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Biomedical subjects

C Cabellos

Publications and source records attributed to C Cabellos.

29 records · Page 2Linked to original sources
PubMed1995

Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis.

Using a rabbit model of meningitis, we sought to determine whether concomitant use of dexamethasone affects the penetration and efficacy of ceftriaxone or vancomycin in cerebrospinal fluid. Rabbits were inoculated with a penicillin-sensitive strain of Streptococcus pneumoniae and treated with ceftriaxone or vancomycin with or without dexamethasone. In the ceftriaxone-treated groups, no statistically significant differences were seen between the group treated with dexamethasone and that without dexamethasone; however, in the vancomycin-treated groups we found statistically significant lower cerebrospinal fluid vancomycin levels at 2 h in the dexamethasone-treated rabbits and differences in bacterial killing.

Animals↗
PubMed1995

Hypersensitivity hepatitis due to pyrazinamide.

Pyrazinamide hepatotoxicity is considered secondary to a direct and dose-related toxic effect. At currently used doses, pyrazinamide provides effective short-term treatment and is free from serious side effects. We report a case of pyrazinamide-induced hepatitis for which the rechallenge data strongly suggest a hypersensitivity mechanism.

Acute Disease↗
PubMed1995

[Protective effect of dexamethasone and phenytoin in the treatment of experimental pneumococcal meningitis].

BACKGROUND: Pneumococcal meningitis has a high morbidity and mortality rate despite effective antibiotherapy, probably due to an exaggerated inflammatory response of the CNS. The use of dexamethasone and phenytoin reduced mortality in adults with pneumococcal meningitis. OBJECTIVE: We sought to determine the effect of dexamethasone, phenytoin or the association of both in several inflammatory parameters in experimental bacterial meningitis. METHODS: The study was performed using a modification of the rabbit model of Dacey and Sande. New Zealand white rabbits were intracisteranly inoculated simultaneously with heat-killed S. pneumoniae R6 dexamethasone, phenytoin or both. CSF leucocytes and concentration of proteins and lactate were determined over 6 hours, as well as the presence of brain edema. RESULTS: Treatment with dexamethasone alone or in association with phenytoin reduced all inflammatory parameters. The administration of phenytoin alone did not prevent an increase of CSF leucocytes or protein concentration, but did prevent the development of brain edema. A trend to wards a protective effect on the lactate concentration was observed. CONCLUSIONS: Our results gives support to the antiinflammatory effect of dexamethasone in experimental pneumococcal meningitis, and suggest that phenytoin may have also a protective effect on brain ischemia. This protective action and the prevention of brain edema could contribute, beyond its anticonvulsivant properties, to the great reduction in the mortality rate observed in some clinical studies in patients with pneumococcal meningitis.

Animals↗
PubMed1993

The biologic activities of peptidoglycan in experimental Haemophilus influenzae meningitis.

While gram-positive bacterial cell walls are known to incite inflammation, the contribution of gram-negative peptidoglycan to disease has not been characterized. The ability of cell wall, purified peptidoglycan, and soluble peptidoglycan subcomponents from Haemophilus influenzae to provoke inflammation was determined in a rabbit model of meningitis. Haemophilus peptidoglycan, with or without associated proteins, produced brain edema at > or = 0.1 micrograms/mL of cerebrospinal fluid (CSF); leukocytosis and protein accumulation in CSF occurred only at > or = 10.0 micrograms/mL of CSF. Solubilized peptidoglycan was 10-fold more active than intact cell wall. The bioactivity of peptidoglycan from ampicillin-resistant H. influenzae was at least twofold greater than that of ampicillin-sensitive strains. Consistent with these pathologic effects of purified peptidoglycan, ampicillin-induced bacterial lysates in which endotoxin was neutralized induced brain edema and protein influx but little leukocytosis. Thus, peptidoglycan seems to contribute to the pathology of gram-negative meningitis, particularly brain edema.

Ampicillin Resistance↗
PubMed1993

Progression of hearing loss in experimental pneumococcal meningitis: correlation with cerebrospinal fluid cytochemistry.

The development of hearing loss and concomitant cerebrospinal fluid (CSF) cytochemical changes in a model of pneumococcal meningitis were examined. Rabbits were injected intracisternally with 10(5) pneumococci. Auditory evoked potentials to clicks and to 10- and 1-kHz tone bursts were recorded hourly; CSF was analyzed every 4 h. Sensorineural hearing loss developed in all animals beginning 12 h after infection and progressed to severe deafness. The onset of hearing loss was preceded by a CSF leukocytosis of > 2000 cells/microL and elevation of CSF protein and lactate concentrations to > or = 1 mg/mL. Temporal bone histopathology showed pneumococci and leukocytes extending from the CSF to the perilymph via the cochlear aqueduct. Hearing loss can develop early in the course of meningitis and is preceded by the abrupt onset of inflammatory changes in CSF. Progression of hearing loss is rapid and proceeds from cochlear base to apex in parallel with the degree of inflammation.

Animals↗
PubMed1992

Bacterial components and the pathophysiology of injury to the blood-brain barrier: does cell wall add to the effects of endotoxin in gram-negative meningitis?

