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Biomedical subjects

M Barza

Publications and source records attributed to M Barza.

At least 19 recordsLinked to original sources

Unusual manifestations of Yersinia enterocolitica infections diagnosed using novel methods.

We report the cases of two patients who had infections due to Yersinia enterocolitica. The first patient exhibited chronic recurrent fever, hepatic and splenic granulomas, and bone marrow abnormalities, and the second patient presented with enterocolitis with leukocytoclastic vasculitis of the skin. Cultures and agglutination titers were negative. Indirect immunofluorescence techniques with use of serotype-specific antisera and antisera to Yersinia outer-membrane proteins (Yops) were applied to biopsy specimens, and immunoblotting techniques for determining class-specific circulating antibodies to Yops were used for demonstrating these unusual manifestations of Y. enterocolitica infections.

Adult

An improved apparatus for transscleral iontophoresis of gentamicin.

The authors previously found that positively charged substances are less well-transported into the vitreous humor by transscleral iontophoresis than are negatively charged substances. There was more bubble formation in the eye cup with positively charged than with negatively charged substances. The authors hypothesized that these bubbles might account for the poorer conductance of the positively charged species by causing interruptions of the current. Therefore, the authors developed a modified eye cup in which the diameter of the fluid column was larger than that in the old device (1.0 rather than 0.5 mm). This modification allowed larger voltage to be applied than with the older device, because bubbles could be more easily cleared from the conjunctiva than with the narrower-bore eye cup. Although the efficiency of the apparatus was the same with the two eye cups (micrograms per milliliter in vitreous humor divided by milliampere minutes of current applied), vitreal concentrations of gentamicin with the modified eye cup were fourfold higher than with the older eye cup (83 versus 19 micrograms/ml; P < 0.001). These studies suggest that modifying the eye cup to permit easier removal of bubbles resulted in improved delivery of gentamicin into the ocular humors.

Animals

Use of quinolones for treatment of ear and eye infections.

Malignant otitis externa is a severe, necrotizing infection of the external auditory canal which is sometimes fatal. The traditional antimicrobial treatment has usually been the combination of an antipseudomonal beta-lactam and an aminoglycoside, given intravenously for 4 to 8 weeks. Over 100 patients have been treated with a fluoroquinolone alone, most commonly ciprofloxacin given by mouth in a dosage of 750 mg b.i.d. for 6 to 12 weeks. About 90% of patients have been cured. Treatment with a quinolone has the advantage over older treatments that it can be given orally and has a low rate of side-effects. The ocular penetration of the fluoroquinolones has been studied in patients with unifected eyes. After the administration of a single dose of ciprofloxacin, pefloxacin, ofloxacin or norfloxacin, penetration into the aqueous humor, expressed as the ratio of the peak concentration in the aqueous humor to that in the serum, is about 20%. The penetration of ciprofloxacin into the vitreous humor, based primarily on the data from one report, is about 20%. The concentrations are likely to be higher after repeated doses or in the inflamed eye. Whether the concentrations achieved will be adequate for therapeutic or prophylactic purposes has not been determined.

4-Quinolones

Neuraminidase activity in acanthamoeba species trophozoites and cysts.

Acanthamoeba species, a widely distributed group of free-living amoeba, can infect humans and spread hematogenously after direct interaction with the mucosal surfaces. The mechanism underlying Acanthamoeba damage to the target cell is unknown. The authors report that trophozoites and cysts of Acanthamoeba species exhibit a neuraminidase activity that is membrane associated and released into the culture medium at the start of the logarithmic phase of growth. The enzyme activity is optimal at pH 5 and at 25-30 degrees C. Live parasites release sialic acid from human cells. Therefore, the neuraminidase of Acanthamoeba species could be relevant in the colonization and damage of the sialic acid-rich corneal epithelium and in the alterations of glycolipids associated with meningoencephalitis.

Acanthamoeba

Bacterial adherence to extended wear soft contact lenses.

The authors studied the adherence of Pseudomonas aeruginosa and Staphylococcus aureus to extended wear soft contact lenses (EWSCLs) with and without focal deposits using both a radiolabeling technique and electron microscopy. P. aeruginosa showed significant adherence to contact lenses in vitro. In contrast, S. aureus failed to show significant adherence to contact lenses in vitro (i.e., the radioactive uptake was not significantly above background). The extent of adherence of Pseudomonas was proportional to the number of focal deposits on the lenses. Results of electron microscopic examination showed the bacteria to be adherent primarily to large focal deposits (greater than or equal to 150 microns). There was no pseudomonal adherence to the small focal deposits (less than or equal to 50 microns) and little adherence to the areas in between the focal deposits. The authors hypothesize that worn lenses, especially those with large focal deposits, serve as a vehicle for the transport of P. aeruginosa to the cornea. This hypothesis could be a partial explanation for the high incidence of keratitis caused by P. aeruginosa in EWSCL patients.

