Biomedical subjects

Ian C Michelow

Publications and source records attributed to Ian C Michelow.

7 recordsLinked to original sources

PubMed2005

The mannose-binding lectin: a prototypic pattern recognition molecule.

The innate immune system is comprised of a sophisticated network of recognition and effector molecules that act together to protect the host in the first minutes or hours of exposure to an infectious challenge. The mannose-binding lectin (MBL) is an evolutionary conserved circulating host defense protein that acts as a broad-spectrum recognition molecule against a wide variety of infectious agents. Target binding triggers the MBL pathway of complement activation. MBL can be considered conceptually as an 'ante-antibody' because it has a role in mammals during the lag period that is required to develop an antibody response against infectious agents. Additionally, there are MBL-like homologues in animals that lack adaptive immunity that activate a primitive complement system, and under these circumstances these MBL-like molecules play an analogous role to antibodies in higher animals. These molecules might be considered to be functional antecedents of antibodies. Recent work also indicates that MBL recognizes altered self-antigens, and as such MBL has a role that extends beyond a traditional role in first line host defense as it appears to play a role as a modulator of inflammation.

Animals↗

PubMed2004

Diagnostic utility and clinical significance of naso- and oropharyngeal samples used in a PCR assay to diagnose Mycoplasma pneumoniae infection in children with community-acquired pneumonia.

PCR assays of naso- and oropharyngeal samples among hospitalized children appear equally effective for the diagnosis of serologically confirmed community-acquired mycoplasmal pneumonia. However, the combination of results from both sites yields optimal sensitivity (57%), specificity (98%), and positive (92%) and negative (82%) predictive values when compared with Mycoplasma pneumoniae enzyme-linked immunosorbent assay.

Child↗

PubMed2004

Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children.

OBJECTIVES: The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. METHODS: Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. RESULTS: One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months (range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (> or = 38.4 degrees C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4-3.5) and the presence of pleural effusion (odds ratio: 6.6; 95% confidence interval: 2.1-21.2) were significantly associated with bacterial pneumonia. CONCLUSIONS: This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children. The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia. These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines.

Adolescent↗

PubMed2003

Garenoxacin (BMS-284756) and moxifloxacin in experimental meningitis caused by vancomycin-tolerant pneumococci.

The emergence of multidrug-resistant strains of Streptococcus pneumoniae drives the development and evaluation of new antipneumococcal agents, especially for the treatment of bacterial meningitis. The aims of the present study were to assess the antibacterial effectiveness of two new quinolones, garenoxacin (BMS; BMS-284756) and moxifloxacin (MOX) in experimental meningitis caused by a vancomycin (VAN)-tolerant S. pneumoniae strain and to compare the results with those obtained by therapy with VAN and ceftriaxone (CRO) in combination. Meningitis was induced in young male New Zealand White rabbits by intracisternal inoculation of a VAN-tolerant pneumococcal strain (strain Tupelo) from a child with meningitis. Sixteen hours after inoculation, therapy was given by intravenous administration of BMS at 20 mg/kg of body weight, followed 5 h later by administration at a dosage of 10 mg/kg (n = 9 animals) or MOX as two doses of 20 mg/kg every 5 h (n = 8 animals). For comparison, we studied the following groups: (i) animals treated with VAN (20 mg/kg every 5 h, three doses) and CRO (125 mg/kg, one dose) (n = 9), (ii) animals infected with a VAN-tolerant strain but not treated (n = 8), (iii) animals infected with a VAN-tolerant pneumococcus isolated from the nasopharynx of a carrier and treated with BMS (n = 8), and (iv) animals infected with a cephalosporin-resistant type 6B S. pneumoniae strain and treated with BMS (n = 6). The MICs of penicillin, CRO, VAN, BMS, and MOX for the Tupelo strain were 2, 1, 0.5, 0.06, and 0.03 micro g/ml, respectively. The rates of killing of strain Tupelo (the change in the log(10) number of CFU per milliliter per hour) in cerebrospinal fluid at 5 h were -0.70 +/- 0.35, -0.61 +/- 0.44, and -0.49 +/- 0.36 for BMS, MOX, and VAN-CRO, respectively. Therapy with BMS and MOX was as effective as therapy with VAN-CRO against VAN-tolerant pneumococcal meningitis in rabbits.

Animals↗

PubMed2002

Central nervous system infection in congenital syphilis.

