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Biomedical subjects

J A Setterstrom

Publications and source records attributed to J A Setterstrom.

11 recordsLinked to original sources

Evaluation of hypersensitivity to microencapsulated ampicillin in guinea pigs.

The purpose of this study was to determine if the sustained release of ampicillin from a biodegradable drug-delivery system (microencapsulated ampicillin anhydrate (MEAA)) will increase or decrease the intensity of a hypersensitivity reaction compared with that observed with free drug. Ovalbumin, which is known to elicit a marked hypersensitivity reaction in guinea pigs, and microencapsulated ovalbumin (MOVA) were tested in parallel with ampicillin and MEAA. Guinea pigs were sensitized biweekly by subcutaneous and intramuscular injections of ampicillin, MEAA, ovalbumin, MOVA or placebo microspheres (test articles), each mixed with Freund's adjuvant, and challenged 2 weeks later, intradermally, with the free compounds. In a separate set of experiments, guinea pigs were sensitized by implantation of the same agents in the caudal thigh of anaesthetized animals. Skin allergic reactions were tested at 1 and 3 weeks following local implantation of the test articles. Sera of sensitized guinea pigs were tested for specific IgG antibodies by enzyme-linked immunosorbent assay, and skin samples from the site of the inflammatory reaction were fixed, stained and evaluated histologically. Guinea pigs sensitized systemically with MEAA or MOVA showed smaller, but not statistically different skin allergic response than animals given corresponding free compounds. However, guinea pigs sensitized by local implantation of MEAA showed a significantly lower inflammatory response (P < 0.0001) than those given an equivalent dose of the free drug. Guinea pigs sensitized with placebo microspheres showed a low inflammatory skin reaction which was similar to those sensitized with all doses of MEAA. There was no significant difference in specific IgG antibody response in the sera of guinea pigs sensitized locally with either free or microencapsulated ampicillin or ovalbumin. Histology of skin revealed a milder inflammatory reaction with MEAA or MOVA than with ampicillin or ovalbumin, respectively. We conclude that the encapsulated ampicillin or ovalbumin and subsequent release of each agent will elicit a reduced hypersensitivity reaction in guinea pigs than will the free agent.

Ampicillin↗

Effect of microencapsulated ampicillin on cell-mediated immune responses in mice.

The effects of free ampicillin, microencapsulated ampicillin anhydrate (MEAA) and antibiotic-free microspheres on the cell-mediated immune response in Balb/c mice were measured by lymphoproliferation assay, delayed-type hypersensitivity (DTH) and cytokine production. Injection into mice for seven consecutive days with equivalent subcutaneous doses of ampicillin, MEAA or placebo microspheres did not produce any consistent change in lymphocyte proliferation nor did it affect DTH responses or interleukin-2 production. Although the production of interleukin-4 in mice treated with ampicillin or MEAA increased compared with the control mice, this increase was not statistically significant. These results indicate that ampicillin and MEAA have similar effects on cell-mediated immunity in mice.

Ampicillin↗

Evaluation of biodegradable ampicillin anhydrate microcapsules for local treatment of experimental staphylococcal osteomyelitis.

Successful treatment of chronic osteomyelitis requires sustained high concentrations of antibiotics locally within the infected bone. The efficacy of biodegradable (poly-DL-lactide-co-glycolide) microspheres containing 30.7% ampicillin anhydrate for the local treatment of experimental staphylococcal osteomyelitis was evaluated in rabbits. In the initial experiment, antibiotic therapy was initiated immediately following injection of Staphylococcus aureus into the proximal tibial metaphysis. A single intramedullary injection of microencapsulated ampicillin (100 mg) prevented osteomyelitis in all seven animals tested and was as effective as a two-week course of parenteral ampicillin administration. When antibiotic therapy was delayed for seven days, osteomyelitis developed in four of eight animals treated locally with microencapsulated ampicillin and in six of eight animals that received parenteral ampicillin therapy. When antibiotic therapy was delayed for seven days and was preceded by debridement, all ten animals treated locally with microencapsulated ampicillin had sterile bone cultures. In contrast, seven of ten animals treated locally with unencapsulated ampicillin powder developed osteomyelitis. Biodegradable antibiotic-loaded microspheres may be of clinical benefit for the local treatment of chronic osteomyelitis.

Ampicillin↗

Infection in war wounds: experience in recent military conflicts and future considerations.

War wounds are characterized by devitalized tissue, the presence of debris, and contamination by bacteria--factors that contribute to the establishment of wound infection. A review of the literature regarding the incidence of wound infection in recent military conflicts strongly suggests that infection in open war wounds occurs with relative frequency despite strict adherence to the principles of surgical debridement and administration of "prophylactic" antibiotics. Further research leading to improved methods of preventing wound sepsis is warranted in order to reduce the incidence of wound infections in the future.

Acute Disease↗

Spandra: a sustained release battlefield wound dressing.