Bacterial Adhesion

Therapy for shigellosis. II. Randomized, double-blind comparison of ciprofloxacin and ampicillin.

Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin-treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis.

Adult

Binding of Pseudomonas aeruginosa to neutral glycosphingolipids of rabbit corneal epithelium.

35S-labeled Pseudomonas aeruginosa isolates were shown to bind to neutral glycosphingolipids (NGSLs) of rabbit corneal epithelia in culture by a thin-layer chromatogram overlay procedure. The lipids of the corneal epithelial cells grown in culture were extracted and partitioned into a chloroform-rich lower phase containing NGSLs and an aqueous upper phase containing gangliosides. By using a dot-blot assay, at least six times more radiolabeled P. aeruginosa isolates were shown to bind to the lipids in the lower phase compared with those in the upper phase. Thin-layer chromatography of the lower-phase lipids followed by staining with an orcinol spray revealed at least 10 NGSL components and several fast-migrating, nonglycosylated neutral lipid components (including cholesterol). 35S-labeled P. aeruginosa was shown to bind to NGSL components 1, 2, 5, 6, and 9. P. aeruginosa-reactive NGSL components 6 and 9 migrated with chromatographic mobilities similar to those of the standards ceramide trihexoside (CT) and ceramide monohexoside, respectively. Components 1 and 2 migrated slightly ahead of asialo GM1, and component 5 migrated faster than globoside but slower than CT. Among the various standards tested, P. aeruginosa bound to asialo GM1 and, to a lesser extent, to ceramide dihexoside and CT but not to GM1, GD1A, GM3, or ceramide monohexoside. It remains to be determined whether any of the five P. aeruginosa-reactive NGSL components of corneal epithelium identified in this study plays a role in the development of corneal infection. However, we have previously shown that component 9, one of the five P. aeruginosa-reactive NGSL components identified in this study, is present in significantly greater amounts in migrating epithelia than it is in nonmigrating epithelia (N. Panjwani, G. Michalopoulos, J. Song, G. Yogeeswaran, and J. Baum, Invest. Ophthalmol. Vis. Sci., in press). This may prove to be of biological significance because it is generally believed that traumatized (migrating) epithelia are more susceptible to infection than normal (nonmigrating) epithelia are.

Animals

Differential binding of P. aeruginosa and S. aureus to corneal epithelium in culture.

Adherence of bacteria to corneal epithelium is a prerequisite for corneal infection. We used two methods to study the binding of Pseudomonas aeruginosa and Staphylococcus aureus to rabbit corneal epithelial cells in culture. In the first method, rabbit corneal epithelial cells grown on glass slides were incubated with P. aeruginosa or S. aureus (10(7) CFU/ml) at room temperature for 90 min, and the bacterial binding to the epithelial cells was examined by light microscopy. Both P. aeruginosa and S. aureus bound to epithelial cells. P. aeruginosa was bound to the cell periphery whereas S. aureus was bound randomly to the cell surface. In the second method, suspension cultures of corneal epithelial cells were used. In contrast to the findings in cultures on slides, binding pattern with cells in suspension was similar for both species and resembled that for S. aureus in cultures on slides. A much greater number of P. aeruginosa (186 +/- 11 bacteria/epithelial cell) than S. aureus (30 +/- 1.5 bacteria/epithelial cell) bound to epithelial cells grown on glass slides. In contrast, a similar number of P. aeruginosa (25 +/- 5.1) and S. aureus (20 +/- 4.7) bound to epithelial cells grown in suspension cultures. Using either method, Escherichia coli and Streptococcus pyogenes did not bind significantly (less than 5/cell) to corneal epithelial cells. The above methods should prove useful for characterization of bacterial binding to corneal epithelial cells in culture.

Animals

Effect of lid closure on contact lens-associated Pseudomonas keratitis.

New or used extended-wear soft contact lenses, preincubated in suspensions of Pseudomonas aeruginosa, were placed on the corneas of rabbits. The lids were then sutured shut for either 1 or 2 weeks. Bacterial keratitis occurred in 9 of 9 eyes fitted with the used contaminated lenses but in none of 12 eyes fitted with new contaminated or new noncontaminated lenses. Similar experiments were carried out with other lenses specifically designed to fit the cornea of rabbits. Some of these lenses were preworn by rabbits for 1 week (used), whereas others were new. A significantly greater incidence of bacterial keratitis was found in eyes that had undergone lid closure after the placement of used contaminated lenses (4 of 5) than in closed eyes with new contaminated lenses (1 of 8) and in open eyes with used contaminated lenses (0 of 13). These findings suggest that extended eyelid closure is a risk factor in the experimental model and may be a factor in clinical Pseudomonas keratitis associated with the wearing of extended-wear soft contact lenses.

