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Biomedical subjects

S R Ash

Publications and source records attributed to S R Ash.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of systemic inflammatory response syndrome by push-pull powdered sorbent pheresis: a Phase 1 clinical trial.

An FDA-approved Phase 1 feasibility study was performed in two centers to determine the safety of the BioLogic-DTPF (detoxifier/plasma filter) system for the treatment of patients with systemic inflammatory response syndrome (SIRS). This device combines hemodiabsorption (dialysis of blood against powdered sorbents with the BioLogic-DT system) with push-pull sorbent-based pheresis (the PF add-on module). Eight adult ICU patients with both SIRS and multiple organ failure participated in the study. One 6 h treatment was planned for each patient with powdered charcoal as sorbent for 4 patients and a combination of charcoal/silica in the PF sorbent bag for 4 patients. The treatments appeared to have no negative effects in 7 patients, but 1 patient died during treatment due to progressive cardiac failure. Sepsis was resolved in 5 of the 8 patients. However, there were only 2 long-term survivors of the group. The addition of the PF module should improve the chemical function of the BioLogic-DT by allowing removal of protein-bound toxins such as cytokines. The selected patients tolerated treatment by the DTPF system well, but proof of benefit of the device remains to be proven in a Phase 2 clinical trial with randomized controls.

Adsorption↗
PubMed2001

Powdered sorbent liver dialysis and pheresis in treatment of hepatic failure.

The Liver Dialysis Unit (the Unit) is a liver-assist device that employs hemodiabsorption (dialysis of blood against powdered sorbents) to selectively remove numerous small molecular weight toxins of hepatic failure. The Unit has been cleared by the Food and Drug Administration and is indicated and marketed for treatment of acute hepatic encephalopathy (AHE) due to decompensation of chronic liver disease (A-on-C) or fulminant hepatic failure (FHF). Controlled, prospective, and randomized studies of liver dialysis were conducted at several centers, enrolling 56 patients with AHE, grades II-IV with or without renal and respiratory insufficiency or failure. Liver dialysis treatments were for 6 h daily, 1-5 days with similar observation periods for control patients. Physiologic status, neurologic status, and outcome (recovery of hepatic function, improvement for transplant, or death) were measured, and results were compared for treated patients versus controls for patients with A-on-C and patients with FHF. Liver dialysis resulted in physiologic and neurologic improvement of patients with AHE, regardless of etiology. Liver dialysis significantly improved the incidence of positive outcomes (recovery of hepatic function or improvement for transplant) of A-on-C patients versus controls (71.5% treated, 35.7% control, p = 0.036), but had an insignificant improvement in the outcome of patients with FHF as compared with the control group. Among the overall 31 treated patients, 51.6% survived. Outcome was not negatively affected by the presence of kidney failure or respiratory failure. The plasmafilter unit (PF-Unit) combines hemodiabsorption with push-pull sorbent-based pheresis (the PF add-on module, with powdered sorbent surrounding plasmafilters). At blood flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids at 120-160 ml/min, unconjugated bilirubin at 20-40 ml/min, and cytokines at 15-25 ml/min. The PF-Unit has been tested in a few patients with hepatic failure with Grades III and IV encephalopathy, and respiratory, and kidney insufficiency. Treatment appeared to be safe, and there were no significant hematologic changes. Physiologic changes included improved blood pressure, and encephalopathy, and stable urine output. Chemical changes included a decrease in the plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and IL-1beta. The PF add-on module adds the capability to the Unit to remove bilirubin and other strongly protein-bound toxins from treated patients and may be of clinical benefit in the management of patients with the most severe hepatic failure and encephalopathy, including patients with FHF or concomitant sepsis.

Blood Component Removal↗
PubMed2000

Push-pull sorbent-based pheresis and hemodiabsorption in the treatment of hepatic failure: preliminary results of a clinical trial with the BioLogic-DTPF System.

The BioLogic-DTPF System combines hemodiabsorption (the BioLogic-DT System with dialysis against powdered sorbent) with push-pull sorbent-based pheresis (the BioLogic-PF System with powdered sorbent surrounding plasma filters). At blood flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids at 120-160 ml/min, unconjugated bilirubin at 20-40 ml/min, and cytokines at 15-25 ml/min. This article outlines a study of the DTPF System in treatment of patients with hepatic failure with Grade 3 or 4 encephalopathy and respiratory and kidney insufficiency. Treatment appeared to be safe, and there are no significant hematologic changes. Physiologic changes include improved blood pressure and encephalopathy and stable urine output. Chemical changes include decrease in plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and interleukin-3 (IL-1beta). The BioLogic-DT System is now marketed for treatment of acute hepatic failure with encephalopathy. The BioLogic-DTPF System adds the capability of removing bilirubin and other strongly protein-bound toxins from treated patients and may be of clinical benefit in management of patients with the most severe hepatic failure and encephalopathy.

