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Biomedical subjects

S D Davis

Publications and source records attributed to S D Davis.

At least 91 records · Page 5Linked to original sources
PubMed1979

Experimental Pseudomonas keratitis in guinea-pigs: therapy of moderately severe infections.

We have previously shown that antibiotic therapy of experimental Pseudomonas keratitis was more effective in early moderate infections than in late severe infections. The purpose of this study was to determine the relative efficacies of various drugs, routes, and vehicles in the treatment of moderately severe infection. As in the late severe infections, the most consistently effective regimen was an aminoglycoside applied topically in solution. No synergistic or additive effect was observed with a combination of aminoglycoside given topically and a penicillin given intramuscularly. Topical therapy with antibiotic in ointment was less effective than topical therapy with antibiotic in solution.

Administration, Topical↗
PubMed1978

Topical tobramycin therapy of experimental Pseudomonas keratitis: an evaluation of some factors that potentially enhance efficacy.

We evaluated several therapeutic modifications in an attempt to improve efficacy of topical therapy with tobramycin of experimental Pseudomonas keratitis in guinea pigs. Removal of corneal epithelium enhanced efficacy of topical therapy with 0.3 mg/ml and 3 mg/ml tobramycin sulfate but did not influence therapy with 40 mg/ml or 400 mg/ml tobramycin. The highest concentration of antibiotic was the most effective; 7 of 12 infected corneas treated with 400 mg/ml tobramycin were sterile in 48 hours. Therapy begun soon after the infection was established, when there were relatively few organisms present, was more effective than therapy begun later, when there were many more bacteria in the cornea. Our results are consistent with a basic therapeutic concept. The most effective regimen is one that achieves the highest safe concentration of antibiotic at the site of infection as early in the course of infection as possible.

Administration, Topical↗
PubMed1978

Corticosteroid in experimentally induced Pseudomonas keratitis: failure of prednisolone to impair the efficacy of tobramycin and carbenicillin therapy.

The effect of prednisolone on tobramycin and carbenicillin therapy for experimentally induced Pseudomonas keratitis was evaluated. Results were assessed quantitatively by determining the number of bacteria that survived in the cornea. Simultaneous administration of prednisolone did not adversely alter results of treatment with carbenicillin or tobramycin. In another trial, pretreatment with prednisolone for 48 hours before antibiotic therapy was begun did not change significantly the results of therapy with intramuscular tobramycin or carbenicillin. We conclude that corticosteroid therapy does not affect adversely results of antibiotic therapy with tobramycin or carbenicillin in this experimental model.

Administration, Topical↗
PubMed1978

Staphylococcal keratitis. Experimental model in guinea pigs.

An experimental model of staphylococcal keratitis in guinea pigs was devised that is suitable for quantitative evaluation of therapy. The growth curve in the cornea of a virulent strain of Staphylococcus aureus was determined. The organism multiplied rapidly, reached a peak in about 12 hours, and began to decline in numbers after three days. Infections were relatively resistant to therapy begun 24 hours after infection was established. Treatment started earlier when fewer bacteria were present was more effective than treatment begun later. Treatment begun at the time of infection, which might be considered prophylaxis, was highly effective. When treatment was begun eight hours after infection, tobramycin sulfate and gentamicin sulfate solutions administered topically in doses of 20 mg/ml were more effective than topical bacitracin, erythromycin, clindamycin phosphate, or a solution containing polymyxin B sulfate, neomycin sulfate, and gramicidin. Bacitracin and erythromycin ointments were ineffective.

Administration, Topical↗
PubMed1978

Pathogenesis of experimental Pseudomonas keratitis in the guinea pig: bacteriologic, clinical, and microscopic observations.

Uniformly severe corneal infections were produced in guinea pigs by intracorneal injection of about 10 viable Pseudomonas aeruginosa. After a brief lag period, multiplication of bacteria was rapid, reaching geometric means of 280,000 after 24 hr and of 5 million after 48 hr. Within 8 hr after inoculation, polymorphonuclear leukocytes (PMNs) began to infiltrate the anterior two thirds of the stroma. Stromal cells adjacent to the injection site became necrotic and appeared to be engulfed by PMNs. By 14 to 16 hr, an abscess containing a dense aggregate of PMNs and multiplying bacteria developed in the central stroma. By 16 to 24 hr, collagen breakdown was apparent within and around the abscess. Ultrastructural evidence of collagen breakdown included loss of intact collagen fibrils, tactoid formation, and accumulation of amorphous electron-dense material. The area of liquefactive necrosis gradually enlarged, and many corneas perforated after 3 to 4 days. Because the course of infection is highly reproducible, this model should prove useful for many studies of experimental Pseudomonas keratitis.

Abscess↗
PubMed1978

Bacteriologic cure of experimental Pseudomonas keratitis.

Two long-term therapy trials with high concentrations of antibiotic were carried out to determine the duration of therapy required to achieve bacteriologic cure of experimental Pseudomonas keratitis in guinea pigs. In the first study, corneas still contained Pseudomonas after 4 days of continual topical therapy with either tobramycin 400 mg/ml, amikacin 250 mg/ml, ticarcillin 400 mg/ml, or carbenicillin 400 mg/ml. In an 11-day trial of topical therapy with tobramycin 20 mg/ml, 34 of 36 corneas grew no Pseudomonas after 6 or more days of therapy. The bacteriologic response to therapy in this model occurred in two phases. About 99.9% or more of the organisms in the cornea were killed in the first 24 hr of therapy. The numbers of bacteria remaining in the cornea declined gradually over the next several days until the corneas were sterile. Optimal antibiotic therapy may include two stages: initial intensive therapy with high concentrations of antibiotic applied frequently to achieve a large rapid decrease in numbers of organisms in the cornea, followed by prolonged, less intensive therapy to eradicate organisms and prevent relapse.