Animals

Antibacterial agents in the treatment of ocular infections.

There are a number of barriers to the ocular transport of poorly lipid-soluble antibiotics such as beta-lactams and aminoglycosides. Knowledge of these barriers can help the physician in the choice of agent and the route of administration for specific ocular infections. Because of the corneal epithelial barrier, topically applied drugs should be administered frequently; "fortified" drops afford higher corneal concentrations than commercially available drops. Periocular injections may occasionally be of benefit in the treatment of refractory corneal ulcers. The mainstay of treatment of bacterial endophthalmitis should be intravitreal injection of antimicrobial agents; ancillary treatments include the periocular and systemic administration of antimicrobial agents, the systemic administration of probenecid, the administration of corticosteroids, and the use of vitrectomy.

Animals

Use of antibacterial agents in infections of the central nervous system.

The movement of drugs from the systemic circulation into the central nervous system is restricted by several factors, including the blood-brain and blood-CSF barriers, an active transport system that affects primarily the beta-lactam antibiotics, and the high degree of serum protein binding of certain agents. The functions of the blood-brain and blood-CSF barriers and of the active transport system are reduced but not abolished by inflammation. For most antimicrobial agents, the major determinant of passage aside from serum protein binding is the degree of lipid-solubility of the drug. The beta-lactam and aminoglycoside antibiotics and vancomycin penetrate the central nervous system relatively poorly, whereas chloramphenicol, metronidazole, the fluoroquinolones and trimethoprim-sulfamethoxazole fare better. Knowledge of the relative capacity of various drugs to penetrate the central nervous system after systemic administration may help the physician to choose an optimum regimen for the treatment of bacterial meningitis and brain abscess.

Anti-Bacterial Agents

Bilateral keratitis as a manifestation of Lyme disease.

An 11-year-old girl developed bilateral keratitis, which we believe was a manifestation of Lyme disease. She had had several attacks of Lyme arthritis and was twice treated with parenteral penicillin. The keratitis developed five years after the initial episode of Lyme arthritis at a time when there were no other manifestations of Lyme disease. It cleared completely in both eyes after topical corticosteroid therapy.

Child

Prospective study comparing imipenem-cilastatin with clindamycin and gentamicin for the treatment of serious surgical infections.

Surgical infection remains a leading cause of hospital morbidity and mortality. We compared the efficacy and toxicity of imipenem-cilastatin sodium in 32 patients with that of clindamycin phosphate and gentamicin sulfate in 25 patients. In the imipenem-cilastatin group, 87.5% had a favorable outcome, with a 12.5% failure rate and 13 adverse reactions. In the clindamycin-gentamicin group, 80% had a favorable outcome, with a 20% failure rate and ten adverse reactions. Two significant superinfections with Pseudomonas and Candida were noted in patients treated with impenem-cilastatin. Each group had one case of Clostridium difficile-associated colitis. Cost analysis showed no differences between treatment arms, except in the appendicitis subgroup. For serious surgical infections, single-agent therapy with imipenem-cilastatin appears to be as efficacious as combination therapy with clindamycin and gentamicin.

Adolescent

Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin 1.

Natural and synthetic immunomodulators that increase nonspecific resistance to infection are also known to induce interleukin 1 (IL 1) production. Previous studies have demonstrated a protective effect of recombinant human IL 1 beta against death from infection caused by Pseudomonas aeruginosa. In the present study we investigated the effect of IL 1 beta or IL 1 alpha on the survival of neutropenic mice with a lethal Candida albicans infection. Mice with cyclophosphamide-induced neutropenia were injected with 3 X 10(5) C. albicans i.v. When 80 ng IL 1 beta was given as a single i.p. injection 24 h before the infection, survival compared to that in control animals was as follows: 100% vs. 97% at 24 h, 83% vs. 70% at 48 h and 70% vs. 23% at 72 h after the infection (p less than 0.01). The effect of IL 1 was also apparent when it was given 1/2 h before or 6 h after the infection. The results obtained with 80 ng IL 1 alpha given at 24 h before infection were similar to that obtained with IL 1 beta. The numbers of Candida cultured from the blood, liver, spleen, and kidney were not significantly different in IL 1 beta-treated and control animals. Passive transfer of serum obtained from mice pretreated with IL 1 to recipient mice did not provide protection against a subsequent lethal candidal infection. In conclusion, the present study demonstrates that IL 1 beta and IL 1 alpha prolong survival in neutropenic mice with a lethal C. albicans infection.

Agranulocytosis