Acute Disease↗
PubMed2000

Effect of hemodiabsorption and sorbent-based pheresis on amino acid levels in hepatic failure.

Changes in plasma amino acid concentrations were measured in patients with hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis Unit, "the Unit") or hemodiabsorption plus sorbent-based pheresis treatment (using the Liver Dialysis Plasmafilter Unit, "the PF-Unit") Systems. Eight patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin and/or creatinine levels and respiratory or renal failure were treated for 1-3 days with the Unit alone. Three of these were also treated with the Unit containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic failure treated with the PF Unit also had 10 g of branched chain amino acid (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post-plasma samples were drawn and high performance liquid chromatography (HPLC) was used to separate and detect amino acids in the plasma. Both the Unit and the PF-Unit have the capability to selectively remove various amino acids, especially aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and isbolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and PF-Unit patients was 1.43 (+/- 0.58). Treatments by both systems resulted in an increase of BCAA levels in blood and concomitant decrease of AAA levels, with an average Fischer ratio improvement of 30-38% for the Unit and PF-Unit without BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels of many other amino acids (such as alanine, glycine, proline or lysine) increased during both Unit and PF-Unit treatments. The removal of strongly protein-bound toxin and amino acids such as tryptophan and sulphydryl amino acids was more effective by the PF-Unit. Both the Unit and the PF-Unit have the unique capability to remove toxic aromatic amino acids while increasing BCAA levels in patient. The increase in many amino acid levels may be related to the removal of toxins that interfere with normal amino acid metabolism. The addition of the PF module improves the removal of bilirubin and similarly protein-bound chemicals. Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with other extracorporeal devices.

Adsorption↗
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↗
PubMed1999

"Lycostrobus" chinleana, an equisetalean cone from the Upper Triassic of the southwestern United States and its phylogenetic implications.

Detailed study of the cone Lycostrobus chinleana Daugherty shows that the fossil was incorrectly attributed to the Lycopodiales by the author and to the quillworts by Retallack and that it actually should be assigned to the Equisetales. The cone, which occurs in the Upper Triassic Chinle Formation at several localities in the southwestern United States, is ∼2.5 cm wide and nearly 6 cm long and consists of a stout axis bearing whorls of peltate sporangiophores. Each sporangiophore is composed of a slender stalk and a hexagonal disk, which typically bears a single, generally long, lanceolate, forward-directed leaf-like umbo tip on the outer surface and several recurrent sporangia on the inner surface. Small round to oval trilete spores occur in the sporangia. Since the leaf-like umbo tip is similar to the sterile leaves found in certain calamite cones and the recurrent sporangia are equisetalean-like, it appears that the cone may represent a intermediate stage between Calamites and modern Equisetum. According to this hypothesis, the nonbracteate Equisetum cone could have developed from a bracteate calamite cone, through reduction and fusion of the bracts and the sporangiophores, rather than by the loss of whorls of bracts of the Calamites cone as suggested earlier by others. As a result of this study the cone is assigned to the new Equisetalean genus Equicalastrobus and redescribed under the name E. chinleana (Daugherty) Grauvogel-Stamm and Ash, n. comb.

Journal Article↗
PubMed1998

Hemodiabsorption in treatment of hepatic failure.

Conducted at the University of California, Los Angeles, this randomized, prospectively controlled study was designed to measure the effects of a hemodiabsorption device in the treatment of 11 patients with hepatic failure and stage III to IV encephalopathy. The results of 5 days of treatment with the hemodiabsorption device were compared with those of standard intensive care procedures. The BioLogic-DT System, a simple sorbent-based system, demonstrated a slight improvement in the neurologic status of patients, a significant improvement in the physiologic status of patients, and an improved outcome for treated patients as opposed to nontreated patients.

Adult↗
PubMed1998

Bedside peritoneoscopic peritoneal catheter placement of Tenckhoff and newer peritoneal catheters.

