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Biomedical subjects

C Washington

Publications and source records attributed to C Washington.

At least 37 records · Page 2Linked to original sources
PubMed1995

Structure and toxicity of amphotericin B/triglyceride emulsion formulations.

This paper investigates the relationship between the in-vitro toxicity of amphotericin B/triglyceride emulsion formulations, and their phospholipid composition and method of manufacture. Emulsion toxicity, as measured by the erythrocyte potassium leakage assay, was found to be dependent on the transition temperature of the phospholipid emulsifier, and the thermal history of the emulsion. Emulsions made using unsaturated phospholipids showed a low toxicity irrespective of the method of manufacture. Emulsions made using phospholipids with phase transition temperatures above the maximum process temperature displayed a toxicity comparable to the deoxycholate-solubilized formulation. This toxicity was significantly reduced when such formulations were heated to a temperature above the phase transition temperature for the phospholipid. We interpret these data as demonstrating that the amphotericin molecule must be inserted fully into the phospholipid emulsifier in order to produce a low toxicity emulsion, and that this insertion is critically dependent on the composition of the emulsifier and its phase transition properties.

Amphotericin B↗
PubMed1995

Enhanced protoplast growth at the interface between oxygenated fluorocarbon liquid and aqueous culture medium supplemented with pluronic F-68.

Protoplasts isolated from cell suspensions of albino Petunia hybrida were grown for 10 d at the interface between aqueous culture medium and oxygenated perfluorodecalin. Protoplasts synthesised new cell walls and divided normally at the fluorocarbon/culture medium interface, the mean division frequency of protoplasts being increased by 37% (P < 0.05) in this system when the perfluorodecalin was saturated with oxygen prior to use. The mean division frequency of protoplasts was further increased to a maximum of 52% above control (P < 0.01) when the medium overlaying the oxygenated perfluorodecalin was supplemented with 0.01% (w/v) of the co-polymer surfactant, Pluronic F-68. These results demonstrate a beneficial and synergistic effect of supplementing protoplast culture systems with oxygenated perfluorodecalin and Pluronic F-68.

Cell Division↗
PubMed1993

Computational prediction of the stability of lipid emulsions in total nutrient admixtures.

The relationships between the stability of lipid emulsions in a number of parenteral total nutrient admixtures (TNAs) and their electrokinetic properties were examined. Previous studies have attempted to measure or calculate zeta potentials of lipid emulsions in nutrient admixtures to rationalize their stability behavior, but there has been no demonstration that zeta potentials do actually determine emulsion stability or that such computational approaches can be successful. The present study demonstrates that emulsion stability in a range of TNAs is dependent on the emulsion zeta potential and also that van der Waals forces, influenced by the presence of glucose, are important. By accounting for these factors we show that it is possible to calculate the stability of TNAs by Deryaguin-Landau-Verwey-Overbeck-based methods and obtain reasonable agreement with experimental stability data in most systems.

Drug Stability↗
PubMed1993

Physicochemical properties of parenteral fat emulsions containing 20% triglyceride; Intralipid and Ivelip.

The paper describes an in-depth study of the parenteral fat emulsions, Intralipid 20% and Ivelip 20%. A large number of emulsion samples from separate containers and batches was sampled. The parameters measured were droplet size (both by photon correlation and laser diffraction), pH and zeta potential. These parameters were re-measured after the emulsions were subjected to a number of accelerated stability tests (freeze-thaw cycling, autoclaving and shaking). The results demonstrate that although the Intralipid is stable, it can show some variability between separate batches. The stability of Ivelip is high, and the variability between separate batches is extremely low.

Calcium↗
PubMed1993

Head-up tilt testing with and without isoproterenol infusion in healthy subjects of different ages.

Passive head-up tilt testing with or without infusion of isoproterenol is used in the investigation and management of patients with syncope. Twenty-five healthy asymptomatic volunteers prospectively grouped according to age (young [28 +/- 1.7 years]: n = 9; middle [51 +/- 3.3 years]: n = 11; elderly [81 +/- 2.4 years]: n = 5; mean +/- SE) were studied during: (1) supine carotid sinus massage; (2) 60 degrees head-up tilt alone; and (3) infusion of isoproterenol to raise the heart rate 20% above supine baseline, prior to 10-minute repeat tilt. Symptoms occurred in three subjects (12%) and only occurred with passive tilting alone. Two young subjects had syncope with sinus pauses greater than 10 seconds. One elderly subject developed atrial flutter. No subject had symptoms or hypotension during tilt plus isoproterenol or a pause greater than 3 seconds with carotid sinus massage. With passive tilt, mean heart rate increased by 16 +/- 6 beats/min and 18 +/- 7.8 beats/min in the young and middle aged subjects (P < 0.05), but only by 6 +/- 5 beats/min in the elderly (P = NS, supine vs 60 degrees in each group). With head-up tilt plus isoproterenol infusion, the mean heart rate elevation in response to tilt was 17 +/- 9 beats/min, 8 +/- 3 beats/min, and 12 +/- 4 beats/min for the young, middle, and elderly subjects, respectively (P < 0.05, supine vs 60 degrees in each group).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Uptake of concentrated perfluorocarbon emulsions into rat lymphoid tissues.

