialyzer with bidirectional flow of sorbent suspension.

Previous theoretical analysis has indicated that adequate mass transfer is possible in a dialyzer with reciprocating membrane motion provided that the dialysate concentration of uremic substances is kept low. Earlier models have utilized a collection of sorbents (charcoal, urease, and a cation exchanger) constrained next to the dialyzer membranes. We have designed a new dialyzer with a sorbent suspension having free access from a reservoir to the spaces between membrane packages. At a treatment rate of 150 ml/min/m2, the in vitro creatinine clearance is 75 ml/min/m2, which agrees within experimental accuracy with the theoretical prediction. The creatinine clearance, flow resistance, and compliance of the dialyzer are constant during four to six hours of testing. In vivo tests have been performed during urea and creatinine infusion in a normal dog and in a dog with 3/4 nephrectomy. The in vivo creatinine clearance agrees within 10% with the in vitro clearance. Sodium, potassium, calcium, and bicarbonate fluxes are acceptable for patients in renal failure. The new design allows a higher capacity for urea and creatinine, since larger amounts of sorbent may be used.

Absorption↗
PubMed1979

Reversible depression of electrically-induced contractions of guinea pig longitudinal muscle by a reversible inhibitor of prostaglandin synthetase.

The pesticide chlordimeform (CDM) depressed the electrically-induced twitch responses of the guinea pig longitudinal muscle ED50 = 3 X 10(-5)M). Naloxone reversed twitch depression induced by morphine but not by CDM. Phentolamine reversed twitch depression induced by either norepinephrine or clonidine, but not by CDM. PGE2 completely reversed twitch depression induced by either CDM or indomethacin, but only partially reversed twitch depression induced by lidocaine. The actions of CDM best resemble those of the nonsteroidal anti-inflammatory agents. The reversibility of the CDM depression by washing indicates that the guinea pig ileal preparation is a convenient screen for distinguishing reversible from irreversible inhibitors of prostaglandin biosynthesis.

Amidines↗
PubMedDate not supplied

Push-pull sorbent based pheresis for treatment of acute hepatic failure: the BioLogic-detoxifier/plasma filter System.

The BioLogic-DT (detoxifier) System is an extracorporeal blood treatment device that uses the membranes of a cellulosic plate dialyzer to propel blood in and out through a single lumen access (on a 12 sec cycle) and circulates a suspension of powdered charcoal and cation exchanger through the dialysate spaces to absorb many soluble toxins in the treatment of hepatic failure. The BioLogic-DTPF (detoxifier/plasma filter) System adds two Gambro plasma filters downstream from the plate dialyzer, which allows most of the blood plasma to pass out of the blood, contact powdered charcoal in a suspension, and then return to the blood during each 12 sec cycle (creating push-pull sorbent based pheresis). A roller pump exchanges charcoal suspension between the plasma filter case and a 700 ml bag of powdered charcoal suspension. At a blood flow rate of 150-200 ml/min, 100 ml/min of plasma moves bidirectionally through the plasma filter membranes. Direct contact of plasma with charcoal outside the plasma filter membranes removes creatinine with a clearance rate equal to plasma flow (100 ml/min); clearance of strongly protein bound toxins, such as unconjugated bilirubin, is lower (10-40 ml/min). In this article, the authors explain the mechanisms of operation of this system and present in vitro tests that define its chemical efficiency. Also described are potential problems, tests that indicate the severity of these problems, and monitors and algorithms to detect or avoid these problems in clinical use of the system. The results of the treatment of two patients with acute hepatic failure and coma using the BioLogic-DTPF System are reviewed.

Aged↗
PubMedDate not supplied

Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System.

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.

Adult↗
PubMedDate not supplied

Neurologic improvement of patients with hepatic failure and coma during sorbent suspension dialysis.

Fifteen patients with acute deterioration of liver function, high serum ammonia, and an average coma level of 3.9 (of 4) were treated for 8-12 hrs daily with a system that uses the membranes of a cellulosic plate dialyzer to pump blood through a single access at 200-225 ml/min, and includes a sorbent suspension as dialysate. Neurologic status of the patients was declining before treatment, but significantly improved during each treatment and over the course of 1-12 (average, 4) treatments. Diastolic blood pressure and pulse rate normalized. For half the patients, treatment with the BioLogic-DT system served as a bridge to liver transplant or liver recovery.

Adult↗
PubMedDate not supplied

Effect of sorbent-based dialytic therapy with the BioLogic-DT on an experimental model of hepatic failure.

An experimental model of hepatic failure in the dog has been developed in which the liver is devascularized in two stages. Under general anesthesia, a portacaval shunt is created, ligatures placed around the hepatic and gastroduodenal arteries, and the dog recovered. Two days later under general anesthesia, the ligatures are pulled, converting hepatic insufficiency to hepatic failure. Five control animals developed hypotension, severe lactic acidosis, hypoglycemia, and increasing liver enzyme levels during 6 hrs of follow-up. The BioLogic-DT system includes a cellulosic plate dialyzer with a suspension of powdered charcoal and cation exchangers as dialysate. Five animals were treated with the BioLogic-DT for 6 hrs after creation of hepatic failure. These animals were more stable physiologically, developed less lactic acidosis and less enzyme elevation, and maintained high normal blood glucose levels. The results help explain the clinical improvement demonstrated in patients with hepatic failure treated by the BioLogic-DT, and confirm that many of the toxins of hepatic failure are dialyzable and bound by simple sorbents such as charcoal and cation exchangers.

Ammonia↗