The success of Tenckhoff chronic peritoneal dialysis catheters depends more upon the skill of the physician in placing catheters and on the technique of placement than it does on the exact design of the peritoneal catheter. In this summary article, the existing types of peritoneal catheters are reviewed, including two recent alternative designs: Tenckhoff catheters with larger internal diameters, and the T-fluted catheter with grooved limbs adjacent to the parietal peritoneum. The three types of placement procedures for catheters (peritoneoscopy, surgical or dissective, and blind techniques) are described, and the complications of Tenckhoff catheters are compared according to placement technique.

Catheters, Indwelling↗
PubMed1997

Lack of removal of calcitriol during hemodialysis procedures.

In this study, an in vitro study with blood was performed to determine whether calcitriol (Calcijex) is either bound or removed from blood by dialyzer circuits. The study utilized five different dialyzers, each with a widely varying membrane type, and standard dialysate blood lines. One liter of fresh whole bovine blood was injected with 0.6 microg calcitriol and was dialyzed against 5 L of acetate-based dialysate for 180 min. By measurement of changes in blood and dialysate levels of calcitriol, there was no evidence of any calcitriol dialytic clearance and no evidence of calcitriol binding to the blood side components for any of the dialysis circuits. The results of this study indicate that calcitriol can be injected intravenously at any time during a dialysis procedure, without significant removal of the drug from the blood by dialyzer clearance or by binding to materials in the dialyzer circuit.

Animals↗
PubMed1996

Effect of whole-body hyperthermia on AIDS patients with Kaposi's sarcoma: a pilot study.

The safety and possible efficacy of extracorporeal whole-body hyperthermia (WBHT) were evaluated in the first FDA-approved feasibility study of WBHT in persons with AIDS. Six gay men, aged 20-50 years, CDC class C-3, underwent 1 h of WBHT at either 40 degrees C or 42 degrees C, employing a system that minimizes the physiological and biochemical changes that occur during WBHT. All subjects had Kaposi's sarcoma (KS), were free of opportunistic infections, and had significant elevations of plasma HIV RNA. During the treatment, there were no adverse side effects and all subjects tolerated WBHT without problems. KS lesions partially regressed immediately following WBHT in all subjects but returned to pretreatment status in five of six patients at 1 week. In subjects treated at 40 degrees C, CD4 counts decreased during the 8-week follow-up period; they remained unchanged, however, following 42 degrees C WBHT. Viral load remained unchanged following WBHT in subjects treated at 40 degrees C. Treatment at 42 degrees C resulted in an immediate reduction in HIV RNA that was not sustained at 1 week post-WBHT. We conclude that WBHT is safe in subjects with advanced HIV disease and that it may have a role in treating HIV infection. A larger controlled trial involving two treatments in less immunocompromised subjects is currently in progress to test this hypothesis.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Peritoneal dialysis for acute renal failure: the safe, effective, and low-cost modality.

With the emphasis on acute renal failure and the popularity of continuous renal replacement therapy, peritoneal dialysis is a frequently overlooked and undervalued method of dialytic support. This review is purposefully set in a "continuous" format and addresses the frequently encountered problems that arise with these systems. Continuous peritoneal dialysis delivery in the intensive care unit and other forms of continuous therapies are compared using the following criteria: access, efficiency, biocompatibility, and hemodynamic stability. Specific study results are reviewed comparing the outcome of patients supported with peritoneal dialysis versus hemodialysis in the intensive care setting, and extrapolations from the chronic support areas are also drawn. Specific advantages and shortcomings are listed for each therapy.

Acute Kidney Injury↗
PubMed1994

Hemodiabsorption in treatment of acute hepatic failure and chronic cirrhosis with ascites.

Hemodiabsorption is a selective chemical removal process during which blood passes through dialysis membrane packages surrounded by a suspension of fine sorbent particles. The BioLogic-DT system contains charcoal and cation exchangers in a suspension that passes through dialysate spaces of a cellulosic membrane plate dialyzer. The system has proven effective in treatment of patients with serious drug overdose and has demonstrated positive effects in treatment of stage 4 coma due to hepatic failure. Recently, the charcoal in this system has been preloaded with branch chain amino acids to return these acids to patients while aromatic amino acids are removed. Further improvements include addition of osmotically active agents to the priming fluid and sorbent to increase blood oncotic pressure and transfer of ascitic fluid to blood while ultrafiltration transfers fluid out of the blood. Clinical testing of these improvements is now beginning in patients with ascites and encephalopathy due to chronic hepatic insufficiency and cirrhosis. Future improvements will include protein permeable membranes to increase removal of protein-bound toxins and addition of hepatic cells downstream from the hemodiabsorption unit.

Ascites↗