The effects of injecting (10-30 mL kg-1) either perfluorodecalin (FDC) emulsions of increasing phase fraction (20-60% w/v) or the commercial formulation, Fluosol, on lymphoid tissues have been studied for up to 7 days in male rats. Tissue weights increased by up to 123% (P < 0.05) in proportion with quantity of perfluorochemical (PFC) injected, with spleen responses consistently greater than those of the liver. PFC droplets recovered from these tissues at 72 h after injection of 30% (w/v) FDC emulsion (10 mL kg-1) had mean diameters in the 1-10 microns range, with those from the spleen being larger than those from the liver. Recovered droplet diameters were considerably greater than freshly-prepared emulsion mean particle sizes (0.21-0.25 microns). These results suggest that coalescence of emulsion droplets following accumulation in lymphoid tissue is a pre-requisite for the eventual excretion of PFC vapour through the lungs.

Animals↗
PubMed1993

Emulsified perfluorochemicals as respiratory gas carriers: recovery of perfluorodecalin emulsion droplets from rat tissues.

To further understand the in-vivo biokinetic behaviour of perfluorochemical (PFC) emulsions, male rats were injected (10 mL kg-1) with 30% (w/v) emulsified perfluorodecalin (FDC) and uptake into tissues assessed. At 72 h after injection, the mean (+/- s.e.m.) diameters of FDC droplets recovered from liver and spleen were 2.24 +/- 0.04 and 2.78 +/- 0.10 microns, respectively; droplets recovered from lung after 72 h (mean: 1.73 +/- 0.13 micron) were significantly smaller (P < 0.01). After 7 days, FDC droplet diameters in liver had increased to 3.31 +/- 0.13 microns (P < 0.01) and those in lung to 2.71 +/- 0.14 microns (P < 0.01); droplets in spleen after 7 days (2.22 +/- 0.09 microns) were similar to those at 72 h. These data support the hypothesis that significant initial coalescence of FDC droplets occurs in the rat liver and spleen, with further coalescence in the liver up to 7 days. The mean percentage of the injected FDC dose recovered from the liver after 72 h was 2.2 +/- 0.4%, and after 7 days was 0.07 +/- 0.05% (P < 0.01). A smaller decrease in the percent injected FDC in spleen also occurred over the same period (72 h: 1.9 +/- 0.3%; 7 days: 0.8 +/- 0.5%; P < 0.01). The percent injected FDC in lung was similar at 72 h (0.007 +/- 0.004%) and 7 days (0.005 +/- 0.001%). FDC was undetectable (< 0.001%) in all blood samples. The greater rate of FDC elimination from the liver than from the spleen may be related to differences in the rates of reticuloendothelial system processing between these organs.

Animals↗
PubMed1993

Rheology of model aerosol suspensions.

The rheological properties of model aerosol suspensions at phase fractions of less than 5% w/v (phase ratio of 0.05) were investigated. The rheological profiles of lactose in chloroform, lactose in trichlorofluoromethane (Propellent 11, P11), and salbutamol sulphate in P11 have been investigated in the presence and absence of lecithin, a phospholipid surface-active agent. The relative viscosities of these disperse systems correlated with the increasing disperse phase fractions and the addition of surfactant was found to reduce these viscosities to a relative viscosity of approximately 1.0. The results suggest that the relative viscosity is a useful indicator of flocculation in these systems, and may be valuable in formulation development.

Aerosols↗
PubMed1993

Non-invasive detection of gastro-oesophageal reflux using an ambulatory system.

