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Biomedical subjects

P D Mangino

Publications and source records attributed to P D Mangino.

3 recordsLinked to original sources

Pamidronate.

OBJECTIVE: The primary objective of this article is to introduce readers to the use of a new agent, pamidronate. The article discusses its use in hypercalcemia of malignancy (HCM), osteolytic lesions, and Paget's disease. Pharmacokinetic data and clinical trials are reviewed, as well as adverse effects and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify English-language studies involving pamidronate for the period from 1970 to 1992. STUDY SELECTION: As comparative trials were few in number, trials using pamidronate as a single agent were also reviewed. DATA EXTRACTION: Sparse pharmacokinetic data were obtained from clinical trials. All clinical trials available at the time of publication that met the following criteria were reviewed: (1) allowed for adequate rehydration prior to drug therapy; (2) reported standardized and corrected serum calcium concentrations; (3) separated data obtained from patients who received pamidronate alone from those who received pamidronate and concurrent chemotherapy. RESULTS: Pamidronate has a pharmacologic profile similar to that of etidronate, but pamidronate is more potent and has a longer duration of effect. It has been investigated primarily in the treatment of HCM as well as in the treatment of osteolytic bone metastases and Paget's disease. In hypercalcemia of malignancy it appears to be as effective as established agents with the advantage that a single dose of pamidronate 90 mg iv provides a durable response. In Paget's disease chronic oral administration has also been shown to be effective in relieving bone pain. Adverse reactions with intravenous administration are transient and self-limiting and usually occur with the first dose. The most common adverse effect is a transient and self-limiting fever. Chronic oral administration of doses greater than 600 mg/d is associated with gastrointestinal toxicities. CONCLUSIONS: Although more well-designed clinical trials comparing pamidronate with standard therapies and other available agents are necessary, initial results indicate that pamidronate is an effective and promising alternative for use in the treatment of HCM.

Bone Neoplasms↗

Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures.

Antibiotic-impregnated polymethylmethacrylate (PMMA) beads have been useful in treating orthopedic infections. Local delivery has been reported to establish wound antibiotic levels well above the therapeutic range while avoiding serum levels associated with increased incidence of side effects. After operative debridement, 70 patients with compound fractures were treated prophylactically with tobramycin-impregnated PMMA beads. Observations of antibiotic levels in 27 patients demonstrated antibiotic levels in the wound drainage and clot that were significantly in excess of the usual therapeutic range for tobramycin and simultaneous nontoxic serum levels. Significant levels of tobramycin can be achieved in the extracellular fluid at the fracture site when tobramycin-impregnated PMMA beads are placed in the wound after irrigation and debridement.

Debridement↗

In vitro characteristics of tobramycin-PMMA beads: compressive strength and leaching.

Antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement beads have been used as a local drug delivery system for the treatment of bone and soft tissue infections. The beads deliver a high local level of antibiotic with a decreased risk of toxic systemic levels. This study was undertaken to determine the antibiotic release characteristics of tobramycin-impregnated beads over time and to determine the compressive strength of these beads. Acrylic resin (PMMA) bone cement beads were prepared with three different concentrations of tobramycin. The beads were tested for compressive strength, and their antibiotic release characteristics were determined over a 21 day period by radioimmunoassay and by biological testing against a variety of bacteria. The compressive strength of the beads was found to be adequate to avoid fragmentation during their clinical use. There was gradual release of tobramycin from the beads over the entire 21 days, but the release was most marked during the first 48 hours. There was antibiotic activity against both gram-negative and gram-positive organisms, except Enterococcus, for the entire 21 day period. The release of tobramycin followed a curvilinear relationship and was directly related to the initial antibiotic concentration of the bead. Tobramycin-impregnated polymethylmethacrylate beads may represent a reliable method of local antibiotic delivery with sustained activity against a broad spectrum of organisms.

Bone Cements↗