In animal models, the lipopolysaccharide (LPS) from Haemophilus influenzae contributes to all the signs of meningitis associated with living bacteria. However, when tested in vitro, the amount of LPS in cerebrospinal fluid (CSF) in natural disease shows much greater effects on leukocytes than on endothelial permeability. To investigate whether other bacterial components act with LPS to incite meningeal inflammation, animals were challenged intracisternally with H. influenzae lysates. Upon neutralization of endotoxin, leukocytosis was greatly attenuated, but protein accumulation in CSF persisted. Cell wall from H. influenzae induced meningeal inflammation in a pattern opposite to that of LPS. Its ability to induce blood-brain barrier permeability greatly exceeded its ability to induce leukocytosis in vivo. Thus, cell wall, by acting on endothelia, and LPS, by inducing leukocytosis, may cooperate to induce inflammation in H. influenzae meningitis. Optimal reduction of inflammation and tissue damage in meningitis may require agents directed against cell wall as well as LPS.

Animals↗
PubMed1992

Differing roles for platelet-activating factor during inflammation of the lung and subarachnoid space. The special case of Streptococcus pneumoniae.

Although well-characterized in the lung, the role of platelet-activating factor (PAF) in inflammation in the central nervous system is undefined. Using rabbit models of meningitis and pneumonia, PAF was found to induce significant blood-brain barrier permeability and brain edema at doses five times lower than those required to generate leukocyte recruitment to the subarachnoid space. Both leukocytosis and increased vascular permeability occurred in response to PAF in the lung. Antibody to the CD-18 family of leukocyte adhesion molecules inhibited leukocyte recruitment in response to PAF in the brain (greater than 80%); a similar level of inhibition in the lung required treatment with a combination of a PAF receptor antagonist (L-659,989) and anti-CD18 antibody. Treatment with L-659,989 decreased abnormal cerebrospinal fluid cytochemical values induced by intracisternal challenge with pneumococci but not Haemophilus influenzae, indicating a special role for PAF in pneumococcal disease. Antibodies directed at phosphorylcholine, a unique, shared determinant of bioactivity of PAF and pneumococcal cell wall, obviated the inflammatory potential of both agents. However, no evidence for a direct PAF-like activity of pneumococcal cell wall components was detected in vitro by bioassay using platelets or neutrophils. It is concluded that PAF can induce inflammation in the subarachnoid space. In brain, PAF effects appear to be mediated through CD-18-dependent events, while in lung, PAF effects independent of CD-18 are also evident. At both sites, PAF is of particular clinical importance during inflammation induced by pneumococci apparently due to a unique proinflammatory relationship between the pneumococcal cell wall teichoic acid and PAF.

Animals↗
PubMed1991

Integrin-mediated localization of Bordetella pertussis within macrophages: role in pulmonary colonization.

The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough but the significance of bacterial attachment to macrophages has not been determined. Adherence to cilia and macrophages is mediated by two large, nonfimbrial bacterial proteins, filamentous hemagglutinin (FHA), and pertussis toxin (PT). PT and FHA both recognize carbohydrates on cilia and macrophages; FHA also contains an Arg-Gly-Asp (RGD) sequence which promotes bacterial association with the macrophage integrin complement receptor 3 (CR3). We determined that virulent B. pertussis enter and survive in mammalian macrophages in vitro and that CR3 is important for this uptake process. We then determined the relative contribution of CR3 versus carbohydrate-dependent interactions to in vivo pulmonary colonization using a rabbit model. B. pertussis colonized the lung as two approximately equal populations, one extracellular population attached to ciliary and macrophage surface glycoconjugates and another population within pulmonary macrophages. Loss of the CR3 interaction, either by mutation of FHA or treatment with antibody to CR3, disrupted accumulation of viable intracellular bacteria but did not prevent lung pathology. In contrast, elimination of carbohydrate-bound bacteria, either by a competitive receptor analogue or an anti-receptor antibody, was sufficient to prevent pulmonary edema. We propose that CR3-dependent localization of B. pertussis within macrophages promotes persistence of bacteria in the lung without pulmonary injury. On the other hand, the presence of extracellular bacteria adherent to cilia and macrophages in carbohydrate-dependent interactions is associated with pulmonary pathology.

Adhesins, Bacterial↗
PubMed1989

Intravenous ciprofloxacin therapy in severe infections.

Fifty evaluable patients (34 men and 16 women; mean age, 47 years) with severe infections were given intravenous ciprofloxacin (200 mg every 12 hours) for a mean of 14 days. Therapy was continued with oral ciprofloxacin 500 to 750 mg every 12 hours in 34 cases for a mean of 57 days. The sources of the infections were bone and joint (26 patients), respiratory tract (10 patients), urinary tract (four patients), soft tissue (four patients), abdominal (three patients), bacteremia of unknown origin (two patients), and right-sided endocarditis (one patient). Fifteen patients (30 percent) were bacteremic. Causative organisms included Pseudomonas aeruginosa (32 patients), other gram-negative bacilli (18 patients), and gram-positive cocci (nine patients). Minimal inhibitory concentrations ranged between 0.03 and 1 microgram/ml. Mean peak serum concentrations were 1.58 micrograms/ml (intravenous) and 2 micrograms/ml (oral); mean trough serum concentrations were 0.23 micrograms/ml (intravenous) and 0.32 micrograms/ml (oral). Serum bactericidal activity values achieved after intravenous and oral therapy were similar. Response to therapy was evaluated separately in patients with or without osteomyelitis. In 30 patients with infections other than osteomyelitis, clinical cure was achieved in 27 (90 percent), and therapy failure occurred in three patients. In the 20 remaining patients with osteomyelitis, 15 (75 percent) had a satisfactory response, with apparent cure after a mean follow-up of 11 months, whereas five had therapeutical failure (P. aeruginosa became resistant in four of them). Overall, no major adverse effects were encountered. Superinfection by a resistant P. aeruginosa was observed in three patients. Intravenous ciprofloxacin is an effective and safe agent for the therapy of severe infections caused by susceptible organisms.

Adolescent↗