The aim of this study was the separate measurement of reflux of food and acid into the oesophagus in 37 healthy, ambulant subjects. This was performed by radiolabelling the food and monitoring its reflux with a small directional gamma detector, which was placed externally over the oesophagus, and connected to an ambulatory data recorder. The pH was measured with a conventional oesophageal pH electrode. This method permitted the separate characterisation of acid and neutral (food) components of gastro-oesophageal reflux. The gastric emptying characteristics of the test meal were also monitored by gamma scintigraphy in a separate experiment. The oesophageal pH fell below 4 for 3.2 + 8.6/-2.3% (mean (SD)) of the recording time. Food reflux alone occurred for 17.8 + 53.2/-13.8% of the recording time. Simultaneous food and acid reflux occurred for only 0.95 + 5.2/-1.2% of the time. Not every reflux event detected by a fall in pH was seen as an increase in counts as a result of reflux of food, and vice versa. This poor correlation of food and acid reflux implies incomplete mixing of food and acid in the stomach, and further shows the inadequacy of reflux diagnosis methods that depend on pH detection alone.

Adult↗
PubMed1992

Lymphoid tissue responses to concentrated perfluorochemical emulsions in rats.

The effects of injecting perfluorochemical (PFC) emulsions of varying concentrations on lymphoid tissues have been studied in rats. Tissue weights were increased in proportion with quantity of PFC injected, with spleen responses consistently greater than those of the liver. PFC droplets recovered from tissues had mean diameters in the 1-10 microns range, with those from the spleen being larger than from the liver. Recovered droplet diameters were considerably greater than freshly-prepared emulsion mean particle sizes (0.20-0.25 microns). This suggests that coalescence of emulsion droplets following accumulation in tissues is a pre-requisite to the eventual excretion of PFC vapour through the lungs.

Animals↗
PubMed1991

Toxicity of amphotericin B emulsion to cultured canine kidney cell monolayers.

The effect of amphotericin B in an emulsion formulation on the integrity of monolayers of kidney cells has been studied. Whereas a conventional solubilized amphotericin formulation (Fungizone, Squibb) caused a loss in monolayer integrity at concentrations above 1 microgram mL-1, the emulsion formulation had no measurable effect on confluence at amphotericin concentrations up to 100 micrograms mL-1. The emulsion retained a comparable antifungal activity to that of Fungizone against Saccharomyces cerevisiae in suspension culture. These results parallel the observed erythrocyte lysis data obtained previously using amphotericin B emulsions, and suggest that the emulsion formulation may have a lower toxicity and improved therapeutic potential over existing formulations.

Amphotericin B↗
PubMed1991

Wadia type olivopontocerebellar degeneration: a case history and review of literature.

Olivocerebellar pontine degeneration of the Wadia type is characterized by progressive symmetrical cerebellar ataxia, slow eye movements, absent deep tendon reflexes, autosomal dominant inheritance, and onset between the second and fourth decades. The only available treatments are genetic counseling, social and psychological support, and physiotherapy. This article presents a case of this subtype of hereditary ataxia and a review of the literature.

Adult↗
PubMed1990

Cardiovascular effects of doxorubicin.

1. Doxorubicin dose-dependently increased the cardiac contractility of isolated frog heart within the dose-range of 1.0 to 10.0 x 10(-7) M and dose-dependently increased the cardiac output of frog heart in situ with a dose-range between 10(-7) and 10(-5) M. 2. The results of the in situ investigation, using cardiac output as the index of cardiac contractility, were in agreement with the in vitro results. The positive inotropic effects of doxorubicin climaxed around 10(-5) M beyond which there was a dose-dependent decreased in contractility. 3. Haloperidol (10(-6) M), a dopaminergic receptor blocker, and propranolol (10(-8) M), a beta-adrenergic blocker, did not block the positive inotropic effects of doxorubicin. 4. These results provide sufficient basis to suggest that doxorubicin is acting on the isolated amphibian heart through a mechanism which is not associated with beta-adrenergic and/or dopaminergic receptors.

Animals↗
PubMed1989

Purification of pluronic F-68 for perfluorochemical emulsification.

A novel technique for purification of Pluronic F-68 has been developed involving passage through a silica-Amberlite resin column. Impurities present in commercial grade Pluronic could be readily removed, as confirmed by analysis of absorption and fluorescence emission bands. Intravenous injection of a 4% (w/v) unpurified Pluronic solution in male rats increased mean liver weight by 14% (P less than 0.05) after 24 h and increased spleen weight in female rats by 29% (P less than 0.01) after 7 days. No corresponding tissue weight changes occurred following injection of purified Pluronic solution. Haematocrit and red cell counts were also unchanged throughout. We propose that the use of purified Pluronic for perfluorochemical emulsification may reduce previously reported side-effects.

Animals↗