BACKGROUND: Identification of infants with Treponema pallidum infection of the central nervous system remains challenging. METHODS: We used rabbit-infectivity testing of the cerebrospinal fluid to detect T. pallidum infection of the central nervous system in infants born to mothers with syphilis. The results were compared with those of clinical, radiographic, and conventional laboratory evaluations; IgM immunoblotting of serum and cerebrospinal fluid; polymerase-chain-reaction (PCR) assay testing of serum or blood and cerebrospinal fluid; and rabbit-infectivity testing of serum or blood. RESULTS: Spirochetes were detected in the cerebrospinal fluid of 19 of 148 infants by rabbit-infectivity testing. Exposure of the infant to antibiotics before cerebrospinal fluid was obtained for rabbit-infectivity testing was associated with a negative test result (P=0.001). Spirochetes were detected in the cerebrospinal fluid in 17 of 76 infants (22 percent) who had no prior antibiotic exposure. These 17 infants included 41 percent (16 of 39) of those with some abnormality on clinical, laboratory, or radiographic evaluation; 60 percent (15 of 25) of those with abnormal findings on physical examination that were consistent with congenital syphilis; and 41 percent (17 of 41) of those with a positive result on IgM immunoblotting or PCR testing of serum, blood, or cerebrospinal fluid, or a positive result on rabbit-infectivity testing of serum or blood. Only one infant who had normal findings on clinical evaluation had a positive cerebrospinal fluid rabbit-infectivity test. Overall, central nervous system infection was best predicted by IgM immunoblotting of serum or PCR assay of serum or blood. CONCLUSIONS: Most infants with T. pallidum infection of the central nervous system can be identified by physical examination, conventional laboratory tests, and radiographic studies. However, the identification of all such infants requires the use of additional tests, including IgM immunoblotting and PCR assay.

Adult↗

PubMed2001

Diagnosis of Streptococcus pneumoniae lower respiratory infection in hospitalized children by culture, polymerase chain reaction, serological testing, and urinary antigen detection.

A prospective study of 154 consecutive high-risk hospitalized children with lower respiratory infections was conducted to determine the clinical utility of a pneumolysin-based polymerase chain reaction (PCR) assay compared with blood and pleural fluid cultures and serological and urinary antigen tests to determine the incidence of Streptococcus pneumoniae. Whole blood, buffy coat, or plasma samples from 67 children (44%) tested positive by PCR. Sensitivity was 100% among 11 promptly tested culture-confirmed children and specificity was 95% among control subjects. Age, prior oral antibiotic therapy, and pneumococcal nasopharyngeal colonization did not influence PCR results, whereas several surrogates of disease severity were associated with positive tests. Although serological and urinary antigen tests had comparable sensitivity, specificity varied among infected children, and statistical agreement among all assays was limited. These findings support the use of PCR tests to evaluate the protective efficacy of pneumococcal conjugate vaccines and to identify promptly children with pretreated or nonbacteremic pneumococcal lower respiratory infections.

Adolescent↗

PubMedDate not supplied

Pneumonia in term neonates: laboratory studies and duration of antibiotic therapy.

OBJECTIVES: To compare 2 days of antibiotic therapy (AT) to 4 days of AT in neonates with pneumonia and to assess the usefulness of neutrophil values (NV), C-reactive protein (CRP), and procalcitonin (PCT) in this population. DESIGN: The study population consisted of consecutive, eligible term neonates begun on AT for suspected pneumonia. Of 51 neonates, 26 qualified for randomization (14, 2-day group; 12, 4-day group). NV were obtained with the initial evaluation and 12 and 24 hours later. CRP and PCT were obtained 12 and 48 hours after the initial evaluation. RESULTS: None of the 12 neonates in the 4-day group developed recurrent respiratory symptoms. Three of the 14 neonates randomized to the 2-day group had recurrence of symptoms, resulting in study termination. NV, CRP, and PCT were similar in the 2- and 4-day groups. In the three neonates who developed respiratory symptoms, all absolute total neutrophil values and five out of nine absolute total immature neutrophil values were abnormal. However, all immature:total neutrophil values were normal, and CRP was strikingly elevated in only one neonate; only one of six PCT values was abnormal. In a secondary analysis of all 51 study neonates, CRP and PCT did not provide additional benefit over NV in differentiating neonates with pneumonia. CONCLUSIONS: Four days of AT appears to be adequate for selected term neonates with pneumonia; however, 2 days of AT appears to be inadequate for this population. Relative to NV, CRP and PCT appear to have a limited role.

Ampicillin↗