In 1981, our laboratories developed a family of elastomers which could be cured by ultraviolet (UV) radiation. Curing by UV radiation was a significant advance in chemistry, since it allowed ultra-fast curing of elastomers in a matter of seconds, as compared to several hours at 110 degrees C for conventional heat curing. We applied for a patent based on this technology, and the patent was allowed in mid-1984 [29]. Based on this technology, Thermedics submitted a proposal to the US Army for the development of a sustained-release battlefield wound dressing containing antibiotics and coagulants. The drugs were evenly distributed in the oligomer matrix, and subsequently cured in seconds under UV illumination, without the use of heat, organic solvents or water. Because delicate drugs are not subjected to heat, organic solvents or water, the pharmacological activity of the drugs is insured. Therefore, theoretically any drug may be incorporated into our dressing. Sustained release dressings were first developed at Thermedics in 1983, spurred by a contract from the US Army Medical Research and Development Command. Under this contract, the Company developed a new type of wound dressing capable of accelerating the healing process, retarding infection, and minimizing pain. Based on our TECOFLEX materials technology, the dressing performs like temporary artificial skin. Its transmission properties for oxygen, carbon dioxide, and water vapor are similar to those of intact skin. Thus, while excluding bacteria from the wound site, the dressing maintains an optimal moist environment for the promotion of rapid healing. The new drawing shown in Figure 10 minimizes pain during healing by preventing dehydration and shrinkage in the wound. Patient comfort is also enhanced by the incorporation of a special fabric which imparts flex properties to the bandage that are almost identical to those of human skin, with greater stretch in one direction than in another. This also facilitates application to complex body contours by only one attendant, an important feature in both hospital and emergency situations. Materials currently in use in hospitals are difficult to handle, requiring two or three nurses to apply large dressings. Thermedics' military wound dressing not only has the significant advantage of ease of application, but this dressing can also be used for delivery of drugs to a specific site.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Cutaneous↗

The antibacterial effects of calcium hydroxide apexification pastes on Streptococcus sanguis.

Four calcium hydroxide-based apexification pastes were tested for their antibacterial effects on Streptococcus sanguis. Their zones of growth inhibition on blood agar plates were measured at 2, 4, 6, and 8 days. Only the camphorated parachlorophenol and the metacresylacetate pastes showed zones of inhibition. Both of these zones of inhibition decreased with time; however, the zones of inhibition for the parachlorophenol paste decreased at a slower rate.

Calcium Hydroxide↗

Immunoglobulins in periodontal tissues. II. Concentrations of immunoglobulins in granulation tissue from pockets of periodontosis and periodontitis patients.

In recent years evidence in the literature has indicated that the immune response may play an important role in the initiation and progression of the periodontal diseases. A study was initiated to determine the IgA, IgG, and IgM concentrations in the granulation tissue removed from deep infrabony pockets of patients with periodontosis and advanced periodontitis. Comparison of mean immunoglobulin levels between the periodontosis and periodontitis groups revealed a statistically significant increase (P less than 0.05) for IgG in the granulation tissue from the periodontosis group. The possible implications of these findings are discussed.

Adolescent↗

Immunoglobulins in periodontal tissues. III. Concentrations of immunoglobulins in dilantin-induced and idiopathic gingival hyperplastic tissues.

Immunoglobulin levels in both Dilantin-induced and idiopathic hyperplastic gingiva were determined and compared with the concentrations in normal gingival tissue. A statistically significant increase in IgG was found in Dilantin hyperplastic tissue, but no significant difference could be shown for idiopathic gingival hyperplasia. IgA levels did not differ significantly in the three types of tissue assayed. IgM was detected in 90% of the Dilantin hyperplastic gingival specimens assayed (mean GI = 1.2) and in 75% of the idiopathic hyperplastic tissue (mean GI = 0.7). This incidence of IgM detection was higher than that reported for normal and inflamed gingiva from periodontitis patients. The significance of these findings and possible correlation with the degree of tissue inflammation are discussed.

Adolescent↗

Comparison of Minitek and conventional methods for the biochemical characterization of oral streptococci.

Fifty-six strains of viridans streptococci were tested in the Minitek system (BBL Microbiology Systems, Cockeysville, Md.), and the results were compared with those obtained by conventional methods. An overall agreement of 98.9% was obtained when the Minitek tests were performed as follows. (i) All disks were incubated anaerobically for 48 h except for esculin and arginine, which required 5 to 7 days. (ii) The arginine disks were overlaid with 0.1 ml of sterile mineral oil even though incubated anaerobically. (iii) The Voges-Proskauer tests were performed under aerobic and anaerobic conditions. (iv) All tests for carbohydrate fermentation except for raffinose and salicin were read after the addition of 2 to 3 drops of 0.025% phenol red (pH 7.2). Of all the tests performed, only the fermentation of starch resulted in such poor agreement as to be considered unreliable. Results for inulin (unavailable in the Minitek system) were obtained by conventional methods.

Arginine↗

The effects of thermal and electrical injury on pulpal histamine levels.

The present investigation was undertaken to determine possible quantitative changes in porcine pulpal histamine levels following thermal and electrical insult. Quantitative spectrophotofluorometric assays revealed a fourfold increase in pulpal histamine levels within 30 minutes of thermal injury. These findings suggest that histamine may play a role in the initial stages of pulpal inflammation. Electrical insult was found to have no significant effect on pulpal histamine contents 30 minutes after insult. The possible implications of these findings are discussed.

Animals↗