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Biomedical subjects

D Musher

Publications and source records attributed to D Musher.

At least 19 recordsLinked to original sources
PubMed1998

Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein.

Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed that variants differ in the presence of ChoP on the cell surface-exposed outer core of the lipopolysaccharide. During nasopharyngeal carriage in infant rats, there was a gradual selection for H. influenzae variants that express ChoP. In addition, genotypic analysis of the molecular switch that controls phase variation predicted that the ChoP+ phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP+ variants of nontypable H. influenzae were more sensitive to the bactericidal activity of human serum unrelated to the presence of naturally acquired antibody to ChoP. Serum bactericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway. Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype).

Amino Acid Sequence↗
PubMed1990

Levels of rifampin and ciprofloxacin in nasal secretions: correlation with MIC90 and eradication of nasopharyngeal carriage of bacteria.

To predict the efficacy of antibiotics in eliminating nasopharyngeal carriage of organisms such as Neisseria meningitidis, Haemophilus influenzae, and methicillin-resistant Staphylococcus aureus (MRSA), a novel approach for measuring drug concentrations in nasal secretions was developed. Five healthy individuals received four doses of rifampin and then, at a later date, ciprofloxacin. At 2, 5, and 8 h after the last dose, serum, saliva, and cold-stimulated nasal secretion samples were collected, and drug levels were analyzed by high-performance liquid chromatography. Nasopharyngeal levels of rifampin reached but did not substantially exceed 90% of the minimal inhibitory concentration (MIC90) for H. influenzae, exceeded the MIC90 for N. meningitidis, and were well above that for MRSA. Ciprofloxacin levels in nasal secretions far exceeded the MIC90 for meningococci and Haemophilus organisms but were below that for MRSA. These findings are consistent with the clinical studies showing that rifampin eliminates, in most instances, the nasal carriage of N. meningitidis and to a lesser extent H. influenzae. A single dose of ciprofloxacin has been shown to eradicate meningococci, yet a long course of treatment with this drug is not adequate for MRSA. On the basis of these results, clinical trials with ciprofloxacin to eliminate nasopharyngeal carriage of H. influenzae appear to be warranted.

Carrier State↗
PubMed1990

Syphilis.

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HIV Infections↗
PubMed1989

Cephalosporin penetration into soft tissue of paralyzed limbs.

Poor penetration of antibiotics into paralyzed tissue may contribute to the difficulty of curing soft tissue infections in paralyzed limbs. A novel model of spinal cord hemisection was used to induce paralysis of one hind leg in mice. Five, 10, or 20 days after induction of paralysis, six groups of 10 mice were injected intravenously with a single dose or with four sequential doses of cefepime, a new broad-spectrum cephalosporin, and then sacrificed. High-performance liquid chromatography was used to compare cefepime levels in soft tissue homogenates of paralyzed and normal hind legs; no significant differences were found in any group. Factors other than antibiotic delivery may be responsible for difficulty in curing infections in paralyzed soft tissue.

Animals↗
PubMed1986

Immunity to Haemophilus influenzae type b in young adults: correlation of bactericidal and opsonizing activity of serum with antibody to polyribosylribitol phosphate and lipooligosaccharide before and after vaccination.

Naturally acquired humoral immunity is thought to protect adults against serious infections due to Haemophilus influenzae type b (Hib). Antibody to the polyribosylribitol phosphate (PRP) capsule is generally considered protective; antibody to lipooligosaccharide (LOS) or outer membrane protein (OMP) may also play a role. Serum from 23 of 50 healthy young adults had no bactericidal effect (BE) against Hib yet opsonized these organisms for approximately 30% uptake by polymorphonuclear leukocytes. The degree of bactericidal and opsonizing activity in serum from the other 27 subjects generally correlated with the level of antibody to PRP but not to LOS or OMP. However, serum from some individuals had levels of antibody to PRP as high as 4.9 micrograms/ml without BE, and seven of 27 subjects with BE had antibody levels of less than 1 microgram/ml. After vaccination with 20 micrograms of conjugated PRP, the level of antibody to PRP was greater than 5 micrograms/ml in all 50 subjects. BE appeared in 22 of those who originally lacked it, and opsonization increased to approximately 50%.

Adult↗
PubMed1984

Nontypable Haemophilus influenzae are unencapsulated both in vivo and in vitro.

Some investigators have suggested that nontypable Haemophilus influenzae isolated from sputum of adults with pneumonia are variant forms of typable H influenzae that have lost their capsule during passage in vitro. We examined colonies of both typable and nontypable H influenzae after they had been grown in vitro, as well as bronchopulmonary secretions from patients with pneumonia or acute, purulent tracheobronchitis due to H influenzae; electron microscopy combined with ruthenium-red staining was used to detect the presence of capsular glycocalyx. H influenzae types a, b, and e', whether grown in vitro or observed directly in bronchopulmonary secretions, had readily detectable capsular glycocalyx external to the cell membrane. In contrast, non-typable H influenzae appeared to be unencapsulated after cultivation in vitro or when directly visualized in bronchopulmonary secretions of infected patients.

Bronchitis↗
PubMed1983

Sepsis and empyema caused by Yersinia enterocolitica.

Yersinia enterocolitica is the cause of gastrointestinal infection in the overwhelming majority of recognized cases, although extraintestinal sites are occasionally involved. We report a case of Y. enterocolitica septicemia and empyema complicated by the adult respiratory distress syndrome. The organism was also recovered from the patient's feces by alkaline enrichment and persisted through at least 19 days of antibiotic treatment.

Empyema↗
PubMed1982

Fever and infection in spinal cord injury patients.

Fever, infection, or both occurred at some time during hospitalization in 67% of patients on referral spinal cord injury service. A single cause of fever was generally found, with urinary tract and soft-tissue infections predominating; these responded well to appropriate management. In contrast, spinal cord injury patients on other services seen in consultation by the infectious disease service had far more complicated and advanced disease. Multiple infections were diagnosed in the majority of these patients, with urinary tract and decubitus ulcers predominating. Complicating osteomyelitis was present in more than half of those who had infected decubitus ulcers. In both groups of patients, diagnosis required careful attention to physical and laboratory examination because multiple potentially infected areas could be identified and because usual symptoms were sometimes masked by altered sensation.

Adult↗
PubMed1980

A 100-foot fall.

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Adult↗