Administration, Topical↗
PubMed1978

Therapeutic effect of topical antibiotic on untreated eye in experimental keratitis.

We studied the systemic absorption ot topical tobramycin and amikacin in experimental Pseudomonas keratitis in guinea pigs. After giving two drops of tobramycin 40 mg/ml every 30 minutes for 24 hours to both infected eyes (the corneal epithelium having removed) the mean serum concentration was 1.5 mcg/ml. Treatment of one of the infected eyes with the same strength of tobramycin or amikacin drops did not alter the number of viable bacteria in contralateral eyes treated with saline. Tobramycin 400 mg/ml or amikacin 250 mg/ml however, decreased the number of viable bacteria in the contralateral eyes. We conclude that the therapeutic effect on the contralateral eye was the result of systemic absorption.

Absorption↗
PubMed1977

Antibiotic therapy of experimental Pseudomonas keratitis in guinea pigs.

Antibiotic therapy of experimental Pseudomonas keratitis was evaluated quantitatively by determining numbers of viable bacteria in the cornea of guinea pigs. Topically applied carbenicillin disodium, gentamicin sulfate, and tobramycin sulfate were often significantly more effective than topically applied polymyxin B sulfate. Intramuscular therapy with tobramycin was as effective as topical therapy, and the results exhibited less variability. Topical tobramycin every 30 minutes was significantly more effective than topical therapy every 60 minutes. No combination of antibiotics was significantly better than a single effective drug. The concentration of tobramycin in the aqueous correlated more closely to therapeutic efficacy than did the concentration in the cornea. Although all antibiotics reduced numbers of bacteria in the cornea by more than 99% in the first 24 hours of therapy, none was able to sterilize the cornea in four additional days of continuous therapy. Persistence of organisms despite apparently adequate topical therapy may explain some reported cases of relapse in humans.

Administration, Topical↗
PubMed1977

Autoimmunity in the relatives of patients with immunodeficiency diseases.

Autoimmune disorders are reportedly more frequent than expected in immunodeficient patients and in their relatives. The hypothesis that genetic factors related to immunodeficiency may predispose to the development of autoimmunity was studied in relatives of patients with variable immunodeficiency (VID), ataxia-telangiectasia (A-T), or X-linked infantile agammaglobulinaemia (X-LA). Close relatives of patients with VID or A-T had thyroid and gastric autoantibodies significantly more frequently than did control subjects. No abnormalities were detected in unaffected relatives of X-LA patients. The increased incidence of organ-specific autoantibodies in close relatives of VID patients was confined to those families with more than one member with immunodeficiency. These data suggest that there are at least two forms of VID, one of which is associated with familial autoimmunity. It is postulated that heterozygous carriers of the A-T gene and persons with genes involved in the development of VID may exhibit T-lymphocyte dysfunction which predisposes them to autoimmunity.

Adolescent↗
PubMed1975

Partial antibiotic therapy in Haemophilus infuenzae meningitis. Its effect on cerebrospinal fluid abnormalities.

To examine the influence of partial antibiotic therapy on laboratory findings in Haemophilus influenzae meningitis, 272 untreated cases and 202 partially treated, culture-positive cases from 1953 through 1971 were reviewed. There was no significant difference between the two groups with respect to several cerebrospinal fluid (CSF) values. Both the untreated and partially treated groups had a similar proportion of cases with negative Gram stain and CSF glucose level over 40 mg/100 ml or a predominance of CSF mononuclear cells. Eight patients had received ampicillin sodium, chloramphenicol, or tetracycline for two days or more. The CSF findings of these patients resembled those of the untreated group. The data support the conclusion that antibiotics in the usual outpatient dosages seldom interfere with the diagnosis of H influenzae meningitis.

Ampicillin↗
PubMed1975

Defective antibody response to bacteriophage phichi 174 in Down syndrome.

Antibody responses to bacteriophage phichi 174 were studied in 17 institutionalized patients with trisomy 21 and in six mentally retarded control patients with normal karyotype. Primary antibody response was significantly impaired in 11 of the 17 patients. Secondary immune response was normal in one, moderately impaired in seven, and very low in nine patients. Tertiary immunization further differentiated the two groups: those with moderately impaired secondary immune responses developed normal serum titers of predominantly IgG antibody; patients with low secondary immune responses had extemely impaired tertiary immune responses consisting mainly of serum IgM antibody.

Adolescent↗
PubMed1975

Efficacy of modified human immune serum globulin in the treatment of experimental murine infections with seven immunotypes of Pseudomonas aeruginosa.

Modified immune serum globulin, prepared from human immune serum globulin by a nonenzymatic method, is apparently safe for intravenous administration to humans. The efficacy of the preparation was determined in experimental murine infections with seven immunotypes of Pseudomonas aeruginosa. Intravenously administered 0.85 percent NaCl, 0.3 m glycine, and 10 percent human albumin did not protect against lethal pseudomonas infection, whereas modified immune serum globulin given by the same route did protect mice. In the mouse protection test, the mean dose of the preparation that saved 50 percent of mice infected with any of eight strains of P. aeruginosa was 480 mg/kg (range, 12-2,333 mg/kg). For five strains the 50 percent effective dose was smaller than 200 mg/kg. There was no correlation between the efficacy of modified immune serum globulin in the mouse protection test and titers of antibody, as determined by bacterial agglutination. Therapy of pseudomonas infection in mice with modified immune serum globulin was followed by a prompt and persistent decrease in the numbers of intraperitoneal bacteria. This finding is consistent with the interpretation that modified immune serum globulin acts primarily as an opsonin and not as an antitoxin. Modified immune serum globulin may prove to be useful in the treatment of human infections.

Agglutination Tests↗