Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage-directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991).

Administration, Intranasal↗

PubMedDate not supplied

Cardiac volume.

Explore the source record for details and available documents.

Cardiac Volume↗

PubMedDate not supplied

[Report on coronary angioplasty by the joint working group of the International Society and Federation of Cardiology and the World Health Organization].

Explore the source record for details and available documents.

Angioplasty, Balloon↗

PubMedDate not supplied

Computer-modulated patient-controlled analgesia. Preliminary evaluation of a prototype.

BACKGROUND AND OBJECTIVES: To provide patients with better postoperative pain relief, the authors developed a prototype computer-controlled infusion pump capable of establishing a steady drug plasma concentration based on patient needs. METHODS: A two-compartment pharmacokinetic model was used to compute the required infusion scheme. Using known pharmacokinetic parameters, the model and the pump's accuracy were studied in four dogs. In the first part of the study, the morphine pharmacokinetic profile of each dog was analyzed and used to develop the parameters of a model tailored to that particular dog. In the second part, this tailored model was implemented to test whether the infusion device was able to achieve the desired concentration profile. RESULTS: The computer-controlled infusion device was able to achieve all the desired plasma concentrations. CONCLUSIONS: These data suggest that it is possible to refine postoperative pain management with adaptive computer algorithms implemented to establish stable plasma analgesic concentrations and to automatically wean the analgesic over time.

Algorithms↗

PubMedDate not supplied

Cyclosporine increases the intracellular free calcium concentration in electrically paced isolated rat cardiomyocytes.

The effect of cyclosporine on the mean cytoplasmic free calcium concentration in electrically paced single cardiomyocytes from adult rats was studied. Cardiac myocytes were paced by electrical field stimulation with either 2 or 3 Hz in the presence of 5 micrograms/ml cyclosporine or the solvent cremophor. Exposure to cyclosporine during 40 minutes of electrical pacing caused irreversible hypercontracture in most cells, only 22.1% +/- 1.2% (mean +/- SEM) remained rod-shaped versus 64.1% +/- 3.2% in the solvent (p = 0.01). The cytoplasmic free calcium concentration was measured by means of digital image processing of fura-2 fluorescence. Electrical field stimulation increased the cytoplasmic free calcium from 69.7 +/- 5.4 to 124.9 +/- 24.5 nmol/L Ca2+ in the presence of the solvent and from 84.2 +/- 25.4 to 250.1 +/- 55.9 nmol/L in the presence of cyclosporine (p = 0.036 versus solvent). The data provide direct evidence that cyclosporine enhances the cytoplasmic free calcium concentration in single paced rat cardiomyocytes. These findings may be of importance in the consideration of a possible cardiotoxicity of cyclosporine.

Animals↗

PubMedDate not supplied

Evaluation of two dose individualisation methods for carboplatin.

The pharmacokinetics of carboplatin are usually evaluated by measuring plasma concentrations of ultrafiltered platinum (UP). This approach, however may be less reliable than measuring the plasma concentration of total platinum (TP). In a group of 14 patients, which constituted a reference group, the clearance of TP was highly correlated with creatinine clearance, as estimated by the method of Cockroft and Gault. This relationship, together with only morphological and biological parameters, was used to estimate TP clearance, Vc and AUC, in a validation group of 8 patients. Estimated TP clearance was 97.9 +/- 18% of the actual value. The TP pharmacokinetic parameters of the reference group were used to estimate those of the validation group, using only two or three plasma concentration measurements (Bayesian approach). With the Bayesian approach, the estimated TP clearance was up to 99.9 +/- 2.7% of the actual value. In conclusion, estimation of TP pharmacokinetics may be reliably estimated as an alternative to UP in clinical practice.

Adult↗